Jama Murray 2021 Vp 210033

Opinion

COVID-19: BEYOND TOMORROW VIEWPOINT The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a Recurrent Seasonal Infection?

4 Christopher J. L. Thereisgrowingoptimismandhopethatbyvirtueofon- 49%, andastatisticallynonsignificantpercentage,respec- Murray, MD going immunization efforts, seasonality (declining infec- tively.IftheB.1.351variantbecomesdominant,asimplecal- Institute for Health tions through August), and naturally acquired immunity, culation suggests that the aggregate effectiveness of vac- Metrics and Evaluation, by spring and early summer 2021 in the US there will be a cinesforpreventingB.1.351transmissionintheUScouldbe University of Washington, Seattle. substantial decline in the number of deaths and hospital- only50%(ie,basedoncurrenteffectivenessof90%topre- izationsrelatedtoCOVID-19.However,thisoptimismmust ventsymptomaticdisease×20%reductionofefficacyfor Peter Piot, MD be tempered by several important factors. The likelihood preventinginfectioncomparedwithsymptomaticdisease London School of ofachievingherdimmunityagainstSARS-CoV-2islowsim- and assuming an average reduction in efficacy for B.1.351 Hygiene and Tropical ply because not all individuals in the US are eligible to be of 33% [excluding the statistically insignificant protection Medicine, London, England. vaccinated and a quarter of eligible individuals will likely from the AstraZeneca vaccine]). decline to be immunized. Moreover, the vaccines do not Second,notenoughindividualswillreceivethevaccine. provide full immunity against infection, and the currently Because the vaccines are currently not authorized for use availablevaccinesarelesseffectiveagainstvariantB.1.351, in children, only approximately 75% of US individuals are Multimedia and possibly other variants. Accordingly, the public and eligible to be immunized. Perhaps more important in the healthsystemsneedtoplanforthepossibilitythatCOVID- longrun,notallindividualsarewillingbeimmunized.Data 19 will persist and become a recurrent seasonal disease. collecteddailythroughFacebook’sDataforGoodinitiative Herd immunity is a theoretical construct from infec- provide timely information on the proportion of individu- tious disease modeling that posits that in a population in alswhorespondyesor“yes,probably”tothequestion,Will which every individual is equally likely to encounter ev- youtakethevaccineifofferedit?Thesepositiveresponses ery other individual, transmission will not be sustained regarding likelihood of vaccine receipt increased in Janu- when immunity through past infection, vaccination, or ary 2021 and have reached 71%,5 similar to the 72% re- both reaches the level of 1 − (1/R), where R is the number sponse in a nationally representative sample.6 Even with of infections caused by a single infection in a population aneffectiveapprovedvaccineforchildren,ifB.1.351orsome in which everyone is susceptible.1 Reality diverges from other variant becomes dominant, the US can expect this simple notion. First, because COVID-19 is clearly sea- vaccine-derived immunity to reach only 37.5% (the esti- sonal, like other coronaviruses, the herd immunity level mated potential 50% aggregate efficacy for transmission will be lower in the summer and higher in the winter. Sec- ×75%ofindividualsreceivingthevaccine)in2021ifallsup- ond,herdimmunitydependsonhowmuchinteractionin- ply and administration difficulties are overcome. dividuals have with one another, which will vary by state Third,thereisconcernabouttheextenttowhichpre- or city after social distancing mandates are lifted. Third, vious infections from one variant protect individuals from nonrandom mixing (individuals are not equally likely to reinfectionwithsomenewvariants.Novavaxreportedthat interactwithoneanother)canleadtomodificationsofthe in a phase 2b clinical trial in South Africa, the COVID-19 in- level of immunity required to stop transmission. Despite cidence rate in the placebo group, predominantly from these factors, some public health officials suggest that variant B.1.351, was 3.9% both among individuals with achieving winter herd immunity in the presence of new COVID-19 seropositivity and those who were COVID-19 more contagious variants will require more than 70% to seronegative.7 The interpretation by Novavax of this find- 80% of individuals to be immune. ing has been that past infection provides no immunity Threekeyconsiderationswillmakeachievingherdim- against new variants. If that is true, herd immunity can be munity against COVID-19 challenging. First, vaccines will achieved only through vaccination. But if B.1.351 spreads have a reduced effect on preventing infection from the widely,vaccine-derivedimmunitywilllikelybemuchlower B.1.351variant.ModernaandPfizervaccineshaveanover- than the levels required to reach herd immunity by the all effectiveness against symptomatic disease of approxi- 2021-2022 northern hemisphere winter. mately 95% for wild-type variants, whereas adenovirus Various models suggest continuing COVID-19 surges vector vaccines, such as the Janssen/Johnson & Johnson are possible even without B.1.351 dominance.8 A winter vaccine, have effectiveness closer to 70%. Evidence on surge of infection with B.1.351 dominance may occur in Corresponding vaccineefficacyforpreventinginfection,however, comes 2021-2022.Hospitalizationanddeathrates,however,may Author: Christopher J. L. Murray, MD, onlyfrom1groupintheAstraZenecatrialthatshowed55% be expected to be lower, assuming vaccines remain more Institute for Health protection against infection as measured through weekly effective for preventing symptomatic disease and re- Metrics and Evaluation, nasalswabsvs70%protectionforsymptomaticdisease.2 maineffectiveforpreventingseverediseaseanddeath.For University of Furthermore, for the 3 vaccines tested against the B.1.351 example, the Janssen vaccine was more than 85% effec- Washington, 3980 15th Ave NE, Seattle, WA variant, Janssen, Novavax, and AstraZeneca reported ef- tive against severe disease, even in South Africa, with no 98195 ([email protected]). fectiveness estimates for symptomatic disease of 57%,3 hospitalizations or deaths reported in the trial, albeit with

