Radiological and Functional Lung Sequelae of COVID-19

A Systematic Review and Meta-Analysis

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


BMC Pulm Med. 2021;21(97) 

In This Article


The salient findings of our systematic review are the following; (1) the frequency of CT abnormalities after hospital discharge was 55.7% (95% CI 41.2–70.1), Ground glass opacity and parenchymal bands/fibrous stripe were the most frequent findings; (2) the frequency of PFT abnormalities after hospital discharge was 44.3% (95% CI 32.2–56.4). Despite relatively low frequency of restrictive or obstructive pulmonary dysfunction, impaired diffusion capacity was the most prominent findings among these PFT results. It is noteworthy that the frequency of chest CT abnormalities was high despite the high proportion of non-severe cases (77.6%, 2211/2849 patients) in this combined data. As previously described in studies from outbreaks of SARS,[5] our combined data regarding the frequency of chest CT abnormalities observed in follow-up period of about 3 months in COVID-19 patients was about 60%, and the most frequently observed functional lung sequelae was impaired diffusion capacity. Our combined data of decreased diffusion capacity frequency was higher than that reported in SARS in a similar follow-up period.[7,8] Furthermore, compared to radiological lung sequelae of MERS, our data revealed higher rate of residual CT abnormalities.[11]

Interestingly, despite the absence of macro level of lung dysfunction represented as reduced lung volume (restrictive lung dysfunction) or impaired airway dynamics (obstructive lung dysfunction), impaired diffusion capacity was more prominent, which indicates the disorder of interstitial structure and microvasculature of lungs. This result may represent underlying microthrombus formation in the lungs as previously reported in autopsy cases of COVID-19 diseases.[32–35] Hypercoagulable state in COVID-19 has been reported more and more frequently,[36,37] leading to the robust use of inpatient thromboprophylaxis and extended thromboprophylaxis following hospital discharge for select patients.[38] As demonstrated by Zhao et al.,[20] elevated serum D-dimer was associated with decreased diffusion capacity in follow-up PFT. This finding is also consistent with possible microthrombus formation as underlying pathophysiology of COVID-19 disease. Finally, British Thoracic Society guidance on Respiratory follow up of patients with a clinic-radiological diagnosis of COVID-19 pneumonia has defined follow-up algorithms for COVID-19 pneumonia patients, which suggests to obtain chest radiography follow-up at 12 weeks after discharge and consider full PFT based on severity of COVID-19 disease. Any abnormalities in these tests encourage us to take high resolution CT or CT pulmonary angiography for possible residual interstitial lung disease or pulmonary embolism and recommend referral to either interstitial lung disease or pulmonary hypertension specialist services.[39]

This study has several limitations. First, the description of follow up timing was variable and inconsistent between studies such as different starting point of duration and scale of duration, which made it difficult to precisely compare the proportion of patients with residual abnormalities. Second, each article reported CT abnormalities findings with different radiological terminology and PFT abnormalities were reported with different definition of restrictive or obstructive pattern, which made it difficult to accurately assess the proportion of each finding. Third, some studies reported only moderate severity of COVID-19 cases while others included moderate to critical diseases, which can be a factor leads to selection bias as well as low participation of patients in some studies which leads to non-response bias (Additional file 1: Figure S2A–S2B). More follow up data need to be published in the near future and further depict the long-term characteristics of radiological findings and lung function in COVID-19 disease.