Characteristics of the enrolled COVID-19 patients
This study evaluated a total of 102 patients. Five patients were excluded for underage. Twenty-four patients were not included as it was less than 30 days after discharge. Three patients were excluded due to neurological or mental illness. In addition, eight patients had been out of contact. At last, 57 patients had been included and completed the serial assessments in the study (Figure1). There were 26 men and 31 women with a mean age of 46.72±13.78 years (age range, 19 to 71 years),the mean body mass index was 23.99±3.55kg / m2.Among the 57 subjects, 46 (80.7%) had a history of direct contact with Wuhan, Hubei. Nine patients(15.7%)had a history of smoking. Twenty-one patients (36.8% ) had preexisting medical illness. The four most common preexisting illnesses were hypertension (eleven patients), diabetes (four patients), malignant tumor (three patients) and cardiovascular disease (three patients). All of these conditions were either healed, or stable and well controlled at the time of testing during the study. No patient was reported having chronic respiratory diseases.
Among all subjects, seventeen were severe cases (29.8%), forty were non-severe cases (70.2%). There were mainly male patients(70.6%)in the severe group, and the average age of patients was older compared with non-severe cases. The mean Pao2/Fio2 ratio among severe cases was significantly lower than non-severe cases (198.47[SD, 97.04]; 355.51[SD, 37.23], P<0.001).Meanwhile, severe cases had higher serum lactate dehydrogenase (LDH), C-reactive protein (CRP) peaks and lower lymphocyte count compared with non-severe cases. But there was no significant difference in the values of white blood cells, creatine kinase (CK), lactic acid peaks and length of hospitalization between the two groups (Table 1).
Lung function tests and respiratory muscle strength
Table 2 presents the results of pulmonary function tests and respiratory muscle strength among COVID-19 patients. During follow-up at 1 month after hospital discharge, there were 30 individuals (52.6%) with abnormal diffusion capacity among the 57 patients participating in our study. According to the ATS recommendations for evaluating respiratory impairment [8], twenty-six patients (86.7%) had mild impairment of DLCO, while the other four (13.3%) had moderate impairment. There was significant difference in impaired diffusing-capacity between the two groups, which accounted for 42.5% in non-severe cases, and 75.6% in severe cases, respectively (p<0.05, table3).
The group means of forced expiratory volume in 1 second(FEV1), static lung volumes were within normal limits (>80% predicted). However, several cases of abnormalities in FVC, FEV1, and FEV1/FVC ratio were detected. Five patients (8.7%) had mild impairment of FVC, one (1.8%) had moderate impairment of FVC, 5 (8.7%) had mild impairment of FEV1, and 25 (43.9%) had mild impairment of FEV1/FVC. There were 8 patients (14.0%) and 10 patients (17.5%) had increased R5 and R20 more than 150% of the predicted value, respectively. Up to 12.2%(n=7)of patients had reduction in parameters of lung volume (TLC) at 1 month. Among them, 6 had mild impairment, one had moderate impairment. TLC declined more significantly in severe cases (p=0.048). There was no difference in FVC, FEV1, and FEV1/FVC between the two groups. Table 4 shows the detailed pulmonary function data of all 57 subjects.. The majority of the impairment in FEV1 and FVC suggests a restrictive abnormality. One patient without history of asthma had obstructive abnormality with a FEV1/FVC ratio<70% predicted (up to 72% after bronchodilation), who had significant history of cigarette smoking. Although no complained of symptoms of asthma, one other patient had a significant bronchodilator response with increments of FEV1>200 ml after inhalation of salbutamol.
More than half of the subjects had impairment in respiratory muscle strength. There were 28 patients (49.1%) and 13 patients (22.8%) had Pimax and Pemax values less than 80% of the predicted value, respectively.13 patients had moderate impairment of respiratory muscle strength, of whom 11 were non-severe cases (table 4). When grouped by the administration of steroid, no statistical significance was found in respiratory muscle strength between the glucocorticoid group and the regular group (table 5).
Chest radiographs and correlations with lung function
During follow-up at 30 days after discharge, six patients (10.5%) complained of slight cough, four (7.0%) had shortness of breath, and three (5.3%) had occasional wheezing. Follow-up CT scan at this time showed that 31 patients (54.4%) had residual abnormality, of which 16 were severe cases (94.1%) and 15 were non-severe cases (37.5%).Most of the residual imaging abnormalities was patchy ground glass opacity with periphery distribution, which had obvious absorption compared with the worst chest CT scan (Figure 2.A-B). Four patients had pulmonary fibrosis (Figure 2.C-D), all of whom were severe patients. Compared with non-severe cases, severe patients had a significantly higher CT score (3.94[SD, 2.23]; 0.83 [SD, 1.39]; p<0.01). At the acute phase, lung total severity score was negatively correlated with TLC and R20 (P=0.049,0.044,figure 3), but the correlation disappeared during follow-up period.
6-minute walk test
The mean 6-minute walking distance (6MWD) in all subjects was 561.97m (± 45.29m). Severe patients had a shorter 6 minutes walking distance than non-severe patients (517.43m [SD, 44.55m]; 573.52m [SD, 38.38m], P=0.012). And the 6MWD of severe cases reached only 88.4% of the predicted values, which was significant lower than non-severe cases (p =0.011, table 2).