Single and Multiple Effects of COVID-19 Post-Acute Sequelae: 6-Month Follow-Up Cohort Study

Abstract

Background: Medical research is progressing to clarify the full spectrum of sub-acute and long-term effects of post-acute sequelae of COVID-19. However, most manuscripts published to date only analyze the effects of long COVID in patients discharged from hospital, which may induce significant bias. This work aims to analyze the single and multiple association between long-term post-COVID features and patients with/without previous respiratory diseases, hospitalized or not, and the abnormalities of chest CT images. Methods: The cohort study was conducted at the University Hospital Virgen de la Nieves, one of the hospitals assigned for patients with COVID-19 in Granada, Spain. Two visits were scheduled in the follow-up period from May to October 2020. The first follow-up consultation (FFuC) was two months after the diagnosis of COVID-19 infection. Here, the basal, clinical, and physical examination parameters were collected. Chest HRCT scan images were recorded at mm intervals in the supine position, including the serology for SARS-CoV-2 for patients with radiological or clinical involvement with dyspnea. The results were evaluated separately by two independent reviewers. The second follow-up consultation (SFuC) — 6-months after the initial diagnosis — the patients were re-appointed with laboratory tests, pulmonary function, and chest HRCT according to the criteria set forth above. Findings: At the first consultation, 217 patients after infection with SARS-CoV2 — from February to April 2020 — were referred to the University Hospital Virgen de la Nieves. The second consultation was carried out from July to September 2020, and 207 of the 217 attended. The median age and BMI were 59 (interquartile range, 49-68) and 28 (26-32), respectively, of which 116 (53·5%) were men. The most frequent features were: dyspnea, fatigue, dry cough, myalgia, loss of taste/smell, air loss as clinical characteristics; emotional affectation, depression, the cognitive deficit as mental health affectations; hemoglobin, ferritin, and d-dimer as abnormal laboratory indices. The clinical features were more frequent in women than in men. However, mental affections were more frequent in females in the first consultation and more frequent in males in the second consultation. Bivariate or multivariate logistic adjustments showed a strong statistically significant association of the following characteristics: abnormal body mass index, former smoker, dyspnea, fatigue, emotional affectation, depression, FEV1, DLCO, and FEV1/FVC below their normal limits with pre-existing respiratory diseases; male sex, age>59 years, non-heath worker, fatigue, and venous thrombosis with hospitalization status. Bilateral lung involvement, subpleural reticulum, ground-glass opacity, peripheral lung lesions, and bronchiolectasis were the most common findings from the high-resolution chest CT images. A strong statistically significant association was found between male sex, age>59 years, ex-smoker, non-smoker, and abnormal radiographs with an abnormal result of CT images. Interpretation: At six months follow-up, PASC characteristics fatigue, arthralgia, fever, breathlessness, emotional disturbance, depression, cognitive deficit, hemoglobin, total bilirubin, and ferritin are correlated with the gender of the patient. Patients with previous respiratory diseases and abnormal BM, ex-smoker, and dyspnea had a robust statistically significant association. Non-hospitalized patients may suffer more. Funding: None to declare. Declaration of Interest: The authors declared no conflict of interest. Ethical Approval: The study was conducted in accordance with the requirements of the Declaration of Helsinki (Tokyo revision, October 2004), and the Spanish Data Protection Act of 15/1999. The study was approved by the Center's Ethics Committee.