ABSTRACT
SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Azetidines/administration & dosage , COVID-19 Drug Treatment , COVID-19/immunology , Macaca mulatta , Neutrophil Infiltration/drug effects , Purines/administration & dosage , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Animals , COVID-19/physiopathology , Cell Death/drug effects , Cell Degranulation/drug effects , Disease Models, Animal , Inflammation/drug therapy , Inflammation/genetics , Inflammation/immunology , Janus Kinases/antagonists & inhibitors , Lung/drug effects , Lung/immunology , Lung/pathology , Lymphocyte Activation/drug effects , Macrophages, Alveolar/immunology , SARS-CoV-2/physiology , Severity of Illness Index , T-Lymphocytes/immunology , Virus Replication/drug effectsABSTRACT
Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.
ABSTRACT
OBJECTIVE. Coronavirus disease (COVID-19) is a global pandemic. Studies in the radiology literature have suggested that CT might be sufficiently sensitive and specific in diagnosing COVID-19 when used in lieu of a reverse transcription-polymerase chain reaction test; however, this suggestion runs counter to current society guidelines. The purpose of this article is to critically review some of the most frequently cited studies on the use of CT for detecting COVID-19. CONCLUSION. To date, the radiology literature on COVID-19 has consisted of limited retrospective studies that do not substantiate the use of CT as a diagnostic test for COVID-19.