key: cord-0077410-iao3pgj5 authors: Huntley, Christopher C.; Patel, Ketan; Bil Bushra, Shahnoor-E-Salam; Mobeen, Farah; Armitage, Michael N.; Pye, Anita; Knight, Chloe B.; Mostafa, Alyaa; Kershaw, Marie; Mughal, Aishah Z.; McKemey, Emily; Turner, Alice M.; Burge, P. Sherwood; Walters, Gareth I. title: Pulmonary Function Test and CT features during follow-up after SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis date: 2022-04-21 journal: ERJ Open Res DOI: 10.1183/23120541.00056-2022 sha: a146d07a50957eb23431bc003a00efd0c26c7792 doc_id: 77410 cord_uid: iao3pgj5 BACKGROUND: The COVID-19 pandemic follows SARS and MERS coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remains unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. METHODS: This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random effects model) and proportion of CT features (Freeman-Tukey transformation random effects model) were performed. FINDINGS: Persistent reduction in the diffusing capacity for carbon monoxide (DLco) following SARS, and COVID-19 infection is seen at 6 months follow-up and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity (GGO), linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation reported less. Severe/ critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/ moderate infection. INTERPRETATION: Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome (PCOILS) – it is yet to be determined if this is a regressive or progressive disease. Coronaviruses are enveloped single-stranded RNA viruses (family Coronaviridae, order Nidovirales, genus Betacoronavirus 1, 2 ) first identified in the 1960s and have historically caused avian and animal respiratory and gastrointestinal illness. Whilst traditionally associated with the human common cold 3 , since the turn of the 21 st century, three novel coronaviruses have emerged in humans (following zoonosis from animal reservoirs), resulting in significant morbidity and mortality: Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2; also referred to as COVID-19) 4-6 . The clinical course of COVID-19 varies, ranging from asymptomatic or mild, self-limiting illness to severe pneumonia and multi-organ failure requiring intensivist treatment. Patients who survive the acute phase of COVID-19 similarly experience a varied clinical recovery, with the natural history and long-term impact on the lungs unclear. It is, however, increasingly apparent that many individuals suffer from residual respiratory symptoms with functional impairment -these are often included under the umbrella term 'long-COVID' which can be misleading or misinterpreted, as these symptoms more likely represent sequelae in the lungs following the acute infection. Prior to the UK COVID-19 vaccination programme, it was estimated that 20% of patients have persistent symptoms (related to any organ) at five weeks and 10% at 12 weeks after COVID-19 infection respectively 7 . The estimated prevalence of persistent dyspnoea, cough and sputum production in the first three months after infection is 24%, 19% and 3% respectively 8 . However, the underlying pathophysiology of these symptoms has yet to be defined, with concern surrounding the development of a post-COVID interstitial lung disease (ILD) 9, 10 . Likewise, reports of 'pulmonary fibrosis' following SARS and MERS infection have previously been described 11-12 . With similarities between SARS-CoV-2 and SARS-CoV and MERS-CoV lineage and genomic homology (79.5% and 50% respectively 13 ) in mind, the primary aim of this systematic review and meta-analysis is to describe and compare the longitudinal pulmonary function and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19 during follow-up. A secondary aim is to assess whether the severity of the acute COVID-19 infection influences pulmonary function and CT features seen during follow-up. This systematic review and meta-analysis includes studies published in the first 20 months of the COVID-19 pandemic. Meta-analyses and systematic review were performed in accordance with MOOSE guidelines and reported in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA-P) 14, 15 . The protocol was registered and can be viewed in full on the PROSPERO international database (PROSPERO ID: CRD42020202643). We present a summary of the methodology. FEV1 was 97.8% predicted (89.2 -106.3 , I 2 97 .8%) at 6 months after SARS infection, 98 .84% predicted (94.9 -102.8, I 2 98 .9%) at 6 months after COVID-19 infection and 90.7% predicted (79.9 -101.5, I 2 81 .1%) at 12 months after MERS infection ( Figure 2 ). There was no difference between mild/ moderate and severe/ critical COVID-19 infection (Figure 3 ). [86.2 -91.4 ], I 2 83.8%) than after mild/ moderate disease (103.8% predicted [98.6 -108.9 ], I 2 94 .6%) -this pattern is observed until 8-12 months follow-up ( Figure 3) . RV was 103.3% predicted (98.5 -108.1, I 2 40 .0%) at 3 months after SARS infection and 94.1% predicted (90.7 -97.6 , I 2 98.2%) 3 months after COVID-19 infection ( Figure 2 ). Thoracic CT At 6 months after SARS infection, 76% (45 -97%, I 2 86 .7%) of patients had ground glass opacity (GGO), 59% (30 -85%) had linear opacities, 71% (50 -89%) had reticulation and 3% (0 -9%) had consolidation present on CT. 6% (1 -14%) of CTs at 6 months after SARS featured honeycombing and 18% (10 -28%) had traction bronchiectasis and bronchiolectasis (Figure 4) . At 18 months after SARS infection, 21% (14 -29%) of CTs showed persisting GGO and 25% (17 -34%) had linear opacities. There was no data available following MERS infection. [Insert Figure 4 here] At 6 months after COVID-19 infection, 32% (16 -50%, I 2 93.1%) of patients had GGO, 34% (14 -57%, I 2 93.9%) had linear opacities, 15% (6 -27%, I 2 86.2%) had reticulation and 5% (0 -15%, I 2 82.2%) had consolidation present on CT. 1% (0 -5%, I 2 45.4%) of CTs featured honeycombing and 15% (6 -26%, I 2 88.0%) had traction bronchiectasis and bronchiolectasis ( Figure 4) . Early data reported at 12 months after COVID-19 suggests that linear opacities and GGO are the commonest persisting CT features, although at lower proportions than seen at 6 months. All CT features were present at lower proportions in the first 6 months after mild/ moderate acute COVID-19 infection compared with severe/ critical COVID-19 infection ( Figure 5) . GGO To the authors' knowledge, this is the first systematic review and meta-analysis of PFT and CT features following infection with SARS, MERS and COVID-19. Following SARS and COVID-19 infection, a mild reduction in the FVC and TLC suggest a transient restrictive defect in the first 3 months of follow-up, with a return to the normal limits for an individual's lung volumes noted at 6 months onwards. The most significant physiological abnormality seen in SARS, MERS and COVID-19 is a persistent reduction in the DLco. Considering this, one can deduce that in the follow-up period after SARS and COVID-19, microvascular abnormalities, reduced alveolar membrane