Most downloaded biology preprints, all time
in category epidemiology
8,252 results found. For more information, click each entry to expand.
360,504 downloads medRxiv epidemiology
COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID- 19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.
291,750 downloads medRxiv epidemiology
Eran Bendavid, Bianca Mulaney, Neeraj Sood, Soleil Shah, Emilia Ling, Rebecca Bromley-Dulfano, Cara Lai, Zoe Weissberg, Rodrigo Saavedra-Walker, James Tedrow, Dona Tversky, Andrew Bogan, Thomas Kupiec, Daniel Eichner, Ribhav Gupta, John Ioannidis, Jay Bhattacharya
Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in a community sample drawn from Santa Clara County. Methods On April 3-4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a sample of individuals living within the county by demographic and geographic characteristics. We estimate weights to adjust our sample to match the zip code, sex, and race/ethnicity distribution within the county. We report both the weighted and unweighted prevalence of antibodies to SARS-CoV-2. We also adjust for test performance characteristics by combining data from 16 independent samples obtained from manufacturer's data, regulatory submissions, and independent evaluations: 13 samples for specificity (3,324 specimens) and 3 samples for sensitivity (157 specimens). Results The raw prevalence of antibodies to SARS-CoV-2 in our sample was 1.5% (exact binomial 95CI 1.1-2.0%). Test performance specificity in our data was 99.5% (95CI 99.2-99.7%) and sensitivity was 82.8% (95CI 76.0-88.4%). The unweighted prevalence adjusted for test performance characteristics was 1.2% (95CI 0.7-1.8%). After weighting for population demographics of Santa Clara County, the prevalence was 2.8% (95CI 1.3-4.7%), using bootstrap to estimate confidence bounds. These prevalence point estimates imply that 54,000 (95CI 25,000 to 91,000 using weighted prevalence; 23,000 with 95CI 14,000-35,000 using unweighted prevalence) people were infected in Santa Clara County by early April, many more than the approximately 1,000 confirmed cases at the time of the survey. Conclusions The estimated population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection may be much more widespread than indicated by the number of confirmed cases. More studies are needed to improve precision of prevalence estimates. Locally-derived population prevalence estimates should be used to calibrate epidemic and mortality projections.
287,428 downloads medRxiv epidemiology
Martina Patone, Winnie Xue Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter J Watkinson, Kamlesh Khunti, Anthony Harnden, Carol AC Coupland, Keith M Channon, Nicholas L Mills, Aziz Sheikh, Julia Hippisley-Cox
In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy.
254,074 downloads medRxiv epidemiology
AimsStudies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methodsFrom February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findingsFor the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. SignificanceAmong patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. Trial registrationURL: https://www.clinicaltrials.gov/. The unique identifier: ChiCTR2000029559.
205,128 downloads medRxiv epidemiology
Jiao Zhao, Yan Yang, Hanping Huang, Dong Li, Dongfeng Gu, Xiangfeng Lu, zheng zhang, Lei Liu, Ting Liu, Yukun Liu, Yunjiao He, Bin Sun, Meilan Wei, Guangyu Yang, Xinghuan Wang, Li Zhang, Xiaoyang Zhou, Mingzhao Xing, Peng George Wang
The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.
