ABSTRACT
Antibodies are used to estimate prevalence of past infection. However, T cell responses against SARS-CoV-2 may more accurately define prevalence because SARS-CoV-2-specific antibodies wane. In November-December 2021, we studied serological and cellular immune responses in residents of rural Kenya who had not experienced any respiratory symptom nor had contact with COVID-19 cases. Among participants we detected anti-spike antibodies in 41.0% and T cell responses against [≥]2 SARS-CoV-2 proteins in 82.5%, which implies that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. Distinct from cellular immunity in European and Asian COVID-19 convalescents, strong T cell immunogenicity was observed against viral accessory proteins in these asymptomatic Africans, as well as a higher IL-10/IFN-{gamma} ratio cytokine profile, suggesting that environmental or genetic factors modulate pro-inflammatory responses.
Subject(s)
COVID-19ABSTRACT
The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-{gamma}, IL-4, IL-6, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma} and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF- and IL-1{beta}) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
SARS-CoV-2 is a novel ssRNA+ virus from the Coronaviridae family, which has caused the global COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest of RNA viruses, comprising of 26 known protein-coding loci. This study aimed to explore the coding potential of negative-strand RNA intermediate for its potential to contain additional protein coding-loci. Surprisingly, we have found several putative ORFs and one brandt new functional SARS-CoV-2 protein-coding loci and called it Avo1 (Ambient viral ORF1). This sequence is located on negative-sense RNA intermediate and bona fide coding for 81 amino acid residues long protein and contains strong Kozak sequence for translation on eukaryotic ribosomes. In silico translated protein Avo1 has a predominantly alpha-helical structure. The existence of Avo1 gene is supported also by its evolutionarily and structural conservation in RaTG13 bat coronavirus. The nucleotide sequence of Avo1 also contains a unique SREBP2 binding site which is closely related to the so-called cytokine storm in severe COVID-19 patients. Altogether, our results suggest the existence of still undescribed SARS-CoV-2 protein, which may play an important role in the viral lifecycle and COVID-19 pathogenesis.