The coronavirus disease 2019 (COVID-19) pandemic overwhelmed the healthcare systems in many countries with large numbers of acutely ill patients. However, as months passed, chronic sequelae came to be recognized.
A new paper in Scientific Reports examines lung complications in COVID-19 survivors in order to provide a tentative guideline for future monitoring of COVID-19 patients.
By June 2023, over 700 million cases of COVID-19 were documented worldwide, and it was calculated that about one in a hundred people died of the disease. Between 30 to 50% of hospitalized COVID-19 patients had severe or critical disease, as shown by their admission to intensive care units (ICU) or death.
Among COVID-19 survivors, cough and breathlessness have been reported, along with other respiratory symptoms, even after three months from infection. Some earlier research suggested that these might result from structural and functional lung damage. This included lung fibrosis and restricted gas diffusion, reported in almost one in three survivors at one year from infection.
Similarly, 30 to 70% of survivors also report reduced mental health and a lower quality of life. In view of this, survivorship clinics were set up to manage those with lung-related symptoms after discharge from ICU care. However, there was little guidance on how many other non-ICU patients might need such follow-up and for how long.
The current study aimed to provide prospective evidence to guide such decisions by helping to understand what to expect and how best to manage such clinics.
What did the study show?
The scientists conducted a single-center cohort study including 46 COVID-19 survivors (almost all Delta variant) from May 1, 2020, to April 31, 2022. Patients were prospectively enrolled. There were 17 participants with a history of severe to critical COVID-19.
None of the participants were pregnant, had uncontrolled hypertension or a recent heart attack, or had cognitive impairment. Only those who could understand English well enough to take the tests were recruited. The mean age was 52 years, and 80% were males.
About 75% had never smoked nor had pre-existing chronic lung disease. Of the rest, that is, six patients, four had asthma, one had obstructive sleep apnea, and one had chronic obstructive pulmonary disease (COPD).
Survivors of severe or critical COVID-19 took much longer for complete resolution of their chest X-ray findings, at an average of ~130 days, compared to a week for those with mild or moderate disease.
All participants were monitored with pulmonary function tests (PFTs) at 6, 9, and 12 months, along with a health survey using the Short Form-36 (SF-36) tool. Any participant whose PFT showed abnormalities could undergo a computed tomography (CT) scan of the chest.
Among the PFT abnormalities, diffusion capacity of the lung for carbon monoxide (DLCO) was the most common, observed in 15 of 23 patients. Restrictive lung defects hindering lung expansion were present in 13 of 23 patients, with 10 patients showing overlapping DLCO and restrictive ventilatory defects.
Restrictive ventilatory defects could be due to obesity more than fibrotic lung changes because of COVID-19, as earlier studies show. Obstructive PFT results were due to pre-existing obstructive conditions.
The differences in outcome became most apparent at the six-month follow-up. The findings revealed a higher risk of DLCO defects among survivors of severe or critical COVID-19 compared to those who had mild or moderate illness. These may reflect ventilatory loss, damage to the alveolar membrane, or the microvascular bed caused by the cytokine storm that characterizes this condition.
People with DLCO defects had a higher proportion of severe disease with acute respiratory distress syndrome (ARDS) requiring ventilation. They also had lower SF-36 scores. In particular, the physical performance in the first group showed a significantly lower summary score, at 45, vs 52 in those with mild to moderate illness.
Risk factors for lung deterioration included older age, higher levels of inflammatory markers, and the presence of widespread infiltrates in the lungs seen on chest radiographs.
In most cases, the earliest PFT showed the abnormality. Encouragingly, patients with normal PFTs had a low risk of future lung complications. New abnormalities were rarely reported on their chest X-rays, and they were unlikely to need repeat PFTs.
This was also the case with the mild to moderate COVID-19 survivors, who showed little change in either DLCO or SF-36 scores over the period of monitoring. However, in the group with DLCO abnormalities, 8 of the 23 patients had another PFT at 18 months, with normal scores in half the cases.
Notably, 9 of 23 patients with PFT abnormalities had either asthma or COPD or suffered from morbid obesity. These conditions must be ruled out before attributing such changes to COVID-19-related lung damage.
Of the 13 patients who had a chest CT, nine had DLCO defects. The observed subpleural bands, ground glass opacities, and reticulate markings might explain most. Another cause was morbid obesity in five patients.
The researchers also found that patients with severe or critical COVID-19 tended to have the lowest quality of life, corroborating the findings of earlier studies.
What are the implications?
The study indicates the need to follow up with patients who have survived severe or critical COVID-19, especially if they presented with severe and widespread inflammation and had X-ray or CT changes.
However, PFT should be conducted no earlier than six months or so from the infection to give time for acute injury to resolve, leaving room for the detection of chronic sequelae.
The most common findings on PFT in this group were, as expected, DLCO defects, as expected from earlier studies. DLCO defects may resolve slowly, even when other PFT measures show considerable improvement. Significant lung fibrosis was rare.
In conclusion, any severe or critical COVID-19 survivor with an abnormal PFT at six months from infection should be monitored using 6-monthly PFTs until the results stabilize, with no new lesions and resolution of earlier findings. If the PFTs continue to show abnormalities, the possibility of other etiologies should be duly excluded.
CT scans may be reserved for those with severe disease if there is sufficient reason to suspect pulmonary fibrosis or pulmonary embolism.
Following severe or critical COVID-19, survivors must be recognized to be at risk for lung damage, mental ill-health, and poor quality of life, all of which may be improved by proper pulmonary rehabilitation.