195,199 downloads medRxiv epidemiology
OBJECTIVETo evaluate the relative risk of COVID-19 death in people <65 years old versus older individuals in the general population, to provide estimates of absolute risk of COVID-19 death at the population level, and to understand what proportion of COVID-19 deaths occur in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATACountries and US states or major cities with at least 250 COVID-19 deaths as of 4/4/2020 and with information available on death counts according to age strata, allowing to calculate the number of deaths in people with age <65. Data were available for Belgium, Germany, Italy, Netherlands, Portugal, Spain, Sweden, and Switzerland, as well as Louisiana, Michigan, Washington states and New York City as of April 4, 2020. MAIN OUTCOME MEASURESProportion of COVID-19 deaths that occur in people <65 years old; relative risk of COVID-19 death in people <65 versus [≥]65 years old; absolute risk of death in people <65 and in those [≥]80 years old in the general population as of 4/4/2020; absolute death risk expressed as equivalent of death risk from driving a motor vehicle. RESULTSIndividuals with age <65 account for 5%-9% of all COVID-19 deaths in the 8 European epicenters, and approach 30% in three US hotbed locations. People <65 years old had 34- to 73-fold lower risk than those [≥]65 years old in the European countries and 13- to 15-fold lower risk in New York City, Louisiana and Michigan. The absolute risk of COVID-19 death ranged from 1.7 per million for people <65 years old in Germany to 79 per million in New York City. The absolute risk of COVID-19 death for people [≥]80 years old ranged from approximately 1 in 6,000 in Germany to 1 in 420 in Spain. The COVID-19 death risk in people <65 years old during the period of fatalities from the epidemic was equivalent to the death risk from driving between 9 miles per day (Germany) and 415 miles per day (New York City). People <65 years old and not having any underlying predisposing conditions accounted for only 0.3%, 0.7%, and 1.8% of all COVID-19 deaths in Netherlands, Italy, and New York City. CONCLUSIONSPeople <65 years old have very small risks of COVID-19 death even in the hotbeds of the pandemic and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.
164,525 downloads medRxiv epidemiology
The OpenSAFELY Collaborative, Elizabeth J Williamson, Alex J Walker, Krishnan Bhaskaran, Seb Bacon, Chris Bates, Caroline E Morton, Helen J Curtis, Amir Mehrkar, David H Evans, Peter Inglesby, Jonathan Cockburn, Helen I Mcdonald, Brian MacKenna, Laurie A Tomlinson, Ian J Douglas, Christopher T Rentsch, Rohini Mathur, Angel YS Wong, Richard Grieve, David A Harrison, Harriet Forbes, Anna Schultze, Richard Croker, John Parry, Frank Hester, Sam Harper, Rafael Perera, Stephen Evans, Liam Smeeth, Ben Goldacre
Background Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Data sources Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. Population 17,425,445 adults. Time period 1st Feb 2020 to 25th April 2020. Primary outcome Death in hospital among people with confirmed COVID-19. Methods Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. Results There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10); older age and deprivation (both with a strong gradient); uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56); severe asthma (HR 1.25 CI 1.08-1.44); and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57; fully adjusted HR 1.71 95% CI 1.44-2.02); with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18; fully adjusted HR 1.62 95% CI 1.43-1.82). Conclusions We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation; further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients' records; we will update and extend these results regularly. Keywords COVID-19, risk factors, ethnicity, deprivation, death, informatics.
144,979 downloads medRxiv epidemiology
Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.
