The new pandemic virus SARS-CoV-2 emerged in China and spread around the world in <3 months, infecting millions of people, and causing countries to shut down public life and businesses. Nearly all nations were unprepared for this pandemic with healthcare systems stretched to their limits due to the lack of an effective vaccine and treatment. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19). COVID-19 is respiratory disease that can result in a cytokine storm with stark differences in morbidity and mortality between younger and older patient populations. Details regarding mechanisms of viral entry via the respiratory system and immune system correlates of protection or pathogenesis have not been fully elucidated. Here, we provide an overview of the innate immune responses in the lung to the coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2. This review provides insight into key innate immune mechanisms that will aid in the development of therapeutics and preventive vaccines for SARS-CoV-2 infection.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS□CoV□ 2) is a highly pathogenic corona virus which causes COVID-19 and resulted in millions of deaths and led to a global public health emergency. An effective and appropriate immune response is essential to control and eliminate viral infections, however, dysregulated immune responses may lead to immunopathology in viral infections. Clinical data showed that COVID-19 may promote the development of cardiovascular disorders (CVDs). However, exact mechanism associated with CVDs in COVID-19 patients is currently unknown. Monocytes are one of the major immune cell subsets that contribute to host defense against many infections but also associated with immunopathology and development of CVDs. Thus, in this study we investigated the role of monocyte subsets in COVID-19 associated CVDs. By using high dimensional flowcytometry, immune biomarker assays and multi variant data analysis in healthy donors (n=17), severe-COVID-19 patients (n=20) (ICU) and COVID-19 recovered individuals (n=30), we found elevated intermediate monocytes and Monocyte chemoattractant protein-1, one of the most important chemokines that regulates migration and infiltration of monocytes to the subendothelial space, where they may become foam cells. Spearman correlation network analysis showed that strong correlation between increase intermediate monocytes in the whole blood and plasma cardimetabolic biomarkers such as fatty acid binding protein 4, C-reactive protein, soluble CD14 and LPS binding protein in ICU patients. Our data show for the first time that the possible role of monocytes in the development of CVDs in ICU patients.

Covid-19, the disease caused by SARS-CoV-2 infection, has resulted in millions of deaths and led to a global public health emergency. SARS-CoV-2 infected patients exhibit a wide variety of phasic clinical manifestations ranging from asymptomatic to severe complications and death. SARS-CoV-2 infection can lead to excessive immune activation, inflammation and multi-organ damage. Clinical data showed that COVID-19 may promote the development of cardiovascular disorders (CVDs). Immune activation, thrombosis, cytokine storm, and altered adhesion molecule expression on leukocyte populations have been proposed as possible mechanisms that trigger COVID-19 associated CVDs. A lack of systematic studies on how SARS-CoV-2 infection triggered immune responses that may lead to CVDs, hinder early risk identification and therapeutic interventions. In this study, by using deep immune profiling and extensive cytokine and chemokine profiling, we explore potential mechanisms of developing CVDs in severe COVID-19 patients (ICU) (n=20) as well as patients recovered from COVID-19 (RD) (n=30). We identify core immune signatures in ICU patients and RD compared to healthy controls (n=17) that may predict potential cardiovascular risk. We found that significantly elevated eosinophils and neutrophils and increased circulating levels of tissue factor, fatty acid binding protein 4 and, LPS binding protein in ICU patients suggested increased immune activation and thrombotic risk. Interestingly, we found significant elevation of several immune parameters (TIMP-1, TIMP-2, Monocytes) that were associated with cardiometabolic risk, in RD group. Thus, our data suggest a possible mechanistic link between severe COVID-19 and cardiometabolic risk.

COVID-19, the disease caused by SARS-CoV-2, has led to a global public health emergency. Severity of disease course may be related to a dysregulated immune response and pre-existing health conditions. Recent studies have demonstrated that SARS-CoV-2 infection may directly or indirectly lead to an increase in cardiometabolic complications in patients with pre-existing type-2 diabetes mellites (T2DM) when compare to non-DM patients. A lack of mechanistic and systematic studies on how SARS-CoV-2 infection related immune responses may contribute to increase risk of cardiometabolic complications in pre-existing T2DM patients, hinder early risk identification and therapeutic interventions. Thus, in this study we investigate the biomarkers of cardiometabolic risk in non-DM and T2DM, severe COVID-19 patients admitted to the Intensive care unit. Using high-dimensional flowcytometry and immune biomarker assays, we investigated functional and phenotypic changes in immune subsets in whole blood and plasma biomarkers of cardiovascular disease in healthy donors (n=17), T2DM severe-COVID-19 patients (n=10), non-diabetic severe-COVID-19 patients (n=10) admitted to the OSU medical center's intensive care unit. We found neutrophils and Intermediate monocytes (ITM) were significantly higher in the T2DM group compared to non T2DM patients. However, activated (HLA-DR+) NKT-like cells and NKG2A+ CD56 Dim CD16+ NK cells, were significantly lower in the T2DM-COVID-19+ group. Interestingly, LBP, FABP4, sCD14, IL-1b, RANTES and MIP-1a were significantly higher in the COVID-19 T2DM patients. In this study, we identify core immune signatures that may predict increased cardiovascular disease risk in T2DM patients who had severe COVID-19. Supported by PI's startup funding