Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study.
To estimate the infection fatality risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on deaths with confirmed coronavirus disease 2019 (covid-19) and excess deaths from all causes.
Nationwide seroepidemiological study.
First wave of covid-19 pandemic in Spain.
Community dwelling individuals of all ages.
The main outcome measure was overall, and age and sex specific, infection fatality risk for SARS-CoV-2 (the number of covid-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections) in the community dwelling Spanish population. Deaths with laboratory confirmed covid-19 were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all cause deaths from the Monitoring Mortality System (MoMo), up to 15 July 2020. SARS-CoV-2 infections in Spain were derived from the estimated seroprevalence by a chemiluminescent microparticle immunoassay for IgG antibodies in 61 098 participants in the ENE-COVID nationwide seroepidemiological survey between 27 April and 22 June 2020.
The overall infection fatality risk was 0.8% (19 228 of 2.3 million infected individuals, 95% confidence interval 0.8% to 0.9%) for confirmed covid-19 deaths and 1.1% (24 778 of 2.3 million infected individuals, 1.0% to 1.2%) for excess deaths. The infection fatality risk was 1.1% (95% confidence interval 1.0% to 1.2%) to 1.4% (1.3% to 1.5%) in men and 0.6% (0.5% to 0.6%) to 0.8% (0.7% to 0.8%) in women. The infection fatality risk increased sharply after age 50, ranging from 11.6% (8.1% to 16.5%) to 16.4% (11.4% to 23.2%) in men aged 80 or more and from 4.6% (3.4% to 6.3%) to 6.5% (4.7% to 8.8%) in women aged 80 or more.
The increase in SARS-CoV-2 infection fatality risk after age 50 appeared to be more noticeable in men than in women. Based on the results of this study, fatality from covid-19 was greater than that reported for other common respiratory diseases, such as seasonal influenza.
Pastor-Barriuso R
,Pérez-Gómez B
,Hernán MA
,Pérez-Olmeda M
,Yotti R
,Oteo-Iglesias J
,Sanmartín JL
,León-Gómez I
,Fernández-García A
,Fernández-Navarro P
,Cruz I
,Martín M
,Delgado-Sanz C
,Fernández de Larrea N
,León Paniagua J
,Muñoz-Montalvo JF
,Blanco F
,Larrauri A
,Pollán M
,ENE-COVID Study Group
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《BMJ-British Medical Journal》
Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.
Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.
35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test).
Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test.
The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave.
Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.
Pollán M
,Pérez-Gómez B
,Pastor-Barriuso R
,Oteo J
,Hernán MA
,Pérez-Olmeda M
,Sanmartín JL
,Fernández-García A
,Cruz I
,Fernández de Larrea N
,Molina M
,Rodríguez-Cabrera F
,Martín M
,Merino-Amador P
,León Paniagua J
,Muñoz-Montalvo JF
,Blanco F
,Yotti R
,ENE-COVID Study Group
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Estimated SARS-CoV-2 infection rate and fatality risk in Gauteng Province, South Africa: a population-based seroepidemiological survey.
Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
We undertook a population-based serosurvey for SARS-CoV-2 infection in 26 subdistricts, Gauteng Province (population 15.9 million), South Africa, to estimate SARS-CoV-2 infection, infection fatality rate (IFR) triangulating seroprevalence, recorded COVID-19 deaths and excess-mortality data. We employed three-stage random household sampling with a selection probability proportional to the subdistrict size, stratifying the subdistrict census-sampling frame by housing type and then selecting households from selected clusters. The survey started on 4 November 2020, 8 weeks after the end of the first wave (SARS-CoV-2 nucleic acid amplification test positivity had declined to <10% for the first wave) and coincided with the peak of the second wave. The last sampling was performed on 22 January 2021, which was 9 weeks after the SARS-CoV-2 resurgence. Serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin-G (IgG) was measured using a quantitative assay on the Luminex platform.
From 6332 individuals in 3453 households, the overall RBD IgG seroprevalence was 19.1% [95% confidence interval (CI): 18.1-20.1%] and similar in children and adults. The seroprevalence varied from 5.5% to 43.2% across subdistricts. Conservatively, there were 2 897 120 (95% CI: 2 743 907-3 056 866) SARS-CoV-2 infections, yielding an infection rate of 19 090 per 100 000 until 9 January 2021, when 330 336 COVID-19 cases were recorded. The estimated IFR using recorded COVID-19 deaths (n = 8198) was 0.28% (95% CI: 0.27-0.30) and 0.67% (95% CI: 0.64-0.71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n = 21 582). Notably, 53.8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG seronegative.
The calculated number of SARS-CoV-2 infections was 7.8-fold greater than the recorded COVID-19 cases. The calculated SARS-CoV-2 IFR varied 2.39-fold when calculated using reported COVID-19 deaths (0.28%) compared with excess-mortality-derived COVID-19-attributable deaths (0.67%). Waning RBD IgG may have inadvertently underestimated the number of SARS-CoV-2 infections and conversely overestimated the mortality risk. Epidemic preparedness and response planning for future COVID-19 waves will need to consider the true magnitude of infections, paying close attention to excess-mortality trends rather than absolute reported COVID-19 deaths.
Mutevedzi PC
,Kawonga M
,Kwatra G
,Moultrie A
,Baillie V
,Mabena N
,Mathibe MN
,Rafuma MM
,Maposa I
,Abbott G
,Hugo J
,Ikalafeng B
,Adelekan T
,Lukhele M
,Madhi SA
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Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis.
