Immune Response Gaps Linked to SARS-CoV-2 Infection: Cellular Exhaustion, Senescence, or Both?

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 13734
• Main Authors: Barbosa, Leonardo Vinicius, Prá, Daniele Margarita Marani, Nagashima, Seigo, Pereira, Marcos Roberto Curcio, Stocco, Rebecca Benicio, da Silva, Francys de Luca Fernandes, Cruz, Milena Rueda, Dallagassa, Djessyka, Stupak, Thiago João, da Rosa Götz, George Willian Xavier, Nasimoto, Georgia Garofani, Cracco, Luiz Augusto Fanhani, Silva, Isabela Busto, de Moura, Karen Fernandes, Deus, Marina de Castro, Martins, Ana Paula Camargo, Spitzenbergen, Beatriz Akemi Kondo Van, Amaral, Andréa Novais Moreno, de Paula, Caroline Busatta Vaz, Machado-Souza, Cleber, de Noronha, Lucia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-11-2022; MDPI
• Subjects: Arginase; CD20 antigen; CD3 antigen; CD4 antigen; CD57 antigen; CD8; CD8 antigen; cellular exhaustion; Coronaviruses; COVID-19; Cytokines; Humans; Immune clearance; Immune response; Immune response (cell-mediated); Immune system; Immunity, Cellular; inflammation; Influenza A Virus, H1N1 Subtype; Interleukin 4; Lungs; Morbidity; Natural killer cells; Nitric-oxide synthase; Pandemics; Paraffins; pathogenesis; PD-1 protein; Perforin; SARS-CoV-2; Senescence; Severe acute respiratory syndrome coronavirus 2; Sphingosine; Viral infections; Viruses; senescence; pathogenesis; SARS-CoV-2; perforin; inflammation; CD8; cellular exhaustion
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232213734

The COVID-19 pandemic, promoted by the SARS-CoV-2 respiratory virus, has resulted in widespread global morbidity and mortality. The immune response against this pathogen has shown a thin line between protective effects and pathological reactions resulting from the massive release of cytokines and poor viral clearance. The latter is possibly caused by exhaustion, senescence, or both of TCD8+ cells and reduced activity of natural killer (NK) cells. The imbalance between innate and adaptive responses during the early stages of infection caused by SARS-CoV-2 contributes to the ineffective control of viral spread. The present study evaluated the tissue immunoexpression of the tissue biomarkers (Arginase-1, CCR4, CD3, CD4, CD8, CD20, CD57, CD68, CD138, IL-4, INF-α, INF-γ, iNOS, PD-1, Perforin and Sphingosine-1) to understand the cellular immune response triggered in patients who died of COVID-19. We evaluated twenty-four paraffin-embedded lung tissue samples from patients who died of COVID-19 (COVID-19 group) and compared them with ten lung tissue samples from patients who died of H1N1pdm09 (H1N1 group) with the immunohistochemical markers mentioned above. In addition, polymorphisms in the Perforin gene were genotyped through Real-Time PCR. Significantly increased tissue immunoexpression of Arginase, CD4, CD68, CD138, Perforin, Sphingosine-1, and IL-4 markers were observed in the COVID-19 group. A significantly lower immunoexpression of CD8 and CD57 was also found in this group. It is suggested that patients who died from COVID-19 had a poor cellular response concerning viral clearance and adaptive response going through tissue repair.