diffusion and/ or extra-pulmonary restriction may be present in some patients. There was no physiological evidence of obstructive lung disease during follow-up of SARS, MERS or COVID-19 infection. Whilst direct parenchymal injury is likely responsible for most physiological findings in recovery, it is important for physicians to consider the presence of respiratory muscle weakness, similar to that seen in post-intensive care syndrome and critical illness myopathy [125] [126] [127] . It is estimated that respiratory muscle weakness is two-times that of limb muscle weakness after one day of invasive mechanical ventilation 128 . This may in part explain the observations seen in these meta-analyses when comparing mild/ moderate and severe/ critical disease outcomes, although more probable, this is the result of greater interstitial injury acquired in worse infection. To date, the prevalence of respiratory muscle weakness is unknown post-COVID-19 infection, however, small studies demonstrate inspiratory muscle training has physiological benefits during the recovery phase 129, 130 . Furthermore, studies assessing the role of pulmonary rehabilitation in COVID-19 survivors have demonstrated similar benefits 131 . Respiratory muscle weakness is an important additional factor to consider, especially in patients with severe or critical acute disease when prolonged intubation and intensivist support was required, and may contribute to the abnormalities seen physiologically, complicating interpretation. Other studies 44, 87 have compared the DLco and transfer factor of the lung for nitric oxide (TLno) during follow-up after COVID-19 infection -the DLco is more sensitive to microvascular alterations whilst TLno is more indicative of alveolar membrane diffusive conductance 132, 133 . Both studies demonstrate that greater proportions of patients have reduced TLno than DLco during follow-up at 3 months 87 and 8 months 44 which correlates with persistent symptoms and CT abnormalities. This is suggestive that an alveolar membrane abnormality persists after infection, causing reduced oxygen diffusion rather than a microvascular disease, supporting the presence of a post-COVID-19 interstitial lung abnormality or disease. In addition, there are sparse reports of pulmonary embolism (PE) months after COVID-19 infection. Thoracic CT scans after SARS and COVID-19 demonstrate similar patterns: there is a significant burden of GGO, linear opacities, reticulation and architectural distortion (after . This indicates a persistent abnormality in the interstitium and suggests an explanation for the observed reduction of the diffusion capacity of the lung physiologically. Considering the low proportions of honeycombing and traction bronchiectasis reported throughout the follow-up periods of both infections to date, it is likely the CT pattern does not represent usual interstitial pneumonia (UIP). Organising pneumonia (OP) is a feature of acute COVID-19 infection 134, 135 and has been reported during follow-up after COVID-19 infection 85 . It is likely that a subgroup of patients develop this post-COVID-19 interstitial pattern, although whether it is the dominant pattern is yet to be determined. When interpreting individual CT features, it is important to consider undiagnosed premorbid interstitial disease and acknowledge that some features can be indicative of non-ILD pathology (such as reticulation and GGO in isolation)unfortunately this information was not clear in many studies. Therefore, the role of ILD specialist teams is paramount in the assessment of these patients. Advances in imaging modalities between the SARS epidemic and COVID-19 pandemic have enabled attempts to assess pulmonary physiology and radiology in synchrony. Hyperpolarised 129 Xenon gas MRI of the thorax is an emerging research imaging modality and evaluates both pulmonary gas-exchange function and the lung microstructure. Li et al 73 have demonstrated patients recovering from COVID-19 have reduced gas exchange function with an average higher percentage of ventilation defects compared with healthy controls, whilst areas of GGO that have been reabsorbed on CT demonstrate a persistent reduction in ventilation. This suggests the presence of interstitial thickening and perfusion defects in the post-COVID-19 recovery phase is caused by alveolitis and possible early fibrosis. This review highlights that the severity of acute infection determines the risk of persistent physiological and CT abnormalities in follow-up after COVID-19. Those with severe or critical acute COVID-19 (i.e. a greater acute lung parenchymal injury) have a greater severity of physiological and CT abnormalities compared with mild and moderate infection during follow-up. Those who have survived severe and critical illness still demonstrate improvement over time, and at 8-12 months show a similar degree of CT and physiological abnormality compared with mild/ moderate infections. These sequelae may therefore represent a regressive interstitial syndrome 136 and not a diffuse progressive interstitial lung disease (ILD). Considering this, in the interim, the term post-COVID-19 interstitial lung syndrome (PCOILS) may be more appropriate than post-COVID-19 ILD. For physicians managing these patients, we would advocate surveillance of these patients, until clinical (symptom), radiological and physiological resolution has occurredalthough this should be individualised to each patient based on their acute disease and comorbidities. In SARS studies, it was not possible to differentiate and perform subgroup analysis by acute infection severity as we have with COVID-19. It is estimated 20-36% of patients infected with SARS required intensive care treatment 137 which is higher than estimates in COVID-19 infection The main limitation of this systematic review and meta-analysis of PFTs and CT features concerns the high level of heterogeneity seen. Some variation occurs due to an inability to control analysis for confounders such as pre-morbid comorbidity and functional status, ethnicity and acute treatments received (this would require individual participant data metaanalysis). It was unclear from many studies whether a pre-existing ILD or chronic respiratory disease might explain some of the PFT and CT findings. Both PFT and CT studies (especially when retrospective) are vulnerable to a variety of selection, investigator, publication and reporting biases, as evidenced in risk of bias assessments (Tables S6a-c). Only a single retrospective study of PFTs was available at 12 months' follow-up following MERS infection, which is vulnerable to bias and requires caution when interpretingno other data was available at other time points for MERS. Some heterogeneity arising in the COVID-19 subgroup analysis will have resulted from inter-study variation in the classification of acute COVID-19 severity. Challenges arose in differentiating acute moderate and severe COVID-19 disease as per the WHO