143,132 downloads medRxiv epidemiology
Globally, there have been more than 404 million cases of SARS-CoV-2, with 5.8 million confirmed deaths, as of February 2022. South Africa has experienced four waves of SARS-CoV-2 transmission, with the second, third, and fourth waves being driven by the Beta, Delta, and Omicron variants, respectively. A key question with the emergence of new variants is the extent to which they are able to reinfect those who have had a prior natural infection. We developed two approaches to monitor routine epidemiological surveillance data to examine whether SARS-CoV-2 reinfection risk has changed through time in South Africa, in the context of the emergence of the Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. We analyze line list data on positive tests for SARS-CoV-2 with specimen receipt dates between 04 March 2020 and 31 January 2022, collected through South Africa's National Notifiable Medical Conditions Surveillance System. Individuals having sequential positive tests at least 90 days apart were considered to have suspected reinfections. Our routine monitoring of reinfection risk included comparison of reinfection rates to the expectation under a null model (approach 1) and estimation of the time-varying hazards of infection and reinfection throughout the epidemic (approach 2) based on model-based reconstruction of the susceptible populations eligible for primary and second infections. 105,323 suspected reinfections were identified among 2,942,248 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days prior to 31 January 2022. The number of reinfections observed through the end of the third wave in September 2021 was consistent with the null model of no change in reinfection risk (approach 1). Although increases in the hazard of primary infection were observed following the introduction of both the Beta and Delta variants, no corresponding increase was observed in the reinfection hazard (approach 2). Contrary to expectation, the estimated hazard ratio for reinfection versus primary infection was lower during waves driven by the Beta and Delta variants than for the first wave (relative hazard ratio for wave 2 versus wave 1: 0.71 (CI95: 0.60-0.85); for wave 3 versus wave 1: 0.54 (CI95: 0.45-0.64)). In contrast, the recent spread of the Omicron variant has been associated with an increase in reinfection hazard coefficient. The estimated hazard ratio for reinfection versus primary infection versus wave 1 was 1.75 (CI95: 1.48-2.10) for the period of Omicron emergence (01 November 2021 to 30 November 2021) and 1.70 (CI95: 1.44-2.04) for wave 4 versus wave 1. Individuals with identified reinfections since 01 November 2021 had experienced primary infections in all three prior waves, and an increase in third infections has been detected since mid-November 2021. Many individuals experiencing third infections had second infections during the third (Delta) wave that ended in September 2021, strongly suggesting that these infections resulted from immune evasion rather than waning immunity. Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection. In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. This finding has important implications for public health planning, particularly in countries like South Africa with high rates of immunity from prior infection. Further development of methods to track reinfection risk during pathogen emergence, including refinements to assess the impact of waning immunity, account for vaccine-derived protection, and monitor the risk of multiple reinfections will be an important tool for future pandemic preparedness.
137,482 downloads medRxiv epidemiology
The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus. One-sentence summaryBy collecting and analyzing spatiotemporal data, we estimated the transmission potential for 2019-nCoV.
133,563 downloads medRxiv epidemiology
Jordan Peccia, Alessandro Zulli, Doug E. Brackney, Nathan D. Grubaugh, Edward H Kaplan, Arnau Cassanovas-Massana, Albert Ko, Amyn Abdul Malik, Dennis Wang, Mike Wang, Joshua L Warren, Daniel M Weinberger, Saad B. Omer
We report a time course of SARS-CoV-2 RNA concentrations in primary sewage sludge during the Spring COVID-19 outbreak in a northeastern U.S. metropolitan area. SARS-CoV-2 RNA was detected in all environmental samples, and when adjusted for the time lag, the virus RNA concentrations tracked the COVID-19 epidemiological curve. SARS-CoV-2 RNA concentrations were a leading indicator of community infection ahead of compiled COVID-19 testing data and local hospital admissions. Decisions to implement or relax public health measures and restrictions require timely information on outbreak dynamics in a community.
128,150 downloads medRxiv epidemiology
Background: COVID-19 pandemic mitigation requires evidence-based strategies. Because COVID-19 can spread via respired droplets, most US states mandated mask use in public settings. Randomized control trials have not clearly demonstrated mask efficacy against respiratory viruses, and observational studies conflict on whether mask use predicts lower infection rates. We hypothesized that statewide mask mandates and mask use were associated with lower COVID-19 case growth rates in the United States. Methods: We calculated total COVID-19 case growth and mask use for the continental United States with data from the Centers for Disease Control and Prevention and Institute for Health Metrics and Evaluation. We estimated post-mask mandate case growth in non-mandate states using median issuance dates of neighboring states with mandates. Results: Earlier mask mandates were not associated with lower total cases or lower maximum growth rates. Earlier mandates were weakly associated with lower minimum COVID-19 growth rates. Mask use predicted lower minimum but not lower maximum growth rates. Growth rates and total growth were comparable between US states in the first and last mask use quintiles during the Fall-Winter wave. These observations persisted for both natural logarithmic and fold growth models and when adjusting for differences in US state population density. Conclusions: We did not observe association between mask mandates or use and reduced COVID-19 spread in US states. COVID-19 mitigation requires further research and use of existing efficacious strategies, most notably vaccination.
