Nature India Special Issue: COVID-19 Crisis

Special Issue/June 2020

COVID-19 CRISIS Nature India examines the pandemic

The full picture Vaccine race Dangerous ideas In association with Why patient data The most promising Combatting viral matters approaches misinformation 2 | Nature India | Vol 576 | 5 December 2020 30 June 2020

EDITORIAL New Delhi, India [email protected] From the editor Editor-in-chief: Subhra Priyadarshini Editors: Rebecca Dargie, Sara Phillips, Amanda Rider Art and design: Paula Lock, Marian Karam Photographic editor: Amany Shawkey Subhra Priyadarshini introduces this special Project management: Shaimaa Ramadan Creative director: Wojtek Urbanek COVID-19 issue of Nature India. STRATEGIC PARTNERSHIPS Senior Manager, India Sonia Sharma or most of us, 2020 will be marked as the year of great imponderables. We seem to know Tel: +91 9650969959 [email protected] as much about the new coronavirus SARS-CoV-2 and its effects on the human body and societies at large, as we don’t. Ever since the virus broke out, ‘uncertainty’ is one of the SUBSCRIPTIONS AND REPRINTS [email protected] most commonly used words in conversation, news reportage and emails. Across the globe, very few lives have been untouched by the direct or indirect effects REGISTERED OFFICE Fof the novel coronavirus. China, the most populous nation on Earth, bore its brunt as the virus Springer Nature India Pty Ltd: 7th floor, Vijaya Building, 17 Barakhamba Road jumped into human populations in the country’s Hubei province in late 2019. Though China New Delhi, 110 001 India reacted quickly to contain it, the contagion had spread via international travellers. Email [email protected] www.natureasia.com/en/nindia India, the world’s second most populous nation, reported the first case of the novel coronavirus on 30 January 2020. The number of people becoming infected by the virus began to © 2020 Springer Nature Limited. All rights reserved. rise quickly, prompting the government to impose a two-month complete shutdown of the country – the longest ever in its history.

DISCLAIMER An enormous population, a weak healthcare system, and traditionally meagre investments Nature India Special Issues are sponsored supplements in scientific research and development meant there was enough reason to worry. However, that aim to stimulate interest and debate around a subject of interest to the sponsor, while satisfying the NRG the severe economic and social fallouts, like elsewhere in the world, forced the government editorial values and our readers’ expectations. Most of our to allow a regulated easing out of lockdown. special issues focus on affairs pertaining to science and Nature India started reporting on COVID-19 in India from the outset. As the pandemic began research in India and at the same time are of significance to the global scientific community. unsettling every facet of life from healthcare to education and community life to businesses, our coverage embraced a new normal, going beyond pure science to a parallel reflection of its The Nature India Special Issues are available freely for download at www.nature.com/nindia. links with society, culture and life. Nature India’s special issue on COVID-19, therefore, seeks to consider answers from the Connect with us: facebook.com/npgindia @NatureInd future. In a rapidly evolving pandemic, some of the articles in this special issue bear a time stamp. However, they will hopefully remain relevant for a long time to come as chronicles of

Cover image: the biggest human crisis any of us has faced in our lifetimes. As we scrutinize India’s response Ashish Vaishnav/SOPA Images/LightRocket via Getty to the mammoth healthcare challenge, we also look at vaccines and drugs being tested across Image the world in a hope to arrest the respiratory infection. We dive into the science of how the immune system responds to the virus and question whether submitting genome sequences to global repositories at record speeds makes any sense without accompanying patient data. We explore how the packaging of the future would look, and explain how to care for the elderly and critically ill in times when hospitals are struggling to accommodate COVID-19 patients. Everyone has a COVID-19 story to tell. We feature some extraordinary everyday stories — a doctor on the frontline handling COVID-19 patients in a Delhi hospital, a scientist in the southern state of Kerala who hasn’t been able to start her dream laboratory due to the lockdown, and an Arctic explorer who endured months of darkness and isolation in the north pole before coming back to a world struck by a new virus. This special issue also features the story of Ayurveda, and why it is time for India to apply scientific rigour to the study of the ancient system of medicine. We talk of the importance of socially influential groups, scientists, and religious leaders, in spreading the right messages and scotching misinformation in a public health emergency. In many countries including India, the pandemic is testing the limits of science and of human perseverance. It is taking a toll on our mental health – how we live, work and communicate are set to change for a long time to come. Science will hopefully find a solution to this unprecedented human suffering soon.

Subhra Priyadarshini Editor-in-chief

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A lifeline vaccine must be universal p. 6 Coronavirus sequencing efforts urgently Spreading the word in times of fear p. 34 need patient data. p11

Editorial 22 A call to sow seeds for nutrition 32 Misinformation and myths security go viral 1 Subhra Priyadarshini introduces India announced free food grains From the belief that drinking tea this special COVID-19 issue of for more than 800 million people will protect against COVID-19, to Nature India. during the COVID-19 lockdown. poisonings, misunderstanding and Features and comments However, nutrition security is hoaxes are common in this time of more important than food security uncertainty. 4 Indian scientists in vital search during this crisis and beyond, 34 Spreading the word in times for solutions experts say. Finding rapid approaches at all of fear levels to protect the world’s second 24 Protecting the elderly from the Religious leaders can help largest population will be crucial. risks of isolation disseminate important messages in The physical and psychological the COVID-19 crisis. 6 A lifeline vaccine must be health of our senior citizens 36 From deep freeze to a lockdown universal demands urgent attention, now Polar scientist Vishnu Nandan It is time to revamp global supply more than ever before. mechanisms to ensure everyone returned home from a four-month has access to a coronavirus vaccine 26 As COVID-19 takes its toll, burden lockdown in the Arctic. He talked when it becomes available. of other health crises too heavy to Nature India about coming back to bear into a world fighting a pandemic. 11 Coronavirus sequencing efforts Doctors struggle to treat those 38 For doctors, intensive care takes urgently need patient data with compromised immunity as on a whole new meaning Unless each sequence of the virus the pandemic stretches healthcare When Viny Kantroo, a respiratory in the global open repositories system capacity. comes with additional patient diseases specialist, started seeing information, the practical benefits 28 Packaging the future of industry COVID-19 patients in her Delhi of such record sequencing are lost. Safe delivery of materials is key to hospital, a grim reality unfolded, successful resumption of economic professionally and personally. 14 A tug of war in the immune activity. system 39 Starting a lab in a pandemic Developing an understanding of 30 Time to bring scientific rigour On the brink of starting her first the root of SARS-CoV-2 is proving to the complex challenge of laboratory, COVID-19 threw difficult, despite an urgent and Ayurvedic medicine Poonam Thakur’s lofty plans into widespread search. A look at traditional approaches disarray. in the context of the COVID-19 40 Let COVID-19 expand awareness 20 Carbon in the time of COVID-19 pandemic. Near-real-time data show which of disability tech sectors, countries and events had The pandemic’s disruption shows the most impact on slashing carbon how much academia could learn emissions, but it is unclear how from the disability community. long the dip will last.

Nature India COVID-19 Special | June 2020 | 3 Feature INDIAN SCIENTISTS IN VITAL SEARCH FOR SOLUTIONS Finding rapid approaches at all levels to protect the world’s second largest population will be crucial. By Vanita Srivastava

ndia’s scientists are racing to find interdis- multi-agency empowered committee to speed ciplinary solutions in the country’s high- up research and development decisions in stakes fight against the novel coronavirus view of the critical need to increase testing pandemic. facilities for COVID-19. With an unprecedented demographic Scientists at the CSIR- Institute of Genomics challenge at hand and struggling with the WE ARE WELL EQUIPPED and Integrative Biology (IGIB) may have found traditionally limited budgets allocated TO TAKE A VACCINE a solution that can be scaled up. A team led by to science, the country’s researchers are Souvik Maiti and Debojyoti Chakraborty has Iworking overtime to provide small and big CANDIDATE FROM designed a paper strip-based testing assay that solutions – from predicting statistical trends can detect the viral RNA of the novel corona- and making mathematical models to develop- THE LABORATORY TO virus SARS-CoV-2 within an hour, “making any ing rapid paper-based test kits and low-cost lab with a thermal cycler capable of perform- ventilators. INDUSTRY.” ing this test,” Chakraborty said. Some are mass-producing masks and hand The paper-strip test uses CRISPR-Cas9 tech- sanitisers while others repurpose drugs and nology – the assay works by converting the ambitiously work towards a vaccine to flatten and entrepreneurs. C-CAMP chief executive, viral RNA into DNA, amplifying it, and deploy- the curve of the disease. Taslimarif Saiyed said innovators will be able to ing the Cas9 complex to detect any genetic Soon after Prime Minister Narendra Modi take advantage of an ecosystem of scientists, material from the virus. “It can work with very announced a nation-wide lockdown (from 25 regulators, investors and industry in “closing low RNA copies in the sample. The kit would March 2020), India’s Department of Science last-mile gaps in commercializing their tech- cost less than 500 rupees,” Chakraborty said. and Technology (DST) set up a COVID-19 Task nologies”. IGIB director Anurag Agrawal said the Force to hunt for leads in its R&D labs, aca- Faced with the public health emergency, institute was also developing a ‘sample to demic institutions, start-ups and small enter- a group of scientists urged the government sequence’ strategy, where test samples can prises. Of the 200 proposals this task force to devise measures that can bolster corona- be diagnosed by next generation sequencing received, DST identified 20 for swift funding virus-related research in India. “During this (NGS). This could help surveillance efforts to to scale up promising products in diagnostics, lockdown, we request the government to keep track the spread of the virus. drugs, ventilators and protection gear. those research laboratories operational which “Sequencing can strengthen genomic epi- “We mapped their supply along with that of are working on finding a cure for the disease,” demiology, genetic variants linked with vir- breathing aids, disinfectant systems, rapid inex- the scientists said in a joint statement on 31 ulence, evolution and transmission pattern,” pensive diagnostics and monitoring technol- March 2020. “Many scientists are attempting said Rajesh Pandey, who is leading this genom- ogies, and will try to match the demand,” DST to create social awareness about the disease. ics effort. His team is using a combination of secretary Ashutosh Sharma told Nature India. We urge the government to take advantage of sequencing platforms to meet the dual tar- In Bengaluru, the Department of Biotech- the resources and expertise available within get of scale and sensitivity for any India-spe- nology’s bioincubator Centre for Cellular and the scientific community.” cific strain. “It is important to ascertain the Molecular Platforms (C-CAMP) quickly cata- genomic sequence of strain(s) prevalent in pulted a technology accelerator in partner- Rapid testing India vis-a-vis other geographical locations ship with the United Nations Health Innovation India has been criticized for its poor mass and symptom spectrum. This information Exchange (UNHIE) and the non-profit firm, testing capability owing to a shortage of test- would be important to correlate specific Social Alpha, to help innovators, start-ups ing kits. The government has now created a strains with virulence or aggressive nature of

4 | Nature India COVID-19 Special | June 2020 develop an antibody-based therapy,” said NII director Amulya Panda. Studies are also underway on the spike protein of the novel coronavirus to develop a vaccine. “We have previously developed an immunomodula- tor for leprosy and are well equipped to take a vaccine candidate from the laboratory to industry,” he said.

Private enterprise Beyond the action in government laboratories, technologists are devising interesting ways to stop the spread of the virus. One such government-led effort is the ‘Corona Kavach’ app that can alert users when they come in proximity of a confirmed coronavirus positive person. Many state governments, including Maharashtra, Goa, Karnataka, Tamil Nadu and Kerala, have launched similar track- ing apps. Another team of researchers at the Indian Institute of Technology Delhi has developed an app that alerts the user to a population sus- pected to be infected. “The app uses bluetooth technology to identify people who may have come within the

TAUSEEF MUSTAFA/AFP VIA GETTY IMAGES MUSTAFA/AFP TAUSEEF range of two metres around a coronavirus-in- A patient in Kashmir has his temperature tested. fected patient,” said Vikas Upadhyay the lead researcher of the team. The secure server data the virus, and tailor-make contingency plans drug development through public-private can be analysed to identify, trace and monitor for India,” he said. partnership, creating biomarkers for disease social distancing norms. Pandey and colleagues are developing severity,” Basu said. Private players are also chipping in to sequencing strategies, combining the num- Epidemiology research should take cen- provide testing solutions. A Pune-based ber and length of sequences, for mass bar- tre stage, said clinician-scientist Gagandeep molecular diagnostics company Mylab Dis- code-based screening. “It’s a multi-pronged Kang. That would help understand where the covery Solutions developed the first COVID- sequencing strategy, which in conjunction disease has spread and to what extent. Kang, 19 testing kit in India and is producing about with other epidemiological data, would help who is the executive director of the Transla- 200 kits a day, each kit capable of testing public health authorities manage the outbreak tional Health Science and Technology Institute 100 samples. and design potential regions or targets for (THSTI) in Faridabad, said that her institution “We are delivering these kits to govern- screening,” Pandey said. is working on an ELISA test for serological stud- ment- authorized labs,” said Gautam Wank- ies across the country which will essentially hede, Mylab’s director for medical affairs. Taming the virus help understand how much the disease has The kit can give test results within 2.5 hours. Another group of virologists at the National spread in India. The company’s executive director, Rahul Institute of Virology in Pune is focusing its “The Indian population is dense and there Patil said in emergency conditions, they can energies on how the virus interacts with its are so many poor people,” she said. Social dis- ramp up production to enable 50,000 tests host by imaging virus infected host cells with tancing, therefore, may be a difficult proposi- a day. ultrastructural tools. NIV Deputy Director tion. The first task should be boosting public NovaLead Pharma, another company from Atanu Basu told Nature India that they are also health research to help control the spread. The Pune in Maharashtra, the state with the highest trying to identify key cellular sites of replica- next step should be research for developing number of novel coronavirus infected people tion, virus morphogenesis and development. additional diagnostic tools, drugs and vac- in India, has deployed computational tech- “This will give us better knowledge to supple- cines, Kang said. nology for identifying existing drugs poten- ment studies by drug development groups,” “We are also working on rapid diagnostic tially effective against the SARS-Cov2 virus as Basu said. tests,” she said. well as for minimizing its impact on the human Basu’s team was the first to image the novel The Indian Council of Medical Research body. coronavirus from an Indian patient using a (ICMR) maintains that India will soon start Through a complex and extensive compu- transmission electron microscope. “Native manufacturing serological testing kits. “We tational study involving 2010 approved drugs images in clinical material can be very use- are hopeful that India will be able to develop and 30 potential viral and human targets, ful for pathogenesis studies,” he said. NIV is at least one serological diagnostic testing tool NovaLead has identified 42 existing drugs looking to collaborate with structural biology in the next few months,” the council’s chief epi- which may be helpful to patients at different groups and to pool resources, especially in the demiologist and communicable disease expert stages of SARS-Cov-2 infection. “Use of exist- area of cryoelectron microscopy, to study the R R Gangakhedkar told Nature India. ing drugs already approved by the regulators replication and organization of this virus in Delhi-based National Institute of Immunol- can offer a huge relief in the short to medium depth. “We should prioritize development ogy (NII) is procuring viral samples and blood term, if found effective against Covid 19,” of in-vitro and in-vivo animal models for bio- from recovered patients. “We will analyse the said NovaLead managing director Supreet assays. Besides, we should aim at antiviral antibody quality in the blood with an aim to Deshpande.

Nature India COVID-19 Special | June 2020 | 5 Comment A lifeline vaccine must be universal

Arun Kumar and Tung Thanh Le

It is time to revamp global supply mechanisms to ensure everyone has access to a coronavirus vaccine when it becomes available. © UNIVERSITY OF QUEENSLAND © UNIVERSITY When a safe and effective vaccine against COVID-19 is licensed for use, there will be a global clamour for access to supplies.