guidelines 17often studies determined severity by an oxygen requirement instead of oxygen saturation on air. Whilst we attempted to differentiate COVID-19 severity from the information provided, some studies were not included in subgroup analysis due to uncertainty arising over severity classification. Almost all COVID-19 studies select participants from patients admitted to hospital during their infection, with mild acute COVID-19 infection in the community (the majority of total COVID-19 cases) disproportionately under-represented in studies -these results likely over-represent sequelae after COVID-19. It is important to recognise that each time-period analysed in this review refers to a different cohort of patients, meaning longitudinal analysis between time periods is not possible and focus on single time points in turn should be applied. Furthermore, we have not been able to identify or quantify the proportion of lung parenchyma affected by CT features during recovery, nor identify the proportion of patients who experience complete CT resolution, Limited studies have included CT severity scores during recovery from COVID-19 64, 139 , with one demonstrating median CT score declines steadily over time 139 . This correlates with our earlier suggestion of a potentially regressive interstitial lung syndromefuture studies should consider the use of CT quantification methods, alongside describing which specific CT features arise during the recovery period. The evidence base on the long-term respiratory impact of COVID-19 is ever increasing and it is important to recognise that this review represents the evidence available from the first 20 months of the COVID-19 pandemic. The authors are aware that since the searches were performed, additional studies (of large scale) have been released 140, 141 . Larger research studies will continue to report in time, with focus on the natural history, histopathological findings and treatment options of persistent post-COVID-19 pulmonary disease required. Studies such as the UKILD-Long COVID study 142 with sub-studies POSTCODE (POST COvid-19 interstitial lung DiseasE) and XMAS (Xenon MRI investigation of Alveolar dysfunction) and PCOILS 143 are eagerly anticipated. The emergence of COVID-19 variants and the utilisation of vaccination also require consideration in future studies of post-COVID-19 sequelae. A significant proportion of patients recovering from SARS and MERS have experienced persistent pulmonary physiological and radiographic abnormalities during the follow-up period. A similar pattern has emerged in COVID-19 survivors. Physiological parameters suggest a persistent alveolar diffusion defect due to persisting interstitial injury with or without respiratory muscle weakness. Thoracic CT demonstrates persisting GGO, linear opacities and reticulation and may be indicative of a post-COVID-19 interstitial lung syndrome. CT features decline at subsequent time points but are present in significant proportions of survivors at 6 months. Severe and critical acute COVID-19 infection causes greater pulmonary physiological impairment and greater proportions of CT abnormality. CCH and KP conceived the idea for the study. CCH, KP, AMT, PSB and GIW designed the study and wrote the protocol. CCH and KP conducted initial database searches. CCH, KP, SBB, FM, MNA, AP, CBK, ALM, MK, AZM and EM conducted the initial review of search results against eligibility criteria, with all authors involved with full-text review and data extraction (ensuring two authors independently extracted data from each included study). All authors had full access to the data. CCH conducted the data analysis and verified the data. GIW verified the data and the analysis. All authors reviewed the analysis results. CCH wrote the original and final version of the manuscript with editing and review by all co-authors. AMT, PSB and GIW supervised the study. There was no funding source for this study. We declare no competing interests in relation to this study. Coronaviruses are enveloped single-stranded RNA viruses (family Coronaviridae, order Nidovirales, genus Betacoronavirus 1, 2 ) first identified in the 1960s and have historically caused avian and animal respiratory and gastrointestinal illness. Whilst traditionally associated with the human common cold 3 , since the turn of the 21 st century, three novel coronaviruses have emerged in humans (following zoonosis from animal reservoirs), resulting in significant morbidity and mortality: Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2; also referred to as COVID-19) 4-6 . The clinical course of COVID-19 varies, ranging from asymptomatic or mild, self-limiting illness to severe pneumonia and multi-organ failure requiring intensivist treatment. Patients who survive the acute phase of COVID-19 similarly experience a varied clinical recovery, with the natural history and long-term impact on the lungs unclear. It is, however, increasingly apparent that many individuals suffer from residual respiratory symptoms with functional impairment -these are often included under the umbrella term 'long-COVID' which can be misleading or misinterpreted, as these symptoms more likely represent sequelae in the lungs following the acute infection. Prior to the UK COVID-19 vaccination programme, it was estimated that 20% of patients have persistent symptoms (related to any organ) at five weeks and 10% at 12 weeks after COVID-19 infection respectively 7 . The estimated prevalence of persistent dyspnoea, cough and sputum production in the first three months after infection is 24%, 19% and 3% respectively 8 . However, the underlying pathophysiology of these symptoms has yet to be defined, with concern surrounding the development of a post-COVID interstitial lung disease (ILD) 9, 10 . Likewise, reports of 'pulmonary fibrosis' following SARS and MERS infection have previously been described [11] [12] . With similarities between SARS-CoV-2 and SARS-CoV and MERS-CoV lineage and genomic homology (79.5% and 50% respectively 13 ) in mind, the primary aim of this systematic review and meta-analysis is to describe and compare the longitudinal pulmonary function and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19 during follow-up. A secondary aim is to assess whether the severity of the acute COVID-19 infection influences pulmonary function and CT features seen during follow-up. This systematic review and meta-analysis includes studies published in the first 20 months of the COVID-19 pandemic. Meta-analyses and systematic review were performed in accordance with MOOSE guidelines and reported in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA-P) 14, 15 . The protocol was registered and can be viewed in full on the PROSPERO international database (PROSPERO ID: CRD42020202643). We present a summary of the methodology. Studies were eligible for inclusion if they included adult patients (18 years and older) and met the eligibility criteria in Table S1 . Medline (Ovid) and Embase (Ovid) electronic databases were searched for articles published between 1 st January 2000 and 23 rd July 2021. Searches applied a combination of index terms and text words relating to SARS, MERS or COVID-19 coronaviruses, respiratory diseases, sequelae and outcome measures ( Table S2a-b) . No study design or language restrictions were implemented. Study selection against pre-determined inclusion and exclusion criteria (Table S2) was performed independently by two reviewers (CCH, KP, SBB, FM, MNA, AP, CBK, ALM, MK, AZM or EM), reviewing the title and abstracts then the full-texts of those eligible. Disagreements were resolved by discussion or review by a third independent reviewer (CCH, KP or GIW). Data was extracted from each eligible study using a pre-determined standardised, piloted data extraction sheet (which included a risk of bias tool) by two independent reviewers (all authors). A third reviewer checked the data extracted and risk of bias assessment and resolved any conflicts (CCH, KP or GIW). For studies not in English-language, study selection and data extraction process was performed by one reviewer (AMT) alongside a lay speaker of the language. Risk of bias and quality assessment was performed using the Newcastle-Ottawa scale for cohort and case-control studies and the Joanna Briggs Institute critical appraisal tool for analytical cross-sectional studies (longitudinal or cross-sectional studies). Authors of studies with incomplete or missing data or data reported in an alternative format, were contacted to provide additional information and excluded if an unsatisfactory or no response was received. Studies were grouped according to the outcomes they reported. For physiological results, the percentage of predicted values (% predicted) of the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), total lung capacity (TLC) and/ or residual volume (RV) were collected at time points reported after admission or discharge. Where the median and interquartile range (IQR) were reported, the mean and standard deviation (SD) was estimated as per Hozo, et al 16 Follow-up time points were grouped ordinally into follow-up time periods to allow for minor variations in the follow-up reported as well as whether the study reported data from postadmission or post-discharge (Table S3) . If a study reported more than one timepoint in the same period (e.g. 1 month and 2 month) the later data set was included to avoid duplicate publication bias. Two expert physicians in ILD reviewed and categorised all terms reported due to variations observed in CT feature terminology between studies (Table S4) . 51,120 studies were identified from the search strategy, with 108 studies eligible for inclusion in the meta-analyses (Figure 1) . A summary of all included studies is shown in Table 2 . A list of the excluded studies at full-text review is available from the authors at request. All included studies were of adult patients who had required admission to hospital for SARS, MERS or COVID-19 infection. Measurement of the follow-up time varied between studies, commonly reporting from the time of hospital admission, coronavirus confirmation or discharge. All eligible studies had a risk of bias assessment completed by two reviewers independently (Tables S6a-c) . [Insert Figure 1 and Table 1 Figures S1a-9f) . Many studies reported PFT by subgroups based on specific variables (e.g. severity of the acute coronavirus pneumonia or ventilation strategy) and are listed on the individual forest plots. Results of meta-analyses of PFTs are reported as mean % predicted value (95% confidence interval, I 2 estimate of heterogeneity). CT meta-analyses are reported as proportion (%) of participants (95% confidence interval, I 2 estimate of heterogeneity). 81 .1%) at 12 months after MERS infection (Figure 2) . There was no difference between mild/ moderate and severe/ critical COVID-19 infection (Figure 3) . (Figure 2) . There was no difference between mild/ moderate and severe/ critical COVID-19 infection (Figure 3) . (Figure 4) . At 18 months after SARS infection, 21% (14 -29%) of CTs showed persisting GGO and 25% (17 -34%) had linear opacities. There was no data available following MERS infection. [Insert Figure 4 here] At 6 months after COVID-19 infection, 32% (16 -50%, I 2 93.1%) of patients had GGO, 34% (14 -57%, I 2 93.9%) had linear opacities, 15% (6 -27%, I 2 86.2%) had reticulation and 5% (0 -15%, I 2 82.2%) had consolidation present on CT. 1% (0 -5%, I 2 45.4%) of CTs featured honeycombing and 15% (6 -26%, I 2 88.0%) had traction bronchiectasis and bronchiolectasis ( Figure 4) . Early data reported at 12 months after COVID-19 suggests that linear opacities and GGO are the commonest persisting CT features, although at lower proportions than seen at 6 months. All CT features were present at lower proportions in the first 6 months after mild/ moderate acute COVID-19 infection compared with severe/ critical COVID-19 infection ( Figure 5) . Whilst direct parenchymal injury is likely responsible for most physiological findings in recovery, it is important for physicians to consider the presence of respiratory muscle weakness, similar to that seen in post-intensive care syndrome and critical illness myopathy [125] [126] [127] . It is estimated that respiratory muscle weakness is two-times that of limb muscle weakness after one day of invasive mechanical ventilation 128 . This may in part explain the observations seen in these meta-analyses when comparing mild/ moderate and severe/ critical disease outcomes, although more probable, this is the result of greater interstitial injury acquired in worse infection. To date, the prevalence of respiratory muscle weakness is unknown post-COVID-19 infection, however, small studies demonstrate inspiratory muscle training has physiological benefits during the recovery phase 129, 130 . Furthermore, studies assessing the role of pulmonary rehabilitation in COVID-19 survivors have demonstrated similar benefits 131 . Respiratory muscle weakness is an important additional factor to consider, especially in patients with severe or critical acute disease when prolonged intubation and intensivist support was required, and may contribute to the abnormalities seen physiologically, complicating interpretation. Other studies 44, 87 have compared the DLco and transfer factor of the lung for nitric oxide (TLno) during follow-up after COVID-19 infection -the DLco is more sensitive to microvascular alterations whilst TLno is more indicative of alveolar membrane diffusive conductance 132, 133 . Both studies demonstrate that greater proportions of patients have reduced TLno than DLco during follow-up at 3 months 87 and 8 months 44 which correlates with persistent symptoms and CT abnormalities. This is suggestive that an alveolar membrane abnormality persists after infection, causing reduced oxygen diffusion rather than a microvascular disease, supporting the presence of