127,158 downloads medRxiv epidemiology
BACKGROUND Infection with SARS-CoV-2 provides substantial natural immunity against reinfection. Recent studies have shown strong waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODS Data on confirmed SARS-CoV-2 infections were extracted from the Israeli Ministry of Health database for the period August to September 2021 regarding all persons previously infected or vaccinated. We compared infection rates as a function of time since the last immunity-conferring event using Poisson regression, adjusting for possible confounding factors. RESULTS Confirmed infection rates increased according to time elapsed since the last immunity-conferring event in all cohorts. For unvaccinated previously infected individuals they increased from 10.5 per 100,000 risk-days for those previously infected 4-6 months ago to 30.2 for those previously infected over a year ago. For individuals receiving a single dose following prior infection they increased from 3.7 per 100,000 person days among those vaccinated in the past two months to 11.6 for those vaccinated over 6 months ago. For vaccinated previously uninfected individuals the rate per 100,000 person days increased from 21.1 for persons vaccinated within the first two months to 88.9 for those vaccinated more than 6 months ago. CONCLUSIONS Protection from reinfection decreases with time since previous infection, but is, nevertheless, higher than that conferred by vaccination with two doses at a similar time since the last immunity-conferring event. A single vaccine dose after infection helps to restore protection.
126,466 downloads medRxiv epidemiology
The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021. Epidemiologic surveillance has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence, although interpretation of these changes presents challenges due to differential protection against Omicron or Delta (B.1.617.2) variant SARS-CoV-2 infections associated with prior vaccine-derived and naturally-acquired immunity, as well as longer-term changes in testing and healthcare practices. Here we report clinical outcomes among 222,688 cases with Omicron variant infections and 23,305 time-matched cases with Delta variant infections within the Kaiser Permanente Southern California healthcare system, who were followed longitudinally following positive outpatient tests between 15 December, 2021 and 17 January, 2022, when Omicron cases were almost exclusively BA.1 or its sublineages. Adjusted hazard ratios of progression to any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death were 0.59 (95% confidence interval: 0.51-0.69), 0.59 (0.51-0.68), 0.50 (0.29-0.87), 0.36 (0.18-0.72), and 0.21 (0.10-0.44) respectively, for cases with Omicron versus Delta variant infections. In contrast, among 14,661 Omicron cases ascertained by outpatient testing between 3 February and 17 March, 2022, infection with the BA.2 or BA.1/BA.1.1 subvariants did not show evidence of differential risk of severe outcomes. Lower risk of severe clinical outcomes among cases with Omicron variant infection merits consideration in planning of healthcare capacity needs amid establishment of the Omicron variant as the dominant circulating SARS-CoV-2 lineage globally, and should inform the interpretation of both case- and hospital-based surveillance data.
125,365 downloads medRxiv epidemiology
The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.
121,075 downloads medRxiv epidemiology
Importance: There is limited evidence on the effectiveness of the BNT162b2 vaccine for children, particularly those 5-11 years and after the Omicron variant's emergence. Objective: To estimate BNT162b2 vaccine effectiveness against COVID cases and hospitalizations among children 5-11 years and 12-17 years during December, 2021 and January, 2022. Design: Analyses of cohorts constructed from linked statewide immunization, laboratory testing, and hospitalization databases. Setting/Participants: New York State children 5-17 years. Main outcomes/measures: New laboratory-confirmed COVID-19 cases and hospitalizations. Comparisons were made using the incidence rate ratio (IRR), comparing outcomes by vaccination status, and estimated vaccine effectiveness (VE: 1-[1/IRR]). Results: From December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, VE against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). VE against hospitalization declined changed from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76% (95% CI: 71%, 81%) and by 28-34 days it was 56% (95% CI: 43%, 63%). For children 5-11, VE against cases declined from 65% (95% CI: 62%, 68%) to 12% (95% CI: 8%, 16%) by 28-34 days. Conclusions and Relevance: In the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission.
