Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal Patient Cohort Study

Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal... applyparastyle “fig//caption/p[1]” parastyle “FigCapt” Open Forum Infectious Diseases MAJOR ARTICLE Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal Patient Cohort Study 1,a 2,a 1 3 1 1 1 1 2 2, 1 Xuejiao Liao, Ying Wang, Ziyi He, Yongxing Yun, Ming Hu, Zhenghua Ma, Ling Huang, Qingxian Cai, Lin Xu, Yuantao Hao, and Lei Liu National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 2 3 Guangdong, China, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China, and Department of Radiology, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China Background. This study aimed to investigate pulmonary function and radiological outcomes in a group of coronavirus dis- ease 2019 (COVID-19) survivors. Methods. One hundred seventy-two COVID-19 survivors in a follow-up clinic in a referral hospital underwent high- resolution computed tomography (CT) of the thorax and pulmonary function at 3 months aer h ft ospital discharge. Results. e m Th edian duration from hospital discharge to radiological and pulmonary function test (interquartile range) was 90 (88–95) days. Abnormal pulmonary function was found in 11 (6.40%) patients, and abnormal small airway function (FEF ) 25-75% in 12 (6.98%). Six (3.49%) patients had obstructive ventilation impairment, and 6 (3.49%) had restrictive ventilatory impairment. No significant differences in lung function parameters were observed between the nonsevere and severe groups. Of 142 COVID-19 patients who underwent CT scan, 122 (85.91%) showed residual CT abnormalities and 52 (36.62%) showed chronic and fibrotic changes. The ground-glass opacities absorption in the lungs of severe cases was less satisfactory than that of nonsevere patients. The severe patients had higher CT scores than the nonsevere cases (2.00 vs 0.00; P < .001) Conclusions. Of the COVID-19 survivors in our study, 6.40% still presented pulmonary function abnormality 3 months aer ft discharge, which did not vary by disease severity during hospitalization; 85.91% of patients had abnormalities on chest CT, with fi- brous stripes and ground-glass opacities being the most common patterns. Keywords.: COVID-19; pulmonary function assessment; SARS-CoV-2. Coronavirus disease 2019 (COVID-19) is new respiratory ill- As of July 7, 2020, we found 3 studies describing the pulmo- ness that can cause serious pneumonia and lung failure [1]. nary function of COVID-19 patients at or aer ft hospital dis- The World Health Organization (WHO) declared COVID-19 charge [4–6]. One study of 110 COVID-19 patients showed that a public health emergency of international concern on January at discharge the abnormal spirometry parameters ranged from 30, 2020, and this pandemic quickly spread globally to more 4.5% to 47.2% [4]. Another study including 18 COVID-19 pa- than 200 countries. This novel disease has triggered enormous tients showed that 39% suffered from pulmonary impairments human casualties and serious economic loss around the globe 1  month aer r ft ehabilitation and discharge [5]. Another study [2]. Due to its highly contagious nature, there are few data reported clinical manifestation of lung function and chest radi- describing pulmonary function in the acute phase of the dis- ology in 2 critically ill patients with COVID-19 3 months aer ft ease. Evaluation of lung function in recovered patients will en- onset [6], with the younger patient (aged 20  years) showing able better understanding of the prognostic characteristics of complete recovery on both radiology and pulmonary function COVID-19 [3]. tests, whereas the older patient showed residual radiological changes and impaired lung function. As the above 2 studies with follow-up for >1 month aer di ft s- charge were small in size (ie, only 2 and 18 patients included), Received 24 September 2020; editorial decision 25 October 2020; accepted 9 November 2020. Equal contribution we evaluated the radiology and pulmonary function of a larger Correspondence: Yuantao Hao, Sun Yat-Sen University School of Public Health, Guangzhou, sample of COVID-19 patients with longer follow-up. Our Guangdong, China (haoyt@mail.sysu.edu.cn). ® study aims at, first, describing the characteristics of radiology Open Forum Infectious Diseases 2020 © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases and pulmonary function in a larger sample of COVID-19 pa- Society of America. This is an Open Access article distributed under the terms of the Creative tients with a longer follow-up and, second, evaluating the re- Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any sults of chest CT and pulmonary function by baseline disease medium, provided the original work is not altered or transformed in any way, and that the severity. All patients were recruited from the only referral hos- work is properly cited. For commercial re-use, please contact journals.permissions@oup.com pital in one of the largest cities in China, Shenzhen. Awareness DOI: 10.1093/ofid/ofaa540 XXXX • ofid • 1 of the characteristics of radiology and pulmonary function at symptoms but with normal radiological images or with mild 3 months aer di ft scharge may enable a better understanding of changes on chest radiography were identified as nonsevere cases the prognosis of COVID-19 patients. [11]. The degree of radiological change was differentiated by multiple small patchy shadows and interstitial changes, mainly METHODS in the outer zone of the lung and under the pleura. Severe pneu- monia was diagnosed by any of the following conditions: (1) Study Design and Participant Criteria significantly increased respiratory rate (RR): RR ≥30 times/ Our study consisted of 172 patients consecutively hospital- min; (2) hypoxia: oxygen saturation (resting state) ≤93%; (3) ized from January 11, 2020, to February 21, 2020, at the Third blood gas analysis: partial pressure of oxygen/fraction of in- People’s Hospital of Shenzhen. The Third People’s Hospital of spired oxygen (PaO /FiO ) ≤300 mmHg; or (4) the occurrence 2 2 Shenzhen is the only referral hospital authorized by the govern- of respiratory or other organ failure that requires intensive care ment in Shenzhen to care for and treat patients with COVID- unit (ICU) monitoring and treatment or shock. 19. COVID-19 was diagnosed according to the WHO interim guidance [7]. All patients were followed until June 13, 2020. Follow-up Examination for Radiology and Pulmonary Function Assessment Data obtained from electronic medical records included ep- Of the patients who returned for follow-up examination idemiological, clinical, laboratory, and radiological informa- 3 months after discharge, all were invited to have chest com- tion as well as the treatment and progression of the disease. puterized tomography (CT) scan. Results of the CT scans Information of confirmed COVID-19 patients was collected by were evaluated by radiology experts, with the severity status nurses, physicians, or other medical staff at the hospital. marked. In addition, these patients had a normal oxygen sat- uration, and the results of the 6-minute walking test were Patient Consent Statemen normal. Their lung function was evaluated using spirometry This study was approved by the ethics committee of the Third to obtain relevant indices including first second exhalation People’s Hospital of Shenzhen (IRB No. 2020 108). All partici- volume (FEV ), forced vital capacity (FVC), FEV /FVC%, 1 1 pants signed informed consent. It was not appropriate or pos- forced expiratory flow rate at 50% and 75% of FVC (FEF , 50% sible to involve patients or the public in the design or conduct FEF ), forced expired flow at 25–75% of FVC (FEF ), in- 75% 25-75% of our research. spiratory reserve volume (IRV), tidal