a post-COVID-19 interstitial lung abnormality or disease. In addition, there are sparse reports of pulmonary embolism (PE) months after COVID-19 infection. Thoracic CT scans after SARS and COVID-19 demonstrate similar patterns: there is a significant burden of GGO, linear opacities, reticulation and architectural distortion (after . This indicates a persistent abnormality in the interstitium and suggests an explanation for the observed reduction of the diffusion capacity of the lung physiologically. Considering the low proportions of honeycombing and traction bronchiectasis reported throughout the follow-up periods of both infections to date, it is likely the CT pattern does not represent usual interstitial pneumonia (UIP). Organising pneumonia (OP) is a feature of acute COVID-19 infection 134, 135 and has been reported during follow-up after COVID-19 infection 85 . It is likely that a subgroup of patients develop this post-COVID-19 interstitial pattern, although whether it is the dominant pattern is yet to be determined. When interpreting individual CT features, it is important to consider undiagnosed premorbid interstitial disease and acknowledge that some features can be indicative of non-ILD pathology (such as reticulation and GGO in isolation)unfortunately this information was not clear in many studies. Therefore, the role of ILD specialist teams is paramount in the assessment of these patients. Advances in imaging modalities between the SARS epidemic and COVID-19 pandemic have enabled attempts to assess pulmonary physiology and radiology in synchrony. This review highlights that the severity of acute infection determines the risk of persistent physiological and CT abnormalities in follow-up after COVID-19. Those with severe or critical acute COVID-19 (i.e. a greater acute lung parenchymal injury) have a greater severity of physiological and CT abnormalities compared with mild and moderate infection during follow-up. Those who have survived severe and critical illness still demonstrate improvement over time, and at 8-12 months show a similar degree of CT and physiological abnormality compared with mild/ moderate infections. These sequelae may therefore represent a regressive interstitial syndrome 136 and not a diffuse progressive interstitial lung disease (ILD). Considering this, in the interim, the term post-COVID-19 interstitial lung syndrome (PCOILS) may be more appropriate than post-COVID-19 ILD. For physicians managing these patients, we would advocate surveillance of these patients, until clinical (symptom), radiological and physiological resolution has occurredalthough this should be individualised to each patient based on their acute disease and comorbidities. In SARS studies, it was not possible to differentiate and perform subgroup analysis by acute infection severity as we have with COVID-19. It is estimated 20-36% of patients infected with SARS required intensive care treatment 137 which is higher than estimates in COVID-19 infection The main limitation of this systematic review and meta-analysis of PFTs and CT features concerns the high level of heterogeneity seen. Some variation occurs due to an inability to control analysis for confounders such as pre-morbid comorbidity and functional status, ethnicity and acute treatments received (this would require individual participant data metaanalysis). It was unclear from many studies whether a pre-existing ILD or chronic respiratory disease might explain some of the PFT and CT findings. Both PFT and CT studies (especially when retrospective) are vulnerable to a variety of selection, investigator, publication and reporting biases, as evidenced in risk of bias assessments (Tables S6a-c) . Only a single retrospective study of PFTs was available at 12 months' follow-up following MERS infection, which is vulnerable to bias and requires caution when interpretingno other data was available at other time points for MERS. Some heterogeneity arising in the COVID-19 subgroup analysis will have resulted from inter-study variation in the classification of acute COVID-19 severity. Challenges arose in differentiating acute moderate and severe COVID-19 disease as per the WHO guidelines 17often studies determined severity by an oxygen requirement instead of oxygen saturation on air. Whilst we attempted to differentiate COVID-19 severity from the information provided, some studies were not included in subgroup analysis due to uncertainty arising over severity classification. Almost all COVID-19 studies select participants from patients admitted to hospital during their infection, with mild acute COVID-19 infection in the community (the majority of total COVID-19 cases) disproportionately under-represented in studies -these results likely over-represent sequelae after COVID-19. It is important to recognise that each time-period analysed in this review refers to a different cohort of patients, meaning longitudinal analysis between time periods is not possible and focus on single time points in turn should be applied. Furthermore, we have not been able to identify or quantify the proportion of lung parenchyma affected by CT features during recovery, nor identify the proportion of patients who experience complete CT resolution, Limited studies have included CT severity scores during recovery from COVID-19 64, 139 , with one demonstrating median CT score declines steadily over time 139 . This correlates with our earlier suggestion of a potentially regressive interstitial lung syndromefuture studies should consider the use of CT quantification methods, alongside describing which specific CT features arise during the recovery period. The evidence base on the long-term respiratory impact of COVID-19 is ever increasing and it is important to recognise that this review represents the evidence available from the first 20 months of the COVID-19 pandemic. The authors are aware that since the searches were performed, additional studies (of large scale) have been released 140, 141 . Larger research studies will continue to report in time, with focus on the natural history, histopathological findings and treatment options of persistent post-COVID-19 pulmonary disease required. Studies such as the UKILD-Long COVID study 142 with sub-studies POSTCODE (POST COvid-19 interstitial lung DiseasE) and XMAS (Xenon MRI investigation of Alveolar dysfunction) and PCOILS 143 are eagerly anticipated. The emergence of COVID-19 variants and the utilisation of vaccination also require consideration in future studies of post-COVID-19 sequelae. A significant proportion of patients recovering from SARS and MERS have experienced persistent pulmonary physiological and radiographic abnormalities during the follow-up period. A similar pattern has emerged in COVID-19 survivors. Physiological parameters suggest a persistent alveolar diffusion defect due to persisting interstitial injury with or without respiratory muscle weakness. Thoracic CT demonstrates persisting