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a very wide CI for these outcomes.3 If transmission remained similar tion. A shift to recurrent seasonal COVID-19 makes it unlikely govern- towhatoccurredthiswinter,hospitalizationsanddeathsshouldbeless ments would adopt social distancing mandates every winter, poten- in winter 2021-2022. But the magnitude of the winter surge also de- tially leading to hospitalizations for influenza and COVID-19. ICU bed pends on behavior. Through mask wearing and social distancing, only availability pressure could require halting elective procedures in peak anestimated19%ofUSresidentshavebeeninfectedsofar.Inthenext months such as December and January. Hospitals may need to de- winter, it will be problematic to maintain social distancing mandates velop greater capacity to respond to surges with sufficient bed capac- due to public fatigue and the potential lasting effect of the pandemic ity and personnel, and anticipate associated financial implications. on the economy.Despite the protection from vaccination, effective R Financing mechanisms that address that currently hospital income is in the absence of concerted social distancing and low levels of mask driven by elective procedures would need to be considered. use could be higher next winter than this winter. 4. Reduce transmission in peak months through employer and If new variants continue to appear, winter surges may become educational institution action. Although it is unlikely that the fed- the norm. This prospect requires advance planning and consider- eral government or state governments will use social distancing man- ation of a range of strategies to mitigate the consequences for com- dates every winter, employers and educational institutions could munities and health systems. Five strategies should be considered adopt certain measures. Actions could include establishing manda- and vigorously debated in the months ahead. tory vaccination, requiring masks during peak transmission months, 1. Intensify global vaccination efforts. New variants can appear and avoiding superspreader events by moving meetings or classes anywhere and more transmission will increase the likelihood of their with attendance above a certain number to digital platforms. Re- emergence. Intensified expansion of vaccination in low- and middle- quiring vaccination where legally allowed could help increase vac- income countries along with high-income countries could help re- cination rates. Requiring mask use in the winter months could con- duce the harm of recurrent seasonal COVID-19 and could reduce the tribute both to reduced transmission in those settings and cultural frequency of new variants. change toward accepting mask use as normal. 2. Monitor the epidemic and the emergence of new variants and 5. Modify behavior of at-risk individuals. Increased risk of death accelerate the modification of vaccines to enhance their efficacy for in a winter surge may be large enough to motivate at-risk individu- emerginghigh-riskvariantsiftheyareshowntosignificantlyreducevac- als to change their behavior. Higher-risk individuals (eg, aged Ն65 cineprotection.TheUS,EuropeanUnion,andotherhigh-incomecoun- years or with comorbidities) would need to consider winter behav- tries should invest in global surveillance, including with genome se- ioral modification such as mask wearing and avoiding congregate set- quencing,tofacilitateearlydetectionofvariantsandtracktrendsatthe tings such as bars, indoor dining, concerts, and sports events, and locallevel.Strategiesofcreatingmultivalentvaccinesandadaptingvac- any setting in which transmission risk is high. cines to new variants through boosters will need to be deployed rap- ItisnotclearwhetherCOVID-19willbecomeachronicseasonaldis- idlytomaintainoverallvaccineefficacy.Ifvariantscontinuetoemerge, ease.Thereistoomuchuncertaintyabouttheprobabilityandfrequency it is possible that annual vaccination will be needed, similar to that for ofemergenceofnewvariants,thereductioninvaccineefficacyforeach seasonal influenza. However, Centers for Disease Control and Preven- variant, the critical question of cross-variant immunity,and the consis- tiondataindicatethatseasonalinfluenzavaccineuptakeaveraged50% tencyofsafehumanbehavior.However,theprospectofpersistentand andestimatedvaccineefficacyaveraged35%from2014to2019.9 For seasonalCOVID-19isreal.IfimmunityfrominfectionforthesameSARS- COVID-19,theidentificationofnewvariantsandmodificationofvaccines CoV-2variantorvaccine-derivedimmunitywanes,theprospectwould to be efficacious for these variants would need to be more effective. increasefurther.Thereismuchtolearninthecomingmonthsaboutvari- 3. Manage and finance winter hospital surges. COVID-19 has bur- ants, vaccines, and immunity. Recurrent seasonal COVID-19 could re- dened intensive care units (ICUs) in the US this winter. Social distanc- quirebothhealthsystemchangeandprofoundculturaladjustmentfor ing measures have reduced COVID-19 transmission and substantially thelifeofhigh-riskindividualsinthewintermonths.Thereisanurgent reducedinfluenzatransmission.UShospitalshaveavoidedthedouble need to prepare for such a scenario by aligning surveillance, medical pressure on bed availability from both influenza and COVID-19 infec- response, public health response, and socioeconomic programs.

