High SARS-CoV-2 seroprevalence in Lagos, Nigeria with robust antibody and cellular responses

BackgroundEarly evidence suggested that the impact of the COVID-19 pandemic was less severe in Africa compared to other parts of the world. However, more recent studies indicate higher SARS-CoV-2 infection and COVID-19 mortality rates on the continent than previously documented. Research is needed to better understand SARS-CoV-2 seroprevalence and immunity in Africa. MethodsOur collaboration with the Lagos State COVID-19 Taskforce, enabled secondary analyses of immune responses in healthcare workers (HCWs) and Oxford/AstraZeneca COVID-19 vaccine recipients from the general population across 5 local government areas (LGAs) in Lagos State, Nigeria. Western blots were used to simultaneously detect SARS-CoV-2 spike and nucleocapsid (N) antibodies and stimulation of peripheral blood mononuclear cells with N followed by an IFN-{gamma} ELISA was used to examine T cell responses. FindingsAntibody data demonstrated high SARS-CoV-2 seroprevalence of 71.6% (96/134) in HCWs and 54.8% (63/115) in the general population. Antibodies directed to only SARS-CoV-2 N, suggesting pre-existing coronavirus immunity, were seen in 10.4% (14/134) of HCWs and 20.0% (23/115) of the general population. T cell data showed that IFN-{gamma} responses against SARS-CoV-2 N were robust in detecting exposure to the virus, demonstrating 87.5% sensitivity and 92.3% specificity. InterpretationThese results have important implications for understanding the paradoxical high SARS-CoV-2 infection with low mortality rate in Africa as compared to other parts of the world, as well as for the development of T cell-based diagnostics and vaccines. FundingHarvard University, Motsepe Presidential Research Accelerator Fund for Africa

Limit of Detection for Rapid Antigen Testing of the SARS-CoV-2 Omicron Variant

There has been debate in the literature about the ability of antigen tests to detect the SARS-CoV-2 Omicron variant including indication on the US Food and Drug administration website that antigen tests may have lower sensitivity for the Omicron variant without provision of data or the potential scale of the issue (see https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests-omicronvariantimpact, accessed 1/27/2022). Here we determined the limit of detection (LoD) for the Omicron variant compared with the WA1 strain used for LoD studies described in the Instructions for Use for all Emergency Use Authorization (EUA)-approved antigen tests. Using live virus (to avoid artifactual findings potentially obtained with gamma-irradiated or heat-killed virus) quantified by plaque forming units (PFU), we examined the analytical sensitivity of three antigen tests widely used in the United States: the Abbott Binax Now, the AccessBio CareStart, and LumiraDx antigen tests. We found that the 95% detection threshold (LoD) for antigen tests was at least as good for Omicron as for the WA1 strain. Furthermore, the relationship of genome copies to plaque forming units for Omicron and WA1 overlap. Therefore, the LoD equivalency also applies if the quantitative comparator is genome copies determined from live virus preparations. Taken together, our data support the continued ability of the antigen tests examined to detect the Omicron variant.

SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load, and Viral Culture Testing on a Large Sample Cohort

The relationship of SARS-CoV-2 antigen testing results, viral load, and viral culture detection remains to be fully defined. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals, and thereby inform how and where to most appropriately deploy available diagnostic testing modalities. We therefore determined the relationship of antigen testing results from three lateral flow and one microfluidics assay to viral culture performed in parallel in 181 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. We found that antigen tests were predictive of viral culture positivity, with the LumiraDx method showing enhanced sensitivity (90%; 95% confidence interval (95% CI) 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver-operator characteristic curves (ROCs) of 0.94-0.97 and 0.92, respectively. In particular, a viral load threshold of 100,000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Taken together, the detection of SARS-CoV-2 antigen identified highly infectious individuals, some of whom may harbor 10,000-fold more virus in their samples than those with any detectable infectious virus. As such, our data support use of antigen testing in defining infectivity status at the time of sampling.