Early cytokine profiles associated with mild and asymptomatic COVID-19 disease severity in Uganda

Abstract

Emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) constituted a global health threat of highly impactful and pandemic proportions. However, low COVID-19 disease severity was observed in Uganda and the early immune responses to SARS-CoV-2 in the Ugandan population are still poorly understood. We postulated that early cytokine modulation could have shaped the inflammatory response that contributed to the mild disease severity. Investigating the cytokine profiles associated with early SARS-CoV-2 infection is important in informing therapeutic and vaccination strategies. Peripheral blood mononuclear cells (PBMCs) were collected from 15 RT PCR confirmed mild and asymptomatic SARS-CoV-2 infected subjects at 0, 7, 14 days since PCR or admission date. The PBMCs were stimulated with peptide megapools traversing the SARS-CoV-2 structural proteins and open reading frames (Orf10, Orf 6, Orf1ab, Orf3a, Orf7a, and Orf8). Supernatants from peptide-stimulated PBMCs were analyzed on a 48–plex Luminex panel for expressions and kinetics of elicited cytokines according to the manufacturer’s protocol. We identified several key cytokine profiles uniquely associated with SARS-CoV-2 during early (mild/ asymptomatic) infection. The Pro-inflammatory cytokines; IL-6, IL-8, GM-CSF and M-CSF, which are essential for the differentiation and activation of innate immune cells were elevated at D0 during infection, while immune regulators; IL-1RA, IL-10, IL-9 and IL-4, which down regulate inflammation effects, were upregulated at D14. Stromal remodeling and tissue-repair growth factors; VEGF-A and PDGF-AB/BB, were adequately expressed at D14 of infection. Taken together, our study showed a well-balanced early response consisting of pro-inflammatory cytokines that enhance the innate immunity, and immune regulators that control inflammation. Thus, our study suggests that the moderate and balanced cytokine expression during early SARS-CoV-2 infection could have been a correlate of protection against COVID-19 in Uganda.