Evaluation of miRNA-16-2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection.

Following the announcement of the pandemic of COVID-19 in December 2019, several studies focused on how to early predict the severity of the disease in symptomatic and asymptomatic patients. Many cytokines including interleukin-6, interleukin-8, and tumor necrotic factors have been concluded as strong indicators for COVID-19 infection. Additionally, miRNAs have been associated with dysregulation in the immune system. The aim of this study are the following: (1) to estimate the level of miRNA-16-2-3P, miRNA-618, IL-8, IL-1ß as predictors for SARS-CoV-2 complications in PCR negative and positive patients; (2) to assess the biological role and effect of these miRNAs on SARS-CoV-2 pathogenicity. Our study showed that the level of IL-1ß had been significantly associated with patient who need hospitalization, also the alteration of the level of miRNA-16-2-3P, miRNA-618 is positively correlated with the admission of these patients and influence the outcomes of SARS-cov-2 infection. Measurement of miRNA-16-2-3P, miRNA-618, IL-1ß could be a good predictor of COVID-19 patient outcome. However the measurement of IL-8 levels during immune responses in the admitted and in ICU patients could have a prognostic value.

Rapid Resolution of Post-COVID-19 Inflammatory Syndrome in an Adult With Targeted Inhibition of Interleukin-1B.

Multisystem inflammatory syndrome (MIS) is a severe inflammatory response that occurs days to weeks following the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to the Centers for Disease Control and Prevention (CDC), leading to the recognition of a new disease MIS in adults (MIS-A). The current treatment options include high-dose steroids, intravenous immunoglobulin (IVIG), and immunosuppressive therapy. However, the pharmacologic approach remains limited to case reports and pending official guidelines to treat cases with MIS-A.  We present a case of an adult patient who had a severe inflammatory state following COVID-19 infection, who was treated with IL-1 antagonist therapy with a successful outcome.

Pyroptosis and Its Role in SARS-CoV-2 Infection.

The pore-forming inflammatory cell death pathway, pyroptosis, was first described in the early 1990s and its role in health and disease has been intensively studied since. The effector molecule GSDMD is cleaved by activated caspases, mainly Caspase 1 or 11 (Caspase 4/5 in humans), downstream of inflammasome formation. In this review, we describe the molecular events related to GSDMD-mediated pore formation. Furthermore, we summarize the so far elucidated ways of SARS-CoV-2 induced NLRP3 inflammasome formation leading to pyroptosis, which strongly contributes to COVID-19 pathology. We also explore the potential of NLRP3 and GSDMD inhibitors as therapeutics to counter excessive inflammation.

Early use of canakinumab to prevent mechanical ventilation in select COVID-19 patients: A retrospective, observational analysis.

INTRODUCTION: The fully-human monoclonal anti-interleukin (IL)-1ß antibody canakinumab may inhibit the production of inflammatory mediators in patients with coronavirus disease 2019 (COVID-19) and the hyperinflammatory response potentially leading to acute respiratory distress syndrome. OBJECTIVES: The goal of our retrospective, observational analysis was to evaluate the safety and efficacy of subcutaneous (s.c.) canakinumab in combination with our standard of care (SOC) treatment of selected patients with COVID-19 with respiratory failure and elevated reactive pro-inflammatory markers. METHODS: Eight participants received two doses of s.c. canakinumab 150 mg (or 2 mg/kg for participants weighing ≤40 kg) in addition to SOC. 12 patients received only SOC treatment. RESULTS: Canakinumab treatment reduced the need for mechanical ventilation and reduced proinflammatory markers, resulting in an amelioration of the final outcome, with respect to the control group who received SOC alone. The treatment was safe and well tolerated; no adverse events were reported. CONCLUSION: The use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.

Alpha-1 antitrypsin for cystic fibrosis complicated by severe cytokinemic COVID-19.

BACKGROUND: The clinical course of severe COVID-19 in cystic fibrosis (CF) is incompletely understood. We describe the use of alpha-1 antitrypsin (AAT) as a salvage therapy in a critically unwell patient with CF (PWCF) who developed COVID-19 while awaiting lung transplantation. METHODS: IV AAT was administered at 120 mg/kg/week for 4 consecutive weeks. Levels of interleukin (IL)-1ß, IL-6, IL-8, and soluble TNF receptor 1 (sTNFR1) were assessed at regular intervals in plasma, with IL-1ß, IL-6, IL-8 and neutrophil elastase (NE) activity measured in airway secretions. Levels were compared to baseline and historic severe exacerbation measurements. RESULTS: Systemic and airway inflammatory markers were increased compared to both prior exacerbation and baseline levels, in particular IL-6, IL-1ß and NE activity. Following each AAT dose, rapid decreases in each inflammatory parameter were observed. These were matched by marked clinical and radiographic improvement. CONCLUSIONS: The results support further investigation of AAT as a COVID-19 therapeutic, and re-exploration of its use in CF.

Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor.

NLRP3 inflammasome mediated release of interleukin-1ß (IL-1ß) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent (IL-1ß IC50 = 35 nM; IL-18 IC50 = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.

BCG vaccination strategy implemented to reduce the impact of COVID-19: Hype or Hope?

The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a adaptive immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.

Cytokine prediction of mortality in COVID19 patients.

Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1ß (IL1ß), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7-39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.