Mohamad Khatib

Despite its pivotal role in drug metabolism, the exact consequences of rising medica-tions count from various therapeutic drug classes on mortality outcomes amongst patients with chronic liver disease remains unexplored. In this study, we investigated the effect of different polypharmacy phenotypes on clinical outcomes including the length of hospitalization, the need for intensive care admission, and mortality in patients with chronic liver disease (CLD). Methods: This retrospective cohort study examined the impact of various polypharmacy phenotypes on clinical outcomes of patients receiving care at tertiary care centres within the Weill Cornell Medi-cine-affiliated Hamad Medical Corporation, Doha Qatar diagnosed with CLD be-tween October 2018 to August 2021. Primary outcomes include all-cause mortality, length of hospitalization, and need for intensive care unit admission. Multivariable regression models were used to assess the associations between the number of liv-er-related and non-liver-related polypharmacy and these clinical outcomes. Results: In this retrospective cohort study, 3331 participants with a median age of 50 years (interquartile range [IQR] 40–63) were included, of which 71.0% (n = 2 366) were males. The total duration of follow-up for the whole cohort was 42 772.6 per-son-days. The median length of stay (LOS) was 5.0 (0.5, 13.6) days, with 762 (22.9%) deaths among those hospitalized. About 46.2% of the study participants were on guideline-directed therapy CLD drugs. Patients with polypharmacy inclusive of liver-related drugs had a higher survival over time compared to the group without polypharmacy (log-rank p< 0.001). Each additional CLD drug is associated with a 51% reduction in mortality risk (hazard ratio [HR] 0.49, 95% CI 0.38–0.62). Conclusion: In a hospitalized cohort of patients with CLD, polypharmacy comprising of medications specific for CLD or its complications was associated with reduced all-cause mortality. However, the role of non-liver-related medications in this context remains unclear, and it is uncertain how the primary cause of liver disease could have potentially impacted these outcomes. Further studies exploring these factors are needed to better inform clinical decision-making regarding polypharmacy management in this patient population

There were increased claims of thrombotic events in ICU-bound patients with COVID-19. We designed this observational study to examine implementation of systemic anti-coagulation on arterial cathete...

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.

Background: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established. Methods: We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis. Results: Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98–6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group. Conclusion: IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1–6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

We report a case of fulminant liver failure in a patient with acute active hepatitis B infection who was found to have COVID-19 without lung involvement. A 24-year-old male was brought by ambulance service to Hamad General Hospital, Emergency Department (ED), in Doha on April 8, 2020, with chief complaints of fever and cough for 3 days. Upon initial evaluation, the patient was febrile (39.4°C), jaundiced, and disoriented regarding time, place, and person, with an unremarkable past medical history. Initial blood tests showed severely elevated urea, creatinine, transaminases, and ammonium in addition to an impaired coagulation profile consistent with fulminant liver failure. A swab was taken for COVID-19 PCR testing and found to be positive. Serological tests revealed hepatitis B surface antigen positivity and other serology indicating acute hepatitis B. Initial X-ray and repeat chest X-rays did not show lung infiltrates. On the 6^th day after admission, the patient developed fixed dilated pupils, with brain edema on CT; cardiac arrest occurred on the 10^th day after admission, and the patient died. Although it is still largely unclear, HBV0-activated sudden-onset strong cytotoxic T lymphocyte response and enhanced viral replication and/or retention of the viral capsid in infected hepatocytes may cause the pathogenesis of FH. These pathophysiological events cause extensive hepatocyte apoptosis and necrosis, which results in deadly severe liver failure. Our findings support that the liver damage occurring in COVID-19 is caused by an impaired innate immune system rather than by direct cell damage caused by SARS-CoV-2. We think that more consideration should be given to the presence of acute hepatitis B, especially in COVID-19 patients.

Our work highlights patients at risk of prolonged viral shedding in COVID‐19 and its implications for isolation strategies and explores possible solution by PCR‐CT value testing (cycle threshold value). We also review the impact of HIV on COVID‐19.