volume (TV), and expir- atory reserve volume (ERV). Confirmation of COVID-19 The real-time reverse transcription polymerase chain reaction Statistical Analysis method was applied to detect severe acute respiratory syndrome All data were analyzed using R, version 4.0.2 (R Core Team, coronavirus 2 (SARS-CoV-2) [8]. Two pairs of primers targeting Vienna, Austria). The qualitative variables were described as the open reading frame 1ab (ORF1ab) and nucleocapsid frequency and percentages, and the quantitative variables as protein (N) were amplified and examined. The corresponding mean and SD, or median and interquartile range (IQR) if they sequences for ORF1ab were 5’-CCCTGTGGGTTTT ACACTT AA-3’ did not follow a normal distribution. For quantitative data that (F), 5’-ACGA T TGTGCA TCAGCTGA -3’ (R), and 5’-CY3-CCGT were normally distributed, independent group t tests were per- CTGCGGTATGTGGAAAGGTTATGG-BHQ1-3’ (probe), formed to compare the means; otherwise, the Mann-Whitney and those for N were 5’-GGGGAACTTCTCCTGCTAGAAT- test was used. Qualitative data were compared using the x test 3’(F), 5’-CAGACATTTTGCTCTCAAGCTG-3’(R), and 5’-FAM-TTG or the Fisher exact test if the counts were small. A 2-sided α of CTGCTGCTTGACAGATT-TAMRA-3’ (probe). Each sample was <.05 was considered statistically significant. run in triplicate with both positive and negative control sets. The identification process strictly complied the diagnostic cri- RESULTS teria recommended by the National Centers for Disease Control A total of 172 confirmed COVID-19 patients admitted to the and Prevention of China (China CDC). The key laboratory of Third People’s Hospital of Shenzhen from January 11, 2020, to the Shenzhen CDC reconfirmed the samples with positive re- February 16, 2020, and followed until June 13, 2020, were in- sults for COVID-19. cluded. The baseline (ie, at hospitalization) characteristics by Severity of COVID-19 Patients disease severity are shown in Supplementary Table 1. Patients According to the national guidelines for community-acquired who were older, smoked, had fever, had chronic obstructive pneumonia and the diagnosis and treatment plan for COVID- pulmonary disease (COPD), or needed ICU care, invasive ven- 19 in China [9, 10], patients were assigned to the severe or mild tilatory support, or noninvasive ventilatory support tended to group based on the results from chest radiography, clinical ex- develop severe COVID-19 (P from <.001 to .02). Moreover, the amination, and symptoms. Those with mild symptoms, such as length of hospitalization was significantly longer in the severe fever, cough, expectoration, and other upper respiratory tract group than the nonsevere group (P < .001). The duration from 2 • ofid • Liao et al discharge to Pulmonary Function Tests was also longer in pa- No significant differences in levels of FEV pred, FVC pred, or tients with nonsevere disease than severe patients (40 ± 11.6 vs FEV /FVC% were observed between the nonsevere and severe 34.7 ± 16.5 days). groups (Table 2). The median (IQR) values of IRV (L), TV (L), All patients evaluated pulmonary function by spirometry. The and ERV (L) were 1.19 (0.83–1.67), 1.11 (0.91–1.36), and 1.17 symptom proles a fi t follow-up are shown in Supplementary Table (0.79–1.62), respectively, with no significant differences be- 2. No significant differences were found between the nonsevere tween the nonsevere and severe groups observed (Table 2). and severe groups. The median (IQR) age of the patients was 47.50 Of the patients who returned for follow-up examination (28–67) years. Of the 172 patients, the median (IQR) FEV , FVC, 3 months aer di ft scharge, 142 (82.56%) had chest CT scans. The and FEV /FVC% were 104.70 (96.78–113.76), 128.49 (119.20– severe patients had higher CT scores than the nonsevere cases 139.49), and 81.39 (77.33–85.09), respectively, with younger pa- (2.00 vs 0.00; P < .001). Of these, 122 (85.91%) had residual tients showing significantly lower FEV % pred and FVC % pred CT abnormalities and 52 (36.62%) showed chronic and fibrotic and higher FEV /FVC than older age groups (P = .002, .003, and changes. The ground-glass opacities (GGO) in the lung were com- <.001, respectively). Patients who smoked had significantly lower pletely absorbed in 77 (54.23%) patients, partially absorbed in FEV % pred and FVC % pred (P = .04 and .03, respectively). 64 (45.07) patients, and increased in 1 severe case. Severe cases Underweight patients had lower FVC % pred and higher FEV / showed higher rates of residual CT abnormalities (ie, GGO) in the FVC% than patients with higher BMI (P = .01 and .001, respec- lungs than nonsevere cases (76.67% vs 37.50%; P = .004) (Table 3). tively). Furthermore, FVC % pred was significantly higher in pa- Supplementary Figure 1 shows the CT scans of a patient with tients with hypertension or headache as initial symptoms (both nonsevere COVID-19. The GGO in the right upper lobe of the P = .03), but lower in those who had fever as an initial symptom lung at admission had begun to disappear at discharge, were fur- (P = .04). Patients who had cough as an initial symptom showed ther absorbed 1 month aer di ft scharge, and had been completely higher FEV /FVC% (P = .03), but FEV /FVC% was lower in those absorbed 3 months aer di ft scharge. Supplementary Figure 2 shows 1 1 who used lopinavir/ritonavir (P = .03) (Table 1). the CT scans of a severe COVID-19 patient. Lung consolidation At 3  months aer di ft scharge, 10 (7.19%) of the nonsevere in the inferior lobes could be seen at admission. The right lower cases and 1 (3.03%) of the severe cases had abnormal pulmo- lobe consolidation was large, and air bronchogram was found. The nary function. Of those with anomalies on pulmonary function lesion was completely absorbed before discharge with mild GGO tests, 6 (3.59%) had abnormal FEV % pred, 4 (2.38%) had ab- remaining. The GGO in the lungs were completely absorbed at normal FVC % pred, and 6 (3.55%) had abnormal FEV /FVC%. 1 month and 3 months aer di ft scharge, without bronchial dilata- Regarding the FEF, 13 (7.56%) patients were had FEF , 2 tion in the bronchial tubes (Supplementary Figure 2). 50% (1.16%) FEF and 12 (6.98%) FEF . Of the 139 patients with 75% 25-75% nonsevere COVID-19, 6 (4.79%) had obstructive ventilation DISCUSSION impairment and 5 (3.73%) had restrictive ventilatory impair- ment. Furthermore, 1 (3.12%) patient in the severe group had In this study, we comprehensively described the characteris- restrictive ventilatory impairment at 3 months aer di ft scharge. tics of radiology and pulmonary function tests in COVID-19 Table 1. Characteristics of 172 Patients With SARS-CoV-2/COVID-19 by Lung Function at 3-Months Follow-up After Hospital Discharge Pulmonary Ventilation Function a b c Characteristics FEV % pred P value FVC% pred P value FEV /FVC% P value 1 1 Median (IQR) 104.70 (96.78–113.76) 128.49 (119.20–139.49) 81.39 (77.33–85.09) Age, median (IQR), y <10 59.86 (57.37–63.89) 64.48 (60.11–71.39) 90.83 (87.61–94.97) 10–19 109.7 (109.3–114.1) 123.90 (120.4–127.9) 88.47 (86.21–91.34) 20–29 101.64 (94.38–114.58) .002 119.60 (113.9–126.4) .003 84.11 (76.91–90.06) <.001 30–49 106.32 (98.26–114.58) 130.46 (121.78–140.36) 82.24 (78.18–86.04) ≥50 101.38 (95.02–153.82) 128.99 (118.27–140.85) 79.80 (76.18–83.73) Gender, Median (IQR) Female 106.45 (97.2–114.67) .26 128.49 (118.84–138.93) .98 81.79 (78.28–86.31) .34 Male 102.23 (96.33–111.77) 128.32 (119.4–140.51) 81.05 (76.88–85.88) BMI, kg/m , Median (IQR) Underweight 101.01 (70.46–106.34) 116.50 (76.55–120.79) 88.08 (87.3–93.5) Normal 106.51 (97.13–114.18) .32 128.97 (122.1–139.78) .01 81.45 (77.24–85.13) .001 Overweight 102.55 (97.22–112.34) 130.50 (119.7–143.1) 79.99 (76.70–84.65) Obesity 99.84 (90.19–112.72) 126.76 (108.82–135.28) 83.94 (78.03–86.53) Pulmonary