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Findings on the efforts and efficacy of vaccines118 and convalescent plasma108, 109 can be found elsewhere, as we will focus here on current, and potential immunotherapeutic approaches to treating COVID-19

Findings on the efforts and efficacy of vaccines118 and convalescent plasma108, 109 can be found elsewhere, as we will focus here on current, and potential immunotherapeutic approaches to treating COVID-19. One of the oldest, and most frequently used anti-inflammatory treatment, corticosteroids, have and are currently being tested in COVID-19 patients. and SARS-CoV-induced pro-inflammatory cytokine responses revealed that MERS-CoV-induced primarily IL-6 and IL-8 compared to SARS-CoV, while SARS-CoV infection resulted in higher TNF and IP-10 levels (Table 1),23,25 suggesting a differential innate immune response between these two viruses. The differential cytokine and chemokine profile of MERS-CoV and SARS-CoV was also confirmed by another study, where MERS-CoV infection of human monocyte-derived macrophages induced higher expression levels of Th1 cytokines and chemokines: IL-12, IFN, IL-8, MCP-1, and RANTES, compared to SARS-CoV.24 C: SARS-CoV-2 The increased morbidity and mortality in SARS-CoV-2-infected patients has been associated with increased pro-inflammatory responses, including cytokine storm.40C42 The innate immune response to SARS-CoV-2 is not fully understood, but recent findings, from small cohorts of primarily male, middle-aged patients, indicate increased total numbers of neutrophils and monocytes in the lungs of infected patients, and high serum levels of the inflammatory cytokines: IL-6, TNF, IL-10, IL-17, and G-CSF, chemokines: CXCL10 (IP-10), CCL2 (MCP-1), and CCL3 (MIP-1), soluble form of the alpha-chain Nitrarine 2HCl of the IL-2 receptor, ferritin, and c-reactive protein.43C48 Such a pro-inflammatory signature indicates a systemic, exaggerated, pathological, innate immune response. Although many immune and non-immune cells could contribute to the production of these pro-inflammatory factors, recent studies identified a population of IL-6+, IL-10+, and TNF+ monocytes (CD14+, CD16+, CD11b+, CD68+, CD80+, CD163+, CD206+) in peripheral blood of a small cohort of COVID-19 patients requiring prolonged hospitalization and ICU admission, compared to COVID-19 patients who did not need ICU hospitalization (Table 2).52 While the authors describe these cells as monocytes, their size and pattern of marker expression actually suggests they may be one of Mouse monoclonal to ERK3 the rare subsets of inflammatory DCs (possibly DC3s), which should certainly be further investigated.61 Increased levels of mRNA transcripts for the CCL2 and CCL7 chemokines have also been detected in bronchoalveolar lavage (BAL) fluid of a small cohort of eight severe COVID-19 patients.62 These findings were also confirmed in a separate study of nine, primarily male, middle-aged COVID-19 patients utilizing single-cell RNA sequencing (scRNA-seq) of BAL from Nitrarine 2HCl severe COVID-19 patients.53 Since these two chemokines function as a potent attractant of CCR2+ inflammatory monocytes, neutralizing CCL2 and CCL7 chemokines might be beneficial to prevent monocyte recruitment and their associated pro-inflammatory responses. Also, RNA-seq analysis of peripheral blood mononuclear cells (PBMCs) of ten recovered Nitrarine 2HCl COVID-19 patients demonstrated increased ratio of CD14+ classical monocytes that have a heightened pro-inflammatory gene expression profile, and IL-1 transcripts in particular, suggesting a potential contribution of the inflammasome to COVID-19.54 However, IL-1 protein levels have been found not to be elevated in COVID-19 patients arguing against a true inflammasome response, Nitrarine 2HCl although it remains possible that only subsets of patients have an induced inflammasome response.63 The heightened pro-inflammatory responses observed in COVID-19 patients were associated with a global T cell lymphopenia, a phenomenon that was more pronounced in the CD8+ T cell subset (Table 2).64 In particular, the presence of IL-6 producing monocytes was positively associated with depletion of T lymphocytes from the spleen and lymph nodes of severe COVID-19 patients.65 Table 2. Immune cell subset changes during SARS-CoV-2 infection studies of B cells from patients.32,101 It appears that many of the most potent neutralizing antibodies target the receptor binding domain (RBD) of the SARS-CoV-2 virus, which prevents interaction with the cellular receptor, ACE2.32,101 Studies on SARS-CoV have shown the humoral response against this virus is capable of generating potently neutralizing antibodies able to provide protection even 24?months post-infection (Table 1).107 This holds promise for both the idea that re-infection will not occur and that convalescent plasma can lead Nitrarine 2HCl to efficacious responses in those with severe COVID-19. It also suggests that a vaccine capable of inducing neutralizing antibodies should provide safety against SARS-CoV-2. It should be noted though that there is some evidence (from a study involving only eight individuals) that antibodies.