ABSTRACT
The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.
Subject(s)
COVID-19ABSTRACT
Globally, key subpopulations have a high risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations, including healthcare workers, persons within the general population previously reporting experiencing key COVID-19 like symptoms and archived plasma specimens collected prior to confirmation of COVID-19 in Uganda. We collected venous blood from HCWs at selected health facilities and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted during the first national lockdown (May-August 2020). Pre-lockdown plasma collected from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (ARCHITECT AdviseDx SARS-CoV-2 IgM) which targets the spike. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive. Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Methods: Serum samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic individuals (Uganda 1077 and Baltimore 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. Results: After first positive PCR in Ugandan samples the sensitivity was: 45% (95% CI 24,68) at 0-7 days; 79% (95%CI 64,91) 8-14 days; and 76% (95%CI 50,93) >15 days. In samples from Baltimore, sensitivity was: 39% (95% CI 30, 49) 0-7 days; 86% (95% CI 79,92) 8-14 days; and 100% (95% CI 89,100) 15 days post positive PCR. The specificity of 96.5% (95% CI 97.5,95.2) in Ugandan samples was significantly lower than samples from Baltimore 99.3% (95% CI 98.1,99.8), p<0.01. In Ugandan samples, individuals with a false positive result were more likely to be male (PR 2.04, 95% CI 1.03,3.69) or individuals who had a fever more than a month prior to sample acquisition (PR 2.87, 95% CI 1.12,7.35). Conclusions: Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.