Function in COVID-19 Patients After Discharge • ofid • 3 Table 1. Continued Pulmonary Ventilation Function a b c Characteristics FEV % pred P value FVC% pred P value FEV /FVC% P value 1 1 Smoke, Median (IQR) No 106.67 (97.57–117.45) .04 128.99 (121.92–139.13) .03 82.07 (78.56–85.98) .05 Yes 89.90 (87.35–92.44) 97.44 (91.74–103.15) 92.97 (90.10–92.97) Personal disease history, Median (IQR) Hypertension No 103.62 (96.6–113.07) .20 127.11 (119.17–138.48) .03 81.79 (77.46–86.02) .15 Yes 107.55 (101.33–114.89) 137.56 (128.02–148.59) 78.47 (76.17–83.68) Cardiovascular disease No 104.32 (96.69–113.79) .56 127.82 (118.68–139.26) .10 81.88 (77.55–85.95) .13 Yes 106.69 (97.07–113) 132.40 (127.7–147.53) 77.32 (74.50–84.86) Liver disease No 104.73 (96.97–113.79) .91 128.49 (119.26–139.49) .56 81.30 (77.33–85.95) .69 Yes 104.70 (94.38–111.29) 127.80 (117.42–138.41) 84.13 (77.58–85.89) COPD No 104.76 (97.06–113.85) .30 128.77 (119.22–139.46) .60 81.61 (77.40–85.93) .20 Yes 96.61 (88.22–110.23) 122.31 (116.34–138.65) 78.29 (64.91–82.59) Initial symptoms, Median (IQR) Fever No 106.66 (98.38–114.49) .10 131.72 (121.61–144.20) .04 81.58 (76.41–84.94) .52 Yes 102.15 (96.48–112.08) 126.60 (117.08–138.48) 81.28 (77.46–86.17) Cough No 102.23 (96.58–111.98) .16 127.82 (119.15–127.97) .62 80.99 (76.25–85.05) .03 Yes 107.55 (97.31–114.82) 128.99 (119.51–139.52) 82.81 (78.78–85.97) Headache No 104.02 (96.61–113.69) .33 127.87 (118.84–138.99) .03 81.77 (77.42–85.92) .07 Yes 111.54 (107.34–113.74) 141.40 (135.4–146.2) 77.05 (70.19–79.03) Diarrhea No 104.83 (97.00–113.76) .28 128.67 (119.23–139.49) .34 81.39 (77.33–85.89) .77 Yes 96.15 (91.58–102.42) 117.30 (108.10–130.30) 79.70 (77.28–83.28) Fratigue No 104.32 (96.69–113.79) .28 127.88 (139.52–118.94) .52 81.35 (77.33–85.95) .73 Yes 106.81 (106.45–109.48) 130.60 (128.40–135.20) 81.77 (81.22–82.77) Treatment, N (%) Lopinavir/ritonavir No 108.44 (97.55–116.98) .03 132.27 (121.49–140.14) .12 82.53 (77.34–86.52) .24 Yes 102.15 (96.48–111.10) 126.42 (117.80–139.32) 81.12 (77.39–85.48) Favipiravir No 104.67 (96.69–113.79) .70 128.58 (119.18–139.42) .90 81.30 (77.33–85.90) .54 Yes 106.18 (103.62–110.08) 122.40 (121.03–148.10) 84.68 (83.68–85.13) Need ICU care No 105.48 (96.69–113.90) .22 128.77 (119.25–139.52) .21 81.35 (77.83–85.95) .98 Yes 97.23 (97.06–98.46) 116.90 (116.60–127.40) 83.23 (79.92–83.70) Invasive ventilatory support No 104.76 (96.61–113.85) .74 128.58 (119.23–139.46) .51 81.35 (77.32–85.93) .72 Yes 98.32 (97.69–105.45) 116.90 (116.80–128.90) 83.23 (81.58–83.72) Non–invasive ventilatory support No 105.48 (96.86–113.85) .38 128.58 (119.23–139.46) .43 81.35 (77.34–85.93) .63 Yes 98.32 (92.17–106.98) 127.3.8 (110.51–136.13) 83.70 (78.62–85.05) Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; FEV , forced expiratory volume in 1 second; FVC, forced vital capacity; IQR, interquartile-range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Five missing values were excluded here only. Four missing values were excluded here only. Three missing values were excluded here only. Eighty-eight missing values were excluded here. 4 • ofid • Liao et al Table 2. Pulmonary Function of 172 COVID-19 Patients by Disease Severity at 3-Month Follow-up After Hospital Discharge Disease Severity Characteristics Nonsevere Severe Total P Value No. (%) 139 (80.81) 3 3(19.19) 172 Pulmonary ventilation function a a FEV % pred, median (IQR) 106.45 (97.18–113.87) 98.47 (94.86–112.11) 104.70 (96.78–113.76) .18 a a FEV % pred, No. (%) <80% 5 (3.73) 1 (3.12) 6 (3.59) 1.00 b b FVC % pred, median (IQR) 128.91 (120.02–139.58) 125.83 (114.09–134.28) 128.49 (119.20–139.49) .08 b b FVC % pred, No. (%) <80% 4 (2.92) 0 (0.00) 4 (2.38) .76 c c FEV /FVC%, median (IQR) 81.12 (76.45–85.94) 83.45 (79.40–85.85) 81.39 (77.33–85.09) .14 c c FEV /FVC%, No. (%) <70% 6 (4.79) 0 (0.00) 6 (3.55) .50 Small airway function Abnormal FEF , No. (%) 12 (8.63) 0 (0.00) 12 (6.98) .17 25-75% Abnormal FEF , No. (%) 12 (7.10) 1 (3.03) 13 (7.56) .47 50% Abnormal FEF , No. (%) 2 (1.44) 0 (0.00) 2 (1.16) 1.00 75% Lung volumes IRV, median (IQR), L 1.20 (0.81–1.70) 1.17 (0.99–1.51) 1.19 (0.83–1.67) .86 TV, median (IQR), L 1.13 (0.91–1.37) 1.06 (0.88–1.28) 1.11 (0.91–1.36) .69 ERV, median (IQR), L 1.21 (0.79–1.65) 1.02 (0.88–1.42) 1.18 (0.79–1.62) .22 Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; ERV, expiratory reserve volume; FEF, forced expiratory flow rate; FEV , forced expiratory volume in 1 second; FVC, forced vital capacity; IRV, inspiratory reserve volume; IQR, interquartile-range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TV, tidal volume. Five missing values were excluded here only.  Four missing values were excluded here only.  Three missing values were excluded here only. patients 3  months after hospital discharge using data from a CT abnormalities than nonsevere patients (presence of GGO designated hospital in Shenzhen, China. Of the 172 COVID- was 76.67% vs 37.50%). 19 patients for whom we evaluated lung function 3  months e p Th revalence of pulmonary function abnormality in our after discharge, we found that only 6 (3.59%) patients had ob- study was lower than that in previous studies [5], which may be structive ventilation impairment and 6 (3.55%) had restrictive attributable to different times of measurement, suggesting that ventilatory impairment. Pulmonary function tests showed no lung function might be continuously improved aer di ft scharge differences between the severe and nonsevere cases. Of 142 and that the disease is unlikely to cause lifelong impairment COVID-19 patients who had chest CT scans, 122 (85.91%) still [12, 13]. It has been reported that patients with COVID-19 still had residual CT abnormalities and 52 (36.62%) had chronic suffer from pulmonary dysfunction during the recovery period and fibrotic changes. Severe cases had higher rates of residual [14]. One recent study including 18 patients who recovered Table 3. Radiological Outcome of 142 COVID-19 Patients by Disease Severity at 3-Month Follow-up After Hospital Discharge Disease Severity Characteristics Nonsevere Severe Total P Value No. (%) 112 (78.87) 30 (21.13) 142 CT score, median (IQR) 0.00 (0.00–2.00) 2.00 (2.00–2.00) 0.00 (0.00–2.00) <.001 CT changes, No. (%) Normal Yes 17 (15.18) 3 (10.00) 21 (14.08) .62 No 95 (84.82) 27 (90.00) 122 (85.91) Chronic and fibrotic changes Yes 41 (36.61) 12 (40.00) 52 (36.62) .84 No 71 (63.39) 18 (60.00) 90 (63.38) Ground-glass opacity Complete absorption 70 (62.50) 7 (23.33) 77 (54.23) .004 Partial absorption 42 (37.50) 22 (73.33) 64 (45.07) Increase 0 (0.00) 1 (3.34) 1 (0.7) Abbreviations: COVID-19, coronavirus disease 2019; CT, computed tomography; GGO, ground-glass opacity; IQR, interquartile range. Pulmonary Function in COVID-19 Patients After Discharge • ofid • 5 from COVID-19 showed that abnormal pulmonary function at the longer-term recovery of lung function are necessary. Third, discharge manifested in 5 (41.7%) nonsevere and 2 (33.3%) se- FEV and FVC were lower in younger COVID-19 patients (ie, vere patients [5]. Another study of 2 COVID-19 patients who <10 years old) than adults, which may be due to the difficulties were discharged from the hospital found that the older case in performing a forceful expiratory manoeuvre to derive reli- had residual radiological changes and impaired lung func- able spirometry results in young children. Thus the pulmonary tion during the 3-month follow-up period [6]. In our study, function of the young patients could be underestimated. of the 172 COVID-19 patients for whom we assessed pulmo- In conclusion, at 3  months aer di ft scharge, of 172 COVID- nary function 3 months aer di ft scharge, patients aged <10 years 19 survivors, 11 (6.40%) presented abnormalities on pulmo- had restrictive ventilation impairment, which may be partly nary function