GGO, linear opacities and reticulation and may be indicative of a post-COVID-19 interstitial lung syndrome. CT features decline at subsequent time points but are present in significant proportions of survivors at 6 months. Severe and critical acute COVID-19 infection causes greater pulmonary physiological impairment and greater proportions of CT abnormality. CCH and KP conceived the idea for the study. CCH, KP, AMT, PSB and GIW designed the study and wrote the protocol. CCH and KP conducted initial database searches. CCH, KP, SBB, FM, MNA, AP, CBK, ALM, MK, AZM and EM conducted the initial review of search results against eligibility criteria, with all authors involved with full-text review and data extraction (ensuring two authors independently extracted data from each included study). All authors had full access to the data. CCH conducted the data analysis and verified the data. GIW verified the data and the analysis. All authors reviewed the analysis results. CCH wrote the original and final version of the manuscript with editing and review by all co-authors. AMT, PSB and GIW supervised the study. There was no funding source for this study. We declare no competing interests in relation to this study. COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses Changes to virus taxonomy and the Statutes ratified by the International Committee on Taxonomy of Viruses (2020) Coronaviruses in animals and humans WHO Cumulative Number of Reported Probable Cases of SARS. Geneva: World Health Organization. Accessed 12th Geneva: World Health Organization. Accessed 12th Geneva: World Health Organization. Accessed 1 st The prevalence of long COVID symptoms and COVID-19 complications. 2020. 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World Health Organisation. 25 th Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: Evaluation with thin-section CT Follow-up study of chest CT manifestations of patients with severe acute respiratory syndrome Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome A follow-up study of 69 discharged SARS patients Correlation of high-resolution CT, symptoms, and pulmonary function in patients during recovery from severe acute respiratory syndrome The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors Thoracic high resolution CT findings of 100 SARS patients in convalescent period The lung function status in patients with severe acute respiratory syndrome after ten years of convalescence in Tianjin. Zhonghua jie he he hu xi za zhi Long-term outcome of acute respiratory distress syndrome caused by severe acute respiratory syndrome (SARS): an observational study Changes in pulmonary function in SARS patients during the three-year convalescent period The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status 1-year pulmonary function and health status in survivors of severe acute respiratory syndrome Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome Exercise capacity and pulmonary function in hospital workers recovered from severe acute respiratory syndrome One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period Thin-section computed tomography manifestations during convalescence and long-term follow-up of patients with severe acute respiratory syndrome (SARS) Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life Exercise ventilatory inefficiency in post-COVID-19 syndrome: insights from a prospective evaluation Prevalence and characteristics of persistent symptoms after non-severe COVID-19: a prospective cohort study Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort Evaluation of long-term radiological findings, pulmonary functions, and health-related quality of life in survivors of severe COVID-19 Lung diffusing capacity for nitric oxide and carbon monoxide following mild-to-severe COVID-19 Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge Short-Term Consequences of SARS-CoV-2-Related Pneumonia: A Follow Up Study Three-month outcomes of recovered COVID-19 patients: prospective observational study Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnoea Residual Lung Function Impairment Is Associated with Hyperventilation in Patients Recovered from Hospitalised COVID-19: A Cross-Sectional Study Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia Six Months Follow-Up of Patients with Invasive Mechanical Ventilation due to COVID-19 Related ARDS Persistent symptoms up to four months after community and hospital-managed SARS-CoV-2 infection Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study On Behalf Of The Respicovid Study Investigators. Importance of Cardiopulmonary Exercise Testing amongst Subjects Recovering from COVID-19 Six-Month Pulmonary Function After Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease Alteration of Diffusion Capacity After SARS-CoV-2 Infection: A Pathophysiological Approach Residual ground glass opacities three months after Covid-19 pneumonia correlate to alteration of respiratory function: The post Covid M3 study Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae Clinical, radiological and functional outcomes in patients with SARS-CoV-2 pneumonia: a prospective observational study Pulmonary Function and Radiologic Features in Survivors of Critical COVID-19: A 3-Month Prospective Cohort Hyperpolarized 129 Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase Lung function in COVID-19 Intensive Care Unit (ICU) survivors assessed with respiratory oscillometry (osc) and conventional pulmonary function tests (PFT) Cardiopulmonary Exercise Testing in Critically Ill Coronavirus Disease 2019 Survivors: Evidence of a Sustained Exercise Intolerance and Hypermetabolism Clinical Characteristics, Exercise Capacity and Pulmonary Function in Post-COVID-19 Competitive Athletes Analysis of clinical symptoms, radiological changes and pulmonary function data 4 months after COVID-19 lung function and CT findings 3 months after hospital admission for COVID-19 Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: a cohort study Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized 129 Xe MRI Three-month Follow-up Study of Survivors of Coronavirus Disease 2019 after Discharge The pulmonary sequalae in discharged patients with COVID-19: A short-term observational study Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City Follow-Up Study of the Chest CT Characteristics of COVID-19 Survivors Seven Months After Recovery A prospective cohort study on radiological and physiological outcomes of recovered COVID-19 patients 6 months after discharge Residual respiratory impairment after COVID-19 pneumonia Symptoms and pulmonary function improvement after 4 months of acute covid 19 in a Mexican population First report on clinical and radiological features of COVID-19 pneumonitis in a Caucasian population: Factors predicting fibrotic evolution Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length Abnormal pulmonary function and imaging studies in critical COVID-19 survivors at 100 days after