Asymptomatic SARS-CoV-2 infection: is it all about being refractile to innate immune sensing of viral spare-parts?-Clues from exotic animal reservoirs

Abstract

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.

Keywords: COVID-19; SARS-CoV-2; asymptomatic; evolution; monocytes; origin.

Figure 1.

Proposed mechanism of existence of β-coronaviruses (β-CoV) in exotic mammalian animal reservoirs. Exotic bats serve as primary reservoirs of β-coronaviruses (β-CoV) from where the later appears to have ‘landed’ into pangolins (not shown) where the virus seems to have undergone a homologous recombination of nucleotide base pairs with insidious pangolin-CoV before getting into the human system (upon consumption or inhalation of virus present in body fluids), potentially initiating an outbreak. It also appears that bats bypass exaggerated inflammation by limiting the assembly of the NLR family pyrin domain containing three (NLRP3) in monocytes, and besides the paucity of functional killer cell Ig-like (KIR), and killer cell lectin-like (KLR) receptor loci expressed classically by NK cells.

Figure 2.

Mechanistic basis of proposed COVID-19 immunopathogenesis in humans. Notwithstanding the proportion of asymptomatic COVID-19 disease warrants an extensive global population screening, some studies have estimated that ∼80% of individuals, diagnosed with the SARS-CoV-2 remain sub-clinical. Despite being an RNA virus, SARS-CoV-2 can activate the STING pathway (Fischer, Tschachler and Eckhart 2020a) to induce cytokine storm syndrome, also fueled by NLRP3 inflammasome activation and production of IL-1β, and IL-18, besides TNF-α, IFN-γ and IL-6 to deteriorate disease severity. A Chinese study has shown that asymptomatic individuals displayed an extended median duration of 19 days of viral shedding compared to symptomatic patients portraying the role of asymptomatic/subclinical disease status with the exponential upsurge in global COVID-19 cases (Long et al. 2020).