A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates

Introduction: An important unknown during the COVID-19 pandemic has been the infection-fatality rate (IFR). This differs from the case-fatality rate (CFR) as an estimate of the number of deaths as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy-makers and the lay public as an estimate of the overall mortality from COVID-19. Methods: Pubmed and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. Results: After exclusions, there were 13 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and April 2020. The meta-analysis demonstrated a point-estimate of IFR of 0.75% (0.49-1.01%) with significant heterogeneity (p<0.001). Conclusion: Based on a systematic review and meta-analysis of published evidence on COVID-19 until the end of April, 2020, the IFR of the disease across populations is 0.75% (0.49-1.01%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents the "true" point estimate. It is likely that different places will experience different IFRs. More research looking at age-stratified IFR is urgently needed to inform policy-making on this front.

[1]  T. Fletcher,et al.  Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections , 2020, medRxiv.

[2]  F. Blyth,et al.  Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. , 2012, Journal of clinical epidemiology.

[3]  Are SARS-CoV-2 seroprevalence estimates biased? , 2020, The Journal of infectious diseases.

[4]  C. Reusken,et al.  Herd immunity is not a realistic exit strategy during a COVID-19 outbreak , 2020 .

[5]  H. Rothan,et al.  The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak , 2020, Journal of Autoimmunity.

[6]  Daniel Eichner,et al.  Seroprevalence of SARS-CoV-2-Specific Antibodies Among Adults in Los Angeles County, California, on April 10-11, 2020. , 2020, JAMA.

[7]  Linus Wilson SARS-CoV-2, COVID-19, Infection Fatality Rate (IFR) Implied by the Serology, Antibody, Testing in New York City , 2020, SSRN Electronic Journal.

[8]  Kai Liu,et al.  Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients , 2020, Journal of Infection.

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

[10]  S. Eubank,et al.  Commentary on Ferguson, et al., “Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand” , 2020, Bulletin of Mathematical Biology.

[11]  Kun Chen,et al.  Characteristics of COVID-19 infection in Beijing , 2020, Journal of Infection.

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

[13]  P. Simon Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic , 2020, medRxiv.

[14]  David Dongkyung Kim,et al.  Estimating case fatality rates of COVID-19 , 2020, The Lancet Infectious Diseases.

[15]  Lin Yang,et al.  Infection fatality risk of the pandemic A(H1N1)2009 virus in Hong Kong. , 2013, American journal of epidemiology.

[16]  R. Eggo,et al.  Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[17]  B. Bassett Strict Lower Bound on the COVID-19 Fatality Rate in Overwhelmed Healthcare Systems , 2020, medRxiv.

[18]  M. Wener,et al.  Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho , 2020, medRxiv.

[19]  C. Whittaker,et al.  Estimates of the severity of coronavirus disease 2019: a model-based analysis , 2020, The Lancet Infectious Diseases.

[20]  Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications , 2020, European Journal of Epidemiology.

[21]  C. Bridges,et al.  Estimating influenza-associated deaths in the United States. , 2009, American journal of public health.

[22]  An Empirical Estimate of the Infection Fatality Rate of COVID-19 from the First Italian Outbreak , 2020 .

[23]  S. Soubeyrand,et al.  Mechanistic-statistical SIR modelling for early estimation of the actual number of cases and mortality rate from COVID-19 , 2020 .

[24]  Dena Goffman,et al.  Universal Screening for SARS-CoV-2 in Women Admitted for Delivery , 2020, The New England journal of medicine.

[25]  R. Krüger,et al.  Prevalence of SARS-CoV-2 infection in the Luxembourgish population: the CON-VINCE study. , 2020, medRxiv.

[26]  S. Hegde,et al.  The important role of serology for COVID-19 control , 2020, The Lancet Infectious Diseases.

[27]  H. Ullum,et al.  Estimation of SARS-CoV-2 Infection Fatality Rate by Real-time Antibody Screening of Blood Donors , 2020, medRxiv.

[28]  Kari Stefansson,et al.  Spread of SARS-CoV-2 in the Icelandic Population , 2020, The New England journal of medicine.

[29]  P. Giorgi Rossi,et al.  Case fatality rate in patients with COVID-19 infection and its relationship with length of follow up☆ , 2020, Journal of Clinical Virology.