the onset of symptoms Cardiopulmonary exercise pattern in patients with persistent dyspnoea after recovery from COVID-19 Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment Severe SARS-CoV-2 pneumonia: Clinical, functional and imaging outcomes at 4 months Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion Laboratory predictors of severe Coronavirus Disease 2019 and lung function in followed-up Recovery after critical illness in COVID-19 ICU survivors Medium-term chest computed tomography (CT) follow-up of COVID-19 pneumonia patients after recovery to assess the rate of resolution and determine the potential predictors of persistent lung changes Functional and radiological follow-up at 3 months of acute respiratory distress syndrome related to SARS-CoV2 in intensive care unit patients Pulmonary function evaluation after hospital discharge of patients with severe COVID-19 Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge Assessment of pulmonary arterial circulation 3 months after hospitalization for SARS-CoV-2 pneumonia: Dual-energy CT (DECT) angiographic study in 55 patients Respiratory follow-up after hospitalization for COVID-19: Who and when? The Long-Term Impact of COVID-19 Pneumonia on the Pulmonary Function of Survivors Trends over Time of Lung Function and Radiological Abnormalities in COVID-19 Pneumonia: A Prospective, Observational, Cohort Study A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia Chest CT in COVID-19 pneumonia: what are the findings in mid-term follow-up? Residual symptoms and lower lung function in patients recovering from SARS-CoV-2 infection Post-discharge critical COVID-19 lung function related to severity of radiologic lung involvement at admission Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19) Pulmonary function and health-related quality of life after COVID-19 pneumonia Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study High Prevalence of Pulmonary Sequelae at 3 Months after Hospital Discharge in Mechanically Ventilated Survivors of COVID-19 COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses Changes to virus taxonomy and the Statutes ratified by the International Committee on Taxonomy of Viruses (2020) Coronaviruses in animals and humans WHO Cumulative Number of Reported Probable Cases of SARS. Geneva: World Health Organization. Accessed 12th Geneva: World Health Organization. Accessed 12th Geneva: World Health Organization. Accessed 1 st The prevalence of long COVID symptoms and COVID-19 complications. 2020. Accessed 12th More than 50 long-term effects of COVID-19: a systematic review and meta-analysis Respiratory follow-up of patients with COVID-19 pneumonia Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience Van Gorkom K. Follow-up chest radiographic findings in patients with MERS-CoV after recovery Genomic characterisation and epidemiology of 2019 novel coronavirus, implications for virus origins and receptor binding Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group Estimating the Mean and Variance from the Median, Range, and the Size of a Sample World Health Organisation. COVID-19 Clinical Management -Living guidance. World Health Organisation. 25 th Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: Evaluation with thin-section CT Follow-up study of chest CT manifestations of patients with severe acute respiratory syndrome Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome A follow-up study of 69 discharged SARS patients Correlation of high-resolution CT, symptoms, and pulmonary function in patients during recovery from severe acute respiratory syndrome The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors Thoracic high resolution CT findings of 100 SARS patients in convalescent period The lung function status in patients with severe acute respiratory syndrome after ten years of convalescence in Tianjin. Zhonghua jie he he hu xi za zhi Long-term outcome of acute respiratory distress syndrome caused by severe acute respiratory syndrome (SARS): an observational study Changes in pulmonary function in SARS patients during the three-year convalescent period The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status 1-year pulmonary function and health status in survivors of severe acute respiratory syndrome Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome Exercise capacity and pulmonary function in hospital workers recovered from severe acute respiratory syndrome One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period Thin-section computed tomography manifestations during convalescence and long-term follow-up of patients with severe acute respiratory syndrome (SARS) Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life Exercise ventilatory inefficiency in post-COVID-19 syndrome: insights from a prospective evaluation Prevalence and characteristics of persistent symptoms after non-severe COVID-19: a prospective cohort study Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort Evaluation of long-term radiological findings, pulmonary functions, and health-related quality of life in survivors of severe COVID-19 Lung diffusing capacity for nitric oxide and carbon monoxide following mild-to-severe COVID-19 Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge Short-Term Consequences of SARS-CoV-2-Related Pneumonia: A Follow Up Study Three-month outcomes of recovered COVID-19 patients: prospective observational study Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnoea Residual Lung Function Impairment Is Associated with Hyperventilation in Patients Recovered from Hospitalised COVID-19: A Cross-Sectional Study Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia Six Months Follow-Up of Patients with Invasive Mechanical Ventilation due to COVID-19 Related ARDS Persistent symptoms up to four months after community and hospital-managed SARS-CoV-2 infection Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study On Behalf Of The Respicovid Study Investigators. Importance of Cardiopulmonary Exercise Testing amongst Subjects Recovering from COVID-19 Six-Month Pulmonary Function After Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease Alteration of Diffusion Capacity After SARS-CoV-2 Infection: A Pathophysiological Approach Residual ground glass opacities three months after Covid-19 pneumonia correlate to alteration of respiratory function: The post Covid M3 study Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae Clinical, radiological and functional outcomes in patients with SARS-CoV-2 pneumonia: a prospective observational study Pulmonary Function and Radiologic Features in Survivors of Critical COVID-19: A 3-Month Prospective Cohort Hyperpolarized 129 Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase Lung function in COVID-19 Intensive Care Unit (ICU) survivors assessed with respiratory oscillometry (osc) and conventional pulmonary function tests (PFT) Cardiopulmonary Exercise Testing in Critically Ill Coronavirus Disease 2019 