Steroids in COVID-19

The role of corticosteroids in treating severe infections has been debatable for some time.  During the coronavirus disease 2019 (COVID-19) pandemic, rigorous data on the efficacy of corticosteroids have been limited. As of July 24, 2020, 55 studies of corticosteroids for the treatment of COVID-19 have been registered on ClinicalTrials.gov. In early July, The Randomized Evaluation ofCOVID-19 Therapy (RECOVERY) trial reported its findings from 6425 patients randomized to 6mg/d of dexamethasone or usual care. Overall, dexamethasone resulted in an absolute reduction in mortality of 2.8 %( 22.9%vs 25.7%for usual care; age-adjusted rate ratio, 0.83 [95%CI, 0.75- 0.93]). The benefit was greatest for patients who were receiving invasive mechanical ventilation at the time of randomization with mortality of 29.3%for dexamethasone vs 41.4%for usual care (rate ratio, 0.64 [95%CI,0.51-0.81]). The signal seen in this trial led most ongoing trials of corticosteroids to suspend recruitment.

Subsequently, The Clinical Characterisation and Management Working Group of the World Health Organization (WHO) conducted a prospective meta-analysis of ongoing randomised clinical trials.

In this prospective meta-analysis of 7 randomized clinical trials that included 1703 critically ill patients with COVID-19 recruited from countries on 5 continents, administration of corticosteroids was associated with –

1. lower all-cause mortality at 28 days after randomization.
2. There was no suggestion of an increased risk of serious adverse events.
3. The odds ratios for the association between corticosteroids and mortality were similar for dexamethasone and hydrocortisone.
4. The comparison of the Association between low-dose corticosteroids and mortality and the association between high-dose corticosteroids and Mortality was imprecisely estimated.
5. Corticosteroids were associated with lower mortality among critically ill patients who were and were not receiving invasive mechanical ventilation at randomization,
6. The ORs for the association between corticosteroids and mortality appeared similar for older and younger individuals, men and women, and for a longer and shorter duration of symptoms before randomization.

Limitations of Meta-analysis –

1. the prospective nature –  implies that lack of participation by some investigators of ongoing trials was based on their knowledge of their trial results.
2. All but 1 of the included trials was assessed as “low risk” of bias for the effect of assignment to the intervention. The trial for which the risk of bias was assessed as “some concerns” (Steroids-SARI; NCT04244591) was relatively small (47 Patients and 26 deaths) and contributed only 3.5%of the weight in the primary meta-analysis. It was the only trial that assessed the effect of methylprednisolone.
3. In many trials, follow-up was censored when participants were discharged from the hospital.
4. The definitions and reporting of serious adverse events were not consistent across the trials. 1 trial reported mortality at 21 days and 1 trial reported mortality at 30 days after randomization, potentially leading to inconsistency between trial results
5. The trials only recruited adults, and the effect of corticosteroids on children remains unclear.
6. The trials were mainly conducted in high-income settings.
7. the RECOVERY trial contributed 57% of the weight in the primary meta-analysis of 28 days all-cause mortality.

Our Conclusion – 

Based on the results of the RECOVERY trial and the meta-analysis performed by REACT group of WHO, we strongly recommend the use of corticosteroids in all severely ill patients with COVID-19.