6 | Nature India COVID-19 Special | June 2020 he COVID-19 pandemic has triggered CEPI is now facilitating the development development, regulatory review, and manu- more than 115 vaccine projects around of nine COVID-19 vaccines, including those facturing — each step can take several years. the world. by Moderna, CureVac, Inovio, the University Some novel platform technologies and After the Ebola outbreak of 2014 in of Oxford, Insitut Pasteur/Themis Biosciences, approaches are reducing these long timelines, West Africa, international research Novavax, the University of Hong Kong, and could provide a universal framework for Tbodies and governments, including of the University of Queensland, and Clo- vaccine design, manufacturing and analytical India and Norway, the Bill and Melinda Gates ver Biopharmaceuticals, across six plat- protocols for known and unknown pathogens. Foundation, the Wellcome Trust, and the World form technologies. At the time of writing, When these standardized and validated pro- Economic Forum, joined forces in the search three candidates have started phase I cesses are applied across multiple vaccine for new vaccines and formed The Coalition clinical trials. targets, they could help with accelerating for Epidemic Preparedness Innovations Vaccine development demands explor- animal and clinical testing, engagement of (CEPI). atory and preclinical research, clinical critical partners and license processes across jurisdictions. Implementation of several steps in parallel, could also accelerate the vaccine development process.

DNA and RNA vaccines Vaccines based on genetic instructions (through DNA or RNA) offer advantages over traditional approaches because of speed, ease of antigen design, and a generic manufacturing process. These vaccines avoid the use of cell culture, are fully synthetic, and can be directly delivered into the cells where protein synthesis takes place.

“Implementation of several steps in parallel could accelerate vaccine development.”

Messenger RNA (mRNA) vaccines (consist- ing of RNA strands coding the antigenic part of the pathogen) are very attractive because of the short-half life and direct delivery of antigen-encoded sequence into the cytoplasm. A chemically modified mRNA vaccine (mRNA- 1273) against SARS-CoV-2 has been developed by Moderna and has started a phase I trial. The previous phase I trial based on this technology induced robust immune responses. Demon- strating the speed of this platform, just after sequence identification, Moderna started the vaccine development process and within 63 days initiated a phase I trial. Another mRNA-based COVID-19 vaccine candidate in pre-clinical stages is being developed by CureVac, a company based in Tubin- gen, Germany. CureVac’s technology uses naturally occurring nucleotides and recently has shown that the one microgram formulation of its Rabies mRNA vaccine can induce a strong immune response in humans. Additionally, CureVac is in the process of developing a fully automated proprietary mobile manufacturing platform, the RNA Printer, which may further enhance speed and help with rapid responses to the outbreak globally. Very recently, BioNTech in partnership with Pfizer started phase I/II clinical trials for a COVID-19 vaccine, BNT162. When a safe and effective vaccine against COVID-19 is licensed for use, there will be a global clamour for access to supplies. Other advanced vaccine development Continued on page 10

Nature India COVID-19 Special | June 2020 | 7 Infographic

A process called AN ARRAY OF VACCINES electroporation Nucleus All vaccines aim to expose the body to an antigen that won’t creates pores in THE RACE FOR cause disease, but will provoke an immune response that can mRNA membranes to block or kill the virus if a person becomes infected. There are increase uptake at least eight types being tried against the coronavirus, of DNA into a cell Viral and they rely on dierent viruses or viral parts. proteins Cell Virus Viral vector Inactivated Replicating CORONAVIRUS Weakened Non-replicating NUCLEIC ACID VACCINES Electroporation Nucleic acid Protein-based At least 20 teams are aiming to use genetic instructions (in the form of DNA Protein subunit DNA or RNA) for a coronavirus Coronavirus By Ewen Callaway; RNA Virus-like particles protein that prompts an immune peptide response. The nucleic acid is design by Nik Spencer. DNA Virus inserted into human cells, which DNA VACCINES then churn out copies of the virus vaccine Multiple vaccines are being developed against SARS-CoV-2 by Viral vector protein; most of these vaccines Coronavirus encode the virus’s spike protein. Body research teams in companies and universities across the world. Nucleic acid spike gene Researchers are trialling dierent technologies, some of which Protein-based RNA- and DNA-based vaccines are Immune response haven’t been used in a licensed vaccine before. At least six groups Other* safe and easy to develop: to produce them involves making have already begun injecting formulations into volunteers in safety 35 RNA 0 5 10 15 20 25 30 genetic material only, not the RNA is often trials; others have started testing in animals. Nature’s graphical Number of vaccines in development virus. But they are unproven: vaccine encased in a no licensed vaccines use this lipid coat so it guide explains each vaccine design. * Other eorts include testing whether existing vaccines against poliovirus or tuberculosis could help to ight SARS-CoV-2 by eliciting a general immune technology. can enter cells response (rather than speciic adaptive immunity), or whether certain RNA immune cells could be genetically modiied to target the virus. VACCINE BASICS: HOW WE DEVELOP IMMUNITY The body’s adaptive immune system can learn to recognize new, invading pathogens, such as the coronavirus SARS-CoV-2. VIRUS VACCINES VIRAL VECTOR VACCINES PROTEIN BASED VACCINES At least seven teams are developing vaccines using the Around 25 groups say they are working on viral-vector vaccines. A virus such as Many researchers want to inject coronavirus virus itself, in a weakened or inactivated form. Many existing measles or adenovirus is genetically engineered so that it can produce proteins directly into the body. Fragments of Coronavirus infection* vaccines are made in this way, such as those against coronavirus proteins in the body. These viruses are weakened so they cannot proteins or protein shells that mimic the Spike protein The virus uses its surface spike protein to lock measles and polio, but they require extensive safety testing. cause disease. There are two types: those that can still replicate within cells and coronavirus’s outer coat can also be used. onto ACE2 receptors on the surface of human Sinovac Biotech in Beijing has started to test an those that cannot because key genes have been disabled. M protein cells. Once inside, these cells translate the inactivated version of SARS-CoV-2 in humans. virus’s RNA to produce more viruses. RNA Weakened virus Inactivated virus Replicating viral vector Non-replicating viral Protein subunits A virus is conventionally weakened In these vaccines, (such as weakened measles) vector (such as adenovirus) Twenty-eight teams are working on vaccines with viral for a vaccine by being passed the virus is rendered The newly approved Ebola vaccine is an No licensed vaccines use this protein subunits — most of them are focusing on the virus’s through animal or human cells uninfectious using example of a viral-vector vaccine that method, but they have a long spike protein or a key part of it called the receptor binding 1. Virus enters until it picks up mutations that chemicals, such as replicates within cells. Such vaccines history in gene therapy. Booster domain. Similar vaccines against the SARS virus protected the body make it less able to cause disease. formaldehyde, or heat. tend to be safe and provoke a strong shots can be needed to induce monkeys against infection but haven’t been tested in people. Body Codagenix in Farmingdale, Making them, however, immune response. Existing immunity to long-lasting immunity. US-based To work, these vaccines might require adjuvants — New York, is working with the requires starting with the vector could blunt the vaccine’s drug giant Johnson & Johnson is immune-stimulating molecules delivered alongside the Serum Institute of India, a vaccine large quantities of eectiveness, however. working on this approach. vaccine — as well as multiple doses. manufacturer in Pune, to weaken infectious virus. ACE2 receptor Coronavirus SARS-CoV-2 by altering its genetic 2. Virus enters Human cell spike gene code so that viral proteins are Virus-like particles 4. Virus assembly a cell Coronavirus produced less eiciently. Empty virus shells mimic the coronavirus Viral genes spike gene Viral RNA translated structure, but aren’t infectious because into proteins Vesicle Viral genes they lack genetic material. Five teams (some inactive) are working on ‘virus-like particle’ (VLP) vaccines, which can trigger a strong immune response, but can be diicult to manufacture. 3. Virus fuses with vesicle 5. Virus Spike and its RNA is released release protein

Immune response* M protein Viral Specialized ‘antigen-presenting cells’ engulf the virus peptide and display portions of it to activate T-helper cells. Virus ingested Virus Antigen- by antigen- T-helper cells enable other immune responses: B cells replicates presenting presenting make antibodies that can block the virus from infecting cell cell (APC) cells, as well as mark the virus for destruction. Cytotoxic Body T cells identify and destroy virus-infected cells.

Vaccine VLP

B cell Anti-coronavirus antibody Cell

T-helper cell Long-lived ‘memory’ Virus Coronavirus Cell replicates peptide destroyed B and T cells that recognize the virus Cytotoxic can patrol the body T cell for months or years, *Simpliied providing immunity Immune response

8 | Nature India COVID-19 Special | June 2020 A process called AN ARRAY OF VACCINES electroporation Nucleus All vaccines aim to expose the body to an antigen that won’t creates pores in THE RACE FOR cause disease, but will provoke an immune response that can mRNA membranes to block or kill the virus if a person becomes infected. There are increase uptake at least eight types being tried against the coronavirus, of DNA into a cell Viral and they rely on dierent viruses or viral parts. proteins Cell Virus Viral vector Inactivated Replicating CORONAVIRUS Weakened Non-replicating NUCLEIC ACID VACCINES Electroporation Nucleic acid Protein-based At least 20 teams are aiming to use genetic instructions (in the form of DNA Protein subunit DNA or RNA) for a coronavirus Coronavirus By Ewen Callaway; RNA Virus-like particles protein that prompts an immune peptide response. The nucleic acid is design by Nik Spencer. DNA Virus inserted into human cells, which DNA VACCINES then churn out copies of the virus vaccine Multiple vaccines are being developed against SARS-CoV-2 by Viral vector protein; most of these vaccines Coronavirus encode the virus’s spike protein. Body research teams in companies and universities across the world. Nucleic acid spike gene Researchers are trialling dierent technologies, some of which Protein-based RNA- and DNA-based vaccines are Immune response haven’t been used in a licensed vaccine before. At least six groups Other* safe and easy to develop: to produce them involves making have already begun injecting formulations into volunteers in safety 35 RNA 0 5 10 15 20 25 30 genetic material only, not the RNA is often trials; others have started testing in animals. Nature’s graphical Number of vaccines in development virus. But they are unproven: vaccine encased in a no licensed vaccines use this lipid coat so it guide explains each vaccine design. * Other eorts include testing whether existing vaccines against poliovirus or tuberculosis could help to ight SARS-CoV-2 by eliciting a general immune technology. can enter cells response (rather than speciic adaptive immunity), or whether certain RNA immune cells could be genetically modiied to target the virus. VACCINE BASICS: HOW WE DEVELOP IMMUNITY The body’s adaptive immune system can learn to recognize new, invading pathogens, such as the coronavirus SARS-CoV-2. VIRUS VACCINES VIRAL VECTOR VACCINES PROTEIN BASED VACCINES At least seven teams are developing vaccines using the Around 25 groups say they are working on viral-vector vaccines. A virus such as Many researchers want to inject coronavirus virus itself, in a weakened or inactivated form. Many existing measles or adenovirus is genetically engineered so that it can produce proteins directly into the body. Fragments of Coronavirus infection* vaccines are made in this way, such as those against coronavirus proteins in the body. These viruses are weakened so they cannot proteins or protein shells that mimic the Spike protein The virus uses its surface spike protein to lock measles and polio, but they require extensive safety testing. cause disease. There are two types: those that can still replicate within cells and coronavirus’s outer coat can also be used. onto ACE2 receptors on the surface of human Sinovac Biotech in Beijing has started to test an those that cannot because key genes have been disabled. M protein cells. Once inside, these cells translate the inactivated version of SARS-CoV-2 in humans. virus’s RNA to produce more viruses. RNA Weakened virus Inactivated virus Replicating viral vector Non-replicating viral Protein subunits A virus is conventionally weakened In these vaccines, (such as weakened measles) vector (such as adenovirus) Twenty-eight teams are working on vaccines with viral for a vaccine by being passed the virus is rendered The newly approved Ebola vaccine is an No licensed vaccines use this protein subunits — most of them are focusing on the virus’s through animal or human cells uninfectious using example of a viral-vector vaccine that method, but they have a long spike protein or a key part of it called the receptor binding 1. Virus enters until it picks up mutations that chemicals, such as replicates within cells. Such vaccines history in gene therapy. Booster domain. Similar vaccines against the SARS virus protected the body make it less able to cause disease. formaldehyde, or heat. tend to be safe and provoke a strong shots can be needed to induce monkeys against infection but haven’t been tested in people. Body Codagenix in Farmingdale, Making them, however, immune response. Existing immunity to long-lasting immunity. US-based To work, these vaccines might require adjuvants — New York, is working with the requires starting with the vector could blunt the vaccine’s drug giant Johnson & Johnson is immune-stimulating molecules delivered alongside the Serum Institute of India, a vaccine large quantities of eectiveness, however. working on this approach. vaccine — as well as multiple doses. manufacturer in Pune, to weaken infectious virus. ACE2 receptor Coronavirus SARS-CoV-2 by altering its genetic 2. Virus enters Human cell spike gene code so that viral proteins are Virus-like particles 4. Virus assembly a cell Coronavirus produced less eiciently. Empty virus shells mimic the coronavirus Viral genes spike gene Viral RNA translated structure, but aren’t infectious because into proteins Vesicle Viral genes they lack genetic material. Five teams (some inactive) are working on ‘virus-like particle’ (VLP) vaccines, which can trigger a strong immune response, but can be diicult to manufacture. 3. Virus fuses with vesicle 5. Virus Spike and its RNA is released release protein

Vaccine VLP

B cell Anti-coronavirus antibody Cell

T-helper cell Long-lived ‘memory’ Virus Coronavirus Cell replicates peptide destroyed B and T cells that recognize the virus First published in Nature 581, 9 (2020) Cytotoxic can patrol the body (©SpringerNature 2020). T cell for months or years,

*Simpliied providing immunity Immune response COVID-19 INSTITUTE LANDSCAPE/MILKEN VACCINE WHO COVID-19 BASED ON ANALYSIS NATURE SOURCES: CHART DISC. HTTP://DOI.ORG/GGRNBR DRUG. REV. LE ET AL. NATURE THANH TRACKER/T. VACCINE AND TREATMENT 18 (2020) 5, ET AL. NPJ VACCINES SHANG (2020)/W. KRAMMER IMMUNITY583–589 52, & F. AMANAT (2020)/F. 2020 SPRINGERNATURE (C) (2020) 576 PAGE 580, VOL PUBLISHED IN NATURE FIRST

