Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review.

OBJECTIVE: Optimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19. METHODS: A systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for "steroid-induced diabetes" or "steroid-induced hyperglycemia." Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality. RESULTS: Initial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19-related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens. CONCLUSION: Few RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.

Use of Steroids in COVID-19 Patients: What is known?

COVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects.

Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum.

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.

Efficacy and safety of steroid therapy in COVID-19: A rapid systematic review and Meta-analysis.

PURPOSE: Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from "SARS-CoV" and "MERS-CoV." Again, most of these studies addressed only one severity category of patients or addressed only one efficacy endpoint (mortality). In this context, we conducted this meta-analysis to evaluate the efficacy and safety of steroid therapy among all severity categories of patients with COVID-19 (mild to moderate and severe to critical category) in terms of "mortality," "requirement of mechanical ventilation," "requirement of ICU" and clinical cure parameters. METHODS: 11 databases were screened. Only randomized controlled trials (RCTs) or high quality (on the basis of risk of bias analysis) comparative-observational studies were included in the analysis. RevMan5.3 was used for the meta-analysis. RESULTS: A total of 15 studies (3 RCT and 12 comparative-observational studies) were included. In the mechanically-ventilated COVID-19 population, treatment with dexamethasone showed significant protection against mortality (single study). Among severe and critically ill combined population, steroid administration was significantly associated with lowered mortality (risk ratio [RR] 0.83 [0.76-0.910]), lowered requirement of mechanical ventilation (RR 0.59 [0.51-0.69]), decreased requirement of intensive care unit (ICU) (RR 0.62 [0.45-0.86]), lowered length of ICU stay (single-study) and decreased duration of mechanical ventilation (two-studies). In mild to moderate population, steroid treatment was associated with a higher "duration of hospital stay," while no difference was seen in other domains. In patients at risk of progression to "acute respiratory distress syndrome," steroid administration was associated with "reduced requirement of mechanical ventilation" (single-study). CONCLUSION: This study guides the use of steroid across patients with different severity categories of COVID-19. Among mechanically ventilated patients, steroid therapy may be beneficial in terms of reduced mortality. Among "severe and critical" patients; steroid therapy was associated with lowered mortality, decreased requirement of mechanical ventilation, and ICU. However, no benefit was observed in "mild to moderate" population. To conclude, among properly selected patient populations (based-upon clinical severity and biomarker status), steroid administration may prove beneficial in patients with COVID-19.

Steroid harms if given early in COVID-19 viraemia.

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.

Safety of pharmacological options for the management of COVID-19 in pregnant women: An Indian perspective.

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.

Predictors and outcomes of healthcare-associated infections in COVID-19 patients.

INTRODUCTION: Healthcare-associated infections (HAI) after viral illnesses are important sources of morbidity and mortality. This has not been extensively studied in hospitalized COVID-19 patients. METHODS: This study included all COVID-19-positive adult patients (≥18 years) hospitalized between 01 March and 05 August 2020 at the current institution. The Centers for Disease Control and Prevention definition of HAI in the acute care setting was used. The outcomes that were studied were rates and types of infections and in-hospital mortality. Several multivariable logistic regression models were constructed to examine characteristics associated with development of HAI. RESULTS: Fifty-nine (3.7%) of 1565 patients developed 140 separate HAIs from 73 different organisms: 23 were Gram-positive, 39 were Gram-negative and 11 were fungal. Patients who developed HAI did not have higher odds of death (OR 0.85, 95% CI 0.40-1.81, p = 0.69). HAIs were associated with the use of tocilizumab (OR 5.04, 95% CI 2.4-10.6, p < 0.001), steroids (OR 3.8, 95% CI 1.4-10, p = 0.007), hydroxychloroquine (OR 3.0, 95% CI 1.0-8.8, p = 0.05), and acute kidney injury requiring hemodialysis (OR 3.7, 95% CI 1.1-12.8, p = 0.04). CONCLUSIONS: HAI were common in hospitalized Covid-19 patients. Tocilizumab and steroids were associated with increased risk of HAIs.

[Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)].

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.