The coronavirus disease 2019 (COVID-19) pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders.* Symptoms of anxiety disorder and depressive disorder increased considerably in the United States during April-June of 2020, compared with the same period in 2019 (1,2). To assess mental health, substance use, and suicidal ideation during the pandemic, representative panel surveys were conducted among adults aged ≥18 years across the United States during June 24-30, 2020. Overall, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of a trauma- and stressor-related disorder (TSRD) related to the pandemic† (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%). The percentage of respondents who reported having seriously considered suicide in the 30 days before completing the survey (10.7%) was significantly higher among respondents aged 18-24 years (25.5%), minority racial/ethnic groups (Hispanic respondents [18.6%], non-Hispanic black [black] respondents [15.1%]), self-reported unpaid caregivers for adults§ (30.7%), and essential workers¶ (21.7%). Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.

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Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic - United States, June 24-30, 2020.

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

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Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications.

COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.PROSPERO (CRD42021256965). 

Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis

Although most cases of coronavirus disease 2019 (COVID-19) have occurred in low-resource countries, little is known about the epidemiology of the disease in such contexts. Data from the Indian states of Tamil Nadu and Andhra Pradesh provide a detailed view into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission pathways and mortality in a high-incidence setting. Reported cases and deaths have been concentrated in younger cohorts than would be expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7 to 10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk. Case fatality ratios spanned 0.05% at ages of 5 to 17 years to 16.6% at ages of 85 years or more. Primary data from low-resource countries are urgently needed to guide control measures.

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Epidemiology and transmission dynamics of COVID-19 in two Indian states

To assess age-specific infection fatality rates (IFRs) for COVID-19, we have conducted a systematic review of seroprevalence studies as well as countries with comprehensive tracing programs. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of each study, reflecting typical lags in fatalities and reporting. Using metaregression procedures, we find a highly significant log-linear relationship between age and IFR for COVID-19. The estimated age-specific IFRs are very low for children and younger adults but increase progressively to 0.4% at age 55, 1.3% at age 65, 4.2% at age 75, and 14% at age 85. About 90% of the geographical variation in population IFR is explained by differences in age composition of the population and age-specific prevalence. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults. Moreover, the population IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to protect vulnerable age groups could substantially decrease total deaths.

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Assessing the Age Specificity of Infection Fatality Rates for COVID-19: Systematic Review, Meta-analysis, & Public Policy Implications

Importance Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. Design, Setting, and Participants This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. Exposures Infection with SARS-CoV-2. Main Outcomes and Measures The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. Results Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. Conclusions and Relevance During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

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Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020.

Importance Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States Design Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies Setting Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State’s (WA) Puget Sound region Participants Persons of all ages with serum collected during intervals from March 23 through May 3, 2020 Exposure SARS-CoV-2 virus infection Main outcomes and measures We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay We standardized estimates to the site populations by age and sex Estimates were adjusted for test performance characteristics (960% sensitivity and 993% specificity) We estimated the number of infections in each site by extrapolating seroprevalence to site populations We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date Results We tested sera from 11,933 persons Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 113% (95% confidence interval [CI] 070-194) in WA to 693% (95% CI 502-892) in NYC (collected March 23-April 1) For sites with later collection dates, estimates ranged from 185% (95% CI 100-323, collected April 6-10) for FL to 494% (95% CI 361-652) for CT (April 26-May 3) The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site Conclusions and relevance Our seroprevalence estimates suggest that for five of six US sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases Seroprevalence and under-ascertainment varied by site and specimen collection period Most specimens from each site had no evidence of antibody to SARS-CoV-2 Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures Key findings Question What proportion of persons in six US sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020? Findings We tested 11,933 residual clinical specimens We estimate that from 11% of persons in the Puget Sound to 69% in New York City (collected March 23-April 1) had detectable antibodies Estimates ranged from 19% in south Florida to 49% in Connecticut with specimens collected during intervals from April 6-May 3 Six to 24 times more infections were estimated per site with seroprevalence than with case report data Meaning For most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases Most persons in each site likely had no detectable SARS-CoV-2 antibodies

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Randall W. Williams

Papers

Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020.

Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020