key: cord-0716356-6jy090dj authors: Bardakci, Mustafa Ilteris; Ozturk, Esin Nagihan; Ozkarafakili, Mufide Arzu; Ozkurt, Huseyin; Yanc, Ugur; Yildiz Sevgi, Dilek title: Evaluation of long‐term radiological findings, pulmonary functions, and health‐related quality of life in survivors of severe COVID‐19 date: 2021-05-31 journal: J Med Virol DOI: 10.1002/jmv.27101 sha: dddebd9c5b5cef997770f945ba6797e042a9f023 doc_id: 716356 cord_uid: 6jy090dj OBJECTIVE: It was aimed to evaluate long‐term radiological changes in severe coronavirus disease 2019 (COVID‐19) patients, to investigate pulmonary function, exercise capacities, and health‐related quality of life results. METHODS: Sixty‐five patients with severe COVID‐19 pneumonia were evaluated in the sixth month after discharge from the hospital. Spirometry, 6 min walking test (6MWT), and short form of health‐related quality of life scale (SF‐36) were applied in the sixth month. Chest computed tomography (CT) was performed and the findings were grouped according to lung involvement. RESULTS: Forty‐nine male and 16 female patients were included in the study. Forced expiratory volume in 1 s (FEV1)% values of 18 patients (30.5%), forced vital capacity (FVC)% values of 27 patients (45.8%), and 6MWT of 13 patients (23.2%) were found lower than expected in the sixth month. On the SF‐36 scale, physical function, energy‐vitality, social functionality, pain, and general health parameters were found lower than normal. Minimal interstitial changes in chest CT were seen in 26 patients. Nine patients had lung area involvement between 10% and 50% of the surface, there was a correlation between FEV1% and FVC% values in this group. There was severe pulmonary fibrosis in four patients. There was a correlation between pulmonary function and physical function and general perception of health from SF‐36 scale subparameters. CONCLUSION: Functional and radiological abnormalities were detected in a significant number of patients in the sixth month after severe COVID‐19 pneumonia. A systematic monitoring plan must be established to assess and properly manage the long‐term problems that may arise. Coronavirus disease-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After the reporting of unexplainable cases of pneumonia in Wuhan, China in December 2019, a new coronavirus that had not been detected in humans before was identified on January 7, 2020, and was named SARS-CoV-2 due to the similarity of the virus to SARS-CoV. Due to the spread and severity of the virus, the World Health Organization declared COVID-10 a global pandemic March 11, 2020. 1 COVID-19 may be clinically asymptomatic or may show various symptoms as a result of the involvement of multiple systems, such as respiratory, cardiovascular, gastrointestinal, and central nervous system in the disease. 2 Deaths may occur due to complications after multisystem involvement. As of February 18, 2021, 109,594,835 cases and 2,424,060 deaths were recorded worldwide. 3 The respiratory system is the most commonly affected system in patients [5] [6] [7] whose viral structures are similar to that of SARS-CoV-2. Considering that the COVID-19 pandemic is still ongoing, it is important to investigate its effects on the long-term pulmonary capacity and functionality with the follow-up of patients who had the infection and to assess the morbidity associated with this disease. The aim of this study is to search the long-term effects of COVID-19 on patients who have had severe COVID-19 pneumonia history. We would like to find out the potential long-term impacts of COVID-19 on pulmonary capacity and health-related quality of life. Patients over 18 years old who were followed up between March 11 and July 30, 2020, in COVID inpatient clinics of our hospital; patients with SARS-CoV-2 PCR (+) and/or SARS-CoV-2 IgM/G (+); patients clinically and radiologically compatible with COVID-19 diagnosis and patients whose cases cannot be identified by any other disease except for COVID-19 according to the T.C. Ministry of Health, Public Health COVID-19 Field Guide. 1 Among these patients, patients with severe pneumonia according to the Ministry's guide were included in this study. According to the Ministry's guide, severe pneumonia findings are shown below: • Patients who have symptoms, such as fever, muscle/joint pains, cough, sore throat, and nasal congestion, have tachypnea (≥30/ min) or have SpO 2 level less than 90% in room air • Poor prognostic measurement in the blood tests taken in the application (number of blood lymphocytes <800/μl or CRP > 40 mg/l or ferritin >500 ng/ml or D-dimer >1000 ng/ml, etc.) • Patients with bilateral diffuse pneumonia findings in pulmonary Xray or CT. Spirometry and 6 min walking test (6MWT) requires good physical function and patient compliance, so among patients covering severe pneumonia criteria, we selected patients who were able to perform spirometry and 6MWT. Patients who had neurological diseases, such as advanced dementia, Alzheimer's, SVD, etc; patients who had a history of orthopedic or other surgical operations, and consequently, were not able to take the walking test; and patients over 90 years old were not included. The volunteer consent form was obtained from the patients who participated in the study. The patient participation scheme is shown in Figure 1 . Patients were called to the outpatient clinic between the sixth and seventh month after discharge from the hospital. The patients were given a pulmonary function test (spirometry), 6MWT. SF-36 form was filled and chest CT was done for each patient. This study is a single-centered, prospective observational case study. Our study has been approved by the ethics committee (April 2, 2020/1489). The patients were subjected to a pulmonary function test (spirometry) and 6 min walking test (6MWT), associated with the daily activity of people. The tests, respectively, were aimed to evaluate F I G U R E 1 Patient participation scheme respiratory functions and musculoskeletal and cardiopulmonary system functions. 