Surviving COVID-19: A Burden Yet to Come?

It has been over a year since COVID-19 was declared a pandemic. Numerous health systems have described the multi-organ effects of SARS-CoV2 in available literature, emphasizing the profound and predominant effect on the respiratory system, particularly in hospitalized patients. Early desperation for targeted therapies led to the evolution of treatment regimens from hydroxychloroquine and azithromycin to targeted antiviral modalities using convalescent plasma and remdesivir. Furthermore, the shift to using dexamethasone, tocilizumab, and additional immunologic agents represents ongoing scientific discoveries amid this global crisis. Prone positioning, use of extracorporeal membrane oxygenation, empiric antibiotics, and empiric anticoagulation have also been part of the treatment; antifibrotic therapies, using pirfenidone and nintedanib, have been used in case reports and are currently under investigation in several clinical trials.4, 5, 6 Through the deployment of new science and therapies indicated for treating COVID-19, we have seen improvement in the survival rates of patients requiring intensive care on mechanical ventilation, resulting in millions of patients recovering from severe SARS-CoV2 infection. We are just beginning to understand the long-term pulmonary consequences of this infection.

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In this issue of CHEST, González-Gutiérrez and colleagues report the long-term sequelae in survivors of ARDS attributable to COVID-19 at 3 months after discharge, focusing on lung function findings via chest imaging. This study included patients from two university hospitals in Spain; the patients were evaluated at 3 months after discharge. Subjective data were obtained via the SF-12 health questionnaire and the Hospital Anxiety and Depression Scale questionnaire. Objective data were collected with pulmonary function tests, 6-minute walk tests, and quantitative CT chest image analysis. A total of 62 patients were evaluated at 3 months. Consistent with many previous studies, the patient population was predominantly middle age, overweight, male, with preexisting hypertension and diabetes. Notably, this group had a relatively low prevalence of preexisting lung disease; only 4.8%. More than 60% of these patients had been on mechanical ventilation during their hospitalization, for a median duration of 17.4 days. At 3 months, half of the patients complained of dyspnea, approximately one third complained of muscular fatigue, and another third had persistent cough. Objectively, 82% of patients presented with low diffusing capacity for carbon monoxide and 37% with low total lung capacity, with a median 6-minute-walk distance of 400 m. Not surprisingly, a higher CT chest severity score was associated with worse diffusion capacity and lower oxygen saturation during exercise. Older age and longer duration of mechanical ventilation was associated with higher CT severity scores at 3 months.

Long-term consequences of ARDS are attributed to the complications of the disease, use of mechanical ventilation, paralytics, high-dose sedation infusions, and use of corticosteroids, leading to almost unavoidable episodes of delirium contributing to prolonged hospitalizations and slow recovery. For now, whether SARS-CoV2 itself is altering the natural history and recovery of ARDS remains unclear. Given the rapid spread and large number of patients with COVID-19 combined with the technical advances that allow good survival rates, the world will bear a large number of survivors of severe COVID-19 in a relatively short period.

Various single-center studies are currently looking at the long-term effects of COVID-19, with a specific focus on pulmonary outcomes.7, 8, 9, 10 Interpretation of these studies and application to the general population is incredibly challenging, for various reasons. First, being a disease of pandemic proportion, it has affected people of different races and ethnicities; applicability of the results of one ethnic group to another might be limited. Second, incidence and prevalence of COVID-19 varies in different regions of the same country, resulting in overwhelming case burden for an area, thereby affecting in-hospital care and certainly long-term outcomes. Finally, resources after discharge may vary, and recruitment of patients into follow-up clinics may be biased.

Arguably, the most fearsome of pulmonary sequalae after ARDS include pulmonary fibrosis, chronic hypoxemia, chronic thromboembolism, and secondary pulmonary hypertension. Burhan et al reported that 25% of ARDS survivors have pulmonary function test abnormalities—mainly restrictive lung disease with low diffusion capacity, associated with CT chest abnormalities. However, these CT chest changes are not necessarily significant, because they may or may not affect health-related quality of life. One prospective study showed improvement in pulmonary function tests, including diffusing capacity for carbon monoxide as well as total lung capacity, over a period of 3 months to 5 years. Only time will tell whether we see similar trends in patients with COVID-19 ARDS.

Commonalities in existing literature are the subjective and objective abnormalities that persist after respiratory failure due to COVID-19. This common denominator emphasizes the importance of continued evaluation and follow-up with specialists familiar with the disease. Multi-center observational studies will be needed to generalize the results. These studies will also help us in stratifying risks associated with long-term complications after COVID-19 but may be applicable to other ARDS survivors as well.