Nature India COVID-19 Special | June 2020 | 9 Comment candidate based on RNA technology, vaccine (NVX-CoV2373) based on proprietary SARS-CoV-2 sequence. CEPI just announced including Imperial College London, Tongji recombinant nanoparticle technology. The a partnership with the Clover Pharmaceuti- University/Chinese Centre for Disease NVX-CoV2373 vaccine is designed to make a cals for development of a SARS-CoV-2 spike Control and Prevention and Translate stable form of prefusion form of spike protein. (S)-protein subunit vaccine candidate based Bio/Sanofi, are also progressing with impres- Immunization of NVX-CoV2373 in animals on innovative Trimer-Tag© technology. Vax- sive speed. showed strong immunogenicity. Novavax ine, SK Bioscience and G+Flas Life Science Inovio’s DNA vaccine (INO-4800) against is expecting to start phase I clinical trial in are also working towards development of COVID-19, initiated phase I trials within mid-May (within 125 days after sequence COVID-19 vaccines based on the recombi- 86 days. Scientists at Inovio started to design identification). This platform has the potential nant approach. and synthesize a DNA vaccine, which con- to rapidly generate and manufacture vaccine When combined with recombinant pro- sists of a DNA plasmid containing genes candidates within 90 days (from the identifi- tein-based vaccines, adjuvants (substances encoding for the SARS-CoV-2 spike pro- cation of gene sequence), as seen in an influ- that modulate and enhance immune response tein. This vaccine can be given through enza A/Anhui/1/2013 (H7N9) and Ebola vaccine when combined with antigen) can help in the skin with the help of a next-generation candidates. Medicago is another advance VLP boosting stronger and long-lasting immunity. electroporation device, which allows candidate with ready material for pre-clinical Furthermore, adjuvants also reduce the dose smooth entry of DNA into the human cells studies. required, allowing more vaccine doses to be with the help of an electric current. In made available, which is especially impor- previous preclinical and clinical studies, Traditional methods and adjuvants tant in a pandemic. GlaxoSmithKline, Seqi- Inovio’s platform technology induced robust Traditional methods such as inactivated rus and Dynavax have committed to making T-cell and antibody responses. Zydus Cadila and live attenuated approaches are among innovative licenced adjuvants (ASo3, MF59 has recently been recommended for funding the most advanced candidates for COVID-19 and CpG 1018), respectively) available to support from India’s Department of Biotech- vaccines. Recently, an inactivated vaccine partners supported by CEPI to enhance the nology (DBT) for advancing its DNA-based developed by Sinovac commenced a phase I development of effective vaccines against COVID-19 vaccine. trial, meanwhile, Wuhan Institute of Biolog- SARS-CoV-2. ical Product’s vaccine began a phase II trial. Vaccines based on viral vectors Indian vaccine developer Bharat Biotech along Vaccines for all Viral-vectors being exploited for gene deliv- with the University of Wisconsin has started Both novel and traditional approaches to ery and vaccines based on this approach offer development of a COVID-19 vaccine based COVID-19 vaccine development offer differ- a high level of protein expression, extended on self-limiting version of influenza virus, ent value propositions in relation to speed of stability and provoke strong humoral (anti- CoroFlu. development and scale of manufacture over body-mediated) and cellular (T-cell mediated) short and long terms. CEPI has a diverse port- immune responses. Antigens of interest can “Fair allocation of vaccines folio of candidates based on a wide range of be expressed efficiently. China’s CanSino vaccine technologies — including novel plat- Biologics with its recombinant COVID-19 must be urgently and form technologies and other more estab- vaccine based on Adenovirus Type-5 vector collectively addressed.” lished approaches — to maximize its chances (Ad5), has moved into a phase II trial. The Uni- of success. versity of Oxford started the development of a Currently, there is no global entity respon- COVID-19 vaccine based on a replication Scientists at the University of Hong Kong sible for financing or ordering vaccine manu- deficient ChAdOx1 platform (chimpanzee (HKU) developed a novel rapid response facture, nor is there a globally fair allocation adenovirus vector) and began phase I/II clin- technology based on live attenuated influ- system for any vaccines produced. It will be ical trials on 23 April 2020. The Serum Insti- enza vaccine platform, DelNS1 LAIV. The vital that such a system is in place to ensure tute of India partnered with the University non-structural protein 1 (NS1) element, which that everyone that no one is left behind. In of Oxford and was slated to start production makes the flu virus strongly immunogenic and response, the WHO and global leaders from of vaccine within 2-3 weeks. Additionally, less virulent, was deleted in DelNS1 LAIV. around the world launched the Access to AstraZeneca will also team up with Oxford Their COVID-19 vaccine candidate was devel- COVID-19 Tool (ACT) accelerator, of which for mass production of the COVID-19 vac- oped by incorporating the receptor binding CEPI is a founding member, to speed up devel- cine. Several clinical trials have proved that domain (RBD) of SARS-CoV-2 into DelNS1 opment, production and access to vaccines it induces immunity and is safe to use against LAIV on its surface. Use of RBD domain and therapeutics. a range of pathogens. Another CEPI funded only may avoid induction of antibody depend- Globally fair allocation of vaccines is a chal- consortium led by the Institut Pasteur, Themis ent enhancement of disease. This vaccine lenge that must be urgently and collectively Biosciences and University of Pittsburgh could prevent both SARS-CoV-2 and influ- addressed by governments, global health is developing a COVID-19 vaccine based on enza infections and can be administered by leaders, and regulators, while the race for a the Measles vector. The low cost of manu- nasal route. A phase I trial is expected to start COVID-19 vaccine picks up pace. facturing and production of large quantities in July. in less time makes viral vectored vaccines The University of Queensland (UQ) has favourable for use in low-income and mid- developed molecular clamp technology dle-income settings. that keeps the spike protein of SARS-CoV-2 in stable form, which allows the immune sys- New platforms tem to be able to recognize it. Influenza, Recombinant nanoparticles are non-infectious Nipah, and MERS coronavirus are some of the particles and mimic conformational and struc- vaccine candidates that are currently under tural properties of the native virus but lack development based on this rapid response genetic material. These properties make them platform technology. Scientists at UQ were *The authors are from the Coalition for a potential platform technology for vaccine able to generate the COVID-19 vaccine can- Epidemic Preparedness Innovations (CEPI), development. Novavax developed a COVID-19 didate within 21 days after publication of Oslo, Norway.

10 | Nature India COVID-19 Special | June 2020 Feature © CSIRO A single-stranded RNA virus.

esearchers mapping the genetic blueprint of the novel coronavirus SARS-CoV-2 have by now shared more than 55,000 genome CORONAVIRUS sequences from across the world on the open platform Global Initi- ative on Sharing All Influenza Data (GISAID). The repository has seen Runprecedented activity since December when SEQUENCING the first sequence from Wuhan in China came in. On NCBI’s GenBank, more than 20,000 nucleotide and protein sequences of the virus have already been submitted. The virus is set to become the most EFFORTS URGENTLY sequenced ever. Researchers, however, warn that unless the sequences are accompanied by de-identified data from patients, the billions of dollars NEED PATIENT DATA being spent in sequencing the virus globally will not be of much clinical or epidemiological Unless each sequence of the virus in the global value, a crucial need during a rapidly evolving open repositories comes with additional patient pandemic. Laboratories, clinicians, epidemiologists information, the practical benefits of such record and governments wanting to quickly use this By Subhra Priyadarshini gold mine of information are meeting a stum- sequencing are lost. bling block as they look for more granular data that should ideally supplement the primary sequence data.

Nature India COVID-19 Special | June 2020 | 11 Feature “We badly need de-identified meta-data the viral genome. The Central Drug Research team recently analysed the genome sequence from the patients from whom these sequences Institute (CDRI), Lucknow and IICB, Kolkata are from a COVID-19 patient from Gujarat, agrees. came so that it makes sense for any kind of also gearing up to sequence the viral genome. “This remains a concern for most of us – to analysis,” says Seshadri Vasan, who leads the With the 1,000-genome project, about 10 correlate this data with our analysis,” she Dangerous Pathogens team at the Austral- more facilities across the country will be pulled told Nature India. “It is extremely important ian Animal Health Laboratory and is senior in to sequence the virus. for us when we want to assign clinical signif- principal research consultant for Health and Virologist Mitali Mukerji, a genomic scien- icance to our sequencing efforts,” she says. Biosecurity at the Commonwealth Scientific tist at IGIB who is coordinating CSIR’s sequenc- The reason this additional data is needed and Industrial Research Organization (CSIRO), ing efforts says at the moment scientists are is that the same viral strain could be fatal for Australia’s national science agency. only trying to analyse the strain of the virus one person, and result in mild, moderate or De-identified data does not reveal the iden- and where the sequences came from. “Clini- severe symptoms in others. “And some strains tity of the patient. Vasan says the minimum set cal history is not getting submitted from any could also be more or less virulent than oth- of de-identified data that researchers need is place. It’s very important since this is not the ers,” Vasan adds. the patient’s age, gender, if they had a mild, end of the outbreak,” she says. Epidemiologists Vasan, says the World Health Organization moderate or severe form of the disease and if need to identity people who might be more at should lead this effort to standardize the they survived. Questions around lifestyle and risk and analysing clinical information will be meta-dataset that can be followed globally, comorbidities, such as whether they smoke, crucial, she says. with consistent definitions to categorize sever- have a pre-existing respiratory illness or diabe- IGIB director and clinician scientist Anurag ity and outcomes of COVID-19. “No country can tes, are also important to add meaning to this Agrawal, who is overseeing a molecular and solve this problem in isolation. It is important data. “We usually get information on country digital surveillance project around the for the WHO to specify the minimal meta-da- and city, but it may be beneficial to have post- genome sequences from India, says it would taset not just for SARS-CoV-2 but also a future code and ethnicity data too,” he says. be extremely useful to know the viral loads ‘Disease X’,” he told Nature India. India has announced an ambitious and numbers of symptomatic versus asymp- In the absence of patient meta-data “we 1,000-genome sequencing project to better tomatic cases. “Nothing is meaningful for don’t know how the disease is progressing, understand the viral and host genomics of molecular epidemiology or our knowledge how long the virus shedding occurs in differ- the COVID-19 outbreak. India’s Council for of clusters unless these clinical parameters ent settings and what kind of immunity levels Scientific and Industrial Research (CSIR), are well defined in the data,” he says. exist in individuals or populations,” says epi- which undertook a 1,008-human genome The biggest barrier, he says, is coordination demiologist Giridhara R Babu from the Public sequencing project last year, has been leading among researchers sequencing the data and Health Foundation of India (PHFI). the sequencing efforts in India. agencies uploading it on to the databases. “We have to be very careful in improv- Scientists at the Centre for Cellular and “We work with the National Centre for Dis- ing the quality of the meta-data and, more Molecular Biology (CCMB), Hyderabad; the ease Control (NCDC), who have the underly- importantly, have it unbiasedly assessed by Institute of Genomics and Integrated Biology ing patient information and since they upload people who don’t run the clinical trials,” Babu (IGIB), Delhi; the Institute of Microbial Tech- the sequences, they do add much more value told Nature India. That way measurement nology, Chandgarh; the National Institute of to the data.” errors and selection biases can be removed Virology, Pune, and the Gujarat Biotechnology Upasana Ray, a virologist at the CSIR-Indian from the data to make it more useful. Research Centre, Gandhinagar are sequencing Institute of Chemical Biology (IICB) whose Information on the severity of symptoms

UNDERSTANDING GENOME SEQUENCES TRANSBOUNDARY AND EMERGING DISEASES JOURNAL EMERGING AND TRANSBOUNDARY

12 | Nature India COVID-19 Special | June 2020 between these data points helps researchers find out about the different strains of the virus – including where they came from and how they continue to evolve,” he says. Vasan, whose team has analysed the first 181 published genome sequences from the current COVID-19 outbreak says the RNA virus can “evolve into a number of distinct clusters that share mutations.” The analysis has already helped determine which strains of the virus are suitable for testing vaccines underway at the Australian Centre for Disease Preparedness in Geelong, Victoria. RNA viruses, Vasan adds, generally evolve into clusters and show ‘quasispecies diversity’, meaning not just a single genotype but an ensemble of related sequences. Quasis- pecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication. The novel coronavirus, an RNA virus, emerged from China and restrictions on air travel and movements of people did not come into place for a while after the outbreak in Wuhan. “Therefore, the clusters do not correspond to countries. For instance, the first 181 published genomic sequences could be grouped into three clusters (with three more emerging), and Australian isolates can be found in each of them,” he says. For this reason it is unhelpful to call the virus ‘an Indian strain’ or ‘Australian strain’ or ‘Chi-

© CSIRO nese strain’ or make claims that one regional Transmission electron microscope image of SARS-CoV-2. strain is more virulent than the other. “Over time, we may likely find clusters with and disease progression dynamics would be varied virulence in all countries. The real ques- immensely helpful when combined with the tion is whether we can link the accumulated genomic sequences. “For instance, one could mutations in the genome to clinical meta-data actually know if there is a sub-group of asymp- and find clinically/epidemiologically meaning- tomatic people who never go on to develop ful correlations,” he says. the disease. They would be way more useful WE MAY FIND CLUSTERS A GISAID statement says the circulating to design a disease modifying mechanism or WITH VARIED VIRULENCE virus strains globally can be classified into immunomodulation, instead of the quest for different number of clades based on genetic a vaccine as the endgame.” IN ALL COUNTRIES.” variation. ”These are part of the natural evo- Disregarding all these data elements lution of the virus currently not known to be eliminates the possibility of other non-phar- associated with any differences in virulence,” macological interventions to disrupt the trans- determine clinical or epidemiological impacts it says. Data from the early outbreak period mission of the virus, Babu says. of these minor mutations without the under- is not enough for a detailed interpretation of lying meta-data. Only 14 out of these 388 the early history of global transmissions from Evolution, mutations and clades sequences had clinical annotations, the rest a few genomes, according to GISAID. The global effort to peer into the genetic were either annotated as unknown or not at all. Ray, whose team reported in a preprint make-up of the pandemic-causing virus since CSIRO has developed a novel visualiza- paper two novel mutations in the spike pro- the start of the COVID-19 outbreak has pro- tion platform — similar to the one used to tein of the SARS-CoV-2 isolate from Gujarat as vided real-time understanding of the organ- analyse the human genome — to pinpoint dif- compared with the Wuhan virus isolates, says ism. Databases such as the GenBank and ferences among the thousands of individual these mutations have a somewhat different GISAID provide ammunition to researchers genetic sequences of COVID-19 now globally origin. “One of the mutations is exclusive in trying to understand the evolution and muta- available. The data visualization platform the virus obtained from Gujarat whereas the tions of viruses. They are also solid tools for highlights evolving genetic mutations of the other was also seen in North American and the research and development of drugs and virus as it continues to change and adapt to European isolates.” vaccines against the virus. new environments. To date, almost 95% of the strains reported The data so far reveals some minor muta- “Analysing global data on the published in global databases are from Wuhan in China tions in the virus which may have no functional genome sequences of this novel corona virus where the outbreak began. “The remaining consequence, Vasan says. “For instance, when will help fast track our understanding of this 5% are from the rest of the world. So some we looked at 388 sequences from Australia, complex disease, how changes in the virus descriptions of virulence being low or high only 162 had protein-changing mutations,” could affect its behaviour and impact,” Vasan in a particular region are wishful thinking at he says. However, his team was unable to says. “Assessing the evolutionary distance best,” Giridhara Babu says.

Nature India COVID-19 Special | June 2020 | 13 Comment A tug of war in the immune system

Lakshmy Ramakrishnan

Developing an understanding of the root of SARS-CoV-2 is proving complicated, despite its urgency.