6MWT provides a standardized, objective, and integrated assessment of cardiopulmonary and musculoskeletal function related to our daily activities. 8 The test (6MWT) conducted under the supervision of a physician involved a 6-min walk along a flat corridor at a pace as quick as the patient can manage. Before and after the test, respiratory rate, heart rate per minute, and arterial blood pressure have been checked, and the walking distances of each patient within six minutes were recorded. The test was conducted in compliance with American Thoracic Society (ATS) protocols. 9 Spirometry was carried out by a spirometry technician wearing protective equipment to prevent contamination in our hospital's Pulmonary Function Testing Laboratory. Spirometry was carried out in accordance with ATS-European Respiratory Society guidelines using MIR Spirolab II (Rome/Italy) device. [10] [11] The patients were informed about maneuvers and three spirograms were performed. The best results that met the criteria for repeatability and acceptability were included in the study. Health-related quality of life is defined as the subjective sensation of the multifaceted effect of disease by patients. 12 The short form 36-point questionnaire (SF-36) is a popular tool for assessing healthrelated quality of life. In this study, we used the Turkish version of SF-36 to evaluate the change in health-related quality of life of our COVID-19 patients in tests conducted after 6 months of their recovery, which we will refer to as "sixth-month controls" in this article. 13 This survey includes eight parameters: physical functioning, physical role difficulties, pain, general health, emotional role difficulties, energy-vitality, mental health, and social functionality. The first four parameters are related to physical health and the others are related to mental health. Scores for each parameter vary between 0 and 100 and higher scores show a better quality of life. Normal values for parameters are different from each other. Using this scale, we planned to assess health-related quality of life and objectively evaluate the physical and mental functionality of the patients after 6 months of recovery. The radiological lung findings of the patients were evaluated with lung chest-CT in the sixth-month controls. It was aimed to evaluate the course of lung involvement and the effect of COVID-19 on the lung in the long term. In the sixth-month controls, 60 patients had nonenhanced chest-CT. The patients were assigned to the protocol, with 100 kV (peak) (kV[p]) and 20 effective milli ampere-second (eff mA-s) during single breathold. Axial images of 2 mm slice thickness were obtained using an image matrix of 512 × 512 pixels. We used a mediatenum window setting (width, 400 HU; level, 100 HU) and a lung window setting (width, 1500 HU; level, -500 HU) for this analysis. Nearly all studies about radiological findings of COVID-19 show and identify the distribution of lesions while active COVID-19 infection is present. There is no scoring that shows interstitial changes, fibrosis intensity, and distribution of lesions in patients who recovered from COVID-19. All physicians who participated in the study have consensus on collecting CT results in five groups by prioritizing tomography findings, interstitial changes, and/or the percentage of distribution of fibrosis. The images were evaluated by two radiologists, both blind to clinical information. CT scans were taken on the same day as the spirometry, 6MWT, and SF-36. CT findings were grouped as shown below: In the sixth-month controls, spirometry was applied to 59 patients. Eighteen of the patients (30.5%) were found to have a low FEV1% value, 27 of the patients (45.8%) had lower FVC% values. 6MWD was also measured as low in 13 of the patients (23.2%), (p < 0.001). Four of our patients were known to have a history of obstructive lung disease (chronic obstructive pulmonary disease/asthma), but BARDAKCI ET AL. | 3 none of them had respiratory distress at the time of the tests and FEV1/FVC ratio measurements were greater than 70%. SF-36 was applied to all 65 patients. This test could be separated into eight parameters. Of the 55 patients (84.6%), the parameter of physical function was lower than expected, energy-vitality parameter in 46 patients (70.8%), social functionality parameter in 53 patients (81.5%), pain parameter in 50 patients (76.9%), and general health perception parameter in 60 patients (92.3%) were found to be lower than expected. Changes in these parameters are statistically significant (p < 0.05). Comparison of SF-36 scores of participants with those of the Turkish population is also shown in Figure 2 Sixty patients were given chest-CT in the sixth-month controls. In this