Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

Abstract

After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.

The Nucleocapsid protein triggers the main humoral immune response in COVID-19 patients

“…One explanation could be that the adaptive immune response of these patients was still early and IgG titers were still very low. Alternatively, innate immunity could have played a role in defense against the SARS-CoV-2 infection in these patients [ 16 , 17 ]. In addition, a few control patients displayed an IgG response to the SARS-CoV-2 N proteins, suggesting that there might be some reactivity with other coronaviruses.…”

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

“…Simply reviewing what is known of the immunological function of the top two over- and top two under-expressed genes ranked by Hedges' g ES contextualizes ACO1 and ATL3 further with hints of a battle of host versus “novel” pathogen, never encountered by the immune system before. The impact on the function of host immune cells during SARS-CoV-1 and MERS infection is driven by their non-structural proteins and affects the normal production of cytokines compared to that of currently circulating viral infections, such as the repression of interferon proteins/ interferons (IFNs) ( Hu et al., 2012 ; Shah et al., 2020 ). Recently, Blanco-Melo et al.…”

T‐cell responses and therapies against SARS‐CoV‐2 infection

“…21 SARS-CoV-2 infects ACE2-expressing cells in the lungs such as type 2 alveolar cells, leading to the dampening of antiviral IFN responses, while the infiltration of adaptive immune cells in the lungs can lead to heightened inflammatory responses resulting in pulmonary oedema. 22 Innate immune responses against SARS-CoV-2 are initially prompted by lung epithelial cells, alveolar macrophages and neutrophils, which then trigger adaptive immune responses involving T and B lymphocytes. 16 Ex vivo models showed that SARS-CoV-2-infected pneumocytes and alveolar macrophages prompted the release of proinflammatory cytokines and antiviral IFN (type I and III) at low levels.…”