he emergence of new pathogens in and 2012. Many bodies have been calling for elucidated three stages of the SARS-CoV-2 humans, that originated in animals, has a ban on wildlife trade ever since infection cycle: the asymptomatic stage with been a disturbing trend. Disruption in detectable or undetectable viral loads, non-se- wildlife habitat and changes in human Dangerous liaisons vere symptomatic stage with detectable viral behaviour are significant contributors Viruses are thrifty organisms; they possess load, and severe disease with high viral load. Tto pathogens crossing the species barrier, with only two major biological molecules, protein Onset of symptoms takes place five to six days globalization an accelerant. Disease-causing and nucleic acids, and yet can do enormous after infection, but studies have reported incu- microorganisms, that once infected only ani- harm. The proteins carry out the processes bation periods varying from 14-30 days in mals, have enhanced their infective repertoire of infecting cells and diverting the cell’s some individuals. Symptoms range from mild to accommodate humans. resources to its own requirements, while the fever, sore throat, cough, myalgia, fatigue, The 2019 SARS-CoV-2 outbreak is reported genetic material replicates, producing more lymphocytopenia and radiographic signs of to have originated in a wet animal market, virus particles. SARS-CoV-2 possesses a large pneumonia. Mild cold and flu-like symptoms, reliant on poaching and the trafficking and RNA genome, which shares significant simi- along with reports of afebrile cases, had ini- trade of wildlife. The demand for wild ani- larity with that of SARS-CoV. This explains the tially pointed at a broader spectrum of caus- mals, which are used as exotic foods and in similarity between the two viruses in infection ative agents, such as dengue infection. This in traditional forms of medicine spurs trade in pattern and their disease outcome in humans. turn, had delayed diagnoses in the early days wildlife. Within these markets live animals and of the pandemic. However, when the severe humans come in close contact. Such situations “Scientists and clinicians disease stage emerged, the fine line between can create a breeding ground for zoonotic ‘flu-like’ and severe became unclear. Severe viruses to jump from animals to humans have elucidated three stages disease can lead to shock, acute respiratory through mutations. of the infection cycle.” distress syndrome, acute cardiac injury, acute The consensus among scientists is that kidney injury, and death. SARS-CoV-2 was transmitted from bats to humans, with pangolins acting as the link. This Transmission of SARS-CoV-2 from humans Fighting back however is not a simple process. Coronavi- to humans is through direct contact or Infected people recover when their immune ruses interchange between cycles of active through respiratory droplets transmitted system elicits a directed and durable response virus production and inactive quiescence from infected individuals. SARS-CoV-2 enters during the first two stages of SARS-CoV-2 infec- during persistent virus infections in bats. The into the respiratory tract and lungs through tion. It is hypothesized that this protective latter acts as a means to avoid detection by the the mucosal membranes of the nasal passage anti-viral immunity mainly occurs under the bat immune system, whilst the former trig- and larynx. It is not yet clear whether it can be setting of overall good health, in the absence gers immune responses against the virus. Such transmitted through the oral-faecal route, and of underlying diseases, and in the presence of responses include the production of reactive uncertainty remains over its infectious poten- an appropriate genetic background. oxygen species, such as superoxide and hydro- tial on inanimate objects. SARS-CoV-2 infection results in severe dis- gen peroxide, which, in turn induce mutations ease and fatality when there is an imbalance in the SARS-CoV-2 genome. This virus-host Target practice in the immune response: a tug of war between interaction generates quasi-species pools of Viruses possess specific proteins, such as the a protective immune response and a dysreg- virus, with adaptive potential, including the spike protein in the case of SARS-CoV-2, that ulated inflammatory response ensues. The ability to infect humans. recognize and target specific types of host former induces protective anti-viral immu- Despite there being regulations oversee- cells, thereby helping viral entry into the cell. nity, while a dysregulated inflammatory ing international wildlife trade, sceptics argue SARS-CoV-2 targets a protein on human cells, response leads to cell death and tissue dam- that CITES (Convention on International namely angiotensin converting enzyme 2 age. Such an inflammatory response occurs Trade in Endangered Species of Wild Flora (ACE2). It is expressed primarily in lung tis- when there is uncontrolled viral replication, and Fauna) is simply an agreement between sue, kidneys and the gastrointestinal tract. a delay in the production of immunomodula- nations and call instead for a complete ban The function of this important enzyme whose tors, an increased infiltration of neutrophils, on illegal trade of wildlife. There was a failure function is to regulate blood pressure and pro- and an increased influx of pro-inflammatory to heed the warnings of the emergence and tect the host from worsening of lung injury. On mediators. The respiratory tract is a major spread of influenza and coronaviruses more entry into the cell, the virus is able to hijack the site of viral attack and this is supported by than a decade ago, particularly during the host cell’s machinery for its own needs. the observation of high ACE2 expression 2009 H1N1 swine flu pandemic and during the Despite the unknowns around this novel in the lungs. Oxygen transfer between the SARS-CoV and MERS-CoV outbreaks of 2002 coronavirus, scientists and clinicians have tiny air sacs (alveoli) and the capillaries that

14 | Nature India COVID-19 Special | June 2020 NIAID Transmission electron micrograph of SARS-CoV-2 virus particles.

Nature India COVID-19 Special | June 2020 | 15 Comment DAVID TALUKDAR/ MOMENT UNRELEASED/ GETTY UNRELEASED/ MOMENT IMAGES TALUKDAR/ DAVID Medics wearing protective suits in a swab sample collection centre.

line the alveoli is impeded due to an influx SARS-CoV-2 may also be striking the cardi- where there is a high expression of ACE2. of inflammatory mediators and cells. This ovascular system: there have been reports of Patients suffering from kidney failure are more results in the formation of dead cells along heart attacks and ischemia (blood vessel con- susceptible to acute kidney injury (AKI) as a with pus, which contributes to the clinical striction) in fingers and toes. It is suggested result of infection. presentation of coughing, fever and shal- that the virus attacks blood vessels and cardiac Another worrying target is the central low breathing, leading to pneumonia. Oxy- muscle, with reports identifying blood clots nervous system (CNS); some patients have gen therapy alleviates symptoms for some lodged in the lungs and brain. This leads to pul- reported loss of smell and developed strokes patients, who are able to recover, while oth- monary embolism and stroke, respectively, or seizures. These symptoms suggest the virus ers struggle, a fall in blood pressure ensues, which have been one of the major causes of has penetrative power into the brain and spinal vascular leakage occurs, blood clots form, morbidity in critical patients. It is thought that cord or these symptoms manifest as a result of and organ failure sets in. This immunological there are other targets on the cardiovascular the dysregulated immune response. A combi- cascade of events results in acute lung injury system, which are yet to be identified. This is nation of both would most likely be the case as (ALI) and acute respiratory distress syndrome of importance in the case of patients suffering SARS-CoV was able to enter the CNS and cause (ARDS). Ultimately, pulmonary infiltration of from hypertension, diabetes, and chronic lung encephalitis. inflammatory cells and mediators is the disease, as they are considered to be more vul- Patients have also reported diarrhoea, vom- major cause of fatality in severe SARS-CoV-2 nerable to such attack. iting and abdominal pain, which was most infections. The kidney is another target of SARS-CoV-2, often diagnosed as a stomach bug, but when

16 | Nature India COVID-19 Special | June 2020 WITTHAYA PRASONGSIN/MOMENT/GETTY WITTHAYA Working on the race for the much-needed vaccine.

“Personal hygiene and used by public health agencies, is highly relevant considering that airborne transmission, respiratory etiquette is the i.e. transmission of the virus while talking or gold standard individual breathing, has not been completely ruled out strategy.” and the infectious dose has not been deter- mined. Researchers suggest increased ventilation indoors and reduced recirculation and, in patients with severe infection, the of air can keep the virus at bay. Use of masks administration of a therapeutic modulator is discouraged in some countries owing to of host inflammatory responses. increased demand in healthcare settings, while some countries believe their use adds The conundrums an extra layer of protection. Encouragement An alarming observation is the presence of of proper personal hygiene and respiratory the virus in patients who have recovered etiquette is the dominant approach currently from SARS-CoV-2. This reappearance of the in play. virus occurs suggests that the host immune A strategy several European countries have response may be partial or the virus has found set out to implement is the phenomenon of a mechanism to remain hidden and escape herd immunity, a concept that suggests that detection, possibly reactivating later on. if a significant proportion of the population Another difficulty in combating SARS-CoV-2 is immunized with a specific pathogen, for is the presence of viral mutant strains. Several instance, by a vaccine, then the remaining lines of thought have delved into the possibil- unvaccinated individuals are unlikely to Medics wearing protective suits in a swab sample collection centre. ity of multiple SARS-CoV-2 strains in circula- become infected, owing to a decrease in the tion, this suggests that the viral genome may spread of the disease. Proponents of herd coughing was also reported, SARS-CoV-2 was be unstable and may diversify to infect differ- immunity are relying on natural immunity found to be the culprit. Endoscopic images ent populations or it may alter its virulence. to kick in and provide an indirect blanket of show that gastrointestinal tract injury occurs Owing to a contrast in the incidence of immunity to the rest of the population. Con- as a result of viral replication. This does pose disease in different regions of the world, a sidering the enormity of the unknown facts the question of oral-faecal route of transmis- predisposition to severe forms of disease or about this virus, it is a huge gamble. sion, but studies have not confirmed this. an inherent resistance to virulent forms have Hospitalized patients have also reported also been taken into consideration. Genome- Humility in the face of death conjunctivitis of the eye and have been wide studies are indicative of this, but require The last few months have forcefully stifled observed to suffer liver damage, the latter a deeper understanding. This could lead to society and halted the consumption of the is most likely due to an overworked immune the development of targeted vaccines to spe- fruits of globalization. There is uncertainty system and the effect of xenobiotic adminis- cific groups of individuals. Collectively, these about what lies ahead, but this period serves tration during the course of treatment. anomalies point to the challenges to vaccine as a time for introspection and evaluation. These observations suggest the need for design and therapeutic interventions. Despite advances in science, technology and therapeutic interventions for varying effects. medicine, we are in uncharted territory. Initially, administration of an agent that can Tackled to the ground boost the natural host immune response in Prevention is the only response in the current Lakshmy Ramakrishnan is a science writer patients who are undergoing mild infections, situation. Physical distancing, the approach based in India.

Nature India COVID-19 Special | June 2020 | 17 ADVERTISEMENT FEATURE

The Bangalore Bioinnovation Centre is the largest hub for life science start-ups in India.

A CATALYST FOR BIOINNOVATION The Bangalore Bioinnovation Centre (BBC) is INCUBATING LIFE SCIENCE START-UPS that are hoping to play a role in the rapid growth of India’s biotechnology sector.

A MESSAGE country. Recently, BBC received successfully commercialize 15 — Jitendra Kumar, managing 70 applications from innovators “INDIA HAS socially impactful products. director of the Bangalore working to find solutions to ease A HUGE Bioinnovation Centre the burden of the pandemic. POPULATION Facilities: BBC’s international- India has a huge population of Of these, it is nurturing about OF ASPIRING standard Central Instrumentation aspiring innovators — and our 30 projects, ranging from INNOVATORS” Facility (CIF) is one of the best- research ecosystem is maturing. diagnostics to therapeutics and rated in India. It includes The Indian government vaccine development. modular plug-and-play has recognized the country’s But BBC’s start-ups were hard The centre: BBC is one India’s laboratories, proteomics and ability to play a vital role in the at work before the pandemic. leading bioincubators for life small molecule analysis systems, international biotechnology At the Global Bio-India 2019 science start-ups. Based in and centrifuge, microbiology, industry and aims to grow its conference, three launched the south-western state of molecular biology, microscopy, current 3% share of the global products, including String Karnataka, BBC is an initiative cell culture and fermentation market to 19% by 2025. Bio’s poultry feed production of Karnataka Innovation and facilities. Its Technical Advisory The COVID-19 pandemic has technology fuelled by waste Technology Society (KITS) and Resource Group (TARG) also seen support for life science methane, Yostra Labs’ handheld the Government of Karnataka’s assesses proposals and innovation increase at both the device for diabetic neuropathy Department of IT, BT and S&T, mentoring innovators through central and state levels. detection, and Next Big Innovation with liberal funding coming each project stage. As a result, more bioincubation Labs’ latest 3D bioprinter. At from the Government of India’s centres, similar to the Bangalore only four years old, we predict Department of Biotechnology Funding: Start-ups at BBC have Bioinnovation Centre (BBC), there are many, many more BBC (DBT). Since its establishement access to a range of funding are being created across the products on the horizon. in 2016, BBC has helped options. For example, the

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Sustainable Entrepreneurship several innovative products in and Enterprise Development weight management, vitamins (SEED) Fund, an initiative of and minerals, and skin and India’s national Biotechnology oral care, using ingredients Industry Research Assistance such as caffeine, curcumin and Council (BIRAC), provides glutathione topical films. The capital to many early-stage start- company was awarded the ups. Since 2017, BIRAC has also Top Innovator Award in the funded a medical technology healthcare sector at the Global accelerator at BBC that helps Bio-India 2019 conference. entrepreneurs develop start-up pitches, go-to market strategies Some BBC incubatees and initiate commercial activities as part of its biotech String Bio has developed a Team Bangalore Bioinnovation Centre. development programme, gas fermentation process Bio-NEST. BBC has also been using engineered bacteria and involved in a number of key methane waste to make protein initiatives from the Government cakes for use in the food and of Karnataka, including ELEVATE agriculture industries. It won the 100, which selected the top 100 BIRAC Innovator Award (2018), technology-based start-ups from L’Oréal Innovation Runway across the state to provide with award (2017), Best World Wide comprehensive entrepreneurship Deep Tech Startup (2017) and support. The initiative taps into Future Food Asia Award (2017). 400 million rupees (approx. $US5.3 million) of government SN Lifesciences has recently Director, BBC A state-of-the-art plug and play laboratory at the Jitendra Kumar, PhD, MBA. Bangalore Bioinnovation Centre. funds. This is the largest pool of developed, among its other funds ever offered by any Indian offerings, an automated RNA state government to start-ups. isolation and isothermal Next Big Innovation Labs for skin diseases, diabetes and amplification kit that could (NBIL) have developed circulation issues. Currently, Some BBC graduates potentially reduce the cost of Innoskin®, a 3D cultured its researchers are working to COVID-19 test kits to as low as skin product that will allow prevent systemic absorption of Jana Care Solutions Pvt Ltd 500 rupees (approx. US$6.60). companies to test chemicals topical treatments. is a company that was formed affordably and reliably, without by Harvard University alumni OmiX Labs offers a platform using animals. NBIL’s patented Yostra Labs have launched to develop diagnostics and for early detection and more 3D bioprinting technology allows NeuroTouch, a point-of-care programmes for chronic accurate identification of it to position cells with micron- screening device for peripheral diseases. Its point-of-care infection-causing organisms. level precision, enhancing cell- neuropathy. Kadam is another diagnostic platform, Aina, tests This start-up is working on to-cell interaction within tissue product already on the market blood sugars, lipid profiles and a COVID-19 rapid detection constructs and reducing the which reduces the healing time haemoglobin. New tests for kit based on isothermal chances of batch inconsistency. of chronic wounds. NT-proBNP (a peptide that can amplification, without the indicate ventricular dysfunction) requirement of preparing VNIR Biotechnologies Biofi Medical Healthcare and serum creatinine (linked samples using reverse develops live cell imaging India Pvt Ltd has developed to kidney dysfunction) are in transcription-polymerase innovations using red/near an economical, non-invasive development. In collaboration chain reaction. infra-red fluorescence detection. diabetic profiler. Using near- with leading academic medical Diagnostic kits and devices that infrared wavelengths highly centres globally, the company Pandorum Technologies’ can detect Alzheimer’s, malaria, specific to blood glucose, has also developed the Habits bioinspired corneal ink could kidney failure at an early stage it is able to detect blood Program, a digital coaching be used to print replacement are in development. glucose levels and associated system for patients with lenticule tissue (a part of the diabetes complications. diabetes and congestive cornea) to treat corneal defects. Atrimed Biotech is working heart failure. It has the potential to restore on technologies that include vision to many. In addition, a plant-based molecules used to BonAyu Lifesciences has mini liver platform they have treat psoriasis and acne, and for developed thin film platforms developed may be able to be pain management. It has created for the biodegradable delivery used as a model in pre-clinical a self-learning engine based of health supplements and drug screenings to reduce drug on Ayurveda that produces cosmetics. It has also launched discovery costs. research leads for treatments

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2019 20192020 2020

CARBON IN THE 3,563 (Emissions3,563 (Emissions MtCO )MtCO ) China China 2 2 China China Power Power GroundGround transport transport IndustryIndustry 3,248 3,248 20 20 0.3 0.3 16 16

UnitedUnited 1,753 1,753 States States 15 15 12 12 1,615 1,615 0.2 0.2

1,153 1,153 10 10 8 8 EuropeEurope GLOBALLY,GLOBALLY, CO2 EMISSIONS CO2 EMISSIONS TIME OF COVID-19 (EU27 &(EU27 UK) & UK) 1,008 1,008 0.1 0.1 Near-real-time data show which sectors, countries and events had the most DROPPEDDROPPED BY 8.3% BY IN 8.3% THE IN THE 5 5 4 4 896 896 FIRST FIRSTFOUR MONTHSFOUR MONTHS OF 2020 OF 2020 India India 0 0 0 0 0 0 impact on slashing carbon emissions, but it is unclear how long the dip will last. 831 831 COMPAREDCOMPARED WITH 2019.WITH 2019. Jan Jan Mar Mar Jan Jan Mar Mar Jan Jan Mar Mar

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ET AL DECLINES ACROSS SECTORS The international response to the coronavirus pandemic has so far slashed global EconomicEconomic activity activity returns returns carbon dioxide emissions by more than 8% compared with last year, according to 40 40 to normalto normal in 6 weeks in 6 weeks detailed estimates from two independent research teams. The largest reductions EconomicEconomic activity activity returns returns

were in the electric power, industry and ground-transport sectors. Daily global emissions ( MtCO Daily global emissions ( MtCO to normalto normal in 12 weeks in 12 weeks This bar chart shows percentage changes in emissions from the same date the 20 20 MinimalMinimal government government restrictions restrictions previous year. retainedretained until the until end the of end2020 of 2020 –25 –25 ; ALL OTHER CHARTS: Z. LIU CHARTS: ; ALL OTHER 0 0

SOURCE: V-SHAPED RECOVERY: C. LE QUÉRÉ RECOVERY: V-SHAPED SOURCE: (2020) JanuaryJanuary FebruaryFebruary March March April April 2000 20002005 2005 2010 2010 2015 2015 2020 2020Jan AprJan AprJul OctJul OctJan Jan

20 | Nature India COVID-19 Special | June 2020 CHINA LEADS DIVERGENT PATHS The country with the largest impact on emissions was China, where Pulling information from a range of sources — including energy and weather reports,

CO2 emissions declined by an estimated 315 million tonnes — roughly satellite-based observations and traffic data collected by vehicle-navigation systems the annual carbon emissions of France. Figures started to fall in — both research teams produced detailed assessments of various sectors in several January, coinciding with the Lunar New Year, and they stayed low, countries. After China’s initial decline, industrial and power emissions there sprang back. accounting for a 10% reduction until the end of March compared with In Europe and the United States, the largest declines have been in the transport sector. last year. As economic activity picked up in China, other countries went into lockdown mode, depressing global emissions throughout April. 2019 2020

China 3,563 (Emissions MtCO2) China Power Ground transport Industry 3,248 20 0.3 16

United 1,753 States 15 12 1,615 0.2

1,153 10 8 Europe GLOBALLY, CO2 EMISSIONS (EU27 & UK) 1,008 0.1 DROPPED BY 8.3% IN THE 5 4 896 FIRST FOUR MONTHS OF 2020 India 0 0 0 831 COMPARED WITH 2019. Jan Mar Jan Mar Jan Mar

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Daily emissions (MtCO 0 0 0 Jan Mar Jan Mar Jan Mar 0 Europe (EU27 & UK) Power Ground transport Industry 5 3 2.0

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0 0 0 Jan Mar Jan Mar Jan Mar

–10 A V-SHAPED RECOVERY? The scale of the emissions reduction this year could be similar to the annual cuts required to meet the objectives of the 2015 Paris climate agreement, which seeks to limit global warming to 1.5–2 °C above pre-industrial levels. If the 2008 economic recession is any guide, however, emissions could recover quickly.

