A recent study published in the International Journal of Infectious Diseases has explained the lower prevalence of coronavirus disease 2019 (COVID-19) in sub-Saharan Africa compared to that in the US, Europe, and Asia.
The study findings demonstrate a significantly higher prevalence of cross-reactive antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the blood samples collected from sub-Saharan African populations. This is probably because of their prior exposure to other human coronaviruses.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for COVID-19), is a single-stranded, positive-sense RNA virus that closely resembles other lethal human coronaviruses, such as SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Besides highly lethal members, the human coronavirus family contains other less pathogenic viruses, such as HCoV-OC43, HCoV-HKU-1, HCoV-NL63, and HCoV-229E, which commonly cause mild infection in the human respiratory tract.
Despite having advanced medical facilities, a significantly higher prevalence of SARS-CoV-2 infection and COVID-19-related deaths has been observed in the United States, Europe, and Asia. In contrast, a much lower COVID-19-related morbidity and mortality rate has been documented in sub-Saharan Africa, despite having comparatively higher socioeconomic burdens and suboptimal medical facilities.
Given the higher incidence rate of infectious diseases in sub-Saharan Africa, such as Ebola, HIV-1, tuberculosis, malaria, and yellow fever, it is possible that populations live in this part of the world have enormous prior exposure to human coronaviruses. The cross-protection developed against SARS-CoV-2 due to prior coronavirus exposure could be one of the significant reasons for lower COVID-19 prevalence in sub-Saharan Africa. In the current study, the scientists aimed at investigating this possibility.
Current study design
The scientists thoroughly analyzed 289 plasma samples collected in the pre-COVID-19 era from people live in sub-Saharan Africa (Tanzania and Zambia) and America. To determine possible serological cross-reactivity between different human coronavirus, they used an immunofluorescence assay to detect the presence of cross-reactive antibodies against the spike protein and nucleocapsid protein of SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-OC43, HCoV-HKU-1, HCoV-NL63, and HCoV-229E.
Moreover, they checked the prevalence of HIV-1 infection in the study cohort to determine whether HIV-1 infection can influence the serological cross-reactivity against SARS-CoV-2.
Of all Tanzanian and Zambian samples, about 6% and 43% tested positive for HIV-1, respectively. In contrast, all US samples tested negative for HIV-1. The immunofluorescence assay data showed the presence of immunoglobulin G (IgG)-specific cross-reactive antibodies against SARS-CoV-2 in pre-COVID samples.
Specifically, cross-reactive anti-SARS-CoV-2 antibodies were detected in 2.4%, 19%, and 14.1% of samples collected from the US, Tanzania, and Zambia, respectively. This indicates that people living in sub-Saharan Africa are more likely to have anti-SARS-CoV-2 cross-reactivity than those living in the USA.
The majority of the sub-Saharan African samples showed cross-reactivity against the nucleocapsid protein of SARS-CoV-2. Interestingly, the scientists observed that Tanzanian samples that showed anti-SARS-CoV-2 cross-reactivity were not positive for HIV-1. Similarly, the majority of cross-reactive Zambian samples were negative for HIV-1. This indicates that people with HIV-1 infection are less likely to develop cross-reactive antibodies against SARS-CoV-2.
Experiments designed to determine the impact of prior coronavirus exposure on anti-SARS-CoV-2 cross-reactively revealed that all samples showing cross-reactivity against SARS-CoV-2 also recognize the spike protein of less pathogenic human coronaviruses that cause mild respiratory infection (HCoV-OC43, HCoV-HKU-1, HCoV-NL63, and HCoV-229E). However, none of the samples showed reactivity against lethal coronaviruses' spike protein (SARS-CoV-1 and MERS-CoV).
Regarding viral nucleocapsid, about 92% and 50% of anti-SARS-CoV-2 cross-reactive samples showed reactivity against the nucleocapsid protein of HCoV-NL63 and HCoV-229E, respectively. Overall, these findings indicate that the spike protein is more specific than nucleocapsid protein in terms of inducing adaptive immune responses.
The study reveals that prior exposure to common human coronaviruses may be the reason behind the low susceptibility of sub-Saharan African populations to SARS-CoV-2 infection. In contrast, a significantly lower prevalence of cross-reactive anti-SARS-CoV-2 antibodies in Americans justifies their susceptibility to SARS-CoV-2 infection.
Although it is still uncertain whether the presence of cross-reactive antibodies can protect people from SARS-CoV-2 infection, the scientists believe that antibody-mediated adaptive immune responses may provide some level of protection against COVID-19 progression.