tests, and 85.91% on chest CT scans, with fibrous due to low compliance during the spirometry test. Moreover, stripes and ground glass opacities being the most common in accordance with previous studies, we showed that abnormal patterns. Further studies with longer follow-up to evaluate pulmonary function was, as expected, mainly manifested in pa- long-term changes in pulmonary function and radiology are tients aged >50  years, because pulmonary function naturally warranted. declines with aging, as indicated by decreases in elasticity and Supplementary Data function of lung tissue as well as muscle strength [15, 16]. Supplementary materials are available at Open Forum Infectious Diseases Moreover, similar fibrotic changes were observed in patients online. Consisting of data provided by the authors to benefit the reader, with SARS, which may not cause lifelong pulmonary damage the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the because recovering patients seem to have the ability of self- corresponding author. rehabilitation, and gradual improvements have been observed over time [3, 17, 18]. Therefore, periodic and regular long-term Acknowledgments follow-up studies are warranted to evaluate changes in lung Financial support. This work was supported by the funds for the function in COVID-19 patients. construction of key medical disciplines in Shenzhen and the Sun Yat-sen univerisity 2020 “Three major” construction major scientific research As CT is more sensitive in detecting lung abnormalities than projects cultivation project. chest x-ray, the abnormality rate was higher than that from pul- Potential coni fl cts of interest. All authors declare no competing inter- monary tests. In COVID-19 survivors aer di ft scharge, 85.91% ests. All authors: no reported conflicts of interest. All authors have sub- of patients still had residual CT abnormalities, and 36.62% of mitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript patients showed chronic and fibrotic changes. A  recent study have been disclosed. suggested that COVID-19 survivors with residual chest CT ab- Author contributions. H.Y. and L.L. conceptualized and designed the normalities might progress to pulmonary fibrosis, especially study and had full access to all data in the study. They take responsibility for the integrity of the data and the accuracy of the data analysis. L.X., W.Y., in severe cases [19]. In our study, of the COVID-19 patients H.Y., L.L., and X.L. contributed to the writing of the report. L.X., H.Z., M.Z., discharged from rehabilitation, 54.23% had complete absorp- Z.L., and Y.Y. contributed to the critical revision of the report. W.Y., C.Q., tion of GGO in the lungs, indicating that with effective anti- and X.L.  contributed to the statistical analysis. All authors contributed to the data acquisition, data analysis, or data interpretation and reviewed and viral treatment during hospitalization and improvement of approved the final version. self-immunity aer di ft scharge, the lesions in both lungs could be improved significantly. Moreover, the GGO progression in References 1 severe patient reflected a less satisfactory absorption of GGO 1. Ahn  DG, Shin  HJ, Kim  MH, et  al. Current status of epidemiology, diagnosis, in severe COVID-19 patients, which calls for more efficient therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol 2020; 30:313–24. therapeutic strategies to protect severe patients from long-term 2. Zhai  P, Ding  Y, Wu  X, et  al. The epidemiology, diagnosis and treatment of lung damage. COVID-19. Int J Antimicrob Agents 2020; 55:105955. 3. Xie L, Liu Y, Xiao Y, et al. Follow-up study on pulmonary function and lung radio- This study has several limitations. First, due to the limited graphic changes in rehabilitating severe acute respiratory syndrome patients after number of confirmed COVID-19 patients from cities outside discharge. Chest 2005; 127:2119–24. the epidemic center, the sample size of the present study is lim- 4. Mo X, Jian W, Su Z, et al. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J 2020; 55:2001217. ited. However, this study has provided the best comprehensive 5. You  J, Zhang  L, Ni-Jia-Ti  MY, et  al. Anormal pulmonary function and residual evidence to date showing the results of pulmonary function tests CT abnormalities in rehabilitating COVID-19 patients after discharge. J Infect. n i press. by spirometry and radiology in COVID-19 patients 3  months 6. Zha L, Shen Y, Pan L, et al. Follow-up study on pulmonary function and radiolog- aer h ft ospital discharge. Second, due to the lack of pulmonary ical changes in critically ill patients with COVID-19. J Infect. i n press. 7. World Health Organization. Clinical management of severe acute respiratory in- function tests at admission or during hospitalization, we did not fection when novel coronavirus (nCoV) infection is suspected: interim guidance. assess changes in pulmonary function tests or CT scans. In our Available at: https://www.who.int/publications-detail/clinical-management-of- severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is- study, no patients developed chronic lung disease, so it might suspected. Accessed 2 July 2020. be reasonable to presume that their basic lung function was 8. Bai  Y, Yao  L, Wei  T, et  al. Presumed asymptomatic carrier transmission of normal. However, longer follow-up examinations to evaluate COVID-19. JAMA 2020; 323:1406–7. 6 • ofid • Liao et al 9. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with 14. Pan F, Ye T, Sun P, et al. Time course of lung changes at chest CT during recovery community-acquired pneumonia. an official clinical practice guideline of the from coronavirus disease 2019 (COVID-19). Radiology 2020; 295:715–21. American Thoracic Society and Infectious Diseases Society of America. Am J 15. Güder G, Brenner S, Angermann CE, et al. GOLD or lower limit of normal defi- Respir Crit Care Med 2019; 200:e45–67. nition? A comparison with expert-based diagnosis of chronic obstructive pulmo- 10. National Health Commission of the People’s Republic of China. Handbook of pre- nary disease in a prospective cohort-study. Respir Res 2012; 13:13. vention and treatment of the pneumonia caused by the novel coronavirus (2019- 16. Thomas ET, Guppy M, Straus SE, et al. Rate of normal lung function decline in nCoV) (in Chinese). Updated 6 February 6 2020. Available at: http://en.nhc.gov. ageing adults: a systematic review of prospective cohort studies. BMJ Open 2019; cn/index.html. Accessed 2 July 2020. 9:e028150. 11. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 17. Liu YX, Ye YP, Zhang P, et al. Changes in pulmonary function in SARS patients cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. during the three-year convalescent period [in Chinese]. Zhongguo Wei Zhong Lancet 2020; 395:507–13. Bing Ji Jiu Yi Xue 2007; 19:536–8. 12. Antonio  GE, Wong  KT, Hui  DS, et  al. Thin-section CT in patients with severe 18. Xie L, Liu Y, Fan B, et al. Dynamic changes of serum SARS-coronavirus IgG, pul- acute respiratory syndrome following hospital discharge: preliminary experience. monary function and radiography in patients recovering from SARS after hos- Radiology 2003; 228:810–5. pital discharge. Respir Res 2005; 6:5. 13. Shichijo S, Keicho N, Long HT, et al. Assessment of synthetic peptides of severe 19. Sun D, Li X, Guo D, et al. CT Quantitative analysis and its relationship with clin- acute respiratory syndrome coronavirus recognized by long-lasting immunity. ical features for assessing the severity of patients with COVID-19. Korean J Radiol Tissue Antigens 2004; 64:600–7. 2020; 21:859–68. Pulmonary Function in COVID-19 Patients After Discharge • ofid • 7 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal Patient Cohort Study

Download PDF
7 pages

Loading next page...
