The Relationship between the Clinical Course of SARS-CoV-2 Infections and Expression of Bruton's Tyrosine Kinase.

OBJECTIVES: The Bruton tyrosine kinase (BTK), an important element for the production of several inflammatory cytokines, may play a role in the pathogenesis of COVID-19. The aim of this study was to investigate the level of BTK gene expression in COVID-19 cases based on the severity and the outcome of the disease. METHODS: In this study, 33 hospitalized patients with COVID-19 were recruited and were divided into two groups based on the severity of the disease: "mild to moderate" and "severe to critical". A blood sample was taken from each patient, peripheral blood mononuclear cells (PBMCs) were extracted, and BTK gene expression was measured. The level of BTK gene expression was compared based on the demographic data, laboratory results, and the severity and outcome of the disease. RESULTS: Among 33 patients, 22 (66.7%) were male. Nearly half of the cases had at least one underlying disease. According to the severity of the disease, 12 patients were in the "mild to moderate" group, and 21 were in the "severe to critical" group; eight (24.2%) eventually died. Age, weight, and BMI had no significant relationship with BTK expression. BTK expression was significantly lower in "severe to critical" and ICU-admitted cases and in subjects with low O2 saturation. There was no significant difference in BTK expression between cured and dead patients (p=0.117). CONCLUSION: BTK gene expression in PBMCs had an inverse relationship with the severity of the disease of COVID-19. However, no correlation between BTK expression and disease outcome was observed.

IgM-enriched immunoglobulin in COVID-19: Case series of 15 severely ill SARS-CoV-2-infected patients.

The healthcare system in Iran, like most around the world, is managing thousands of patients hospitalised with COVID-19. In Iran, in-hospital mortality is in the region of 25%, rising to 50-60% in patients admitted to intensive care. Hyperinflammation, characterised by cytokine storm, appears to be a hallmark of severe COVID-19 and to date only the anti-inflammatory drug dexamethasone has been shown to reduce mortality in those hospitalised with the disease. There is a sound scientific rationale behind the use of IgM-enriched immunoglobulin in the management of patients with severe COVID-19. It has been used successfully in the management of hyperinflammation in patients with sepsis and has led to improved radiographic scores in patients with severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Recently the successful treatment of a patient with COVID-19 with IgM-enriched immunoglobulin was reported. Here we report the outcome of a further 15 patients hospitalised with COVID-19 treated with IgM-enriched immunoglobulin. Improvements in computed tomography (CT) score were observed in nine patients, indicating that further clinical studies into the use of IgM-enriched immunoglobulin in the treatment of severe COVID-19 are warranted.

Combination therapy of IFNß1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.