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The Case of SARS-Cov-2 and Zika Virus

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The Case of SARS-Cov-2 and Zika Virus medRxiv preprint doi: https://doi.org/10.1101/2020.11.20.20235242; this version posted November 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Outbreaks of publications about emerging infectious diseases 1 Outbreaks of publications about emerging infectious 2 diseases: the case of SARS-CoV-2 and Zika virus 1 1,2 3 3 Aziz Mert Ipekci , Diana Buitrago-Garcia , Kaspar Walter Meili , Fabienne 4 5 6 7 4 Krauer , Nirmala Prajapati , Shabnam Thapa , Lea Wildisen , Lucia Araujo 5 Chaveron5, Lukas Baumann8, Sanam Shah5, Tessa Whiteley5, Gonzalo Solís- 9 10 10 1 1 6 García , Foteini Tsotra , Ivan Zhelyazkov , Hira Imeri , Nicola Low , Michel 7 Jacques Counotte1* 8 1. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland 9 2. Graduate School of Health Sciences, University of Bern, Bern, Switzerland 10 3. Department of Epidemiology and Global Health, Umeå University, Umeå, Sweden 11 4. Centre for Ecological and Evolutionary Synthesis (CEES), University of Oslo, Norway 12 5. École des Hautes Études en Santé Publique (EHESP), Saint Denis, France 13 6. Institute of Public Health, Jagiellonian University Medical College, Kraków, Poland 14 7. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland 15 8. Department of Internal Medicine, Kantonsspital Olten, Olten, Switzerland 16 9. Pediatrics Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain 17 10. School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, United 18 Kingdom 19 * corresponding author: [email protected] Page 1 of 12 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.11.20.20235242; this version posted November 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Outbreaks of publications about emerging infectious diseases 20 Summary 21 Background. Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 22 epidemics of Zika virus emerged, largely in Latin America and the Caribbean. In 2020, a novel severe 23 acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 24 2019 (COVID-19). We compared patterns of scientific publications for the two infections over time. 25 Methods. We used living systematic review methods to search for and annotate publications 26 according to study design. For Zika virus, a review team performed the tasks for publications in 2016. 27 For SARS-CoV-2, a crowd of 25 volunteer scientists performed the tasks for publications up to May 28 24, 2020. We used descriptive statistics to categorise and compare study designs over time. 29 Findings. We found 2,286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 30 24 May 2020, of which we analysed a random sample of 5294. For both infections, there were more 31 epidemiological than laboratory science studies. Amongst epidemiological studies for both 32 infections, case reports, case series and cross-sectional studies emerged first, cohort and case- 33 control studies were published later. Trials were the last to emerge. Mathematical modelling studies 34 were more common in SARS-CoV-2 research. The number of preprints was much higher for SARS- 35 CoV-2 than for Zika virus. 36 Interpretation. Similarities in the overall pattern of publications might be generalizable, whereas 37 differences are compatible with differences in the characteristics of a disease. Understanding how 38 evidence accumulates during disease outbreaks helps us understand which types of public health 39 questions we can answer and when. 40 Funding. MJC and HI are funded by the Swiss National Science Foundation (SNF grant number 41 176233). NL acknowledges funding from the European Union’s Horizon 2020 research and 42 innovation programme - project EpiPose (grant agreement number 101003688). DBG is funded by 43 the Swiss government excellence scholarship (2019.0774) and the Swiss School of Public Health 44 Global P3HS. Page 2 of 12 medRxiv preprint doi: https://doi.org/10.1101/2020.11.20.20235242; this version posted November 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Outbreaks of publications about emerging infectious diseases 45 Introduction 46 Scientists publish their findings to understand epidemics caused by novel pathogens. This evidence 47 will guide decisions, actions and interventions to mitigate the effects of the disease through policy, 48 programmes, guidelines and further research.1 Two viral pathogens that have caused epidemics 49 across a large number of countries since 2016 resulted in the declaration of a Public Health 50 Emergency of International Concern (PHEIC) by the World Health Organization (WHO) Director- 51 General.2 Zika virus, a mosquito-borne virus caused epidemics of microcephaly that were first 52 noticed in late 2015 in Brazil, although it was first discovered in 1947 and had caused small 53 outbreaks of infection before then.3 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 54 was first discovered in January 2020 as the cause of a new zoonotic disease, coronavirus disease 55 2019 (COVID-19), spread primarily through the respiratory route.4 There are marked differences in 56 the natural history of the two diseases, where microcephaly caused by Zika virus infection only 57 emerges months after infection, COVID-19 occurs acutely. Intensive research efforts for both 58 infections were catalysed by the needs of national, regional and global health agencies to answer 59 key questions on transmission, prevention, and interventions at the individual and community level.5 60 During the SARS-CoV-2 pandemic, the accumulation of peer-reviewed and preprint publications has 61 been vast; from April, 2020 onwards, an average of 2,000 scientific publications appeared per week.6 62 A similar, albeit smaller surge in publications occurred in 2016 during the Zika virus epidemic. The 63 sudden large increases in publications about these conditions over a short time can also be 64 described as outbreaks. 65 The emergence of a new disease provides an opportunity to examine how research evidence 66 emerges and develops, according to the research question and the feasibility of the study methods. 67 Hierarchies of evidence are often used to rank the value of epidemiological study designs, 68 prioritising experimental methods,7 but these do not take account of purposes, other than the 69 effects of interventions. Anecdotal observations allow for the discovery and description of 70 phenomena, studies with comparison groups are more appropriate to test hypotheses, and 71 randomised trials test the causal effects of interventions.8 Early on in the Zika epidemic, questions 72 about causality were important because the link between clusters of babies born with microcephaly 73 and Zika virus infection was not obvious; congenital abnormalities caused by a mosquito-borne virus 74 had never been reported. In an analysis of 346 publications about Zika virus, we described the 75 temporal sequence of publication of types of study to investigate causality.9 Others have assessed 76 the accumulation of study designs over time during the SARS-CoV-2 outbreak and concluded that 77 early in the outbreak, simple observational studies and narrative reviews were most abundant.10 78 Here, we proposed a hypothetical sequence: first, anecdotal observations are reported in case Page 3 of 12 medRxiv preprint doi: https://doi.org/10.1101/2020.11.20.20235242; this version posted November 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Outbreaks of publications about emerging infectious diseases 79 reports or case series. Analytical observational studies follow. In parallel, basic research studies 80 investigate the biology and pathogenesis of the disease. Mathematical modelling can provide 81 evidence where direct observations are not available. 11 After a delay, controlled trials examining 82 interventions are published. 83 The emergence of SARS-CoV-2 allows a comparison with Zika virus between the timing and types of 84 evidence published at the start of an outbreak of a new disease. The objectives of this study were to 85 analyse the patterns of evolution of the evidence over time during the 2016 Zika virus epidemic and 86 the 2020 SARS-CoV-2 pandemic. We compare the sequence of evidence accumulation with the 87 previously hypothesised pattern.9 88 Methods 89 Data collection 90 Searches and sources. We used databases that were created for the Zika Open Access Project 91 (ZOAP) and COVID-19 Open Access Project (COAP).12 For each pathogen, we ran daily automated 92 searches to index and deduplicate records of articles about Zika virus (from January 1, 2016) and 93 SARS-CoV-2 research (from January 1, 2020) in EMBASE via OVID, MEDLINE via PubMed, and the 94 preprint server bioRxiv (for SARS-CoV-2 we also searched medRxiv). We specify the search terms in 95 the appendix (pp 2). 96 Annotation of records with study design. We screened the title and abstract, or full text when the 97 first was insufficient, and annotated each record with its study design.
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