A Role for Steroids in COVID-19–associated Pneumonitis at Six-Week Follow-Up?

To the Editor:

We read with interest the recent paper by West and colleagues (1) regarding the use of corticosteroids in persistent inflammatory interstitial lung disease (ILD) after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In their timely and well-implemented observational treatment study, 3.6% of patients with coronavirus disease (COVID-19) discharged from the hospital were diagnosed with persisting organizing pneumonia at 6 weeks and deemed eligible for corticosteroid treatment. Cases were assessed in a multidisciplinary team meeting, and lung function was performed before and after treatment.

As ILD physicians in a tertiary referral center, we have extensive experience in treating organizing pneumonia with corticosteroids in the context of autoimmune disease, adverse drug reactions, and infection. We agree that, intuitively, corticosteroids should have a role in the treatment of patients with significant parenchymal disease secondary to COVID-19. From our own large cohort captured during a similar time frame, before acute corticosteroid treatment was the standard of care (2, 3), the incidence of interstitial changes at 6-week follow up is comparable to these data. However, in our cohort without targeted outpatient corticosteroid administration, there was a significant spontaneous recovery in the majority of patients by 12 weeks. This raises the question as to whether there would have been some spontaneous recovery in these patients without any intervention, especially as there is no matched comparator group. Treatment was only offered if patients were not getting better on a weekly basis, but it is not clear how this assessment was made. It is also important to note that, although treatment was for a short duration, these patients had obesity (25.7%), hypertension (31.4%), and diabetes (22.9%) and were therefore a population in which steroids would ideally be avoided if possible.

We applaud the speed and completeness of this work, particularly in the current climate when access to aerosol-generating respiratory physiology testing to robustly quantify changes is challenging. However, there is clearly equipoise about the use and timing of corticosteroid administration and how they affect the natural history of COVID-19 associated with organizing pneumonia. The RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial (2) showed that dexamethasone resulted in reduced 28-day mortality in those patients requiring oxygen and is now standard of care in this cohort of patients for 10 days. In a second much smaller randomized control trial of just 68 patients with hypoxia (oxygen saturation as measured by pulse oximetry < 90%) who were not intubated and ventilated, methylprednisolone was administered at 250 mg/d for 3 days and showed a significant reduction in mortality (4). We also know from this observational treatment study (1), albeit in a small number of patients, that steroids have a beneficial effect when administered at 6 weeks postdischarge. Two large systematic reviews have further identified acute corticosteroid administration has a mortality benefit in patients with severe disease but does not seem to have a significant impact at lower doses (5, 6). What is less clear is if corticosteroids should be prolonged or augmented after completion of dexamethasone and in what patient cohort and using what objective parameters.

To further address this unmet need, we propose ILD physicians, respiratory and general physicians, intensivists, and interested others collaborate to generate clinically valid research questions that can be answered by a randomized control trial.