Ability of the immune system to fight viruses highlighted by cytometry and TCR clonotype assessments: lessons taken prior to COVID-19 virus pandemic outbreak.

Jaskula, Emilia; Lange, Andrzej

The intriguing aspects of SARS-CoV-2 virus are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to build quickly the rationale behind the treatment, taking advantage from past analogues. When a new virus strikes, T-cell receptor (TCR) gamma/delta cells are in the first line of defence, activated by stress molecules and recognising some epitopes in a process that is major histocompatibility complex (MHC) independent but still specific, e.g. cytomegalovirus (CMV), as well as participating in the regulatory mechanism - both characteristics are useful in fighting SARS-CoV-2. The fatalities are mostly due to pneumonitis, in the course of which an overwhelming inflammatory process impairs blood oxygenation, calling for artificial ventilation. In fatal COVID-19 cases the balance between the immune response and the inflammatory outcome fails, due to which the patients at risk, mostly aged, have higher levels of anti-SARS-CoV-2 antibodies and an enhanced inflammatory process in the lung. Apparently there is no feedback control over the antibody production. The investigational use of convalescent plasma, providing antibodies taken from patients who have recovered, was shown to be effective, likely through exerting idiotype associated negative control of antibody production. Similarly, the use of mesenchymal stem cells (MSC) may assist the body regulatory mechanisms, knowing the anti-inflammatory potential of these cells. The use of these two immunotherapeutic tools is understandable on the grounds of basic immunology, whose knowledge may direct the medical community in efforts to fight the virus.