Overall prediction Three possible scenarios 120 –15

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Change in daily global emissions (in megatonnes of carbon dioxide) by sector, from 2019 to 2020 2019 from sector, by Change in daily global emissions (in megatonnes of carbon dioxide) –20 60

Economic activity returns 40 to normal in 6 weeks Economic activity returns

Daily global emissions ( MtCO to normal in 12 weeks 20 Minimal government restrictions retained until the end of 2020 –25

0 January February March April 2000 2005 2010 2015 2020 Jan Apr Jul Oct Jan

Nature India COVID-19 Special | June 2020 | 21 Feature A CALL TO SOW SEEDS FOR NUTRITION SECURITY India announced free food grains for more than 800 million people during the COVID-19 lockdown. However, nutrition security is more important than food security during this crisis and beyond, experts say. By Sandip Das

Farmers harvesting wheat in New Delhi during the national lockdown.

s one of the largest producers of the world’s biggest food security programme, ‘calories’ through NFSA, the focus should rice, wheat, sugarcane, cotton, FCI procures and supplies around 60 million now shift to production and consumption of vegetables, and milk, India was tonnes of rice and wheat grains annually. pulses, oil seeds, vegetables and other com- faced with a tough agrarian chal- modities such as fish and eggs, he told Nature lenge when farming activity halted A nutritious basket India. following the lockdown, just ahead Agricultural scientists say that although India India is also one of the global leaders in of the harvest and sowing seasons. has enough food grains to meet any eventu- the production of pulses, legumes and mil- Earlier, Prime Minister Narendra ality triggered by the pandemic, it is time to lets, which are rich sources of nutrition. The AModi unveiled a package promising to provide enlarge the food basket to include crops such COVID-19 pandemic necessitates nutri- free food grains to 800 million beneficiaries as sorghum and millets to also ensure immu- tious food for the masses now more than under the National Food Security Act (NFSA). nity-providing nutrition. ever before, according to Rajeev Varshney, Along with their existing monthly entitlements “We should also enlarge the purchase and research programme director for genetic of five kilograms of subsidized food grains, Public Distribution System (PDS) so that gains at Hyderabad-based International Crops these beneficiaries were to be given an addi- whatever we purchase from the farmers can Research Institute for the Semi-Arid Tropics tional free five kilograms for three months be distributed,” said Monkombu Sambasivan (ICRISAT). “It’s high time to include other (April to June 2020). Swaminathan, father of India’s ‘Green Revolu- coarse cereals as they are highly nutritious. The Food Corporation of India (FCI) has tion’ responsible for exponentially increasing We need to keep all the people of India healthy, swung into action to transport at least 10 mil- the wheat and rice production of the country and with stronger immune systems,” Varsh- lion tonnes of food grains every month from in the early 1970s. ney told Nature India. India’s grain surplus states such as Punjab, Swaminathan said merely providing food Securing food for a mammoth population Haryana, Madhaya Pradesh, Chhattisgarh, security will not be enough. The country would require solving the problems of 140 Odisha, Andhra Pradesh, and Telangana to needs to move swiftly to provide ‘nutritional million farm families, mostly small and mar- grain deficit states such as Uttar Pradesh, security’ to a large number of people. While ginal. “Give small farmers enough incentive West Bengal, Bihar, and Karnataka. Under around 800 million people are provided with to continue in agriculture. This is particularly

22 | Nature India COVID-19 Special | June 2020 HINDUSTAN TIMES/CONTRIBUTOR/GETTY HINDUSTAN Farmers harvesting wheat in New Delhi during the national lockdown.

important for young farmers — they should for India’s ‘White Revolution’ steeped in the feel that agriculture is technologically inter- concept of cooperatives in milk procure- esting and also economically rewarding,” said ment. “Community harvesting, community Swaminathan, who chaired the National Com- storage, community marketing and the gov- mission on Farmers, which was set up in 2004 ernment ensuring that a fair price is given. We to assess the extent of India’s agrarian crisis. THIS IS A GOOD TIME should do the same thing in agriculture,” India’s rich genetic resources, distinct TO STRENGTHEN he suggested. agro-climatic zones and rainfall variations pro- In order to tide people over through any vide a unique landscape to optimize the use THE COUNTRY’S COVID-19 related insecurities, India must of available land. The coronavirus pandemic ensure an operational food supply chain, pay provides a fresh perspective and many lessons NATIONAL NUTRITION smallholding farmers in advance for unin- for agriculture, Varshney said. terrupted farming operations and avoid any “With shrinking natural resources such as PROGRAMME.” price inflation of farm products, Varshney said. arable land and increasing vagaries of climate “This is a good time to strengthen the coun- change, we must accelerate the development try’s national nutrition programmes and ramp and adoption of varieties that promise higher The lockdown in India saw thousands of up support from local level NGOs and work- gains in farmers’ field,” Varshney said. migrant agricultural labourers return to their ers,” he added. villages. “The labourers have gone home and Varshney emphasized that it is also a good Calamity-proofing agriculture this poses a challenges to the farmers, pro- time to revisit India’s agricultural research Swaminathan said India must now have an curement, storage and marketing,” Swami- policies. “We can develop new and better early warning system network to understand nathan said. varieties through genomics-assisted breed- early on any possible damage to crops, either He suggested that such an eventuality could ing. But there should be supportive policies because of the weather, climate, drought, be avoided by adopting some of the policies to accelerate the release of new crop varieties floods or pests or pandemics. pioneered by Verghese Kurien, responsible in the national system.”

Nature India COVID-19 Special | June 2020 | 23 Comment Protecting the elderly from the risks of isolation

Debanjan Banerjee

The physical and psychological health of our senior citizens demands urgent attention, now more than ever before.

hey talk about social distanc- Respiratory Distress Syndrome (ARDS), ing. My wife had a stroke and which can eventually lead to death. Also, the needs constant care. My son is severity and fatality of the infection is higher stranded abroad. My daily help in the elderly, immunosuppressed, and has stopped coming, and the people with pre-existing respiratory “Tcare providing agency is not able to provide illnesses, chronic medical problems as well as an alternative due to the lockdown. You tell me under-detection of symptoms. The elderly doctor, what type of distancing can I practice?” are at a unique risk of all these vulnerabili- This is a phone conversation I had with a ties together. patient’s husband, regarding his response An age-comparative study among hospi- to the World Health Organization’s three- talized cases of COVID-19 also shows that pronged strategy — social distancing, hand those aged over 55 had increased duration of and respiratory hygiene. hospital stay, delayed clinical recov- The lockdown was necessary but sudden, ery, increased lung effects, faster illness and no-one was adequately prepared, least progression, and greater fatalities. The of all the elderly, who are as vulnerable to the need for mechanical ventilation and oxy- virus as to the isolation needed to contain it. gen therapy was doubled in the elderly Caring for a partner can be isolating for an elderly person without support age-group and their blood also showed Age and ageism decreased lymphocytes and C-reactive chronic illnesses (like diabetes, hyper- A majority of COVID-19 infections are mild, protein, both markers of adequate immune tension, pneumonitis, osteoarthritis and but some involve pneumonia and Acute response to the virus. Issues with mobility, cognitive decline), multiple medications CARING IN CRISIS

Families and caregivers should be aware of guidance to keep the elderly healthy, and mentally strong

• ‘Physical distancing’ rather than social • All elective surgeries like cataract, hernia or to be tested if concerned. distancing: Regular telephone contact knee-replacements (unless urgent) are better to ensure adequate emotional support. to be postponed. • The elderly should not self-medicate with any drug (antivirals, hydroxycholoroquine, • Considering vulnerability. It’s better that • The elderly have the right to remain any herbal supplement or remedies) as the elderly don’t go out to meet too many updated. The status of the pandemic and preventive or curative strategies for COVID- people. Additional effort is necessary necessary precautions need to be explained 19. Seek doctor’s opinion. to supervise hand and respiratory in simple terms, especially for those with hygiene. sensory or cognitive difficulties. • It is natural to be stressed, but signs of excessive panic, depression, sleep problems • It is better to avoid hospital visits • Those in isolation or quarantine need or suicidality need urgent attention from a during the pandemic. Tele-consultations have special care: telephonic counselling, digital mental health professional. been instituted by most places including contact with family, and ensuring adequate central Government institutes nutrition is vital. • The elderly need to be involved in decision like NIMHANS (Bengaluru), AIIMS (New Delhi), making about their own lives, even in times PGI (Chandigarh) and CMC • Family members need to be aware of the of crisis. Their rights, self-respect, and dignity (Vellore). early symptoms of COVID-19 and make sure must be preserved and protected.

24 | Nature India COVID-19 Special | June 2020 THE VULNERABILITY OF ADVANCING YEARS

The COVID-19 pandemic has brought into sharp focus some vulnerabilities of the elderly:

• Frailty (the age-related biological and psycho-social vulnerability of the individual) related to movement restriction, malnutrition and poor immunity.

• Loneliness, neglect, isolation and poor nutrition (more acute in old-age care homes and institutions).

• Sensory problems that can prevent the taking of adequate precautions.

• Chronic illness, use of multiple medicines, increased health-care needs and physical support.

• Impaired cognitive abilities (memory, processing speed, thinking and language) that worsen with age, can thwart comprehension and adherence to instructions. People affected with dementia might have behavioural problems and wandering tendencies that can add to challenges of keeping them isolated.

Caring for a partner can be isolating for an elderly person without support • Social distancing might not always be possible (exposure to various people and increased need for hospitalizations They are prone to chronic bronchitis, involved in their care, including domestic due to other factors further increase sus- obstructive lung disease and the common help for those who stay alone). ceptibility. cold leading to coughs, sore throat and flu- The elderly also suffer due to the prevalent like symptoms which are in common with • The elderly might not be aware of the stigma of ageism. COVID-19. These can be mistaken for the virus latest infection guidelines, and may be at In general, the elderly are marginalized symptoms, leading to social segregation and risk of misinformation. even though traditionally humans are taught impaired esteem and well-being. Overcrowd- to respect and take care of the older genera- ing, and poor self-care in old-age homes are • Less testing and consequently lower tion, the innate fear of ageing, losing vitality other contributing factors. detection puts the elderly at risk of being MAYUR KAKADE/ MOMENT/ GETTY KAKADE/ MOMENT/ IMAGES MAYUR and death are real. Stress impacts immunity and can increase asymptomatic carriers. risk of infection. Autonomy and self-dignity “Seniors might be can be hampered during a lockdown further • Existential issues related to the fear of impacting the mood, appetite and sleep of sen- death. vulnerable and frail due to ior citizens. Many elderly people live alone and age, but they are not weak. are struggling with access to basic amenities • Psycho-social vulnerability, especially Their resilience can be like food, domestic utilities and hygiene, along at times of lockdown and quarantine: amazing.” with fear of the pandemic. loneliness, anxiety and uncertainty can The WHO and CDC have updated data and give rise to depressive disorders, insomnia precautions for the elderly during COVID-19. and chronic stress. Grief and bereavement The seniors might be vulnerable and frail due due to loss or distancing from loved ones Society equates ageing with loss of charm to age, but they are not weak. Their resilience can be significant and prolonged. and beauty and of youth, that can lead to can be amazing, if adequately cared for, and Elderly people are also at increased contempt and neglect. Such stigma can flare we can all borrow from their strengths. risk for post-traumatic stress syndrome. up during an outbreak which has an age-spe- Suicide risk is also higher in the cific vulnerability. Debanjan Banerjee is a geriatric psychiatrist elderly population and is often Common conversations surrounding the at the National Institute of Mental Health and under-reported. susceptibility of the elderly are stigmatizing. Neurological Sciences, Bengaluru.

Nature India COVID-19 Special | June 2020 | 25 Feature AS COVID-19 TAKES ITS TOLL, BURDEN OF OTHER HEALTH CRISES TOO HEAVY TO BEAR Doctors struggle to treat those with compromised immunity as the pandemic stretches healthcare system capacity. By Biplab Das

uman Devi, a patient with pancre- professor in the Department of Community A set of guidelines for managing cancer atic cancer, waited on the footpath Medicine, Yenepoya Medical College, Man- patients drawn up by international research- outside the All India Institute of galuru. “Of course, we need to ensure that ers suggests that oncologists could postpone, Medical Sciences as her husband we are adequately resourcing for a COVID-19 discontinue or modify radiation therapy. Some queued up for charity food nearby. response, but not at the cost of basic services patients may be given the option of home Devi’s ongoing treatment at the at a minimum level.” infusion of chemotherapy to minimize Delhi hospital brought them there the risks of infection. Stem-cell therapy for from a small town in Uttar Pradesh, cancer patients can be reasonably delayed Sbut a nationwide lockdown on 25 March 2020 during the COVID-19 crisis, the researchers hindered their travel back home. say. Devi is among hundreds of other critically- “Certain cancers, such as acute leukemia, ill patients who spent days on the footpath could be life threatening, if not treated early,” waiting their turn for treatment before being THOSE WITH says Kolkata-based haemato-oncologist Pran- shifted to quarantine facilities. Getting an LOW-GRADE tar Chakrabarti. “If the patient is young, has a appointment with doctors for most of these chance of getting cured, and does not have sig- patients has been difficult as healthcare pro- MALIGNANCIES ARE nificant comorbidities, we administer chemo- fessionals were diverted to COVID-19 wards. therapy — that’s the standard protocol Indian Kenyan national, Agnes Kiminza, who has REQUESTED NOT TO haematologists are using,” he says. All such breast cancer, was stuck in Bengaluru for days patients are screened for COVID-19 before after her last radiation therapy ended. She VISIT THE HOSPITALS.” therapy. Those with low-grade malignancies and many others from her country, visitors are being requested not to visit the hospitals to private hospitals in India for treatment, and use home or day care based treatments as were living in cheap hotels, waiting for air much as possible. travel restrictions to lift so that they could go Crisis time cancer care Patients are also concerned about what back home. Oncologists are struggling to protect and treat would happen if they stop, delay or switch As the COVID-19 pandemic puts more pres- cancer patients amidst the pandemic. Manju cancer treatment. “Many of them are asking sure on healthcare facilities in India, uncer- Sengar, an oncologist from the Tata Memorial for tele-consultations, but that is not prac- tainty grips people suffering from other Centre in Mumbai says home caregivers need tically possible,” says Abhishek Shankar, an critical illnesses — cancer, diabetes, chronic to be educated on how to control the spread oncologist from the Lady Hardinge Medical lung and kidney diseases, liver disease, car- of COVID-19 with basic hand hygiene, physi- College in New Delhi. Consultations, he points diovascular diseases, morbid obesity, HIV, cal distancing and cough etiquette. “Cancer out, are based on tests to assess their condition and high blood pressure. Their anxiety is patients should be screened for COVID-19 and progress of the disease, chemotherapy compounded by the fact that these diseases symptoms such as fever, sore throat, cough and radiotherapy, every week, especially for make them more vulnerable to the novel coro- and difficulty in breathing,” she says. aggressive types of cancer. navirus infection. Sengar says oncologists should delay A study from Wuhan in China shows that can- extensive surgeries. Instead, they could pri- Diabetics and COVID-19 cer patients, with compromised immunity, are oritize surgeries for rapidly proliferating and Diabetes has emerged as a major risk fac- at greater risk of viral infection. Elderly people life-threatening brain tumours. Decisions tors responsible for increased mortality due with cancer are also more likely to end up on on chemotherapy should also be taken cau- to COVID-19. In India, sometimes called the ventilators or die due to the viral infection. tiously. “It is better to switch to oral anticancer world’s diabetes capital, the lockdown has “Just because a lot of resources are being drugs,” Sengar points out. Steroid use should meant less exercise, increased snacking and put into COVID-19, we don’t want a rebound be limited and doctors should try to manage decreased availability of glucose-lowering of other diseases. We need to be extra cau- patients using a single anticancer agent or drugs for patients. These factors may increase tious about that,” says Anant Bhan, a visiting fewer drugs, she says. blood glucose and blood pressure.

