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


Protocol and Registration

A review protocol does not exist for this analysis.

Eligibility Criteria

Included studies met the following criteria: the study design was an observational study that was published in peer-reviewed journals, the study population was patients with laboratory confirmed SARS-Cov-2 infections confirmed by using a quantitative real-time polymerase chain reaction (RT-PCR) who had follow-up evaluation of chest CT findings or PFT after recovery. Discharge criteria were either confirmed with two consecutive negative results of RT-PCR or clinical stability. Articles that do not contain original data of patients (e.g. guideline, editorial and review) or data obtained within 1 month of follow-up period after clinical recovery were excluded since the purpose of this review was to clarify the characteristics of lung sequelae in mid to long term follow-up period of patients with clinical recovery.

Information Sources and Search

All observational studies which included patients with COVID-19 diagnosis and follow-up evaluation of chest CT findings or PFT after clinical recovery were identified using a 2-level strategy. Databases including PubMed and EMBASE were searched through January 20th, 2021. Search items included (SARS-CoV-2 or COVID-19 or COVID-19 [MH]) AND [follow-up OR long-term OR (long term)] AND ((Pulmonary function test or Respiratory function test [MH]) OR (computed tomography OR CT)).

Study Selection and Data Collection Process

Relevant studies were identified through a manual search of secondary sources including references of initially identified articles, reviews, and commentaries. Two independent authors (M.S. and H.K.) reviewed the search results separately to select the studies based on inclusion and exclusion criteria. Disagreements were resolved by consensus.

Data Items

Outcomes included age, sex, comorbidities, initial COVID-19 symptoms, residual COVID-19 symptoms after hospital discharge, follow-up timing, disease severity, the proportion of abnormalities in chest CT, chest CT findings at follow-up and type of PFT abnormalities.

Risk of Bias in Individual Studies

Risk of bias in individual studies was reviewed using assessment of risk of bias in prevalence studies[13] (Additional file 1: Figures S2A, S2B).

Summary Measures and Synthesis of Results

To calculate frequency of residual lung abnormalities in follow up chest CT and PFT, retrospective and prospective studies focused on COVID-19 patients who had either follow up chest CT or PFT more than 1 month either after symptom onset or after discharge were utilized and the data regarding the proportion of CT abnormalities, their individual findings in chest CT, the frequency of total PFT abnormality, including obstructive lung function, restrictive lung function, and impaired diffusion capacity were combined using one-group meta-analysis in a random-effect model with DerSimonian-Laird method for continuous value and Wald method for discrete value with OpenMetaAnalyst version 12.11.14 (available from The frequency of comorbidities, initial COVID-19 symptoms, residual COVID-19 symptoms and proportion of severe cases were calculated by summation of events divided by the total number of patients from all studies the information is available. The clinical severity of COVID-19 was defined according to the WHO interim guidance[14] and the guidance from China "Pneumonia diagnosis and treatment program for novel coronavirus infection (trial version 5)" issued by National Health Commission of the People's Republic of China[15] as follows; (1) mild disease: mild symptoms and no evidence of pneumonia in imaging, (2) moderate disease: fever, some respiratory infection symptoms and pneumonia on radiographic imaging, (3) severe disease: meet any of the followings, respiratory distress, respiratory rate > 30/min, SpO2 < 93% at rest, PaO2/FiO2 < 300 mmHg, (4) Critical disease: meet any of the followings, respiratory failure or requiring mechanical ventilation, shock or other organ failures requiring ICU monitoring. Publication bias was assessed by funnel plots with Egger's test using Comprehensive Meta-Analysis version 3 (available from[16]