As the COVID-19 pandemic continues to unfold, the infection-fatality risk (ie, risk of death among all infected individuals including those with asymptomatic and mild infections) is crucial for gauging the burden of death due to COVID-19 in the coming months or years. Here, we estimate the infection-fatality risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New York City, NY, USA, the first epidemic centre in the USA, where the infection-fatality risk remains unclear.
In this model-based analysis, we developed a meta-population network model-inference system to estimate the underlying SARS-CoV-2 infection rate in New York City during the 2020 spring pandemic wave using available case, mortality, and mobility data. Based on these estimates, we further estimated the infection-fatality risk for all ages overall and for five age groups (<25, 25-44, 45-64, 65-74, and ≥75 years) separately, during the period March 1 to June 6, 2020 (ie, before the city began a phased reopening).
During the period March 1 to June 6, 2020, 205 639 people had a laboratory-confirmed infection with SARS-CoV-2 and 21 447 confirmed and probable COVID-19-related deaths occurred among residents of New York City. We estimated an overall infection-fatality risk of 1·39% (95% credible interval 1·04-1·77) in New York City. Our estimated infection-fatality risk for the two oldest age groups (65-74 and ≥75 years) was much higher than the younger age groups, with a cumulative estimated infection-fatality risk of 0·116% (0·0729-0·148) for those aged 25-44 years and 0·939% (0·729-1·19) for those aged 45-64 years versus 4·87% (3·37-6·89) for those aged 65-74 years and 14·2% (10·2-18·1) for those aged 75 years and older. In particular, weekly infection-fatality risk was estimated to be as high as 6·72% (5·52-8·01) for those aged 65-74 years and 19·1% (14·7-21·9) for those aged 75 years and older.
Our results are based on more complete ascertainment of COVID-19-related deaths in New York City than other places and thus probably reflect the true higher burden of death due to COVID-19 than that previously reported elsewhere. Given the high infection-fatality risk of SARS-CoV-2, governments must account for and closely monitor the infection rate and population health outcomes and enact prompt public health responses accordingly as the COVID-19 pandemic unfolds.
National Institute of Allergy and Infectious Diseases, National Science Foundation Rapid Response Research Program, and New York City Department of Health and Mental Hygiene.
Yang W
,Kandula S
,Huynh M
,Greene SK
,Van Wye G
,Li W
,Chan HT
,McGibbon E
,Yeung A
,Olson D
,Fine A
,Shaman J
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SARS-CoV-2 infection and mortality during the first epidemic wave in Madurai, south India: a prospective, active surveillance study.
SARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance.
In this prospective, active surveillance study, we used data collected under expanded programmatic surveillance testing for SARS-CoV-2 in the district of Madurai, Tamil Nadu, India (population of 3 266 000 individuals). Prospective testing via RT-PCR was done in individuals with fever or acute respiratory symptoms as well as returning travellers, frontline workers, contacts of laboratory-confirmed COVID-19 cases, residents of containment zones, patients undergoing medical procedures, and other risk groups. Standardised data collection on symptoms and chronic comorbid conditions was done as part of routine intake. Additionally, seroprevalence of anti-SARS-CoV-2 immunoglobulin G was assessed via a cross-sectional survey recruiting adults across 38 clusters within Madurai District from Oct 19, 2020, to Nov 5, 2020. We estimated adjusted odds ratios (aORs) for positive RT-PCR results comparing individuals by age, sex, comorbid conditions, and aspects of clinical presentation. We estimated case-fatality ratios (CFRs) over the 30-day period following RT-PCR testing stratified by the same variables, and adjusted hazard ratios (aHRs) for death associated with age, sex, and comorbidity. We estimated infection-fatality ratios (IFRs) on the basis of age-specific seroprevalence.
Between May 20, 2020, and Oct 31, 2020, 13·5 diagnostic tests were done per 100 inhabitants within Madurai, as compared to 7·9 tests per 100 inhabitants throughout India. From a total of 440 253 RT-PCR tests, 15 781 (3·6%) SARS-CoV-2 infections were identified, with 8720 (5·4%) of 160 273 being positive among individuals with symptoms, and 7061 (2·5%) of 279 980 being positive among individuals without symptoms, at the time of presentation. Estimated aORs for symptomatic RT-PCR-confirmed infection increased continuously by a factor of 4·3 from ages 0-4 years to 80 years or older. By contrast, risk of asymptomatic RT-PCR-confirmed infection did not differ across ages 0-44 years, and thereafter increased by a factor of 1·6 between ages 45-49 years and 80 years or older. Seroprevalence was 40·1% (95% CI 35·8-44·6) at age 15 years or older by the end of the study period, indicating that RT-PCR clinical testing and surveillance testing identified only 1·4% (1·3-1·6%) of all infections in this age group. Among RT-PCR-confirmed cases, older age, male sex, and history of cancer, diabetes, other endocrine disorders, hypertension, other chronic circulatory disorders, respiratory disorders, and chronic kidney disease were each associated with elevated risk of mortality. The CFR among RT-PCR-confirmed cases was 2·4% (2·2-2·6); after age standardisation. At age 15 years or older, the IFR based on reported deaths was 0·043% (0·039-0·049), with reported deaths being only 11·0% (8·2-14·5) of the expected count.
In a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India.
The Bill & Melinda Gates Foundation, the National Science Foundation, and the National Institute of General Medical Sciences.
For the Hindi translation of the abstract see Supplementary Materials section.
Laxminarayan R
,B CM
,G VT
,Arjun Kumar KV
,Wahl B
,Lewnard JA
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