26 | Nature India COVID-19 Special | June 2020 SONU MEHTA/HINDUSTAN TIMES VIA GETTY IMAGES MEHTA/HINDUSTAN SONU A view of the Delhi State Cancer Institute (East), which struggles to perform usual services during the pandemic.

“To make up for the lack of exercise, I walk in train them to recognize and treat glucose-low- lead to pneumonia and acute respiratory a long corridor or rooftop of my house,” says ering episodes on their own,” says Deep Dutta, disease. Sudip De Sarkar, a 68-year-old diabetic patient a diabetologist from the Seth Sukhlal Karnani Analysis shows that people with chronic from Kolkata. “I avoid snacking, monitor my Memorial Hospital in Kolkata. obstructive pulmonary disease (COPD) are blood glucose levels using a sugar-testing A person with type-1 diabetes may develop associated with a significant, more than five- machine and send the data to my physician diabetic ketoacidosis, a life-threatening prob- fold higher risk of severe COVID-19 infection. through WhatsApp,” he adds. lem when the body starts breaking down fat at Like other viral illnesses such as the flu, During lockdown, telemedicine may prove a rate that is much too fast with the liver mak- COVID-19 can make it harder for the heart to useful for the management of patients with ing a huge amount of blood sugar. “Telemed- work. Persistent immune activation in predis- chronic diseases such as diabetes, a study in icine is not suitable for such patients because posed patients, such as the elderly and those India says. Diabetics could connect with the they need hospital care, adequate intravenous with cardiovascular risk, can lead to secre- physicians through messaging apps or video hydration and modulation of insulin therapy,” tion of specific immune molecules, leading calls on chat platforms, the study suggests. Dutta adds. Telemedicine is also difficult for to multi-organ failure. Inflammation, particu- “More than 90% of people living with dia- the elderly or those without technical skills. larly in the muscular layer of the heart, can betes in India suffer from type-2 diabetes result in myocarditis, heart failure, cardiac (T2DM), which is primarily a lifestyle disorder,” The critically ill arrhythmias, acute coronary syndrome and says Satinath Mukhopadhyay, a diabetologist Patients suffering from asthma, cardiovascu- sudden death. from the Institute of Post Graduate Medical lar diseases and HIV are also highly vulnerable HIV patients with a low count of CD4 cells, a Education and Research in Kolkata. T2DM is to COVID-19 infection. type of white blood cells which trigger immune all about self-management and self-care, and People with moderate to severe asthma response, are at a higher risk of getting very telemedicine may be effective, he says. may be at higher risk of getting very sick from sick from COVID-19. Patients receiving stand- “Besides training patients how to self-moni- COVID-19 since it can affect the respiratory ard anti-HIV drugs might not have increased tor blood glucose, telemedicine can be used to tract, cause an asthma attack, and possibly risk for COVID‐19.

Nature India COVID-19 Special | June 2020 | 27 Feature PACKAGING THE FUTURE OF INDUSTRY Safe delivery of materials is key to successful resumption of economic activity. By Kowthamraj Sangappillai

s India relaxes the lockdown, resuming economic activity will be dependent upon local and global delivery of raw materials, intermediates and finished products. One of India’s largest employment sectors — small RECLAIMING THE TRUST and medium enterprises — are now OF GLOBAL CONSUMERS looking to the country’s research Acommunity for solutions for safe packaging. REQUIRES MORE THAN From local delivery of masala dosa to inter- continental shipping of aeroplane parts, safe JUST TECHNOLOGICAL packaging is a key requirement across indus- CREDIT tries and businesses. Questions over whether INTERVENTIONS.” the packaging can be trusted might slow down the return of free trade. A SARS-CoV-2 resilient packaging material that is cheap and scalable at advanced anti-viral coatings, especially for could be a game-changer for the country’s flow personal protective equipment of frontline of goods. health-workers, as they risk infection while Around the world, restaurant orders have de-robing from PPEs,” said Aravind Kumar fallen as people are worried about surface Chandiran, an assistant professor at the Indian SARS-CoV-2 contamination. This fear might Institute of Technology Madras and a former extend to global shipments as well, as stud- materials scientist at the University of Cali- ies indicate that the virus may stay on sur- fornia, Berkeley. Such solutions, if adapted faces from three to nine days. This is where for scaled delivery, could help make spray Researchers should quickly start looking for viable coronavirus-free packaging materials. packaging and material technology comes coatings for shipping containers resistant to into play. SARS-CoV-2. known to inhibit viral activity, including that Studies indicate that the novel corona- To begin testing for coronavirus-free pack- of H1N1. “However, little has been explored in virus is most stable on plastic and stainless aging materials, researchers should evaluate coating these materials on existing packaging steel. Most packaging involves some plastic a wide variety of permutations and combina- systems,” Chandiran said. To use this low-cost material, and shipping containers are made tions to arrive at viable candidates. The testing material, the researchers should explore the of a variety of stainless steel called ‘corten method (half-life) is simple and inexpensive, possibility of making robust thin film coatings steel’. Evidence also suggests that the virus though availability of viral strains may be a bot- on various packaging materials, and their abil- does not survive long on copper, as copper tleneck. The knowledge of properties needed ity to disinfect pathogens under varied tem- ions kill the microbes landing on the surface. for an anti-SARS-CoV-2 material, however, is peratures and humidity conditions. The ions prevent cell respiration, disrupt the robust and should help narrow down the Besides research, standards also need to be viral coat and destroy the genetic material candidates. “Lessons from food packaging in place for packaging shipments so that the inside. This latter property is important as studies, such as understanding the relation- potential spread of any virus or disease-caus- it means that no mutation can prevent the ship between size of pores on surfaces and ing pathogens can be checked, he said. “Spe- microbe from developing resistance to cop- the survival of the virus might prove crucial in cifically, the time taken by the antiviral coating per. Copper foils could replace aluminium foils designing a packaging material of the future”, to disinfect the pathogens and stability of the for food wrappings, as large scale copper foil said Naveen Kumar Balakrishnan, an advanced coating under different environments should manufacturing is a mature industry. bio-materials researcher at the Maastricht Uni- be standardized immediately,” Chandiran said. Scientists are looking for a range of alter- versity in the Netherlands. Many industrial facilities across the world native packaging materials. “We are looking Zinc oxide is a familiar antiviral material, are gradually resuming operations. Car

28 | Nature India COVID-19 Special | June 2020 Researchers should quickly start looking for viable coronavirus-free packaging materials.

manufacturers such as Toyota, Renault, free’ certification for products is the recom- Saurabh Mukherjea of Marcellus Invest- Hyundai, Volkswagen, and Volvo are among mended best practice by the World Health ments Managers correlates a fall in global © PIXABAY those that have opened or are preparing Organization (WHO) and goods are mandated oil prices, lower yields of the US govern- to restart production in Europe. India is to be packed with SARS-CoV-2 resilient mate- ment’s 10-year bonds and a simultaneous an integral part of the global value chains rial to qualify for the certification, alongside contraction in the US economy. These occur- (GVCs) of international production sharing, shipping containers, which must either be cov- rences have traditionally been followed a process where production is broken into ered in a special material or sanitized using by a strong economic recovery in India. activities carried out in different countries. robotic UV decontamination. Based on Mukherjea’s analysis, there is still A UN estimate suggested that GVCs governed According to US-based trade finance com- hope for a recovery for Indian exports in the by trans-national corporations account pany Drip Capital, the Christmas/Holiday coming months. for 80% of world trade each year, under- season in the US and the European Union has The biggest ever healthcare challenge for scoring the length and breadth of a truly historically driven demand for Indian exports. humanity necessitates an ambitious roll-out of globalized supply chain ecosystem, which A weak rupee against the dollar could very well SARS-CoV-2 resilient packaging to save indus- relies on safe packaging. give a short boost to Indian exports, once tries and help them thrive. global trade gets back on track. Post-pandemic packaging India is a leading exporter in agricultural *The author is a Young Professional in the Reclaiming the trust of global consumers and other essential commodities such as phar- Energy and International Co-operation vertical requires more than just technological inter- maceuticals, which will be in demand during of NITI Aayog, a policy think-tank of the Indian ventions. Imagine a scenario where a ‘virus and in the aftermath of the pandemic. government.

Nature India COVID-19 Special | June 2020 | 29 Comment Time to bring scientific rigour to the complex challenge of Ayurvedic medicine

Jitendra Kumar and Pradip Sinha

A look at traditional approaches in the context of the COVID-19 pandemic.

disclaimer first — herbal supplements the key molecules from a herb for its ability phytopharmaceutical is considered thera- and Ayurvedic medicines are not syn- to mitigate, say, disease symptoms that are peutically relevant — what is visible under onymous demonstrable in an animal model or in cell the ‘streetlight’ of a screening procedure. The ongoing COVID-19 pandemic lines — in the parlance of the conventional drug Other potentially useful phytopharmaceuti- shows that age, co-morbidities and industry, they seek the active pharmaceuti- cals — epistemologically speaking — are then Athe quality of available healthcare impact the cal ingredient. Recent approval for a clinical discarded by ignorance. rate of recovery. Given that no vaccine or tar- trial of phytopharmaceuticals for COVID-19 This approach is also antithetical to Ayurve- geted therapeutics for COVID-19 are in ready is one such example6. The molecule, AQCH, dic principles wherein the totality of the entire sight, India’s Ministry of AYUSH, which focuses is derived from the broom creeper, Coccu- medicine/formulation cannot be reduced on traditional Indian medicines including lus hirsutus, a plant traditionally used for its to its individual components. By the same Ayurveda, has called attention to traditional medicinal benefits. Ayurvedic rationale, what a patient suffers medicines for alleviating symptoms of COVID- Pursuing such a ‘reductionist’ methodology is the sum total of a host of bodily manifesta- 191. However, in the absence of scientific evi- is not surprising since mechanisms of actions tions, which cannot be reduced to only a single dence of cure and safety, Ayurvedic medicines of individual phytopharmaceuticals are rela- symptomatic manifestation. cannot become part of the standard of care for tively easier to resolve than those of Ayurve- COVID-19 therapy or management. Can there dic medicines, which are often combinations Repurposing Ayurvedic medicines be a way forward toward scientifically rigorous of multiple herbs that are believed to act in Ayurveda is founded on traditionally inher- examination of potential benefits of Ayurveda synergy and prepared by complex traditional ited knowledge and is based on empirical evi- in COVID-19 management or therapy? dence. Given the recent origin of COVID-19, The advertized benefits of herbs in many “They could form cohorts an Ayurvedic treatment is therefore not avail- Ayurvedic products fall in the realm of nutri- able. New Ayurvedic medicines also cannot tional supplements where wellness industries for control trials to validate be discovered — unlike in a drug discovery thrive. Such wellness products neither claim, Ayurvedic alleviation of programme of conventional medicine. Thus, nor are their regulatory approvals based on, COVID-19.” cure or management for COVID19 — if these any definitive therapeutic, medicinal or dis- were to be found in Ayurvedic pharmacopeia ease curative benefits. Ayurvedic medicines of India — would fall under the category of drug should not be confused with nutraceuticals, methods. And the merit of a reductionist, phy- repurposing or therapeutic switching, again, the latter only means food supplement with tochemical, approach is not unfounded. The in the parlance of the pharmaceutical industry. potential health benefits. Ayurvedic medicines anti-malarial drug, artemesinin, after all was The concept of repurposing of medicine is or formulations on the other hand are pre- discovered by this approach, starting with a not alien to Ayurveda. The list of medicines, scribed by practitioners who claim a curative medicinal herb, Artemisia annua.7 Therefore, or the combination thereof, that an Ayurve- therapy against a given disease. approaches to discover phytopharmaceuticals dic practitioner may use to treat symptoms And therein lies the barrier to their accept- from traditional medicines, TCM or Ayurveda, of COVID-19 is not inexhaustible and most ance as scientifically proven safe medicines are likely to bring tangible rewards when pur- practitioners would make overlapping, if not for the disease in question: traditional medic- sued with sufficient scientific rigour. These identical, recommendations from the availa- inal mitigations of severe acute respiratory promises notwithstanding, this approach may ble list of Ayurvedic medicines. Their choice of infections (SARI), like COVID-19, have not been hit a road block when seeking a treatment for medicines would be guided by the framework scientifically proven2,3. COVID-19, in which clinical presentation of of mapping pathogenesis set out in Ayurvedic patients is complicated by co-morbidities classifications of a patient’s constitution and Reductionism and the streetlight that are unlikely to be addressed by a single the co-morbidities presented, along with those effect in validating Ayurveda phytopharmaceutical agent. of COVID-19. Even within this finite choice of While traditional medicines from Ayurveda Moreover, this approach to phytopharma- medicines, the prescriptions will be custom- or traditional Chinese medicine (TCM) ceutical discovery calls to mind Noam Chom- ized for individual patients: indeed, there is no encompass the use of traditional medicinal sky’s observation on the scientific method: universal fit in Ayurvedic therapy. concoctions, they are also are known sources “Science is a bit like a joke about the drunk who However, one needs to ask whether such of discovery for phytopharmaceuticals4,5: is looking under a lamppost for a key that he rationale and personalized procedure for that is, individual chemicals isolated from has lost on the other side of the street, because Ayurvedic therapeutics could be timely and a given medicinal herb that can mitigate a that is where the light is. It has no other choice” effective during a pandemic. While one can disease or its associated symptoms. In the Thus, when pathogenesis is partly recapit- draw a rosy picture of traditional medicinal latter approach, chemists try to identify ulated in a cell line, its mitigation by a given panacea for COVID-19, the realities could be

30 | Nature India COVID-19 Special | June 2020 MARILYNA / ISTOCK / GETTY PLUS IMAGES / ISTOCK MARILYNA A selection of foods and plants used in traditional medicines.

