First snap-shot meta-analysis to estimate the prevalence of serum antibodies to SARS-CoV-2 in humans

Background: COVID-19 is arguably the number-one public health concern worldwide, and efforts are now escalating to control its spread. Objective: In this study, we undertake a meta-analysis to estimate the global and regional anti-SARS-CoV-2 seroprevalence rates in humans and assess whether seroprevalence associates with geographical, climatic and socio-demographic factors. Data sources: We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv for peer-reviewed articles or preprints (up to 14 August 2020). Study eligibility criteria: Population-based studies describing prevalence of anti-SARS-CoV-2 serum antibodies in general people. Participants: general people who were tested for prevalence of anti-SARS-CoV-2 serum antibodies. Interventions: There were no interventions. Methods: We used random-effects model to estimate pooled seroprevalence, and then extrapolated these findings to the global population (for 2020). Sub-group and meta-regression analyses explored potential sources of heterogeneity in the data and relationships between seroprevalence and socio-demographic, geographical and climatic factors. Results: In total, 47 serological studies involving 399,265 people from 23 countries met the inclusion criteria. The pooled seroprevalence of SARS-CoV-2 in general people was estimated at 3.38% (95% CI, 3.05%-3.72%; 15,879/399,265). On a regional basis, we determined seroprevalence estimates of 5.27% (3.97-6.57%) in Northern Europe; 4.41% (2.20-6.61%) in Southern Europe; 4.41% (3.03-5.79%) in North America; 3.17% (1.96-4.38%) in Western Europe; 2.02% (1.56-2.49%) in the Eastern Asia; and 1.45% (0.95-1.94%) in South America. Extrapolating to the 2020 world population, we estimated that 263,565,606 individuals had been exposed or infected with SARS-CoV-2 at the first wave of the pandemic. A significantly higher seroprevalence was related to higher income levels and human development indices, higher geographical latitudes and lower mean environmental temperatures. Interpretation This study reinforces that SARS-CoV-2 infection is a very rapidly-spreading communicable disease and calls for routine surveys to constantly monitor temporal changes in seroprevalence around the globe.

[1]  Andrea Benedetti,et al.  Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis , 2020, BMJ.

[2]  D. J. Weber,et al.  Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination☆ , 2015, Journal of Hospital Infection.

[3]  C. Donnelly,et al.  Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults , 2020, medRxiv.

[4]  A. Iwasaki,et al.  Low ambient humidity impairs barrier function and innate resistance against influenza infection , 2019, Proceedings of the National Academy of Sciences.

[5]  John Steel,et al.  Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature , 2007, PLoS pathogens.

[6]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[7]  L. Rénia,et al.  Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control , 2020, Frontiers in Immunology.

[8]  Xiaolong Qi,et al.  Real estimates of mortality following COVID-19 infection , 2020, The Lancet Infectious Diseases.

[9]  D. Cummings,et al.  A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease , 2020, medRxiv.

[10]  Y. Guan,et al.  The severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[11]  Chunbao Xie,et al.  Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China , 2020, Nature Medicine.

[12]  Tomasz Zuk,et al.  Probabilistic model of influenza virus transmissibility at various temperature and humidity conditions , 2009, Comput. Biol. Chem..

[13]  P. Gallian,et al.  Lower prevalence of antibodies neutralizing SARS-CoV-2 in group O French blood donors , 2020, Antiviral Research.

[14]  S. Madhi,et al.  Prevalence of maternal colonisation with group B streptococcus: a systematic review and meta-analysis. , 2016, The Lancet. Infectious diseases.

[15]  T. Hollingsworth,et al.  How will country-based mitigation measures influence the course of the COVID-19 epidemic? , 2020, The Lancet.

[16]  M. Van Ranst,et al.  Diagnostic performance of seven rapid IgG/IgM antibody tests and the Euroimmun IgA/IgG ELISA in COVID-19 patients , 2020, Clinical Microbiology and Infection.

[17]  P. Hotez,et al.  Will COVID-19 become the next neglected tropical disease? , 2020, PLoS neglected tropical diseases.

[18]  Devy M. Emperador,et al.  Antibody tests for identification of current and past infection with SARS‐CoV‐2 , 2020, The Cochrane database of systematic reviews.

[19]  C. Beyrer,et al.  Assessing differential impacts of COVID-19 on black communities , 2020, Annals of Epidemiology.

[20]  A. Heidarzadeh,et al.  Seroprevalence of COVID-19 virus infection in Guilan province, Iran , 2020, medRxiv.

[21]  O. Vandenberg,et al.  Evaluation of two automated and three rapid lateral flow immunoassays for the detection of anti-SARS-CoV-2 antibodies , 2020, Journal of Clinical Virology.