 
/lp/oxford-university-press/three-month-pulmonary-function-and-radiological-outcomes-in-covid-19-xBqp3vP4EB

References (28)

Publisher
Oxford University Press
Copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
eISSN
2328-8957
DOI
10.1093/ofid/ofaa540
Publisher site
See Article on Publisher Site

Abstract

applyparastyle “fig//caption/p[1]” parastyle “FigCapt” Open Forum Infectious Diseases MAJOR ARTICLE Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal Patient Cohort Study 1,a 2,a 1 3 1 1 1 1 2 2, 1 Xuejiao Liao, Ying Wang, Ziyi He, Yongxing Yun, Ming Hu, Zhenghua Ma, Ling Huang, Qingxian Cai, Lin Xu, Yuantao Hao, and Lei Liu National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 2 3 Guangdong, China, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China, and Department of Radiology, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China Background. This study aimed to investigate pulmonary function and radiological outcomes in a group of coronavirus dis- ease 2019 (COVID-19) survivors. Methods. One hundred seventy-two COVID-19 survivors in a follow-up clinic in a referral hospital underwent high- resolution computed tomography (CT) of the thorax and pulmonary function at 3 months aer h ft ospital discharge. Results. e m Th edian duration from hospital discharge to radiological and pulmonary function test (interquartile range) was 90 (88–95) days. Abnormal pulmonary function was found in 11 (6.40%) patients, and abnormal small airway function (FEF ) 25-75% in 12 (6.98%). Six (3.49%) patients had obstructive ventilation impairment, and 6 (3.49%) had restrictive ventilatory impairment. No significant differences in lung function parameters were observed between the nonsevere and severe groups. Of 142 COVID-19 patients who underwent CT scan, 122 (85.91%) showed residual CT abnormalities and 52 (36.62%) showed chronic and fibrotic changes. The ground-glass opacities absorption in the lungs of severe cases was less satisfactory than that of nonsevere patients. The severe patients had higher CT scores than the nonsevere cases (2.00 vs 0.00; P < .001) Conclusions. Of the COVID-19 survivors in our study, 6.40% still presented pulmonary function abnormality 3 months aer ft discharge, which did not vary by disease severity during hospitalization; 85.91% of patients had abnormalities on chest CT, with fi- brous stripes and ground-glass opacities being the most common patterns. Keywords.: COVID-19; pulmonary function assessment; SARS-CoV-2. Coronavirus disease 2019 (COVID-19) is new respiratory ill- As of July 7, 2020, we found 3 studies describing the pulmo- ness that can cause serious pneumonia and lung failure [1]. nary function of COVID-19 patients at or aer ft hospital dis- The World Health Organization (WHO) declared COVID-19 charge [4–6]. One study of 110 COVID-19 patients showed that a public health emergency of international concern on January at discharge the abnormal spirometry parameters ranged from 30, 2020, and this pandemic quickly spread globally to more 4.5% to 47.2% [4]. Another study including 18 COVID-19 pa- than 200 countries. This novel disease has triggered enormous tients showed that 39% suffered from pulmonary impairments human casualties and serious economic loss around the globe 1  month aer r ft ehabilitation and discharge [5]. Another study [2]. Due to its highly contagious nature, there are few data reported clinical manifestation of lung function and chest radi- describing pulmonary function in the acute phase of the dis- ology in 2 critically ill patients with COVID-19 3 months aer ft ease. Evaluation of lung function in recovered patients will en- onset [6], with the younger patient (aged 20  years) showing able better understanding of the prognostic characteristics of complete recovery on both radiology and pulmonary function COVID-19 [3]. tests, whereas the older patient showed residual radiological changes and impaired lung function. As the above 2 studies with follow-up for >1 month aer di ft s- charge were small in size (ie, only 2 and 18 patients included), Received 24 September 2020; editorial decision 25 October 2020; accepted 9 November 2020. Equal contribution we evaluated the radiology and pulmonary function of a larger Correspondence: Yuantao Hao, Sun Yat-Sen University School of Public Health, Guangzhou, sample of COVID-19 patients with longer follow-up. Our Guangdong, China (haoyt@mail.sysu.edu.cn). ® study aims at, first, describing the characteristics of radiology Open Forum Infectious Diseases 2020 © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases and pulmonary function in a larger sample of COVID-19 pa- Society of America. This is an Open Access article distributed under the terms of the Creative tients with a longer follow-up and, second, evaluating the re- Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any sults of chest CT and pulmonary function by baseline disease medium, provided the original work is not altered or transformed in any way, and that the severity. All patients were recruited from the only referral hos- work is properly cited. For commercial re-use, please contact journals.permissions@oup.com pital in one of the largest cities in China, Shenzhen. Awareness DOI: 10.1093/ofid/ofaa540 XXXX • ofid • 1 of the characteristics of radiology and pulmonary function at symptoms but with normal radiological images or with mild 3 months aer di ft scharge may enable a better understanding of changes on chest radiography were identified as nonsevere cases the prognosis of COVID-19 patients. [11]. The degree of radiological change was differentiated by multiple small patchy shadows and interstitial changes, mainly METHODS in the outer zone of the lung and under the pleura. Severe pneu- monia was diagnosed by any of the following conditions: (1) Study Design and Participant Criteria significantly increased respiratory rate (RR): RR ≥30 times/ Our study consisted of 172 patients consecutively hospital- min; (2) hypoxia: oxygen saturation (resting state) ≤93%; (3) ized from January 11, 2020, to February 21, 2020, at the Third blood gas analysis: partial pressure of oxygen/fraction of in- People’s Hospital of Shenzhen. The Third People’s Hospital of spired oxygen (PaO /FiO ) ≤300 mmHg; or (4) the occurrence 2 2 Shenzhen is the only referral hospital authorized by the govern- of respiratory or other organ failure that requires intensive care ment in Shenzhen to care for and treat patients with COVID- unit (ICU) monitoring and treatment or shock. 19. COVID-19 was diagnosed according to the WHO interim guidance [7]. All patients were followed until June 13, 2020. Follow-up Examination for Radiology and Pulmonary Function Assessment Data obtained from electronic medical records included ep- Of the patients who returned for follow-up examination idemiological, clinical, laboratory, and radiological informa- 3 months after discharge, all were invited to have chest com- tion as well as the treatment and progression of the disease. puterized tomography (CT) scan. Results of the CT scans Information of confirmed COVID-19 patients was collected by were evaluated by radiology experts, with the severity status nurses, physicians, or other medical staff at the hospital. marked. In addition, these patients had a normal oxygen sat- uration, and the results of the 6-minute walking test were Patient Consent Statemen normal. Their lung function was evaluated using spirometry This study was approved by the ethics committee of the Third to obtain relevant indices including first second exhalation People’s Hospital of Shenzhen (IRB No. 2020 108). All partici- volume (FEV ), forced vital capacity (FVC), FEV /FVC%, 1 1 pants signed informed consent. It was not appropriate or pos- forced expiratory flow rate at 50% and 75% of FVC (FEF , 50% sible to involve patients or the public in the design or conduct