Survivors: Evidence of a Sustained Exercise Intolerance and Hypermetabolism Clinical Characteristics, Exercise Capacity and Pulmonary Function in Post-COVID-19 Competitive Athletes Analysis of clinical symptoms, radiological changes and pulmonary function data 4 months after COVID-19 lung function and CT findings 3 months after hospital admission for COVID-19 Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: a cohort study Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized 129 Xe MRI Three-month Follow-up Study of Survivors of Coronavirus Disease 2019 after Discharge The pulmonary sequalae in discharged patients with COVID-19: A short-term observational study Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City Follow-Up Study of the Chest CT Characteristics of COVID-19 Survivors Seven Months After Recovery A prospective cohort study on radiological and physiological outcomes of recovered COVID-19 patients 6 months after discharge Residual respiratory impairment after COVID-19 pneumonia Symptoms and pulmonary function improvement after 4 months of acute covid 19 in a Mexican population First report on clinical and radiological features of COVID-19 pneumonitis in a Caucasian population: Factors predicting fibrotic evolution Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length Abnormal pulmonary function and imaging studies in critical COVID-19 survivors at 100 days after the onset of symptoms Cardiopulmonary exercise pattern in patients with persistent dyspnoea after recovery from COVID-19 Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment Severe SARS-CoV-2 pneumonia: Clinical, functional and imaging outcomes at 4 months Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion Laboratory predictors of severe Coronavirus Disease 2019 and lung function in followed-up Recovery after critical illness in COVID-19 ICU survivors Medium-term chest computed tomography (CT) follow-up of COVID-19 pneumonia patients after recovery to assess the rate of resolution and determine the potential predictors of persistent lung changes Functional and radiological follow-up at 3 months of acute respiratory distress syndrome related to SARS-CoV2 in intensive care unit patients Pulmonary function evaluation after hospital discharge of patients with severe COVID-19 Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge Assessment of pulmonary arterial circulation 3 months after hospitalization for SARS-CoV-2 pneumonia: Dual-energy CT (DECT) angiographic study in 55 patients Respiratory follow-up after hospitalization for COVID-19: Who and when? The Long-Term Impact of COVID-19 Pneumonia on the Pulmonary Function of Survivors Trends over Time of Lung Function and Radiological Abnormalities in COVID-19 Pneumonia: A Prospective, Observational, Cohort Study A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia Chest CT in COVID-19 pneumonia: what are the findings in mid-term follow-up? Residual symptoms and lower lung function in patients recovering from SARS-CoV-2 infection Post-discharge critical COVID-19 lung function related to severity of radiologic lung involvement at admission Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19) Pulmonary function and health-related quality of life after COVID-19 pneumonia Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study High Prevalence of Pulmonary Sequelae at 3 Months after Hospital Discharge in Mechanically Ventilated Survivors of COVID-19 Reduced exercise tolerance in long-COVID patients Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation Pulmonary function, computerized tomography features and six-minute walk test at three months in severe COVID-19 patients treated with intravenous pulsed methylprednisolone: a preliminary report. 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Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19 A Follow-Up Study of Lung Function and Chest Computed Tomography at 6 Months after Discharge in Patients with Coronavirus Disease 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study Plasma metabolomic profiling of patients recovered from COVID-19 with pulmonary sequelae 3 months after discharge Follow-up study of pulmonary function among COVID-19 survivors 1 year after recovery Fibrotic Changes Depicted by Thin-Section CT in Patients With COVID-19 at the Early Recovery Stage: Preliminary Experience Time course of exercise capacity in patients recovering from COVID-19-associated pneumonia Eight months follow-up study on pulmonary function, lung radiographic, and related physiological characteristics in COVID-19 survivors Analysis of Chest CT Results of Coronavirus Disease 2019 (COVID-19) Patients at First Follow-Up Comparison of Residual Pulmonary Abnormalities 3 Months After Discharge in Patients Who Recovered From COVID-19 of Different Severity The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans Weaned but weary: one third of adult intensive care patients mechanically ventilated for 7 days or more have impaired inspiratory muscle endurance after successful weaning Mechanical ventilation-induced diaphragm atrophy strongly impacts clinical outcomes Coexistence and impact of limb muscle and diaphragm weakness at time of liberation from mechanical ventilation in medical intensive care unit patients Inspiratory muscle training for recovered COVID-19 patients after weaning from mechanical ventilation. A pilot control clinical study Respiratory rehabilitation in elderly patients with COVID-19: a randomised controlled study Benefits of pulmonary rehabilitation in COVID-19: a prospective observational cohort study Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias Lung diffusing capacities (DL) for nitric oxide (NO) and carbon monoxide (CO): The evolving story Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series Interstitial lung disease after COVID-19 infection: A Catalog of Uncertainties Severe acute respiratory syndrome (SARS): epidemiology and clinical features Intensive care management of patients with COVID-19: a practical approach One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID) A multidisciplinary multicenter study evaluating risk factors, prevalence and characteristics of post-COVID-19 interstitial lung syndrome pcoils We thank Dr Michael Newnham (University of Birmingham and University Hospitals Birmingham NHS Foundation Trust) for reviewing analysis and figures displayed in the manuscript and Dr Malcolm Price at the University of Birmingham for early statistical advice. We would also like to thank Amanda Wood who read Chinese, Korean and Japanese language studies alongside AMT. We thank Dr Michael Newnham (University of Birmingham and University Hospitals Birmingham NHS Foundation Trust) for reviewing analysis and figures displayed in the manuscript and Dr Malcolm Price at the University of Birmingham for early statistical advice. We would also like to thank Amanda Wood who read Chinese, Korean and Japanese language studies alongside AMT.