ARTICLE INFORMATION 3. Johnson & Johnson announces single-shot misinformation on vaccination intent in the UK and Published Online: March 3, 2021. Janssen COVID-19 vaccine candidate met primary USA. Nat Hum Behav. Published online February 5, doi:10.1001/jama.2021.2828 endpoints in interim analysis of its phase 3 2021. doi:10.1038/s41562-021-01056-1 ENSEMBLE trial. January 29, 2021. Accessed Conflict of Interest Disclosures: Dr Piot reports 7. Efficacy data updates from Novavax’ February 10, 2021. https://www.jnj.com/johnson- protein-based vaccine candidate. February 2, 2021. receiving personal fees from the European johnson-announces-single-shot-janssen-covid-19- Commission as an adviser, grants from the Bill & https://www.novavax.com/sites/default/files/ vaccine-candidate-met-primary-endpoints-in- 2021-02/20210202-NYAS-Novavax-Final.pdf Melinda Gates Foundation GBD advisory interim-analysis-of-its-phase-3-ensemble-trial committee, and serving as a nonpaid member of 8. Saad-Roy CM, Wagner CE, Baker RE, et al. the CEPI board during the conduct of the study. No 4. Novavax COVID-19 vaccine demonstrates 89.3% Immune life history, vaccination, and the dynamics other disclosures were reported. efficacy in UK phase 3 trial. News release. January of SARS-CoV-2 over the next 5 years. Science.2020; 28, 2021. https://ir.novavax.com/news-releases/ 370(6518):811-818. doi:10.1126/science.abd7343 REFERENCES news-release-details/novavax-covid-19-vaccine- demonstrates-893-efficacy-uk-phase-3 9. CDC seasonal flu vaccine effectiveness studies. 1. Fine P, Eames K, Heymann DL. “Herd immunity”: Accessed February 10, 2021. https://www.cdc.gov/ a rough guide. Clin Infect Dis. 2011;52(7):911-916. 5. CMU Delphi Research Group. COVID symptom flu/vaccines-work/effectiveness-studies.htm survey. Accessed February 10, 2021. https://cmu- 2. Voysey M, Clemens SAC, Madhi SA, et al. Safety delphi.github.io/delphi-epidata/symptom-survey/ and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2. Lancet. 2021;397 6. Loomba S, de Figueiredo A, Piatek SJ, et al. (10269):99-111. Measuring the impact of COVID-19 vaccine

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