FEF ), forced expired flow at 25–75% of FVC (FEF ), in- 75% 25-75% of our research. spiratory reserve volume (IRV), tidal volume (TV), and expir- atory reserve volume (ERV). Confirmation of COVID-19 The real-time reverse transcription polymerase chain reaction Statistical Analysis method was applied to detect severe acute respiratory syndrome All data were analyzed using R, version 4.0.2 (R Core Team, coronavirus 2 (SARS-CoV-2) [8]. Two pairs of primers targeting Vienna, Austria). The qualitative variables were described as the open reading frame 1ab (ORF1ab) and nucleocapsid frequency and percentages, and the quantitative variables as protein (N) were amplified and examined. The corresponding mean and SD, or median and interquartile range (IQR) if they sequences for ORF1ab were 5’-CCCTGTGGGTTTT ACACTT AA-3’ did not follow a normal distribution. For quantitative data that (F), 5’-ACGA T TGTGCA TCAGCTGA -3’ (R), and 5’-CY3-CCGT were normally distributed, independent group t tests were per- CTGCGGTATGTGGAAAGGTTATGG-BHQ1-3’ (probe), formed to compare the means; otherwise, the Mann-Whitney and those for N were 5’-GGGGAACTTCTCCTGCTAGAAT- test was used. Qualitative data were compared using the x test 3’(F), 5’-CAGACATTTTGCTCTCAAGCTG-3’(R), and 5’-FAM-TTG or the Fisher exact test if the counts were small. A 2-sided α of CTGCTGCTTGACAGATT-TAMRA-3’ (probe). Each sample was <.05 was considered statistically significant. run in triplicate with both positive and negative control sets. The identification process strictly complied the diagnostic cri- RESULTS teria recommended by the National Centers for Disease Control A total of 172 confirmed COVID-19 patients admitted to the and Prevention of China (China CDC). The key laboratory of Third People’s Hospital of Shenzhen from January 11, 2020, to the Shenzhen CDC reconfirmed the samples with positive re- February 16, 2020, and followed until June 13, 2020, were in- sults for COVID-19. cluded. The baseline (ie, at hospitalization) characteristics by Severity of COVID-19 Patients disease severity are shown in Supplementary Table 1. Patients According to the national guidelines for community-acquired who were older, smoked, had fever, had chronic obstructive pneumonia and the diagnosis and treatment plan for COVID- pulmonary disease (COPD), or needed ICU care, invasive ven- 19 in China [9, 10], patients were assigned to the severe or mild tilatory support, or noninvasive ventilatory support tended to group based on the results from chest radiography, clinical ex- develop severe COVID-19 (P from <.001 to .02). Moreover, the amination, and symptoms. Those with mild symptoms, such as length of hospitalization was significantly longer in the severe fever, cough, expectoration, and other upper respiratory tract group than the nonsevere group (P < .001). The duration from 2 • ofid • Liao et al discharge to Pulmonary Function Tests was also longer in pa- No significant differences in levels of FEV pred, FVC pred, or tients with nonsevere disease than severe patients (40 ± 11.6 vs FEV /FVC% were observed between the nonsevere and severe 34.7 ± 16.5 days). groups (Table 2). The median (IQR) values of IRV (L), TV (L), All patients evaluated pulmonary function by spirometry. The and ERV (L) were 1.19 (0.83–1.67), 1.11 (0.91–1.36), and 1.17 symptom proles a fi t follow-up are shown in Supplementary Table (0.79–1.62), respectively, with no significant differences be- 2. No significant differences were found between the nonsevere tween the nonsevere and severe groups observed (Table 2). and severe groups. The median (IQR) age of the patients was 47.50 Of the patients who returned for follow-up examination (28–67) years. Of the 172 patients, the median (IQR) FEV , FVC, 3 months aer di ft scharge, 142 (82.56%) had chest CT scans. The and FEV /FVC% were 104.70 (96.78–113.76), 128.49 (119.20– severe patients had higher CT scores than the nonsevere cases 139.49), and 81.39 (77.33–85.09), respectively, with younger pa- (2.00 vs 0.00; P < .001). Of these, 122 (85.91%) had residual tients showing significantly lower FEV % pred and FVC % pred CT abnormalities and 52 (36.62%) showed chronic and fibrotic and higher FEV /FVC than older age groups (P = .002, .003, and changes. The ground-glass opacities (GGO) in the lung were com- <.001, respectively). Patients who smoked had significantly lower pletely absorbed in 77 (54.23%) patients, partially absorbed in FEV % pred and FVC % pred (P = .04 and .03, respectively). 64 (45.07) patients, and increased in 1 severe case. Severe cases Underweight patients had lower FVC % pred and higher FEV / showed higher rates of residual CT abnormalities (ie, GGO) in the FVC% than patients with higher BMI (P = .01 and .001, respec- lungs than nonsevere cases (76.67% vs 37.50%; P = .004) (Table 3). tively). Furthermore, FVC % pred was significantly higher in pa- Supplementary Figure 1 shows the CT scans of a patient with tients with hypertension or headache as initial symptoms (both nonsevere COVID-19. The GGO in the right upper lobe of the P = .03), but lower in those who had fever as an initial symptom lung at admission had begun to disappear at discharge, were fur- (P = .04). Patients who had cough as an initial symptom showed ther absorbed 1 month aer di ft scharge, and had been completely higher FEV /FVC% (P = .03), but FEV /FVC% was lower in those absorbed 3 months aer di ft scharge. Supplementary Figure 2 shows 1 1 who used lopinavir/ritonavir (P = .03) (Table 1). the CT scans of a severe COVID-19 patient. Lung consolidation At 3  months aer di ft scharge, 10 (7.19%) of the nonsevere in the inferior lobes could be seen at admission. The right lower cases and 1 (3.03%) of the severe cases had abnormal pulmo- lobe consolidation was large, and air bronchogram was found. The nary function. Of those with anomalies on pulmonary function lesion was completely absorbed before discharge with mild GGO tests, 6 (3.59%) had abnormal FEV % pred, 4 (2.38%) had ab- remaining. The GGO in the lungs were completely absorbed at normal FVC % pred, and 6 (3.55%) had abnormal FEV /FVC%. 1 month and 3 months aer di ft scharge, without bronchial dilata- Regarding the FEF, 13 (7.56%) patients were had FEF , 2 tion in the bronchial tubes (Supplementary Figure 2). 50% (1.16%) FEF and 12 (6.98%) FEF . Of the 139 patients with 75% 25-75% nonsevere COVID-19, 6 (4.79%) had obstructive ventilation DISCUSSION impairment and 5 (3.73%) had restrictive ventilatory impair- ment. Furthermore, 1 (3.12%) patient in the severe group had In this study, we comprehensively described the characteris- restrictive ventilatory impairment at 3 months aer di ft scharge. tics of radiology and pulmonary function tests in COVID-19 Table 1. Characteristics of 172 Patients With SARS-CoV-2/COVID-19 by Lung Function at 3-Months Follow-up After Hospital Discharge Pulmonary Ventilation Function a b c Characteristics FEV % pred P value FVC% pred P value FEV /FVC% P value 1 1 Median (IQR) 104.70 (96.78–113.76) 128.49 (119.20–139.49) 81.39 (77.33–85.09) Age, median (IQR), y <10 59.86 (57.37–63.89) 64.48 (60.11–71.39) 90.83 (87.61–94.97) 10–19 109.7 (109.3–114.1) 123.90 (120.4–127.9) 88.47 (86.21–91.34) 20–29 101.64 (94.38–114.58) .002 119.60 (113.9–126.4) .003 84.11 (76.91–90.06) <.001 30–49 106.32 (98.26–114.58) 130.46 (121.78–140.36) 82.24 (78.18–86.04) ≥50 101.38 (95.02–153.82) 128.99 (118.27–140.85) 79.80 (76.18–83.73) Gender, Median (IQR) Female 106.45 (97.2–114.67) .26 128.49 (118.84–138.93) .98 81.79 (78.28–86.31) .34 Male 102.23 (96.33–111.77) 128.32 (119.4–140.51) 81.05 (76.88–85.88) BMI, kg/m , Median (IQR) Underweight 101.01 (70.46–106.34) 116.50 (76.55–120.79) 88.08 (87.3–93.5) Normal 106.51 (97.13–114.18) .32 128.97 (122.1–139.78) .01 81.45 (77.24–85.13) .001 Overweight 102.55 (97.22–112.34) 130.50 (119.7–143.1) 79.99 (76.70–84.65) Obesity 99.84 (90.19–112.72) 126.76 (108.82–135.28) 83.94 (78.03–86.53) Pulmonary Function in COVID-19 Patients After Discharge • ofid • 3 Table 1. Continued Pulmonary Ventilation Function a b c Characteristics FEV % pred P value FVC% pred P value FEV /FVC% P value 1 1 Smoke, Median (IQR) No 106.67 (97.57–117.45) .04 128.99 (121.92–139.13) .03 82.07 (78.56–85.98) .05 Yes 89.90 (87.35–92.44) 97.44 (91.74–103.15) 92.97 (90.10–92.97) Personal disease history, Median (IQR) Hypertension No 103.62 (96.6–113.07) .20 127.11 (119.17–138.48) .03 81.79 (77.46–86.02) .15 Yes 107.55 (101.33–114.89) 137.56 (128.02–148.59) 78.47 (76.17–83.68) Cardiovascular disease No 104.32 (96.69–113.79) .56 127.82 (118.68–139.26) .10 81.88 (77.55–85.95) .13 Yes 106.69 (97.07–113) 132.40 (127.7–147.53) 77.32 (74.50–84.86) Liver disease No 104.73 (96.97–113.79) .91 128.49 (119.26–139.49) .56 81.30 (77.33–85.95) .69 Yes 104.70 (94.38–111.29) 127.80 (117.42–138.41) 84.13 (77.58–85.89) COPD No 104.76 (97.06–113.85) .30 128.77 (119.22–139.46) .60 81.61 (77.40–85.93) .20 Yes 96.61 (88.22–110.23) 122.31 (116.34–138.65) 78.29 (64.91–82.59) Initial symptoms, Median (IQR) Fever No 106.66 (98.38–114.49) .10 131.72 (121.61–144.20) .04 81.58 (76.41–84.94) .52 Yes 102.15 (96.48–112.08) 126.60 (117.08–138.48) 81.28 (77.46–86.17) Cough No 102.23 (96.58–111.98) .16 127.82 (119.15–127.97) .62 80.99 (76.25–85.05) .03 Yes 107.55 (97.31–114.82) 128.99 (119.51–139.52) 82.81 (78.78–85.97) Headache No 104.02 (96.61–113.69) .33 127.87 (118.84–138.99) .03 81.77 (77.42–85.92) .07 Yes 111.54 (107.34–113.74) 141.40 (135.4–146.2) 77.05 (70.19–79.03) Diarrhea No 104.83 (97.00–113.76) .28 128.67 (119.23–139.49) .34 81.39 (77.33–85.89) .77 Yes 96.15 (91.58–102.42) 117.30 (108.10–130.30) 79.70 (77.28–83.28) Fratigue No 104.32 (96.69–113.79) .28 127.88 (139.52–118.94) .52 81.35 (77.33–85.95) .73 Yes 106.81 (106.45–109.48) 130.60 (128.40–135.20) 81.77 (81.22–82.77) Treatment, N (%) Lopinavir/ritonavir No 108.44 (97.55–116.98) .03 132.27 (121.49–140.14) .12 82.53 (77.34–86.52) .24 Yes 102.15 (96.48–111.10) 126.42 (117.80–139.32) 81.12 (77.39–85.48) Favipiravir No 104.67 (96.69–113.79) .70 128.58 (119.18–139.42) .90 81.30 (77.33–85.90) .54 Yes 106.18 (103.62–110.08) 122.40 (121.03–148.10) 84.68 (83.68–85.13) Need ICU care No 105.48 (96.69–113.90) .22 128.77 (119.25–139.52) .21 81.35 (77.83–85.95) .98 Yes 97.23 (97.06–98.46) 116.90 (116.60–127.40) 83.23 (79.92–83.70) Invasive ventilatory support No 104.76 (96.61–113.85) .74 128.58 (119.23–139.46) .51 81.35 (77.32–85.93) .72 Yes 98.32 (97.69–105.45) 116.90 (116.80–128.90) 83.23 (81.58–83.72) Non–invasive ventilatory support No 105.48 (96.86–113.85) .38 128.58 (119.23–139.46) .43 81.35 (77.34–85.93) .63 Yes 98.32 (92.17–106.98) 127.3.8 (110.51–136.13) 83.70 (78.62–85.05) Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; FEV , forced expiratory volume in 1 second; FVC, forced vital capacity; IQR, interquartile-range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Five missing values were excluded here only. Four missing values were excluded here only. Three missing values were excluded here only. Eighty-eight missing values were excluded here. 4 • ofid • Liao et al Table 2. Pulmonary Function of 172 COVID-19 Patients by Disease Severity at 3-Month Follow-up After Hospital Discharge Disease Severity Characteristics Nonsevere Severe Total P Value No. (%) 139 (80.81) 3 3(19.19) 172 Pulmonary ventilation function a a FEV % pred, median (IQR) 106.45 (97.18–113.87) 98.47 (94.86–112.11) 104.70 (96.78–113.76) .18 a a FEV % pred, No. (%) <80% 5 (3.73) 1 (3.12) 6 (3.59) 1.00 b b FVC % pred, median (IQR) 128.91 (120.02–139.58) 125.83 (114.09–134.28) 128.49 (119.20–139.49) .08 b b FVC % pred, No. (%) <80% 4 (2.92) 0 (0.00) 4 (2.38) .76 c c FEV /FVC%, median (IQR) 81.12 (76.45–85.94) 83.45 (79.40–85.85) 81.39 (77.33–85.09) .14 c c FEV /FVC%, No. (%) <70% 6 (4.79) 0 (0.00) 6 (3.55) .50 Small airway function Abnormal FEF , No. (%) 12 (8.63) 0 (0.00) 12 (6.98) .17 25-75% Abnormal FEF , No. (%) 12 (7.10) 1 (3.03) 13 (7.56) .47 50% Abnormal FEF , No. (%) 2 (1.44) 0 (0.00) 2 (1.16) 1.00 75% Lung volumes IRV, median (IQR), L 1.20 (0.81–1.70) 1.17 (0.99–1.51) 1.19 (0.83–1.67) .86 TV, median (IQR), L 1.13 (0.91–1.37) 1.06 (0.88–1.28) 1.11 (0.91–1.36) .69 ERV, median (IQR), L 1.21 (0.79–1.65) 1.02 (0.88–1.42) 1.18 (0.79–1.62) .22 Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; ERV, expiratory reserve volume; FEF, forced expiratory flow rate; FEV , forced expiratory volume in 1 second; FVC, forced vital capacity; IRV, inspiratory reserve volume; IQR, interquartile-range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TV, tidal volume. Five missing values were excluded here only.  Four missing values were excluded here only.  Three missing values were excluded here only. patients 3  months after hospital discharge using data from a CT abnormalities than nonsevere patients (presence of GGO designated hospital in Shenzhen, China. Of the 172 COVID- was 76.67% vs 37.50%). 19 patients for whom we evaluated lung function 3  months e p Th revalence of pulmonary function abnormality in our after discharge, we found that only 6 (3.59%) patients had ob- study was lower than that in previous studies [5], which may be structive ventilation impairment and 6 (3.55%) had restrictive attributable to different times of measurement, suggesting that ventilatory impairment. Pulmonary function tests showed no lung function might be continuously improved aer di ft scharge differences between the severe and nonsevere cases. Of 142 and that the disease is unlikely to cause lifelong impairment COVID-19 patients who had chest CT scans, 122 (85.91%) still [12, 13]. It has been reported that patients with COVID-19 still had residual CT abnormalities and 52 (36.62%) had chronic suffer from pulmonary dysfunction during the recovery period and fibrotic changes. Severe cases had higher rates of residual [14]. One recent study including 18 patients who recovered Table 3. Radiological Outcome of 142 COVID-19 Patients by Disease Severity at 3-Month Follow-up After Hospital Discharge Disease Severity Characteristics Nonsevere Severe Total P Value No. (%) 112 (78.87) 30 (21.13) 142 CT score, median (IQR) 0.00 (0.00–2.00) 2.00 (2.00–2.00) 0.00 (0.00–2.00) <.001 CT changes, No. (%) Normal Yes 17 (15.18) 3 (10.00) 21 (14.08) .62 No 95 (84.82) 27 (90.00) 122 (85.91) Chronic and fibrotic changes Yes 41 (36.61) 12 (40.00) 52 (36.62) .84 No 71 (63.39) 18 (60.00) 90 (63.38) Ground-glass opacity Complete absorption 70 (62.50) 7 (23.33) 77 (54.23) .004 Partial absorption 42 (37.50) 22 (73.33) 64 (45.07) Increase 0 (0.00) 1 (3.34) 1 (0.7) Abbreviations: COVID-19, coronavirus disease 2019; CT, computed tomography; GGO, ground-glass opacity; IQR, interquartile range. Pulmonary Function in COVID-19 Patients After Discharge • ofid • 5 from COVID-19 showed that abnormal pulmonary function at the longer-term recovery of lung function are necessary. Third, discharge manifested in 5 (41.7%) nonsevere and 2 (33.3%) se- FEV and FVC were lower in younger COVID-19 patients (ie, vere patients [5]. Another study of 2 COVID-19 patients who <10 years old) than adults, which may be due to the difficulties were discharged from the hospital found that the older case in performing a forceful expiratory manoeuvre to derive reli- had residual radiological changes and impaired lung func- able spirometry results in young children. Thus the pulmonary tion during the 3-month follow-up period [6]. In our study, function of the young patients could be underestimated. of the 172 COVID-19 patients for whom we assessed pulmo- In conclusion, at 3  months aer di ft scharge, of 172 COVID- nary function 3 months aer di ft scharge, patients aged <10 years 19 survivors, 11 (6.40%) presented abnormalities on pulmo- had restrictive ventilation impairment, which may be partly nary function tests, and 