challenging. COVID-19 symptoms can esca- and their rigorous design might answer ques- properties of plants under different geograph- late precipitously in many patients, requir- tions including whether Ayurvedic therapy can ical conditions can also be resolved. These ing emergency care, foreclosing the option help early and improved recovery of COVID19 steps can address the major concerns about of slow-acting Ayurvedic interventions. Also, patients, or whether such an intervention can efficacy and safety of Ayurveda, while tech- here is cautionary advice against the use of reduce the number of patient requiring critical nological breakthroughs in the coming years herbal or traditional medicines for COVID-192,3 care. may turn on the many streetlights to illuminate even though their potential is documented4,5. the space of complex Ayurvedic formulations. Animal models A clinical trial on Ayurvedic COVID- Safety and toxicity assessments of Ayurvedic Jitendra Kumar and Pradip Sinha are from the 19 management? medicines are possible using the standards Bangalore Bioinnovation Center, Bengaluru Thus, while Ayurvedic treatment for COVID- of evaluation practiced in mainstream phar- and the Indian Institute of Technology Kanpur. 19 cannot be suggested, the opportunity maceutical sciences: for instance, by using

presented by the pandemic could be used animal models to assess toxicity and also 1. Ministry of AYUSH. Government of India Gazette to rigorously design clinical trials to test the recapitulation of severe acute respiratory notification F. No. L1101/8/2020/AS (21 April 2020). claims of Ayurvedic medicine. Many COVID- infections in mouse models for testing actual 2. Cyranoski, D. Nature https://doi.org/10.1038/d41586-020- 01284-x (2020). 19 positive patients display mild symptoms mitigations. Ayurvedic medicinal claims can 3. Yang, Y. Lancet 395, 1689–1690 (2020). and recover under quarantine with no further also be tested in carefully constructed ani- 4. Nature Plant. 6, 177 (2020). treatment, since none may be available yet. mal models of human diseases to assess the 5. Cui, H.-T. et al. Traditional Medicine Research 20, 65–73 (2020). These patients, not requiring hospitalization, cross-talk between Ayurvedic medicines and 6. ICGEB with Sun Pharma: Phase-II clinical trial on AQCH could form ideal cohorts for randomized con- immune system and gut microbiome, an over- for treatment of COVID-19 patients https://www.icgeb. trol trials to validate Ayurvedic alleviation of looked field, to reveal as yet mysterious ways org/icgeb-with-sun-pharma-for-phase-ii-clinical-trial-on- aqch-for-treatment-of-covid-19-patients/ COVID-19. A clear and realistic definition of of working of Ayurvedic medicines. Quality 7. Tu, Y. From Artemisia annua L. to Artemisinins (Elsevier, anticipated outcomes from such clinical trials assurances to overcome the varying medicinal 2017).

Nature India COVID-19 Special | June 2020 | 31 Comment

Misinformation and myths go viral

Sandhya P. Koushika

From the belief that drinking ife as we know it, whether in luxury appear faster than they can be dispelled, travel air-conditioned homes or in over- faster than fact, and can seem indestructible. tea will protect against crowded slums, has been upended. Myths promoting the use of a variety of COVID-19, to confusion As always, a weaker socioeconomic herbs, formulations and medicines as cures NANDA SUMITA with tragic outcomes, status makes for poor outcomes, be it or prophylaxis are widespread. Typically, such Laccess to sanitation and healthcare, or bru- myths originate in traditional beliefs with lit- such as poisonings, tal enforcement of lockdown guidelines. tle modern scientific evaluation. misunderstanding and Socioeconomic disruption and uncertainty The HoaxBuster team of the Indian Scien- contribute to an environment that breeds tists’ Response to COVID-19 (ISRC) said that hoaxes are common in this myths and hoaxes, which feed on these tre- there is insufficient or no evidence that garlic, time of uncertainty. mendous psychological vulnerabilities. tea, applying oil, or steaming protects against A myth can offer solace when little else COVID-19. Several herbs are said to boost immu- is available and is often adopted without nity in general. The ability to ‘boost immunity’ verification. is dependent on the adaptive (acquired) arm Nowadays myths spread faster than the of our immune system. We acquire immunity coronavirus, on WhatsApp and other digital against a specific disease either through getting platforms. In a social media era, rumours that disease or through a vaccine.

32 | Nature India COVID-19 Special | June 2020 A person who thinks of ‘boosting immunity’ We will not contain this epidemic if we is probably just seeking good overall health to ignore either the science, or our humanity. fight off any disease in general and for this, Several efforts have been made to combat diet is but one aspect. For most well-nour- the tsunami of misinformation: the govern- ished people, a regular healthy diet along with ment’s use of the Epidemic Diseases Act, 1897 exercise and sufficient sleep will do more to and Disaster Management Act, 2005 to combat promote good health than drinking five cups fake news, infographics by MyGov, efforts by of tea a day. ISRC, CovidGyan, TNSF, AIPSN, etc. Tradi- The false sense of security provided tional media outlets have also stepped in to by unproven remedies can be doubly danger- combat these myths. The resources in Indian ous because it can sideline the importance languages lag behind those in English, but con- of implementing behavioural changes that certed efforts are being made in this direction. have been proven to help. Moreover, myths Scientists have unique qualifications to can be exploited by quacks to make money combat misinformation, yet they are often by selling products that are useless if not hamstrung by their own training. First, sci- actually harmful. Even if one judges cer- entists are comfortable with uncertainty and tain remedies suggested on social media as nuance. There is a difference between there harmless and decides to follow them, being no evidence for a claim, not enough evi- mitigation strategies that are known to work dence, the claim being likely to be false, and

like physical distancing, wearing masks it being false. But such distinctions are not PIXABAY and good hygiene must still be consistently always appreciated by someone who wants People were poisoned after drinking liquor followed. to know if turmeric milk works for COVID-19. made from ‘virus-shaped’ Datura seeds. A second popular group of myths about Does ‘not enough evidence’ mean it works India’s fight against COVID-19 is that Indians but scientists do not know? Does ‘likely to effort for scientists and scientific institutions have stronger immunity; the virus will not be false’ come from personal prejudice? A to invest time in myth-busting. persist in a hot and humid climate like ours; straightforward answer is not easy for a scien- I found myth-busting an intellectually and the virus in India is weaker. These are par- tist to provide, yet is desired by the public to rewarding process, involving several fierce ticularly attractive since they would mean our make a clear decision. discussions on data with a diverse group of outcomes are likely to be much better than the scientists and science communicators. But I rest of the world. “We will not contain this believe there are larger issues at stake. Unless However, no scientific data suggest scientists communicate how the research pro- that the virus behaves in India or in Indians epidemic if we ignore cess works, convey complex ideas in a simple in unusual ways. The major source of corona either the science or our manner, and share how current understand- virus is infected people in whose respiratory humanity.” ing evolves and changes as new information tract this virus grows and from where it is comes in, the public cannot be expected to poised to infect others. It is too early to trust scientific information, or use it to make know what role, if any, temperature plays Second, scientific progress is typically slow good personal choices. when a highly infectious new virus is tearing and measured. Ideas are tested and argued The pandemic has shown that science must through a population with no current over years, sometimes over decades, before engage more with society to build trust and immunity to it. Finally, the sequenced gen conclusions are drawn. The pandemic has has forced some scientists to think about how omes of the virus in India show no features accelerated this process and exposed it to to communicate the value of science. Not just suggesting that it is behaving differently public view. A recent retraction from The by advertising the latest cool findings but also than elsewhere. Lancet on hydroxychloroquine treatment by promoting critical thinking, for example by Myths in the final group are conspiracy outcomes exposes several fault lines in doing allowing the general public to question and theories that target someone or something science under pandemic pressure. Frustration assess information. This is hard, but impor- as being responsible for COVID-19. The most with the normally slow progress of research tant if we hope to contribute to and keep the popular ones are that the virus was created can lead to rapid publication of results, and support of society. in a lab, that bats spread the virus, and that a withdrawing published research reduces con- All healthy societies have a plurality of opin- particular community spreads the virus. fidence in scientists. ions and vigorous debates, but debates devoid The virus genome sequence shows no Meanwhile, societies are facing long-term of data and its critical analyses are flawed, as evidence to suggest the virus was created economic and social costs, while scientists are debates that do not include a discussion in a lab, so bats, and the trees they nest on have little to offer except masking, handwash- of values which underpin our public policies. should not be disturbed. Zoonosis, a microbe ing and physical distancing. Indian scientists and scientists-in-training jumping from one species to another, is more Lastly, many scientists hesitate to step need greater exposure to and meaningful likely to occur when we disturb ecosystems outside their areas of expertise, built over engagement with the local communities where leading to greater contact between wild ani- several years with the commensurate ability their institutions are based. I hope we can work mals and humans. to evaluate the smallest detail. The current with social scientists and lay citizens to foster Finally, singling out communities does little pandemic needs expertise in several areas ways to have an inclusive scientific dialogue. to stop the virus, but much to divide people like epidemiology, immunology, medicine, when what we need is community engage- physics, engineering, etc. The amount of Sandhya Koushika volunteers with the ISRC ment to fight this pandemic. Blaming specific time to gain sufficient understanding, when and is a team member of CovidGyan. Views groups stigmatizes them, and this mindset has scientists too are struggling like others to keep expressed do not necessarily represent those even led to discrimination against frontline their personal and professional lives moving, of her employer, TIFR. She thanks Edward workers, people we depend on to care for our is considerable. Hynes, Susan Parker, Shubha Tole, Jitendra most seriously ill patients. Despite these difficulties it is well worth the Kumar and Kaushal Verma for comments.

Nature India COVID-19 Special | June 2020 | 33 Comment Spreading the word in times of fear

Sima Barmania and Michael J. Reiss

Religious leaders can help disseminate important messages in the COVID-19 crisis.

here was much discussion about reli- certain public health initiatives are directly gion as the world celebrated major opposed to their freedom to worship and festivals – Pessach, Easter, Vaisakhi, could feel that they, rather than the virus, are Navratri, Buddha Purnima and Rama- under attack. However, religions can be ena- dan – under lockdown. Public health blers of public health, and religious organiza- Tpolicy-makers were sceptical about whether tions can be important partners, especially in physical distancing, the key strategy for most less secular societies. countries struggling to contain COVID-19, could On 7 April 2020, the World Health Organi- be achieved during religious festivities tradi- zation issued an interim guidance titled ‘Prac- tionally marked by large gatherings. And yet, tical considerations for religious leaders and with a few notable exceptions, religious adher- faith-based communities in the context of ents complied with the new normal of physical COVID-19’. The WHO acknowledged that “reli- distancing. Religious leaders will play a major gious leaders, faith-based organizations, and role in deciding the future spread of the virus. faith communities can play a major role in In the UK, all places of worship have been saving lives and reducing illness related closed. The UK’s Chief Rabbi, Ephraim Mirvis, to COVID-19”. said on national radio that there is both a “religious and a moral imperative” to “stay at home”. “Religious leaders often have The Archbishop of Canterbury, Justin Welby, connections with those who broke from tradition and delivered his Easter Sunday address from his kitchen, commending are vulnerable and harder churches across the country for “responding to reach through ‘official’ to this challenge in innovative ways”. channels.” However, in some countries, religion under- mined the public health response to the COVID- 19 pandemic. In the US, Florida Governor Ron DeSantis designated religious services as There have been many examples in the past ‘essential activities’, days after a pastor within where religion had a positive role in tackling the state was charged with unlawful assembly infectious diseases. In India and Pakistan, reli- and violation of a public health emergency gious leaders helped increase the uptake of order. New York City mayor, Bill de Blasio, polio vaccines; in Nigeria, religious leaders criticized a large congregation of mourners at played a key role in mitigating the effects of a Hasidic Jewish funeral, igniting strong con- Ebola, through the provision of health, edu- demnation from members of the community. cation, and social support. In South Korea, the Shincheonji Church, is The WHO guidance also points to the “spe- While religion brings great solace, gathering for worship in the pandemic brings great risk. thought to have been the origin of thousands cial role of religious leaders”, faith-based of first cases in the country. In Malaysia, a gath- organizations and communities in educa- mechanism and a source of emotional sup- ering of 14,000 delegates of the Islamic mis- tion, preparedness and response to COVID- port. This is one place where religion comes sion Tablighi-Jamaat in Kuala Lumpur is widely 19. The organization can help by sharing into play, by understanding a rationale for considered the cause of the second wave of the evidence-based information and avoiding noncompliance with social distancing. But pandemic in the country. Attendees returning large gatherings. religious leaders are often central to com- to Brunei, Indonesia and Cambodia from this munities and have extensive networks within gathering later tested positive for COVID-19. The science-religion balance which to disseminate public health messages, An Islamic gathering in the mission’s Delhi Atheists may find it absurd that a person dis- including the rapidly evolving COVID-19 headquarters also saw thousands infected regards substantial risk of infection in order related guidelines. with the novel coronavirus. to attend an ‘in person’ service. And while ser- Religious leaders often have connections vices may not be seen as ‘essential’ by some, with those who are vulnerable within their Enabling public health they will be for others, especially given that communities, such as the elderly, the poor, Some religious communities believe that religion can serve as an important coping or migrants, who may be harder to reach

34 | Nature India COVID-19 Special | June 2020 While religion brings great solace, gathering for worship in the pandemic brings great risk.

through ‘official’ channels. Religious lead- saying that it was a religious obligation to be enhance health literacy. If not, we may alienate ers as respected figures can make decisions tested. Religion and science are not neces- religious groups, rendering them less inclined earlier than governments to suspend con- sarily opposed. to comply with the public health guidance gregational events. For example, the annual Many religions have laws that are compati- crucial for tackling COVID-19. Public health Hajj pilgrimage, which saw more than two ble with public health strategies and allow the policy will ignore religious communities at million pilgrims descend on Mecca last year, ‘lesser harm’ or ‘public interest’ to prevail. So, great risk. has been restricted to no more than 10,000 empathic, proactive and early engagement this year. with religious leaders and communities Sima Barmania is a consultant at the

NARINDER NANU/AFP VIA GETTY IMAGES NARINDER NANU/AFP Religious leaders can play a direct role in can play an important role in public health United Nations University-International implementing health policy. After attend- emergencies. Institute of Global Health, London/Kuala ants at a religious gathering in Malaysia For their part, health professionals and med- Lumpur. Michael J. Reiss is a Professor of failed to come forward to be tested, the Min- ical scientists must ensure that there is effec- Science Education at the University College ister for Religious Affairs issued a statement tive communication and a serious attempt to London.

Nature India COVID-19 Special | June 2020 | 35 Interview

Vishnu Nandan From deep freeze to a lockdown

Polar scientist, Vishnu Nandan, recently returned to Canada from a four-month lockdown in the Arctic. After being in one of Earth’s most isolated places, he talked to Nature India, about coming back into a world fighting a pandemic. Vishnu Nandan is a radar remote sensing expert on Arctic and Antarctic sea ice, and a post-doctoral researcher at the Centre for Earth Observation Science (CEOS) at the University of Manitoba, Canada. He lived on the German research icebreaker RV Polarstern as part of the MOSAiC International Arctic Drift Expedition, one of the biggest scientific expeditions to the Central Arctic Ocean.

What was it like to be locked down in the Arctic darkness for four months? I have undertaken more than 15 expeditions to the polar regions but this one had its own challenges. We were in the middle of a frozen ocean enveloped by complete darkness for 80 days, temperatures plummeting to -55°C with wind chill and sometimes stormy weather. Working with small metallic nuts, bolts and screws under extreme cold required a lot of effort. When we reached Polarstern on 13 December 2019 on the Russian ice breaker, Kapitan Dranitsyn, I was anxious. We did not want the ice to break up with two ships standing next to each other. Towards the end of February 2020, sometimes the skies were clear and sometimes illuminated by the full moon with Venus in its precincts. At one point, darkness became a way of life for me. Now after returning home, I miss the darkness. I would say that such prolonged periods of darkness have their own beautiful flavour. The German research icebreaker RV Polarstern, Nandan’s home for the expedition.