119,306 downloads medRxiv epidemiology
Contrary to the practice during previous epidemics, with COVID-19 health authorities have treated a single positive result from a PCR-based test as confirmation of infection, irrespective of signs, symptoms and exposure. This is based on a widespread belief that positive results in these tests are highly reliable. However, evidence from external quality assessments and real-world data indicate enough a high enough false positive rate to make positive results highly unreliable over a broad range of scenarios. This has clinical and case management implications, and affects an array of epidemiological statistics, including the asymptomatic ratio, prevalence, and hospitalization and death rates, as well as epidemiologic models. Steps should be taken to raise awareness of false positives and reduce their frequency. The most important immediate action is to check positive results with additional tests, at least when prevalence is low.
118,716 downloads medRxiv epidemiology
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSThe epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Wuhan, China in late 2019 is now pandemic. Reliable estimates of death from coronavirus disease 2019 (COVID-19) are essential to guide control efforts and to plan health care system requirements. The objectives of this study are to: 1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data; 2) give estimates of SARS-CoV-2 mortality adjusted for bias in the two regions with the worlds highest numbers of confirmed Covid-19 deaths: Hubei province, China and northern Italy. Method and FindingsWe developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases; preferential ascertainment of severe cases and delayed mortality (right-censoring). We fitted our transmission model to surveillance data from Hubei province (1 January to 11 February 2020) and northern Italy (8 February to 3 March 2020). Overall mortality among all symptomatic and asymptomatic infections was estimated to be 3.0% (95% credible interval: 2.6-3.4%) in Hubei province and 3.3% (2.0-4.7%) in northern Italy. Mortality increased with age; we estimate that among 80+ year olds, 39.0% (95%CrI: 31.1-48.9%) in Hubei province and 89.0% (95%CrI: 56.2-99.6%) in northern Italy dies or will die. Limitations are that the model requires data recorded by date of onset and that sex-disaggregated mortality was not available. ConclusionsWe developed a mechanistic approach to correct the crude CFR for bias due to right-censoring and preferential ascertainment and provide adjusted estimates of mortality due to SARS-CoV-2 infection by age group. While specific to the situation in Hubei, China and northern Italy during these periods, these findings will help the mitigation efforts and planning of resources as other regions prepare for SARS-CoV-2 epidemics.
109,669 downloads medRxiv epidemiology
Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92.8% (CI: [92.6, 93.0]); hospitalization 94.2% (CI: [93.6, 94.7]); severe illness 94.4% (CI: [93.6, 95.0]); and death 93.7% (CI: [92.5, 94.7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94.8% (CI: [94.4, 95.1]); hospitalization 94.1% (CI: [91.9, 95.7]); and severe illness 96.4% (CI: [92.5, 98.3]). Our results question the need to vaccinate previously-infected individuals.
105,072 downloads medRxiv epidemiology
Background: Although children and adolescents have a lower burden of SARS-CoV-2-associated disease as compared to adults, assessing absolute risk among children remains difficult due to a high rate of undetected cases. However, without more accurate case numbers, reliable risk analyses are impossible. Methods: We combine data from three sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the German statutory notification system and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) - in order to provide reliable estimates on childrens hospitalization, intensive care admission and death due to COVID-19 and PIMS-TS. Results: While the overall hospitalization rate associated with SARS-CoV-2 infection was 35.9 per 10,000 children, ICU admission rate was 1.7 per 10,000 and case fatality was 0.09 per 10,000. Children without comorbidities were found to be significantly less likely to suffer from a severe or fatal disease course. The lowest risk was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.2 per 10,000 and case fatality could not be calculated, due to an absence of cases. The overall PIMS-TS rate was 1 per 4,000 SARS-CoV-2 infections, the majority being children without comorbidities. Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in overall disease burden among all pediatric age groups.
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