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The incidence of GI bleeding, sepsis, and heart failure was increased even with a short steroid burst, defined as oral corticosteroids for 14 days or fewer.

Why does this matter?
Steroids are frequently prescribed from the emergency department for a variety of medical conditions, almost reflexively for certain conditions.  In fact, in this population-based study in Taiwan, 25% of the population (age 20 to 64) received at least one steroid burst during the 3-year study period.  A prior population-based cohort study published in the BMJ in 2017 showed increased adverse events following a short steroid burst which included rates of sepsis, venous thromboembolism and fracture. Due to the adverse effects reported in several studies like this, we should probably consider the risk vs. benefit prior to prescribing.

No buffalo humps or cushingoid faces here…just GI bleeding, sepsis, and heart failure
Authors of this study looked at three pre-defined adverse events following a steroid burst – GI bleeding, sepsis and heart failure.  Based on their review of the National Health Insurance Research Database in Taiwan, authors found the incidence rates per 1000 person-years – all steroids prescribed were converted to prednisone equivalents for comparison.  The incidence rates per 1000 person-years among participants prescribed steroid bursts were 27.1 (95%CI 26.7-27.5) for GI bleeding, 1.5 (1.4-1.6) for sepsis, and 1.3 (1.2-1.4) for heart failure. Compared to the cohort without steroids, incidence rates were 16.8 GI bleeding, 1.4 sepsis, and 0.4 heart failure, respectively. Incidence rate ratios (IRRs) for each adverse event, from 5-30 days, were all higher for the cohort prescribed steroids: 1.8 for GI bleed, 1.99 for sepsis, and 2.37 for heart failure. In addition, all IRRs were still increased during the subsequent 31 to 90 days.  Median dose and duration of steroids were actually quite low (10mg and 3 days respectively) as well as mean age (38 years old), particularly if you consider the prescribing pattern for patients with a COPD exacerbation.  Certainly with the incidence of GI bleeding reported in this study, I will make sure to remind my patients to avoid NSAIDs.

As Thomas Davis previously said:
“If the data for steroids are good, this article doesn’t change a thing.
If the data for steroids are weak, this article makes me pause.
If the data for steroids show improvement in quality of life only, I talk to the patient.”

Source
Association Between Oral Corticosteroid Bursts and Severe Adverse Events: A Nationwide Population-Based Cohort Study. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M20-0432. [Epub ahead of print]

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Why does this matter?
COVID-19 has been running rampant across the world, sickening millions, killing hundreds of thousands, shutting down economies, and drastically changing our way of life. Most patients infected with the SARS-CoV-2 virus are asymptomatic or have mild disease. However, a significant number of individuals develop severe infections that can lead to respiratory failure and death. Several therapeutic options have been investigated, but there has been little evidence that any of them actually reduce mortality. We have been desperate for a glimmer of hope that a treatment modality (besides good supportive care) can help turn the tide on this global pandemic. Researchers believe that immune response may play an important role in the pathophysiology of severe COVID-19. Could glucocorticoids decrease this inflammatory response, reduce mortality, and provide a much-needed tool in our fight against COVID-19?

Improved RECOVERY with Dexamethasone for Severe COVID-19
The RECOVERY trial was a controlled, open-label, pragmatic trial of 6,425 patients hospitalized with COVID-19 comparing 28-day mortality for patients randomly assigned to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days versus usual care alone.

Overall, patients receiving dexamethasone had lower incidence of death compared to usual care (22.9% vs. 25.7%; rate ratio, 0.83; 95% CI, 0.75 to 0.93). The greatest benefit was seen with the sickest patients and those with a longer duration of symptoms. Specifically, there was a significant reduction in mortality for patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94). Patients with no respiratory support at randomization did not have a statistically significant benefit from dexamethasone therapy (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55), and there was even a signal of possible harm, perhaps due to patients being in the early viral replication stage of the disease instead of the later host inflammatory stage.

For secondary outcomes, patients in the dexamethasone group also had shorter duration of hospitalization (median, 12 days vs. 13 days), higher probability of discharge alive within 28 days (rate ratio, 1.10; 95% CI, 1.03 to 1.17), and lower risk of progression to mechanical ventilation (risk ratio, 0.77; 95% CI, 0.62 to 0.95).

Rarely do I immediately change my clinical practice based on a single study, and I would love to see these results validated in a large, blinded, randomized controlled trial.  However, based on these promising results, the fact that dexamethasone is inexpensive and widely available, and with few other evidence-based therapeutic options available to treat patients with COVID-19, I plan to administer dexamethasone to any patient with COVID-19 who requires oxygen or ventilatory support.

Source
Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17. doi: 10.1056/NEJMoa2021436. [Epub ahead of print]

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