How did you handle emerging into the then we were allowed to return to our families change. Previous Arctic expeditions focused pandemic that gripped the rest of the while following all protocols. on specific periods for a few months. The world? data collected from the MOSAiC expedition With the COVID-19 crisis, there was a lot What is the main objective of the MOSAiC will cover all seasons (annually) and a large of uncertainty about our returning home. expedition, and how is it different from the area (as the Polarstern moves with the sea Our whole group was in isolation from the previous Arctic expeditions? ice). As many as 300 scientists will be on outside world for many months, and we did The primary goal of the MOSAiC expedition board Polarstern, rotated in six different legs. not have a clue about the seriousness of this is to investigate the principal components of I was on leg two. Scientists from 20 nations situation. With all countries closing their the Arctic climate system — the atmosphere, are participating on and off board Polarstern. borders on us, we were worried about our sea ice, ocean, ecology and biogeochemistry. safe return home. The focus is on the Arctic, as the epicentre What is the focus of your work? How are you At one point, I was even ready to stay back of global warming, and to gain fundamental going to take this forward? for the next leg, for several more months, But insights to better understand global climate I am a sea ice scientist, specializing in radar

36 | Nature India COVID-19 Special | June 2020 Q&A

all these experiments are short term. They don’t fully capture long-term changes over large areas. MOSAiC is unique. Polarstern is anchored on to a sea ice piece. As she moves along with this piece, propelled by the transpolar drift for one whole year, we will be able to measure critical parameters along the whole corridor, which covers a lot of area. Between the beginning and end of our leg, we had drifted a meandering distance of 675 kilometres, and a straight line distance close to 410 kilometres. These parameters from our measurements will help us improve climate models which help us accurately predict weather, monsoon timing in countries, such as India, and extreme events such as cyclones and flash floods. We had 64 scientists on board from 12 nationalities. I was the only Indian national on board, representing Canada.

What were the working challenges you faced? Sometimes we had to troubleshoot and repair instruments on the ice. Some of the instruments were not meant to be operated under extreme conditions. So we had to improvise. Refurbishing instruments under such conditions was extremely challenging. We even had to work with an instrument which stood 15 feet tall and weighed close to 300 kilograms.

What kind of communication channels did you have? What did you do for entertainment? We were lucky to have WhatsApp access on board, with restrictions (only text, no pictures or videos). We had a gym, swimming pool and sauna. We celebrated The German research icebreaker RV Polarstern, Nandan’s home for the expedition. many birthdays, including mine, celebrated the northernmost Christmas and the New “Our group was in isolation and melting). For MOSAiC, my research work Year. We saw movies, played board games focused on deploying radar sensors on ice, and organized camping trips, where we set for many months and we did operating at multiple radar frequencies, to up tents. And every Wednesday evening, we not have a clue about the improve the accuracy of retrievals of these went group skiing and hiking on the ice. seriousness of this situation.” parameters, which will ultimately help the radar satellites to provide improved and What was the first thing you did after accurate estimates. returning home?

LARS BARTHEL, STEFFEN GRAUPNER STEFFEN LARS BARTHEL, remote sensing. My expertise has always been The first thing I did was to eat a sumptuous in using satellite- and ground-based radar How do these experiments help meal made by my wife. And then I got on remote sensing data to improve the accuracy understanding of global climate? with following the Canadian rule of 14-day of critical snow and sea ice parameters, such Although scientists conduct yearly field- mandatory self-isolation. as snow depth, sea ice thickness, freeze- and based experiments in the Arctic for studying melt-onset (i.e. when sea ice starts forming and answering questions about our planet, Interview by Vanita Srivastava

Nature India COVID-19 Special | June 2020 | 37 From the frontline For doctors, intensive care takes on a whole new meaning

When Viny Kantroo, a respiratory diseases patients. It triggers a vicious cycle inside the brain. This specialist, started seeing COVID-19 patients experience has given me empathy for what my non-COVID in her Delhi hospital, a worrying reality asthma and Chronic Obstructive Pulmonary Disease unfolded, professionally and personally. (COPD) patients feel when they become short of breath every winter. Coming back to that late evening scene in the COVID-19 y heart skips a beat thinking of Thursday. ward, I stood mustering all my courage, my hands trem- That’s the day my scheduled week-long bling as I punched in the code to open the ICU door. The duty starts in COVID-19 wards and intensive smell in there is peculiar, different from outside these care units (ICU) every fortnight. areas. Smell always has a strong relationship with emo- The rotation means constantly staying tions. It sets off a chain reaction inside my imaginary world, Mawake, or rather alert, even when you close your eyes in that the air is full of virus. But I have to make way to the the ward to catch a few winks. The phone usually rings the donning room, and preferably not touch the door handles moment you fall asleep. The mind works constantly with or the door itself. the adrenaline rush that comes with attending to COVID- This comes naturally to me though. My parents taught 19 patients. me the science of fomites and their importance well before On one day in the second week of April 2020, I had to I studied medicine. I would wash my hands after touching get to my hospital late in the evening to insert a chest tube lift buttons, electrical switches, door handles, and staircase in a COVID-19 patient with collapsed lungs (pneumotho- railings, even in normal times. This has made me a villain at home many times, but I have made this practice very clear to both family and friends. So while my colleagues are still coming to terms with My parents the changed reality, I am way more confident of navigating through doors and touching handles. Also, getting ready taught me within 15 to 20 minutes without exposing any part of your the science skin is a mental rather than a physical task. It requires seal- of fomites ing the gaps between eye sockets and visors. I could feel a pronounced silence as I entered the patient and their area that evening. I had to be in very close contact with the importance patient. This was more than the normal daily ICU rounds. long before All I could see were the dark corners and a foggy tunnelled central vision. This was partly the physical reality, partly I studied the constant fogging of my visors, and mostly psycholog- medicine. ” ical. I instantly thought of music. I had brought in a bluetooth speaker the previous day with me to leave in the ICU for everyone. I inserted the chest tube in about 25 minutes, way longer than it normally takes. The extra layers above my coveralls made me sweat profusely. I desperately wanted some air. I saw the other patients on the ward, and sorted out their medication where needed. I checked ventilators and asked my staff if there was anything else I could do to help them (not that I was more capable than them, but some-

VINY KANTROO times asking makes all the difference). I left the area for Viny Kantroo prepares for duty. the designated doffing region and slowly removed the body suit and other layers, in 15 minutes, to avoid creat- rax). I was worried about hurting the patient, and creating ing aerosols. complications because of limited vision resulting from the Each time I came out of the ICU after attending to elaborate eye gear of my personal protective equipment patients, I felt a strange sense of relief. Whether this is (PPE), but more overwhelming was the fact that I was in because I helped somebody, or because I could breathe the middle of a contagion, dealing with a disease with no better, I don’t know. But I surely have started to value treatment. Suddenly, I felt like a student again. Viny Kantroo is a the small little things in life much more than I ever did in I was also constantly battling the fear of carrying infec- Respiratory, Critical the past. tion home. When on COVID-19 duty, I cover myself up, or Care & Sleep One thing which remains universal among healthcare rather my fear, with an extra layer of surgical mask above Medicine specialist workers across the globe is everyone wants to breathe. my N-95 mask. at Indraprastha Everyone is just tired of the FFP 1, 2, 3s and N-95s. It has This actually hampers my breathing. I start panting while Apollo Hospitals, never been so tough before, taking care of your own breath- speaking, but at least my mind stays calm and focused on New Delhi, India. lessness and that of your patients’, simultaneously.

38 | Nature India COVID-19 Special | June 2020 From the bench Starting a lab in a pandemic

On the brink of starting her first laboratory, COVID-19 threw Poonam Thakur’s lofty plans into disarray.

fter years of insecurity with short term post- doctoral contracts, international moves, and personal sacrifices, I had finally landed a cov- eted faculty position in a reputable institute. I was over the moon. I had finally ‘made it’ in Although

Athe highly competitive world of academia, beating all odds. I could not THAKUR POONAM For the first time, I was going to start a life that won’t be fight the Poonam Thakur in her lab at IISER Thiruvananthapuram. uprooted, at least for two to three years. pandemic In early March 2020, I joined the Indian Institute of Sci- these extraordinary circumstances, it was easier to put ence Education and Research (IISER) Thiruvananthapuram from the everything into perspective. — a vibrant campus in the lush green hills of India’s western bench, I tried Although I could not fight the pandemic from the bench, I ghats — with lofty dreams of unrolling my neuroscience to help in tried to help in other ways. I volunteered to translate info- research and teaching programme. The first three to four- graphics on coronaviruses and COVID-19 in my regional days flew by in administrative formalities and in dealing other ways.” language and shared them through social media. I talked with the realization of becoming a principal investigator about the disease to my non-scientist friends, neighbours with more responsibilities, including furnishing the work- and family, and tried to dispel COVID-19 related myths in place and planning for the courses I would teach in the close circles. upcoming semester. I started contacting vendors to obtain quotes for the In the middle of this frantic activity, an email landed equipment I would need to start my lab. Luckily, several about the precautionary measures the institute was under- were still answering calls and responding to emails. I inter- taking against the spread of COVID-19 as it was beginning acted with my colleagues living in the campus. They offered to escalate in India. Classes were suspended and students me not just advice and experience on setting up labs but living on the campus were asked to go home. Faculty living also offered to share their lab equipment and resources on campus were advised not to go out unless extremely until I set up my own. These interactions helped me necessary. No outsiders were allowed on the campus. immensely as I quickly developed collegiality. Under nor- A few days later, the Indian government announced a mal circumstances, it would have taken much longer with countrywide lockdown. That led to the closure of on-cam- everyone busy in their teaching and research schedules. pus daycare leaving many of my colleagues in difficult circumstances. All research plans and purchases came to a Life beyond lockdown halt. Soon the labs started to shut down or operate with Gradually, I started to take the lockdown in my stride. I reduced capacity as most support staff was gone. A campus finally had time to step back, pause and reflect on my long- bustling with life only a few days before, was deserted. We term research goals and strategies. With a fresh mind and were in middle of a pandemic. fewer distractions, I started working on the book chapter A constant barrage of news on the rapidly deteriorat- I had been procrastinating on. ing situation worldwide began making me anxious. As a I was able to focus on preparing material for the courses I researcher, I was trained to be perennially productive. I would eventually teach. I took to running, taking advantage was concerned about the inevitable delay in starting my of the huge campus surrounded by forests and falls. Being research programme and losing precious time from my close to nature, has indeed helped me find peace amidst research grant. all the chaos. I wasn’t trained either in the techniques that may help Being a neurophysiologist, I am reminded of the story of in COVID-19 diagnostics nor in studying the virus struc- Alan Hodgkin and Andrew Huxley, pioneers in the study of ture or finding a cure. In addition to the frustration of not action potential in nerves. Shortly after their first record- being able to jumpstart my lab, I was fighting the feeling ings of intracellular action potential, they had to take part of inadequacy and helplessness as a scientist for not being in war-related activities and suspend primary research able to help humanity during this crisis. Poonam Thakur is for seven long years. Once the war dust settled, they were a DBT/Wellcome reunited and resumed work on action potentials that Joining the cause Trust India Alliance ultimately won them the 1963 Nobel Prize in Physiology For me, the hardest part was to deal with my own expec- Early Career Fellow and Medicine. tations. I had the words of the Roman emperor, Mar- and joined IISER, Although we don’t know when the lockdown will be over, cus Aurelius to draw on: “You have power over your Thiruvananthapuram like everyone else I hope for a pandemic-free world where mind, not outside events. Realize this, and you will find as an Assistant normal life can resume. Despite the fear that a battered strength”. Once I was able to acknowledge that it was rea- Professor in March economy may affect research funding, I am looking for- sonable to feel agitated, frustrated or unproductive in 2020. ward to conducting research with stronger resolve.

Nature India COVID-19 Special | June 2020 | 39 A personal take on science and society World view

By Ashley Shew Let COVID-19 expand awareness of disability tech

The pandemic’s disruption shows the research, we’re well prepared for the current situation how much academia could learn — or for any other. from the disability community. Academia Many disabled people are also adept at managing our energy, and forgiving ourselves for not always meeting is paying conventional metrics of ‘productivity’. My non-disabled isabled people including myself have long cam- for its colleagues are now struggling to adjust, but my team paigned for accommodations to help us live ableism.” appreciates that ‘clocks should bend to our bodies’, not the our lives. The COVID-19 pandemic shows that other way around. Some disabled people call this concept these are not as impractical as we have always Crip Time, reclaiming a derogatory term in pride (much been told. Supermarkets, restaurants and phar- like ‘queer’ for many LGBT+ people). Dmacies (even outside cities) can deliver; remote working, The disability community creates and lobbies for technol- medicine and education are possible for many; and social ogies and infrastructure that work better for all. Deaf and lives can be rewarding without requiring us to leave home. disabled people fought hard for things such as captioning All around me, I see academic colleagues adopting on television, which has since become ubiquitous in sports disability-led hacks and long-sought accommodations. bars and airports and can now be appreciated by people I wish everyone had thought about these workarounds — streaming media while those they live with rest or work. and about disabled people at all — earlier. When lockdowns The bitter irony is that, at the moment when non-disa- end, we must not forget these lessons, not least because bled — or not-yet-disabled — people are beginning to nor- the pandemic will disable people, and the impacts will be malize these disability hacks and hard-won infrastructure, felt most by the most vulnerable parts of society. society’s disregard for disabled people is clear. We are Academia is paying for its ableism. At many universities, dying of COVID-19 in greater numbers than are non-disa- in-person research with human participants and in labora- bled people, in rehabilitation facilities, state institutions tories has been curtailed. If these projects had considered (including prisons), group homes and care homes. disabilities, they might be better off: disabled academics Many accommodations demanded under COVID-19 were already plan in short increments, with built-in flexibility. implemented within weeks, including the ability to work In 2014, I returned to my job as an assistant professor, from home, to have flexible schedules, to get what we need newly multiply-disabled — a hard-of-hearing amputee without excessive and demeaning documentation, to share battered by chemotherapy and more. I felt out of place. and celebrate creative adaptation, to work with the knowl- I could no longer access many spaces, including most of edge that all schedules can change. These are all things my colleagues’ offices, and I sought the camaraderie of that disabled and chronically ill people have wanted for a other disabled faculty members, staff and students. My very long time. I hope that when we’ve flattened the curve disabled comrades and I recognize the diversity of dis and saved as many people as possible, we don’t return to abilities: congenital and acquired; ranging from cognitive a world in which disabled people are ignored (especially to sensory, mobility and more; apparent and not. Many of when COVID-19 will probably produce more of us). us pursue research that emphasizes how disabled people So start making changes that should have been standard are the best experts on the technologies and structures all along. Plan creatively and accessibly to allow more work that meet our needs. offsite, and to include people whose clocks aren’t steady. One of my projects examines accounts of disabled Welcome suggestions from disabled colleagues and stu- people’s lived experiences with technologies, and how they dents about how to make the environment work best for differ from those of the scientists and engineers behind the their neurotype and schedule. Be ready to take criticism: tech. I planned my work intending to recruit disabled stu- too often, work is set up as dictated by convention, rather dents among my researchers. Most of the studies can be than by calling on relevant experiences and possibility.

done remotely, even from bed, and on a funky, asynchronous Ashley Shew is an Make your teaching and scholarly materials multi-modal: 2020). (©SpringerNature (2020) 9 ,

timetable as needed. Last year, when I had lung surgery, assistant professor produce formats that work for people with different phys- 581

my group shifted gears without worry. And because of its in the Department of ical conditions and ways of reading and communicating, disability-led design, my team’s project is pandemic-proof. Science, Technology, sharing and contributing. Think about multiple ways to Nature Another project, to gauge the experiences of students in and Society at allow participation in your funding, reviewing, research civil-engineering classes, was designed to include partici- Virginia Polytechnic and engagement. Let’s see an end to patronizing objecti- pants with a range of disabilities. So we obtained approval Institute and fication and assumptions about what we want and need: for flexibility in communication format: we conduct our State University in include disabled people in boards, teams and studies, and interviews by text, e-mail, Zoom and other means. Because Blacksburg. learn from us. We have had to become masters of invention.

RANDY HEFLIN/ASHLEY SHEW HEFLIN/ASHLEY RANDY we planned for disabled people to lead and participate in e-mail: [email protected] The pandemic has made the value of that clearer than ever. in published First

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