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Review 2: "The infection fatality rate of COVID-19 inferred from seroprevalence data"

This study finds substantial heterogeneity in the infection fatality rate across different locations. Data are useful and add to the emerging picture on IFR, however substantial conclusions cannot be drawn.

Published onAug 23, 2020
Review 2: "The infection fatality rate of COVID-19 inferred from seroprevalence data"
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key-enterThis Pub is a Review of
The infection fatality rate of COVID-19 inferred from seroprevalence data

Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of July 11, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Secondarily, results from national studies were also examined from preliminary press releases and reports whenever a country had no other data presented in full papers of preprints. Results 36 studies (43 estimates) were identified with usable data to enter into calculations and another 7 preliminary national estimates were also considered for a total of 50 estimates. Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%). Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



In this paper, the author analyzes and synthesizes estimates of the infection fatality rate of COVID-19 based on data reported in seroprevalence studies. We recommend publication once the following comments are appropriately addressed:

1) We strongly recommend excluding papers retrieved from preprint servers.

2) For example, we are familiar with the following Japanese studies cited as refs. 11 and 29, and we believe these studies should be excluded from the analysis. Specifically, ref. 11 has low external validity because medical facilities are not "outpatient clinics" but outpatients that attend a tertiary hospital (this study has been criticized in Japan for this reason). Similarly, for the study reported in ref. 29, the authors recruited participants via the Internet. This leads to a critical selection bias and low external validity (generalization).

Hence, this indicates that preprint studies which have not gone through peer review should be excluded from the analysis.
11. Doi A, Iwata Kuroda H, Hasuike T, Nasu S, Kanda A, et al. Seroprevalence of novel coronavirus disease (COVID-19) in Kobe, Japan. medRxiv
"Randomly selected patients who visited outpatient clinics and received blood testing for any reason. Patients who visited the emergency department or the designated fever consultation service were excluded."
29. Takita M, Matsumura T, Yamamoto K, Yamashita E, Hosoda K, Hamaki T, Kusumi E. Regional difference in seroprevalence of SARS-CoV-2 in Tokyo: Results from the community point-of-care antibody testing. medRxiv 2020.06.03.20121020; doi:
"Two community clinics located in the major railway stations in Tokyo (Navitas Clinic Shinjuku and Tachikawa)"

3) It would be helpful to provide a flow diagram of the study selection process in order to clarify the selection criteria.

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