85.91% on chest CT scans, with fibrous due to low compliance during the spirometry test. Moreover, stripes and ground glass opacities being the most common in accordance with previous studies, we showed that abnormal patterns. Further studies with longer follow-up to evaluate pulmonary function was, as expected, mainly manifested in pa- long-term changes in pulmonary function and radiology are tients aged >50  years, because pulmonary function naturally warranted. declines with aging, as indicated by decreases in elasticity and Supplementary Data function of lung tissue as well as muscle strength [15, 16]. Supplementary materials are available at Open Forum Infectious Diseases Moreover, similar fibrotic changes were observed in patients online. Consisting of data provided by the authors to benefit the reader, with SARS, which may not cause lifelong pulmonary damage the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the because recovering patients seem to have the ability of self- corresponding author. rehabilitation, and gradual improvements have been observed over time [3, 17, 18]. Therefore, periodic and regular long-term Acknowledgments follow-up studies are warranted to evaluate changes in lung Financial support. This work was supported by the funds for the function in COVID-19 patients. construction of key medical disciplines in Shenzhen and the Sun Yat-sen univerisity 2020 “Three major” construction major scientific research As CT is more sensitive in detecting lung abnormalities than projects cultivation project. chest x-ray, the abnormality rate was higher than that from pul- Potential coni fl cts of interest. All authors declare no competing inter- monary tests. In COVID-19 survivors aer di ft scharge, 85.91% ests. All authors: no reported conflicts of interest. All authors have sub- of patients still had residual CT abnormalities, and 36.62% of mitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript patients showed chronic and fibrotic changes. A  recent study have been disclosed. suggested that COVID-19 survivors with residual chest CT ab- Author contributions. H.Y. and L.L. conceptualized and designed the normalities might progress to pulmonary fibrosis, especially study and had full access to all data in the study. They take responsibility for the integrity of the data and the accuracy of the data analysis. L.X., W.Y., in severe cases [19]. In our study, of the COVID-19 patients H.Y., L.L., and X.L. contributed to the writing of the report. L.X., H.Z., M.Z., discharged from rehabilitation, 54.23% had complete absorp- Z.L., and Y.Y. contributed to the critical revision of the report. W.Y., C.Q., tion of GGO in the lungs, indicating that with effective anti- and X.L.  contributed to the statistical analysis. All authors contributed to the data acquisition, data analysis, or data interpretation and reviewed and viral treatment during hospitalization and improvement of approved the final version. self-immunity aer di ft scharge, the lesions in both lungs could be improved significantly. Moreover, the GGO progression in References 1 severe patient reflected a less satisfactory absorption of GGO 1. Ahn  DG, Shin  HJ, Kim  MH, et  al. Current status of epidemiology, diagnosis, in severe COVID-19 patients, which calls for more efficient therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol 2020; 30:313–24. therapeutic strategies to protect severe patients from long-term 2. Zhai  P, Ding  Y, Wu  X, et  al. The epidemiology, diagnosis and treatment of lung damage. COVID-19. Int J Antimicrob Agents 2020; 55:105955. 3. Xie L, Liu Y, Xiao Y, et al. Follow-up study on pulmonary function and lung radio- This study has several limitations. First, due to the limited graphic changes in rehabilitating severe acute respiratory syndrome patients after number of confirmed COVID-19 patients from cities outside discharge. Chest 2005; 127:2119–24. the epidemic center, the sample size of the present study is lim- 4. Mo X, Jian W, Su Z, et al. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J 2020; 55:2001217. ited. However, this study has provided the best comprehensive 5. You  J, Zhang  L, Ni-Jia-Ti  MY, et  al. Anormal pulmonary function and residual evidence to date showing the results of pulmonary function tests CT abnormalities in rehabilitating COVID-19 patients after discharge. J Infect. n i press. by spirometry and radiology in COVID-19 patients 3  months 6. Zha L, Shen Y, Pan L, et al. Follow-up study on pulmonary function and radiolog- aer h ft ospital discharge. Second, due to the lack of pulmonary ical changes in critically ill patients with COVID-19. J Infect. i n press. 7. World Health Organization. Clinical management of severe acute respiratory in- function tests at admission or during hospitalization, we did not fection when novel coronavirus (nCoV) infection is suspected: interim guidance. assess changes in pulmonary function tests or CT scans. In our Available at: https://www.who.int/publications-detail/clinical-management-of- severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is- study, no patients developed chronic lung disease, so it might suspected. Accessed 2 July 2020. be reasonable to presume that their basic lung function was 8. Bai  Y, Yao  L, Wei  T, et  al. Presumed asymptomatic carrier transmission of normal. However, longer follow-up examinations to evaluate COVID-19. JAMA 2020; 323:1406–7. 6 • ofid • Liao et al 9. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with 14. Pan F, Ye T, Sun P, et al. Time course of lung changes at chest CT during recovery community-acquired pneumonia. an official clinical practice guideline of the from coronavirus disease 2019 (COVID-19). Radiology 2020; 295:715–21. American Thoracic Society and Infectious Diseases Society of America. Am J 15. Güder G, Brenner S, Angermann CE, et al. GOLD or lower limit of normal defi- Respir Crit Care Med 2019; 200:e45–67. nition? A comparison with expert-based diagnosis of chronic obstructive pulmo- 10. National Health Commission of the People’s Republic of China. Handbook of pre- nary disease in a prospective cohort-study. Respir Res 2012; 13:13. vention and treatment of the pneumonia caused by the novel coronavirus (2019- 16. Thomas ET, Guppy M, Straus SE, et al. Rate of normal lung function decline in nCoV) (in Chinese). Updated 6 February 6 2020. Available at: http://en.nhc.gov. ageing adults: a systematic review of prospective cohort studies. BMJ Open 2019; cn/index.html. Accessed 2 July 2020. 9:e028150. 11. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 17. Liu YX, Ye YP, Zhang P, et al. Changes in pulmonary function in SARS patients cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. during the three-year convalescent period [in Chinese]. Zhongguo Wei Zhong Lancet 2020; 395:507–13. Bing Ji Jiu Yi Xue 2007; 19:536–8. 12. Antonio  GE, Wong  KT, Hui  DS, et  al. Thin-section CT in patients with severe 18. Xie L, Liu Y, Fan B, et al. Dynamic changes of serum SARS-coronavirus IgG, pul- acute respiratory syndrome following hospital discharge: preliminary experience. monary function and radiography in patients recovering from SARS after hos- Radiology 2003; 228:810–5. pital discharge. Respir Res 2005; 6:5. 13. Shichijo S, Keicho N, Long HT, et al. Assessment of synthetic peptides of severe 19. Sun D, Li X, Guo D, et al. CT Quantitative analysis and its relationship with clin- acute respiratory syndrome coronavirus recognized by long-lasting immunity. ical features for assessing the severity of patients with COVID-19. Korean J Radiol Tissue Antigens 2004; 64:600–7. 2020; 21:859–68. Pulmonary Function in COVID-19 Patients After Discharge • ofid • 7

Journal

Open Forum Infectious Diseases – Oxford University Press

Published: Nov 14, 2020

Keywords: COVID-19; pulmonary function assessment; SARS-CoV-2

There are no references for this article.