High prevalence of pre-existing serological cross-reactivity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in sub-Saharan Africa

Int J Infect Dis. 2021 Jan:102:577-583. doi: 10.1016/j.ijid.2020.10.104. Epub 2020 Nov 8.


Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by immunofluorescence assay against the spike and nucleocapsid proteins of all known human coronaviruses (HCoVs).

Results: The prevalence of SARS-CoV-2 serological cross-reactivity was significantly higher in samples from SSA compared with the USA. Most of these cross-reactive samples cross-recognized the SARS-CoV-2 nucleocapsid protein and the spike proteins of other HCoVs. Nucleocapsid proteins from HCoV-NL63 and HCoV-229E were detected in most samples, thereby implicating prior exposure to these two HCoVs as the likely source of cross-reactive antibodies against SARS-CoV-2.

Conclusion: The low incidences of SARS-CoV-2 infection and disease in SSA appear to be correlated with the pre-pandemic serological cross-recognition of HCoVs, which are substantially more prevalent in SSA than the USA.

Keywords: COVID-19; Cross-reactivity; HCoV-229E; HCoV-NL63; Human coronavirus; SARS-CoV-2; Serology; Sub-Saharan Africa.

MeSH terms

  • Adult
  • Africa South of the Sahara / epidemiology
  • Antibodies, Viral / blood*
  • COVID-19 / blood*
  • COVID-19 / epidemiology
  • COVID-19 / virology
  • Cross Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology
  • Pandemics
  • SARS-CoV-2 / immunology*
  • Young Adult


  • Antibodies, Viral
  • Nucleocapsid Proteins