Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

Favipiravir for the treatment of coronavirus disease 2019 pneumonia; a propensity score-matched cohort study.

We retrospectively investigated the clinical outcomes of favipiravir in patients with COVID-19 pneumonia. Patients who between 23 May 2020 and 18 July 2020 received ≥ 24 h of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. The unmatched cohort included 1493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline. Significant baseline differences between the two unmatched groups existed, but not between the PS-matched groups (N = 774). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P < 0.001). Adverse events were common in both groups, but the 93.9% were Grades 1-3. Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.

Dilemma of Tocilizumab therapy for a patient with critical COVID-19 disease and neutropenia: Case report and review of the literature.

Infection following SARS-Co V-2 leading to COVID-19 disease is associated with significant morbidity and mortality. The clinical entity, COVID-19 cytokine storm syndrome (CSS) is a severe immunological manifestation of the disease associated with ominous consequences. Tocilizumab is interleukin-6 inhibitors that has been shown to hamper the catastrophic outcomes of CCS including the need for mechanical ventilation as well as reduce mortality, but the usage is limited by warnings of reactivation of potential latent infections or immune dysfunctions including severe neutropenia. We describe a case of 39-year-old Nepalese male patient with a background of scleritis maintained on azathioprine and rituximab therapy with normal baseline parameters including complete blood count who presented with acute COVID-19 infection including associated leukopenia as well as severe neutropenia (absolute neutrophil count of 300 cells/µl), then progressed to critical disease culminating into CSS. Based on risks and benefits evaluation, the patient was treated with tocilizumab reinforced with granulocytes-colony stimulating factor (G-CSF, Filgrastim) to full recovery and safe outcome including reversal of neutropenia.

Remdesivir for COVID-19 pneumonia in patients with severe chronic kidney disease: A Case series and review of the literature.

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.

Remdesivir therapy causing bradycardia in COVID-19 patients: Two case reports.

The coronavirus disease 2019 (COVID-19) pandemic has been an enormous public health challenge. The pursuit for an effective therapy led to the use of the antiviral drug Remdesivir for hospitalized patients with severe COVID-19 pneumonia. We reported two cases of patients with severe COVID-19 pneumonia and worsening oxygen requirements. Both patients developed sinus bradycardia following the initiation of Remdesivir therapy and reverted after stopping it. One of the patients developed QTc interval prolongation and required intensive care unit admission. The proposed mechanism for Remdesivir-induced bradycardia and cardiac toxicity could be due to the intrinsic electrophysiological properties and the effect on the AV node; yet, further large observational studies are warranted for better understanding and correlation of Remdesivir with cardiac adverse events. Till then, healthcare providers need to be alert of this potential adverse event and to monitor their COVID-19 patients closely while on Remdesivir therapy.

Psychological impact of the COVID-19 pandemic within institutional quarantine and isolation centres and its sociodemographic correlates in Qatar: a cross-sectional study.

SETTING: The State of Qatar has had one of the highest COVID-19 infection rates globally and has used state-managed quarantine and isolation centres to limit the spread of infection. Quarantine and isolation have been shown to negatively affect the mental health of individuals. Qatar has a unique population, with around 90% of the population being economic migrants and a majority being blue-collar workers and labourers. OBJECTIVES: This study was carried out to evaluate the psychological impact of institutional isolation and quarantine during the COVID-19 pandemic outbreak in Qatar. The study also explored the sociodemographic correlates of this psychological impact. DESIGN, PARTICIPANTS AND INTERVENTION: A cross-sectional study involving 748 consenting individuals in institutional quarantine and isolation in Qatar during the months of June and July 2020 was carried out. Relevant sociodemographic data along with depressive and anxiety symptomatology scores were collected from consenting adults at these facilities. RESULTS: 37.4% (n=270) of respondents reported depressive symptoms and 25.9% (n=189) reported anxiety symptoms. The scores were higher for individuals in isolation facilities and higher for migrants from poor socioeconomic group (p<0.001 for both). Within this group, although worries about infection were widely reported, lack of contact with the family was cited as one of the most important sources of distress. Respondents reported that contact with the family and reliable information were important factors that helped during the duration of isolation and quarantine. CONCLUSIONS: Our study reported significantly elevated scores for depression and anxiety during institutional quarantine, which is in keeping with emerging evidence. However, in contrast to other studies reporting mostly from native populations, this study of a population with an overwhelming majority of immigrants highlights the special mental health needs of this specific group and can inform future healthcare policies.

SARS-CoV-2 infection presenting as colitis with chest and abdomen CT findings.

Most of reported symptoms of SARS-CoV-2 infection are related to the respiratory system. Extra pulmonary manifestations of this novel virus infection are being increasingly reported in the literature, with increased attention on the gastrointestinal symptoms which might be the only presenting symptoms in some patients. These GI symptoms are nonspecific and little reported cases in the literature of confirmed gastrointestinal manifestations of SARS-CoV-2 infection by imaging. Colitis related to SARS-CoV-2 is even less reported in the literature. We present a case of SARS-CoV-2 infection of a 40-year-old lady who presented with GI manifestations and features of colitis of the caecum and ascending colon on CT scan. The patient did not have respiratory symptoms but had incidental lung changes in the visualized lung bases. These features were completely resolved as evident clinically and on follow-up CT scan after only 2 weeks, with only supportive care for SARS-CoV-2 infection. GI symptoms, in general, are very common presenting complain for many patients visiting the emergency department; hence, early recognition and high index of clinical suspicion for SARS-CoV-2 infection with the presence of supporting laboratory and imaging findings are to be considered for early protective measures to be undertaken to help in reducing the spread of this virus; in particular, in the middle of global pandemic of this virus and the fact that GI symptoms could be the only presenting symptoms without any respiratory symptoms. More studies and further invasive investigations in patients with features of colitis in imaging are needed to further understand the pathogenesis and its relation to SARS-CoV-2 infection.