Adaptive immune cells are necessary for SARS-CoV-2-induced pathology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic associated with morbidity and mortality in humans. Although disease severity correlates with immune dysregulation, the cellular mechanisms of inflammation and pathogenesis of COVID-19 remain relatively poorly understood. Here, we used mouse-adapted SARS-CoV-2 strain MA10 to investigate the role of adaptive immune cells in disease. We found that while infected wild-type mice lost ~10% weight by 3 to 4 days postinfection, rag-/- mice lacking B and T lymphocytes did not lose weight. Infected lungs at peak weight loss revealed lower pathology scores, fewer neutrophils, and lower interleukin-6 and tumor necrosis factor-α in rag-/- mice. Mice lacking αß T cells also had less severe weight loss, but adoptive transfer of T and B cells into rag-/- mice did not significantly change the response. Collectively, these findings suggest that while adaptive immune cells are important for clearing SARS-CoV-2 infection, this comes at the expense of increased inflammation and pathology.

Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating and inhibitory stimuli, regulators, and molecular targets. Impaired hydroxylase activity contributes to the activation of HIFs. Inflammatory ligands activate NF-κB activity, which leads to the expression of inflammatory and anti-apoptotic genes. The eventual sequelae of the interaction between these two molecular players in immune cells, either bolstering or abrogating functions, is largely cell-type dependent. Importantly, this holds promise for interesting therapeutic interventions against several infectious diseases, as some HIF agonists have helped prevent immune-related diseases. Hypoxia and inflammation are common features of infectious diseases. Here, we highlighted the role of this crosstalk in the light of functional immunity against infection and inflammation, with special focus on various innate and adaptive immune cells. Particularly, we discussed the bidirectional effects of this crosstalk in the regulation of immune responses by monocytes/macrophages, dendritic cells, neutrophils, B cells, and T cells. We believe an advanced understanding of the interplay between HIFs and NF-kB could reveal novel therapeutic targets for various infectious diseases with limited treatment options.

A retrospective cross-national examination of COVID-19 outbreak in 175 countries: a multiscale geographically weighted regression analysis (January 11-June 28, 2020).

OBJECTIVE: This study retrospectively examined the health and social determinants of the COVID-19 outbreak in 175 countries from a spatial epidemiological approach. METHODS: We used spatial analysis to examine the cross-national determinants of confirmed cases of COVID-19 based on the World Health Organization official COVID-19 data and the World Bank Indicators of Interest to the COVID-19 outbreak. All models controlled for COVID-19 government measures. RESULTS: The percentage of the population age between 15-64 years (Age15-64), percentage smokers (SmokTot.), and out-of-pocket expenditure (OOPExp) significantly explained global variation in the current COVID-19 outbreak in 175 countries. The percentage population age group 15-64 and out of pocket expenditure were positively associated with COVID-19. Conversely, the percentage of the total population who smoke was inversely associated with COVID-19 at the global level. CONCLUSIONS: This study is timely and could serve as a potential geospatial guide to developing public health and epidemiological surveillance programs for the outbreak in multiple countries. Removal of catastrophic medical expenditure, smoking cessation, and observing public health guidelines will not only reduce illness related to COVID-19 but also prevent unecessary deaths.