[30]  J. Ioannidis,et al.  COVID-19 antibody seroprevalence in Santa Clara County, California , 2020, medRxiv.

[31]  A. Basu Estimating The Infection Fatality Rate Among Symptomatic COVID-19 Cases In The United States. , 2020, Health affairs.

[32]  S. Bosari,et al.  SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 Milan outbreak , 2020, medRxiv.

[33]  E. Dong,et al.  An interactive web-based dashboard to track COVID-19 in real time , 2020, The Lancet Infectious Diseases.

[34]  F. Turkheimer,et al.  COVID-19: Recovering estimates of the infected fatality rate during an ongoing pandemic through partial data , 2020, medRxiv.

[35]  M. Paradisi,et al.  An empirical estimate of the infection fatality rate of COVID-19 from the first Italian outbreak , 2020, medRxiv.

[36]  Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital , 2020, Nature Communications.

[37]  P. Klenerman,et al.  Neutralising antibodies to SARS coronavirus 2 in Scottish blood donors - a pilot study of the value of serology to determine population exposure , 2020, medRxiv.

[38]  Richard E. Grewelle,et al.  Estimating the Global Infection Fatality Rate of COVID-19 , 2020, medRxiv.

[39]  C. Kahathuduwa,et al.  Case fatality rate in COVID-19: a systematic review and meta-analysis , 2020, medRxiv.

[40]  M. Nöthen,et al.  Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event , 2020 .

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

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

[43]  M. Wener,et al.  Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho , 2020, Journal of Clinical Microbiology.

[44]  Yan Bai,et al.  Presumed Asymptomatic Carrier Transmission of COVID-19. , 2020, JAMA.

[45]  Elisabeth Mahase,et al.  Covid-19: UK starts social distancing after new model points to 260 000 potential deaths , 2020, BMJ.

[46]  COVID-19 Serological Tests: How Well Do They Actually Perform? , 2020, Diagnostics.

[47]  M. Gomes,et al.  Herd immunity thresholds for SARS-CoV-2 estimated from unfolding epidemics , 2020, medRxiv.

[48]  B. Horta,et al.  Population-based surveys of antibodies against SARS-CoV-2 in Southern Brazil , 2020, Nature Medicine.

[49]  A. Ahlbom,et al.  Excess mortality from COVID-19: weekly excess death rates by age and sex for Sweden and its most affected region , 2020, medRxiv.

[50]  M. Lipsitch Estimating case fatality rates of COVID-19 , 2020, The Lancet Infectious Diseases.

[51]  Dusan Petrovic,et al.  Appendix: Seroprevalence of anti-SARS-COV-2 IgG antibodies in a population-based sample from Geneva, Switzerland , 2020 .

[52]  Sheng Zhang,et al.  False negative of RT‐PCR and prolonged nucleic acid conversion in COVID‐19: Rather than recurrence , 2020, Journal of medical virology.

[53]  J. Lessler,et al.  Estimating the burden of SARS-CoV-2 in France , 2020, Science.

[54]  Hiroshi Nishiura,et al.  The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights , 2020, Journal of clinical medicine.

[55]  J. Van Wyk,et al.  Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys , 2020, medRxiv.

[56]  S. Lauer,et al.  Serology-informed estimates of SARS-COV-2 infection fatality risk in Geneva, Switzerland , 2020, medRxiv.

[57]  A. Gylfason,et al.  Early Spread of SARS-Cov-2 in the Icelandic Population , 2020, medRxiv.

[58]  K. Iwata,et al.  Estimation of seroprevalence of novel coronavirus disease (COVID-19) using preserved serum at an outpatient setting in Kobe, Japan: A cross-sectional study , 2020, Clinical Epidemiology and Global Health.

[59]  A. Torres,et al.  The value of serology testing to manage SARS-CoV-2 infections , 2020, European Respiratory Journal.

[60]  J. Ioannidis,et al.  The infection fatality rate of COVID-19 inferred from seroprevalence data , 2020, medRxiv.

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

[62]  N. Linton,et al.  Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases , 2020, Journal of clinical medicine.

[63]  A. Markotić,et al.  SARS-CoV-2 antibody seroprevalence in industry workers in Split-Dalmatia and Sibenik-Knin County, Croatia , 2020, medRxiv.

[64]  C. Whittaker,et al.  Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand , 2020 .