Radiological and Functional Lung Sequelae of COVID-19

A Systematic Review and Meta-Analysis

Matsuo So; Hiroki Kabata; Koichi Fukunaga; Hisato Takagi; Toshiki Kuno

Disclosures

BMC Pulm Med. 2021;21(97) 

In This Article

Results

Study Selection and Study Characteristics (Figure 1)

Figure 1.

Flow diagram of study selection

We identified 712 articles in total that were reviewed based on the title and abstract. 683 articles were excluded as they were regarding irrelevant topics or did not contain original data. Among the 29 articles, 14 articles were excluded because either they did not clearly mention follow-up timing or the follow-up period was within 1 month after discharge or after symptom onset. Among 15 articles include data of baseline characteristics, 13 articles contained follow-up chest CT data and 10 articles contained follow-up PFT data. Clinical characteristics of extracted data are shown in Table 1. Among the 15 retrospective and prospective cohort studies with total of 3066 patients, 8 studies were from China and 7 studies were from other countries, including Iran, The Netherlands, Belgium, Canada, Norway, Italy, and Switzerland. They all clearly defined their population as COVID-19 patients who had either follow-up CT or pulmonary function tests more than 1 month after symptom onset or after discharge from hospital. The discharge criteria included two consecutive negative SARS-Cov2 nucleic acid tests detected at least 24 h apart each in 3 studies.[17–19] The decision to discharge was made clinically based on patients' clinical status and per hospital policy in the other 12 studies.[20–31] Among these studies, 13 studies collected data of chest CT[17–25,27,29–31] and 10 studies collected data of PFT[17,18,20,22,24–29] from the patients with COVID-19 discharged during their study period. Risk of bias of each study is shown in Additional file 1: figure S2.

Baseline Characteristics of Individual Studies (Table 1)

The follow-up timing of chest CT or pulmonary function tests varied from 1 to 6 months after symptom onset. The average approximate follow-up timing after either symptom onset or hospital discharge was 90 days. Mean age was 56.0 ± 14.3, and 54.2% of the cohort was male. Baseline comorbidities were reported in 15 studies: hypertension 28.9% (886/3066), diabetes mellitus 12.4% (379/3066), cardiovascular disease 6.2% (191/3066), chronic pulmonary disease including asthma, chronic obstructive pulmonary disease, chronic bronchitis, pulmonary tuberculosis and interstitial lung disease 3.6% (110/3066), malignancy 2.7% (84/3066), chronic kidney disease 2.3% (69/3066) and cerebrovascular disease 1.6% (48/3066). Initial COVID-19 symptoms were reported in 4 studies: fever 88.2% (350/397), cough 47.1% (187/397), dyspnea 37.8% (150/397), ageusia 17.6% (70), anosmia 15.9% (63/397), fatigue 15.4% (61/397), diarrhea 13.9% (55/397), arthralgia 11.6% (46/397), myalgia 11.3% (45/397). Residual symptoms at follow-up were reported in 9 studies: fatigue 44.1% (1137/2580), sleep difficulty 16.9% (437/2580), hair loss 13.9% (359/2580), anosmia 7.2% (187/2,580), arthralgia 6.9% (179/2580), palpitation 6.4% (165/2580), decreased appetite 5.3% (138/2580), ageusia 5.1% (132/2580), and dyspnea 4.3% (112/2580). Severe COVID-19 diseases were observed in 22.4% (638/2849), and mild to moderate cases were observed in 77.6% (2211/2849).

Follow-up CT Results After Discharge (Table 2)

13 studies were eligible to assess the residual chest CT findings.[17–25,27,29–31] The average approximate follow-up timing after either symptom onset or hospital discharge was 90 days. The frequency of CT abnormalities observed was 55.7% (95% confidential interval (CI) 41.2–70.1, I 2 = 96.2%) (Figure 2). The proportion of each finding observed was as follows; ground glass opacity: 44.1% (95% CI 30.5–57.8, I 2 = 96.2%), parenchymal band or fibrous stripe: 33.9% (95% CI 18.4–49.4, I 2 = 95.0%), thickening of adjacent pleura: 19.9% (95% CI 8.7–31.1, I 2 = 95.4%), bronchovascular distortion or bronchiectasis: 23.7% (95% CI 6.4–40.9, I 2 = 96.3%), interstitial thickening or interlobular septal thickening: 11.1% (95% CI 3.7–18.4, I 2 = 91.6%), consolidation: 8.8% (95% CI 3.9–13.8, I 2 = 91.0%), pleural effusion: 5.0% (95% CI − 1.8–11.8, I 2 = 78.8%) (Additional file 1: Figure S1A–S1G) Table 2.

Figure 2.

Forest plots for follow-up chest CT results (random-effects model); frequency of CT abnormalities observed after hospital discharge

Follow-up Pulmonary Function Test After Discharge (Table 3)

We identified 10 studies regarding PFT results in follow up period after 1 month.[17,18,20,22,24–29] The follow-up timing was approximately 90 days on average. The frequency of follow-up pulmonary function test abnormalities was 44.3% (95% CI 32.2–56.4, I 2 = 82.1%) (Figure 3A). Impaired diffusion capacity was observed in 34.8% of patients (95% CI 25.8–43.8, I 2 = 91.5%) (Figure 3B). Restrictive pattern and obstructive pattern were observed in 16.4% (95% CI 8.9–23.9, I 2 = 89.8%) (Figure 3C) and 7.7% (95% CI 4.2–11.2, I 2 = 62.0%) of patients (Figure 3D) Table 3.

Figure 3.

Forest plots for follow-up PFT results (random-effects model). a Frequency of PFT abnormalities observed after hospital discharge, b frequency of impaired diffusion capacity in follow-up PFT, c frequency of restrictive pattern in follow-up PFT, d: frequency of obstructive pattern in follow-up PFT

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