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

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

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 August of 2023, over 770 million cases of SARS-CoV-2 have been confirmed, spanning all countries and accounting more than 6.9 million deaths. In the US, over 103 million cases of SARS-CoV-2 have been reported with over 1.1 million 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. In Western countries, including the United States, post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. We evaluated 883 individuals with confirmed SARS-CoV-2 infection who participated in a randomized trial of COVID-19 Convalescent Plasma (CCP) vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immunosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratioAOR=2.701.93-3.81), older age (AOR=1.321.17-1.50), and elevated baseline levels of IL-6 (AOR=1.591.02-2.47) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (< 5 days after symptom onset) compared to late CCP treatment. Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development. In contrast to Western countries, the true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. Using samples from Ugandan blood donors collected between October 2019 and April 2022 we examined the presence and concetration of IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased 9-fold over the study period, indicative of multiple exposures to the virus by the end of the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic. In a second study from South Africa, we conducted repeated cross-sectional serosurveys from July 2020 to November 2021 using residual plasma from patients with non-COVID-19 conditions from Cape Town. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio aOR 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19.