The determination of causality of drug induced liver injury in patients with COVID-19 clinical syndrome.

BACKGROUND: Drug induced liver injury (DILI) is a rising morbidity amongst patients with COVID-19 clinical syndrome. The updated RUCAM causality assessment scale is validated for use in the general population, but its utility for causality determination in cohorts of patients with COVID-19 and DILI remains uncertain. METHODS: This retrospective study was comprised of COVID-19 patients presenting with suspected DILI to the emergency department of Weill Cornell medicine-affiliated Hamad General Hospital, Doha, Qatar. All cases that met the inclusion criteria were comparatively adjudicated by two independent rating pairs (2 clinical pharmacist and 2 physicians) utilizing the updated RUCAM scale to assess the likelihood of DILI. RESULTS: A total of 72 patients (mean age 48.96 (SD ± 10.21) years) were examined for the determination of DILI causality. The majority had probability likelihood of "possible" or "probable" by the updated RUCAM scale. Azithromycin was the most commonly reported drug as a cause of DILI. The median R-ratio was 4.74 which correspond to a mixed liver injury phenotype. The overall Krippendorf's kappa was 0.52; with an intraclass correlation coefficient (ICC) of 0.79 (IQR 0.72-0.85). The proportion of exact pairwise agreement and disagreement between the rating pairs were 64.4%, kappa 0.269 (ICC 0.28 [0.18, 0.40]) and kappa 0.45 (ICC 0.43 [0.29-0.57]), respectively. CONCLUSION: In a cohort of patients with COVID-19 clinical syndrome, we found the updated RUCAM scale to be useful in establishing "possible" or "probable" DILI likelihood as evident by the respective kappa values; this results if validated by larger sample sized studies will extend the clinical application of this universal tool for adjudication of DILI.

Rhino-orbital Mucormycosis as a complication of severe COVID-19 pneumonia.

Mucormycosis has multiple clinical phenotypes, which are more common in immunocompromised patients, especially those with diabetes mellitus. Debilitating rhino-orbital-cerebral and pulmonary infections by far represent the most typical clinical phenotypes associated with these fungi. Mucormycosis is an uncommon infection; however, there have been isolated sporadic tiny outbreaks around the world. With the substantial increase in COVID-19 cases in India, there is a parallel increase in the number of cases of Mucormycosis. A few reports raising unusual concomitant mucormycosis in COVID-19 patients have raised a possible association between the two diseases. We report a 59-year-old male with an established history of uncontrolled diabetes mellitus admitted to the hospital with severe COVID-19 pneumonia (severity ascertained according to WHO classification) treated with steroids and discharged home following full recovery. However, one week later, he presented with right eye ophthalmoplegia and complete loss of vision, which was subsequently established as orbital Mucormycosis. This case highlights the need for heightened awareness of this atypical secondary infection (especially systemic mycosis) in patients recovering from COVID-19 infection.

Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety.

The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.