Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

Abstract

SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.

IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection

“…Then, neutralizing anti-RBD IgG and anti-NC titers increased and reached a plateau around the fourth week after symptom onset, while IgA decreased by day 28 ( Sterlin et al., 2021 ). This might be observed also in asymptomatic SARS-CoV-2 infection as we have recently shown ( Carsetti et al., 2020b ).…”

Passive Immunity Should and Will Work for COVID-19 for Some Patients

“…Circulating IgA responses generally parallel those of IgG although not as prolonged [56,62,64,65,[68][69][70]. One study found considerable IgA titres associated with severe respiratory disease [71].…”

“…Affinity maturation is time accrued [50,78]. A small proportion do not seroconvert after infection, and thus not all post-infectious sera may be useful, even though other aspects of post-infection immunity via cell-mediated immunity may have arisen in these patients [33,34,68,[72][73][74]77,[92][93][94].…”

“…A lack of antibody response is particularly noticeable for asymptomatic and out-patients [33,64,68,73,77,85,89,95]. Using a given threshold of anti-RBD antibody, Bartsch et al [89] define a limit above which other immune responses and effector functions are recruited.…”

Assessing inflammatory status in COVID-19: a role in the pandemic?

“…Pathological inflammation was postulated as one determinant of the disease outcomes [2], to the extent that a potential role for immunomodulating therapy was proposed and investigated, with the use of corticosteroids linked to reduced 28 day mortality in hospitalized patients [3]. However, differences in immune responses against COVID-19 may exist [4,5], and the identification of patients with a dysregulated host response may be beneficial to improve prognostic assessment, especially in the first stages of the disease. In this scenario, several biomarkers (including C Reactive Protein (CRP), interleukins (IL), procalcitonin, and serum albumin) have been described and proposed as potentially useful to differentiate the severity of the disease [6][7][8].…”