SARS-CoV-2 Infection Damages Mucosal Immunity


A new study by researchers from Kazan Research Institute of Epidemiology and Microbiology of Rospotrebnadzor-Russia, Kazan State Medical University-Russia and Kazan (Volga Region) Federal University has found that SARS-CoV-2 infections can end up damaging the mucosal immunity of the human host.

SARS-CoV-2-induced, functional, and metabolic impairment of neutrophils of the mucosal immunity system develop in recovered COVID-19 patients, thus providing a scientific rationale for immunomodulatory therapy.
The study findings were published in the peer reviewed journal: BioNanoScience (Springer)

Potential dysfunctions of systemic immunity are currently a proven consequence of COVID-19 [1, 2]. It has been shown that the concentration of immune competent cells in persons with the history of this infection does not return to preinfection levels even a few weeks after recovery [2, 3].

Virus-induced immune response dysregulation leads to significant phenotypic changes in peripheral blood lymphocytes, which persist as long as 4–11 weeks after the disease [2,3,4]. After COVID-19, patients for a long time have an increased percentage of pro-inflammatory monocytes (CD14 + , CD16 +) secreting a number of cytokines, including MCP1, IP-10, and MIP1α, which contribute to the development of a “cytokine storm” [4, 5]. Cytotoxic lymphocytes (NK cells, CD8 + T-cells) show overexpression of activation markers [4, 6].

The consequences of the “cytokine storm,” which develops in some patients and leads to thrombosis, vascular inflammation, and other issues with vital organs, have also been the focus of vast research [7]. In patients with severe and moderately severe COVID-19, progressively high concentrations of IL-2, IL-7, IL-10, G-CSF, MCP1, and TNF-α can persist for a long time at the level of systemic and local immunity, thus causing long-term immune dysfunctions [8].

The study of the effects of SARS-CoV-2 on the cytokine profile shows that multiple structural and non-structural viral proteins counteract the interferon response for a long time [9]. This antagonism occurs at various stages of interferon signaling, e.g., by preventing the recognition of viral RNA by the pattern-recognizing receptor, inhibition of interferon signaling through STAT1, and the degradation of host mRNA [9, 10].

The negative effect of the viral proteins on the interferon response contributes to increased release of apoptosis products, which can later also cause aberrant inflammatory responses [9].

SARS-CoV-2 is primarily spread through airborne transmission. Severe cases progress to acute respiratory distress syndrome, on average 8–9 days from illness onset [11]. The system of local immunity of the mucous membranes of the upper and lower respiratory tract is the main gate for SARS-CoV-2 introduction and replication and it is in the first turn exposed to massive cytopathic effects.

Replication of the SARS-CoV-2 virus in the epithelial cells of the respiratory tract [3, 6, 8, 11] can cause severe destruction and virus-induced apoptosis, which is an inflammatory form of programmed cell death usually observed in cytopathic viral infections [12].

Using various pattern recognition receptors (PRRs) on epithelial and alveolar macrophage cells, the released pathogen-associated molecular patterns (PAMPs) trigger a massive local inflammatory process and stimulate increased secretion of pro-inflammatory cytokines and chemokines IL-6, IFN-γ, MCP1, and IL-10 [7, 8].

Extensive cytopathic effects, cytokine imbalance, and inflammatory cell infiltration at the level of local mucosal immunity can lead to acute damage to cellular structures due to excessive secretion of proteases and reactive oxygen intermediates in addition to direct damage caused by the virus. Also, some aspects of SARS-CoV-2 effect on the mucosal immunity parameters may be associated with COVID-19 treatment, e.g., the use of antibacterial and immunosuppressive drugs.

The state of mucosal immunity after COVID-19 is of particular importance due to the fact that the antigen load during the activation of viral and bacterial pathogens and the vast majority of immune responses occur in barrier tissues [9, 12], and in particular, in the system of mucosa-associated lymphoid tissue (MALT). It has been proved that there is a single basis for the functioning of upper and lower respiratory tracts and the mucosal immunity system in general.

The study of cyto-immunological and inflammatory shifts at the local level—in nasal secretions and induced sputum—can be considered promising both in theory and practice. Cytological characteristics and the interleukin status will make it possible to correctly estimate the need for immunorehabilitation measures after COVID-19.

Despite the fact that literature contains enough information on changes in the systemic immune status of patients recovered from the novel coronavirus infection COVID-19, the state of mucosal immunity remains understudied.


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