Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs

Abstract

The severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2), termed COVID-19, has been highlighted as the most important infectious disease of our time, without a vaccine and treatment available until this moment, with a big impact on health systems worldwide, and with high mortality rates associated with respiratory viral disease. The medical and scientific communities have also been confronted by an urgent need to better understand the mechanism of host-virus interaction aimed at developing therapies and vaccines. Since this viral disease can trigger a strong innate immune response, causing severe damage to the pulmonary tract, immunotherapies have also been explored as a means to verify the immunomodulatory effect and improve clinical outcomes, whilst the comprehensive COVID-19 immunology still remains under investigation. In this review, both cellular and molecular immunopathology as well as hemostatic disorders induced by SARS-CoV-2 are summarized. The immunotherapeutic approaches based on the most recent clinical and nonclinical studies, emphasizing their effects for the treatment of COVID-19, are also addressed. The information presented elucidates helpful insights aiming at filling the knowledge gaps around promising immunotherapies that attempt to control the dysfunction of host factors during the course of this infectious viral disease.

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2

“…Despite the promising viral neutralisation profiles of vaccinated individuals with the Pfizer/BioNTech vaccines in our cohort, a recent sero-epidemiological study showed that reinfection among patients previously infected by SARS-CoV-2 occurs at a lower rate (0.23%) than infection occurrence within previously vaccinated patients (5.1%) [38]. These findings are inconsistent with the outcomes obtained by the seroneutralisation tests, but viral neutralisation tests consist of in vitro approaches that may not reflect the effect of cellular immunity within the human body [39,40], as this technique is based exclusively on antibody-antigen interactions. A study published in May 2020 reported that during a COVID-19 infection, the SARS-CoV-2 spike (S) protein was found to be a nondominant target of the human CD8+ T cell response and that the recognition of the SARS-CoV-2 M (Matrix) antigen was similarly strong to the S antigen, which is unlike other coronaviruses [41].…”

High individual heterogeneity of neutralizing activities against the original 4 strain and 9 different variants of SARS-CoV-2

“…Despite the promising viral neutralization profiles of vaccinated individuals with the Pfizer/BioNTech vaccines in our cohort, a recent sero-epidemiological study showed that reinfection among patients previously infected by SARS-CoV-2 occurs at a lower rate (0.23%) than infection occurrence within previously vaccinated patients (5.1%) [38]. These findings are inconsistent with the outcomes obtained by the seroneutralization tests, but viral neutralization tests consist of in vitro approaches that may not reflect the effect of cellular immunity within the human body [39,40], as this technique is based exclusively on antibody-antigen interactions. A study published in May 2020 reported that during a COVID-19 infection, the SARS-CoV-2 spike (S) protein was found to be a nondominant target of the human CD8+ T cell response and that the recognition of the SARS-CoV-2 M (Matrix) antigen was similarly strong to the S antigen, which is unlike other coronaviruses [41].…”

Two-Step In Vitro Model to Evaluate the Cellular Immune Response to SARS-CoV-2

“…Several studies have already demonstrated that the new coronavirus (SARS-CoV-2) is able to infect not only cells in the respiratory tract, but other organs, such as blood [ 30 , 31 , 32 , 33 ]. Our findings showed that peripheral blood mononuclear cells, such as B and T lymphocytes, monocytes, and natural killer cells, can be infected by SARS-CoV-2.…”