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      Seroprevalence of SARS-CoV-2-Specific IgG Antibodies Among Adults Living in Connecticut: Post-Infection Prevalence (PIP) Study

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          Abstract

          Background

          A seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population, however, most existing reports have used a convenience sample, which may bias their estimates.

          Methods

          We sought a representative sample of Connecticut residents, aged ≥18 years and residing in non-congregate settings, who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 29, 2020. We also oversampled non-Hispanic Black and Hispanic subpopulations. We estimated the seroprevalence of SARS-CoV-2-specific IgG antibodies and the prevalence of symptomatic illness and self-reported adherence to risk mitigation behaviors among this population.

          Results

          Of the 567 respondents (mean age 50 [±17] years; 53% women; 75% non-Hispanic White individuals) included at the state-level, 23 respondents tested positive for SARS-CoV-2-specific antibodies, resulting in weighted seroprevalence of 4.0 (90% confidence interval [CI] 2.0–6.0). The weighted seroprevalence for the oversampled non-Hispanic Black and Hispanic populations was 6.4% (90% CI 0.9–11.9) and 19.9% (90% CI 13.2–26.6), respectively. The majority of respondents at the state-level reported following risk mitigation behaviors: 73% avoided public places, 75% avoided gatherings of families or friends, and 97% wore a facemask, at least part of the time.

          Conclusions

          These estimates indicate that the vast majority of people in Connecticut lack antibodies against SARS-CoV-2 and there is variation by race/ethnicity. There is a need for continued adherence to risk mitigation behaviors among Connecticut residents to prevent resurgence of COVID-19 in this region.

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          Most cited references12

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          Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

          The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
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            Hospitalization and Mortality among Black Patients and White Patients with Covid-19

            Abstract Background Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. Methods In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. Results A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). Conclusions In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.
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              Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19

              To the Editor: A recent article suggested the rapid decay of anti–SARS-CoV-2 IgG in early infection, 1 but the rate was not described in detail. We evaluated persons who had recovered from Covid-19 and referred themselves to our institution for observational research. Written informed consent was obtained from all the participants, with approval by the institutional review board. Blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA) to detect anti–SARS-CoV-2 spike receptor-binding domain IgG. 2 The ELISA was further modified to precisely quantify serum anti–receptor-binding domain activity in terms of equivalence to the concentration of a control anti–receptor-binding domain monoclonal IgG (CR3022, Creative Biolabs). Infection had been confirmed by polymerase-chain-reaction assay in 30 of the 34 participants. The other 4 participants had had symptoms compatible with Covid-19 and had cohabitated with persons who were known to have Covid-19 but were not tested because of mild illness and the limited availability of testing. Most of the participants had mild illness; 2 received low-flow supplemental oxygen and leronlimab (a CCR5 antagonist), but they did not receive remdesivir. There were 20 women and 14 men. The mean age was 43 years (range, 21 to 68) (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). A total of 31 of the 34 participants had two serial measurements of IgG levels, and the remaining 3 participants had three serial measurements. The first measurement was obtained at a mean of 37 days after the onset of symptoms (range, 18 to 65), and the last measurement was obtained at a mean of 86 days after the onset of symptoms (range, 44 to 119). The initial mean IgG level was 3.48 log10 ng per milliliter (range, 2.52 to 4.41). On the basis of a linear regression model that included the participants’ age and sex, the days from symptom onset to the first measurement, and the first log10 antibody level, the estimated mean change (slope) was −0.0083 log10 ng per milliliter per day (range, −0.0352 to 0.0062), which corresponds to a half-life of approximately 36 days over the observation period (Figure 1A). The 95% confidence interval for the slope was −0.0115 to −0.0050 log10 ng per milliliter per day (half-life, 26 to 60 days) (Figure 1B). The protective role of antibodies against SARS-CoV-2 is unknown, but these antibodies are usually a reasonable correlate of antiviral immunity, and anti–receptor-binding domain antibody levels correspond to plasma viral neutralizing activity. Given that early antibody decay after acute viral antigenic exposure is approximately exponential, 3 we found antibody loss that was quicker than that reported for SARS-CoV-1, 4,5 and our findings were more consistent with those of Long et al. 1 Our findings raise concern that humoral immunity against SARS-CoV-2 may not be long lasting in persons with mild illness, who compose the majority of persons with Covid-19. It is difficult to extrapolate beyond our observation period of approximately 90 days because it is likely that the decay will decelerate. 3 Still, the results call for caution regarding antibody-based “immunity passports,” herd immunity, and perhaps vaccine durability, especially in light of short-lived immunity against common human coronaviruses. Further studies will be needed to define a quantitative protection threshold and rate of decline of antiviral antibodies beyond 90 days.
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                Author and article information

                Journal
                Am J Med
                Am J Med
                The American Journal of Medicine
                Published by Elsevier Inc.
                0002-9343
                1555-7162
                29 October 2020
                29 October 2020
                Affiliations
                [1 ]Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT
                [2 ]Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
                [3 ]The Gallup Organization, Washington, DC
                [4 ]Yale Occupational and Environmental Medicine Program, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
                [5 ]Yale Center for Clinical Investigation, Yale School of Medicine, New Haven, CT
                [6 ]Quest Diagnostics, Marlborough, MA
                [7 ]The Jackson Laboratory for Genomic Medicine, Farmington, CT
                [8 ]Department of Pathology, University of Massachusetts Medical School, Worcester, MA
                [9 ]Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT
                [10 ]Department of Health Policy and Management, Yale School of Public Health, New Haven, CT
                Author notes
                [* ] Address for correspondence: Harlan M. Krumholz, MD, SM, 1 Church Street, Suite 200, New Haven, CT 06510 USA. Telephone: 203-764-5885; Fax: 203-764-5653
                [11]

                Twitter: @hmkyale

                Article
                S0002-9343(20)30909-8
                10.1016/j.amjmed.2020.09.024
                7598362
                33130124
                3c40ae5f-4bc8-4bc7-82ed-cec39cb69cdd
                © 2020 Published by Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Categories
                Clinical Research Study

                seroprevalence,sars-cov-2,covid-19,antibodies,connecticut
                seroprevalence, sars-cov-2, covid-19, antibodies, connecticut

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