study, while chest CT was normal in 21 patients (35%), 39 of the patient (65%) had chest CT findings with a spectrum from minimal changes to advanced changes including honeycombs. CT changes were minimal in 26 of the 39 patients with abnormal CT findings. Considerable fibrotic changes were seen in four patients. The distribution of the sixth-month controls of CT findings is shown in Table 2 . As a result of the sixth-month controls, in chest-CT findings of the 60 patients revealed a statistically significant difference in terms of observed and expected values (p < 0.05). Compared to the cases with and without deterioration in chest-CT in the sixth-month controls, FEV1% and FVC% values of the cases with deterioration in chest-CT were significantly lower (p < 0.05). Group 3 (Middle-lower lobe dominant, reticulation + traction, 10%-50% surface area) FVC% and FEV1% values were found to be low (p < 0.05). There was no statistically significant difference between the groups in terms of other variables (p > 0.05) ( Table 3) . When spirometry and 6MWD correlation with SF-36 scores were examined in the sixth-month control; a positive and statistically significant correlation was found between sixth-month 6MWD values and SF-36 physical function, physical role difficulties, vitality, pain, overall health, and health change size scores (p < 0.05). Statistically, a significant correlation was found between FVC% values and SF-36 physical function and overall health perception size scores (p < 0.05). Statistically, a significant correlation was also found between the sixth month FEV1% values and SF-36 physical function, physical role difficulties, vitality, social functionality, and general health perception parameters (p < 0.05) ( that suffered the disease more severely. 18, 19 In the other study, in which 6-month results in China were published, researchers grouped patients and found lower 6MWD in groups receiving oxygen support and/or respiratory support. 20 We measured 6MWD in the sixthmonth controls of our patients. Our results were similar to other study results. The number of studies assessing the respiratory function of patients with COVID-19 is increasing. In the studies carried out by Van der Sar-van der Brugge et al., 21 You et al., 22 They rarely observed pulmonary fibrosis and stated that lesions were more pronounced in those who suffered the disease more severely. 18 Zhao et al. 24 and Truffaut et al. 26 Considerable fibrotic changes were detected in 4 of the patients while 26 of the patients had minimal changes. It is yet unknown whether or not the changes detected in the spirometry and observed in chest CT can be fully recovered. Because of that, we need to continue to work with the first-year controls and continue to search for answers to these questions. The authors declare that there is no conflict of interest that could be perceived as damaging to the impartiality of the reported research. The data that support the findings of this study are available on request from the corresponding author. The data is not publicly available due to privacy or ethical restrictions. Mustafa Ilteris Bardakci https://orcid.org/0000-0002-9038-4049 Esin Nagihan Ozturk https://orcid.org/0000-0001-6652-3582 Mufide Arzu Ozkarafakili https://orcid.org/0000-0002-8345-4539 Dilek Yildiz Sevgi https://orcid.org/0000-0002-6047-4879 Republic of Turkey Ministry of Health General Directorate of Public Health. Covid-19 (SARS-CoV-2 infection) Guideline Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) World Health Organization. Coronavirus disease 2019 (COVID-19) situation report COVID-19 Pnömonisinin Radyolojik Bulguları. Southern Clinics of Istanbul Eurasia Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome The impact of severe acute respiratory syndrome on the physical profile and quality of life Clinical exercise testing Statement: guidelines for the six-minute walk test Standardization of spirometry: 1994 update Standardisation of the measurement of lung volumes Burden of illness and quality-of-life measures in angioedema conditions Validity and reliability of Turkish version of Short form 36: a study of a patients with romatoid disorder. İlaç ve Tedavi Dergisi Radiology perspective of coronavirus disease 2019 (COVID-19): lessons from severe acute respiratory syndrome and Middle East respiratory syndrome Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Long term clinical outcames in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: a systematic rewiew and meta-analysis Functional disability 5 years after acute respiratory distress syndrome Pulmonary function and radiological features four months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Pulmonary function and health-related quality of life after COVID-19 pneumonia Anormal pulmonary function and residual CT abnormalities in rehabilitating COVID-19 patients after discharge Pulmonary function in patients surviving to COVID-19 pneumonia Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivor three months after recovery Predictors of health related quality of life and influencing factors for COVID-19 patients, a follow-up at one month Post-discharge critical COVID-19 lung function related to severity of radiologic lung involvement at admission Evaluation of long-term radiological findings, pulmonary functions, and health-related quality of life in survivors of severe COVID-19