Patients who survive severe-to-critical COVID-19 frequently have significant lung sequelae and residual symptoms for up to 1 year that warrant follow-up, investigators reported in the European Respiratory Journal.
The REspiratory REcovery after COVid-19 sevERe Infection (RE2COVERI) study evaluated patients’ short-, intermediate-, and long-term trajectories of lung-function recovery after severe-to-critical COVID-19 and their determinants. The study was conducted at 13 French university and university-affiliated hospitals.
The prospective study included 485 adults who were previously hospitalized for severe COVID-19 (hospital length of stay ≥7 days and oxygen flow ≥3 L/min, including those managed with noninvasive ventilatory support without further invasive mechanical ventilation [IMV] required) or critical COVID-19 (IMV ≥48 hours). Participants’ median age was 60.7 years, and 73% were men.
Patients were grouped according to maximum disease severity during hospitalization based on the World Health Organization (WHO) clinical progression scale: WHO 5 patients (n=173, 35.7%), WHO 6 patients (n=96, 19.8%), and WHO 7 to 9 patients (n=216, 44.5%).
All 485 study participants received a follow-up assessment at approximately 3 months post hospital discharge and further follow-ups according to study protocol criteria. Patients who had persistent dyspnea, impaired lung function, and/or significant radiologic sequelae at the 3-month follow-up (n=293; 60.4% of participants) were scheduled for a 6-month follow-up reassessment; among patients in whom the condition persisted at 6 months (n=170; 35.1% of participants), a 12-month follow-up reassessment was scheduled.
Although pulmonary function and radiological abnormalities improved up to 1 year post-acute-COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.
At month 3, 34.0% of participants had a restrictive lung defect (total lung capacity [TLC] <80% predicted) and 70.2% had impaired diffusion capacity (diffusing capacity for carbon monoxide [DLCO] <80% predicted). The percentage of patients who had notably impaired gas diffusion (DLCO <70% predicted) was significantly different among the initial disease-severity groups (P =.005) but tended toward significance in the most severe patients (DLCO <50% predicted, P =.07). Pulmonary function test results were frequently abnormal at months 6 and 12, with restriction and markedly impaired DLCO present in about 40% of participants followed up at 6 months and in almost half of those who took part in a 12-month follow-up.
Of the 422 (87.0%) patients who had computed tomography (CT) scans at month 3, the global assessment of residual radiologic lesions attributable to COVID-19 was significantly different in the initial disease-severity groups. Overall, investigators found among the 422 participants receiving a CT scan at the 3-month follow-up, 82 (19.4%) normalized completely, 104 (24.6%) had minimum residual COVID-19-pneumonia signs, and 236 (55.9%) had significant residual lung abnormalities. A majority of scans at month 6 with significant residual lung abnormalities (n = 96/139, 69.1%) showed attenuated lung sequelae, although 33/87 (37.9%) were still affected at month 12.
In analysis of each patient’s last available scan, 196/475 (41.3%) had significant residual lung abnormalities associated with COVID-19: 51/207 (24.6%) at month 3, 53/132 (40.2%) at month 6, and 87/123 (70.7%) at month 12.
Participants had mean DLCO and forced vital capacity (FVC) increases (% predicted), respectively, of 4.1 and 4.3 points at month 6, and of 6.5 and 5.9 points at month 12 (for each, P <.001). DLCO (maximum % predicted) and FVC (maximum % predicted) values in patients who were followed until month 6 or 12 were not significantly lower compared with those of patients whose follow-up ended at month 3. The respiratory trajectories of WHO 6 patients merged with those of WHO 5 patients, and the mean DLCO (but not FVC) values in WHO 7 to 9 patients were lower until month 12.
According to multivariate analysis, underlying chronic respiratory disease, immunodeficiency, COVID-19-attributable lung-abnormality extent (>50%) on CT scans during acute illness, prolonged IMV duration (>14 days), or corticosteroid use during acute COVID-19 were significantly and independently associated with impaired DLCO, and male sex and obesity (body mass index ≥30) were associated with improved functional recovery.
Among several limitations, only 1 recruiting center used the spirometry Global Lung Initiative references, and more than a quarter of the participants who had at least 1 extended follow-up were not reassessed. Furthermore, selection bias could have influenced the findings in the multivariate model, and the cohort only included patients from the first pandemic wave in France.
“Although pulmonary function and radiological abnormalities improved up to 1 year post-acute-COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up,” said the study authors, adding that their findings offered guidance for organizing follow-up of these patients.