COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs

Abstract

IntroductionCoronaviruses (CoVs), mainly targeting human respiratory system, are responsible for health-threatening outbreaks including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and lastly coronavirus disease 2019 (COVID-19) [1]. In December 2019, in the Chinese Province of Wuhan the novel coronavirus has been identified in patients with atypical pneumonia characterized by fever, dry cough and progressive dyspnea [2]. Rapidly, this coronavirus, namely SARS-CoV-2 1 , has spread worldwide, leading to a serious lung inflammation, acute respiratory distress syndrome (ARDS), cardiac and renal injury, especially in patients with older age and comorbidities (diabetes mellitus, hypertension, and heart failure) [3][4][5]. According to disease progression, patients may be roughly divided into two groups; asymptomatic or mild cases that usually 2.The origin and structural features of SARS-CoV2CoVs belong to big family Coronaviridae which consists of two subfamilies: Orthocoronavirinae and Torovirinae.

Successful use of anakinra in a patient with COVID-19- associated pericarditis

“…Viral components and cytosolic danger signals, such as mitochondrial injury, protein aggregates, and aberrant ion concentrations can activate NLR Family Pyrin Domain Containing 3 in ammasome which in turn releases IL-1β, IL-18 and the propyroptotic factor gasdermin D [7]. In a previous study, SARS-CoV-2 has been shown to activate the NLRP3 in ammasome and induce the production of IL-18 by human macrophages by its ion channel-forming E protein and ORF8b, which are also the structural components of SARS-CoV-2 [1]. Therefore, pericarditis is an expected clinical condition in COVID-19 [9].…”

“…COVID-19 is now thought as a virus-induced immune disorder due to constellation of features observed in cytokine storm syndromes. Hypercytokinemia is considered by many to be the main driver of morbidity and mortality in COVID-19 [1]. Therefore, anti-cytokine treatments, as tocilizumab (targeting IL-6), and anakinra (targeting IL-1) pathways are being investigated for the treatment of severe COVID-19 patients [1].…”

“…Hypercytokinemia is considered by many to be the main driver of morbidity and mortality in COVID-19 [1]. Therefore, anti-cytokine treatments, as tocilizumab (targeting IL-6), and anakinra (targeting IL-1) pathways are being investigated for the treatment of severe COVID-19 patients [1]. Based on these common pathogenetic mechanisms between idiopathic pericarditis and COVD-19, we suggest that therapeutic approach in this clinical setting might be the same also for COVID-19-RP [1].…”

An in-silico based clinical insight on the effect of noticeable CD4 conserved residues of SARS-CoV-2 on the CD4-MHC-II interactions

“…Having enlightened on a diverse range of epitopes at the S1-RBD site of SARS-CoV-2 that could indulge in stable interactions with the immune cells such as T-cell, B-cell and MHC-II [47][48][49]; a noticeable adaptive immune response must have been witnessed among the SARS-CoV-2 infected groups. Contradictorily, a reduced level of CD4+T-helper cell fractions was noticed among the larger group of SARS-CoV-2 patients [9,12,45]. However, the cytotoxic CD8+T-cells levels remain fluctuated among the patient groups within which its hyperactive state might contribute to the severe respiratory ailments associated with the hyper-immune activation and cytokine storm [12,13,50].…”

“…helper cells counts on the SARS-CoV-2 patients [9][10][11][12]. It is more likely for the adaptive immune system to get disturbed mimicking the clinical conditions of the HIV-1 affected patients [12][13][14].…”