[22]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[23]  P. Hotez.  Poverty and the Impact of COVID-19: The Blue-Marble Health Approach , 2020 .

[24]  Julian P. T. Higgins,et al.  Meta-Regression in Stata , 2008 .

[25]  Linsey C. Marr,et al.  Dynamics of Airborne Influenza A Viruses Indoors and Dependence on Humidity , 2011, PloS one.

[26]  C. Hillyer,et al.  Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses , 2020, Trends in Immunology.

[27]  M. Sobsey,et al.  Effects of Air Temperature and Relative Humidity on Coronavirus Survival on Surfaces , 2010, Applied and Environmental Microbiology.

[28]  Y. Tie,et al.  Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[29]  A. Flahault,et al.  Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study , 2020, The Lancet.

[30]  Kwok-Hung Chan,et al.  Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens , 2020, Journal of Clinical Microbiology.

[31]  Q. Tao,et al.  Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases , 2020, Radiology.

[32]  A. Meola,et al.  Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics , 2020, medRxiv.

[33]  U. Seljak,et al.  Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis , 2020, medRxiv.

[34]  P. Vineis,et al.  Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[35]  C. Knabbe,et al.  SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[36]  Ralf Bender,et al.  Methods to estimate the between‐study variance and its uncertainty in meta‐analysis† , 2015, Research synthesis methods.

[37]  Z. Munn,et al.  The development of a critical appraisal tool for use in systematic reviews addressing questions of prevalence. , 2014, International journal of health policy and management.

[38]  M. Koopmans,et al.  A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment. , 2020, The New England journal of medicine.

[39]  Beau B. Bruce,et al.  Characteristics Associated with Hospitalization Among Patients with COVID-19 — Metropolitan Atlanta, Georgia, March–April 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[40]  N. Xia,et al.  The prevalence of antibodies to SARS-CoV-2 among blood donors in China , 2020, Nature Communications.

[41]  Jay P Shimshack,et al.  Absolute humidity, temperature, and influenza mortality: 30 years of county-level evidence from the United States. , 2012, American journal of epidemiology.

[42]  D. Cereda,et al.  Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[43]  C. Juma,et al.  [The United Nations Development Program]. , 1969, Die Agnes Karll-Schwester, der Krankenpfleger.

[44]  Yuan Zhang,et al.  Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis , 2020, The Lancet.

[45]  F. L. Schaffer,et al.  Survival of airborne influenza virus: Effects of propagating host, relative humidity, and composition of spray fluids , 2005, Archives of Virology.

[46]  V. Munster,et al.  Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. , 2013, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[47]  Stefani N. Thomas,et al.  Initial determination of COVID-19 seroprevalence among outpatients and healthcare workers in Minnesota using a novel SARS-CoV-2 total antibody ELISA , 2020, Clinical Biochemistry.

[48]  Cesar G Victora,et al.  Remarkable variability in SARS-CoV-2 antibodies across Brazilian regions: nationwide serological household survey in 27 states , 2020, medRxiv.

[49]  F. Miralles-Wilhelm,et al.  Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) , 2020, JAMA network open.

[50]  Akihide Ryo,et al.  Interpreting Diagnostic Tests for SARS-CoV-2. , 2020, JAMA.

[51]  David R. Holtgrave,et al.  Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York , 2020, Annals of Epidemiology.

[52]  M. Hernán,et al.  Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study , 2020, The Lancet.

[53]  P. Biddinger,et al.  Novel Coronavirus and Old Lessons - Preparing the Health System for the Pandemic. , 2020, The New England journal of medicine.

[54]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[55]  Gonzalo H. Otazu,et al.  Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study , 2020, medRxiv.

[56]  E. Price-Haywood,et al.  Hospitalization and Mortality among Black Patients and White Patients with Covid-19 , 2020, The New England journal of medicine.

[57]  F. Cotton,et al.  Monitoring antibody response following SARS-CoV-2 infection: diagnostic efficiency of 4 automated immunoassays , 2020, Diagnostic Microbiology and Infectious Disease.

[58]  C. Reed,et al.  Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020 , 2020, medRxiv.

[59]  P. Bagos,et al.  Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis , 2020, medRxiv.

[60]  G. Gao,et al.  A Novel Coronavirus from Patients with Pneumonia in China, 2019 , 2020, The New England journal of medicine.

[61]  M. Aslan,et al.  Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in Turkey , 2021, Annals of Clinical and Analytical Medicine.

[62]  I. Sam,et al.  Low postpandemic wave SARS‐CoV‐2 seroprevalence in Kuala Lumpur and Selangor, Malaysia , 2020, Journal of medical virology.