Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Importance: Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective: To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants: Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions: Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures: The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results: The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance: In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02517489.

Clinical characteristics and outcome of COVID-19 pneumonia in kidney transplant recipients in Razi hospital, Rasht, Iran.

BACKGROUND: In late December 2019, a novel coronavirus SARS-CoV-2 started to spread around the world in different populations. Its clinical and laboratory characteristics and outcome in kidney transplant recipients are little known. Therefore, we describe 22 kidney transplant recipients with SARS-CoV-2-induced pneumonia. METHODS: All kidney transplant recipients who referred to the Razi Hospital of Rasht with a diagnosis of SARS-CoV-2 infection from February 20 to 19th of April 2020 have been included in this observational study. RESULTS: We present 22 cases of COVID-19 in kidney transplant recipients (median age 52 years [interquartile range 40.75-62.75 years]) and baseline eGFR 60 (mL/min/1.73 m2 ) (44.75-86.75). Patients complained of cough (72.7%), dyspnea (63.6%), fever (68.2%), and chill (72.7%) with greater prevalence. We decreased the dose of immunosuppression and started stress dose of intravenous hydrocortisone or equivalent oral prednisolone. Each patient received antiviral therapy based on the latest updated version of local protocol at the time of admission. CT scan findings in 90.9% of patients showed bilateral multifocal lesions. Acute kidney injury (AKI) was observed in 12 patients during hospitalization. Six patients died after a median of 12 days from admission (IQR, 1-21). CONCLUSIONS: In this small observational study, we observed high AKI occurrence and mortality rate in kidney transplant recipients with COVID-19.

Foot manifestations in a patient with COVID-19 and Epstein-Barr virus: A case study.

SARS-CoV-2 (COVID-19) is highly-contagious. It can lead to respiratory distress-and in some cases-death. Recent reports and observations have identified an association between COVID-19 and manifestations in the feet. However, there are very few reports that describe the course of these foot manifestations in any detail. The authors present a case study chronicling the progression of foot issues in a COVID-19 positive patient who also was positive for the Epstein-Barr virus.

Adrenal Insufficiency and Glucocorticoid Use During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of adrenal insufficiency.

We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.