Epidemiologic and Immunologic Investigations of SARS-CoV-2 (COVID-19) Infections

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged as a global pandemic in early 2020. By the end July of 2022, over 560 million cases of SARS-CoV-2 have been confirmed, spanning almost all countries and accounting for > 6.3 million deaths. In the US, over 89 million cases of SARS-CoV-2 have been reported with over 1,002,000 deaths from COVID-19 disease. With widespread community transmission and with an urgent need for effective therapeutics and prophylaxis, there is a critical need to perform broad-scale population-based testing to better define population infection dynamics, vaccine coverage, transmission, and immunological and therapeutic responses to SARS-CoV-2 infection. Convalescent plasma was demonstrated to be an effective intervention, reducing hospitalization by >50%, if given within 9 days of symptom onset. We participated in a multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults. In our study 1181 adults received a plasma transfusion. Among the 592 participants who received convalescent plasma 17(2.9%) were hospitalized, compared to 6.3% (37/589) who relieved control plasma, p<0.005. The greatest impact of the intervention was seen if the subjects received convalescent plasma5 days from symptom onset. Having abnormal c-reactive protein or absolute lymphocyte counts attenuated the impact of the intervention. Using previously identified viral epitopes targeted by CD8+ T cells (n=52 epitopes) in individuals from the convalescent study (n=30 individuals), we assessed if T-cell epitopes in SARS-CoV-2 are mutated in the newly described Omicron VOC (n=50 mutations). We showed that within this population, only one low-prevalence epitope from the Spike protein, restricted to two HLA alleles and found in 2/30 (7%) individuals, contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time. We performed a serosurvey on samples from Maryland decedents who required an autopsy from 24 May through 30 November 2020. We were able to test the stored blood from 1906 individuals and determined that 305 (16%) had antibodies to SARS-CoV-2. Monthly seroprevalence increased from 11% to 22% over time and was consistently higher than state-level estimates. Hispanic ethnicity was associated with 2- to 3.2-fold higher seropositivity (P < .05) irrespective of sex. Deaths due to motor vehicle crash were associated with 62% increased seropositivity (aPR, 1.62 95% CI, 1.15-2.28) vs natural manner of death. Though seroprevalence was lower in decedents of illicit drug overdose vs non-overdose in early months, this shifted, and seroprevalence was comparable by November 2020.Our study demonstrates how readily available, cost-effective data can be leveraged in a systematic way to provide real-time information on potential signals of infectious disease spread. We developed a serological testing algorithm to differentiate vaccinated, previously infected, and unexposed individuals using standard enzyme-linked immunosorbent assay (ELISA) and lateral flow technology to apply in our emergency department (ED) serosurvey. We developed and validated this approach using 1960 samples from individuals with known SARS-CoV-2 infection and vaccination status. The sample sets included NIH phase 1 vaccine trial (20-003) participants, health care workers who were vaccinated or infected, potential convalescent plasma donors, hospitalized patients, and pre pandemic controls from the ED. Using these samples, we demonstrated that our algorithm could accurately identify samples from vaccinated individuals (sensitivity 100, specificity 98.8%) and previously infected individuals (sensitivity 84.4%, specificity 100%). We performed a serosurvey at the Johns Hopkins Hospital ED from March 16 to April 30 2020 (1536 samples) and January 11 to March 10, 2021 (2824 samples). We demonstrated that in inner city Baltimore, white women and men had the lowest prevalence of infection both in 2020 and 2021. In the 2021 survey, white women accounted for 9% of all infections in 2021 but 27% of all vaccinations. For all other groups, the prevalence of exposure to SARS-CoV-2 was higher than the frequency of vaccination. By the spring of 2021, Hispanic patients had the highest evidence of prior SARS-CoV-2 infection within any ethnic group, at 38%. Our study highlights disparities based on sex and race/ethnicity in SARS-CoV-2 prevalence and vaccine distribution within metropolitan Baltimore during the spring of 2021. We conducted a serosurvey from 30th November 2020 to 8th January 2021, at the Rakai Community Cohort Study and twenty-six health facilities in South-Central Uganda. Samples were collected from 753 health care workers (HCW) and from 227 population-cohort participants who reported either a fever, cough, loss of taste and appetite during the survey period. Additionally, 636 specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda. The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% 95%CI: 23.5, 29.8 with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the survey participants, 15.6% 95%CI: 10.9, 20.3 had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% 95%CI: 1.2, 3.5 were reactive. Our findings high level of infection to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda.