Blood Oxygen Levels

We preprocessed the raw resting-state fMRI data per the following steps. First, we removed the first five data points. Second, we corrected all images by slice-timing, realigning, and manually reorienting images. Third, we coregistered the reoriented images with T1-weighted images, normalized to the MNI152 standard space, and resampled them to a 3 × 3 × 3 mm³ voxel. Fourth, we regressed out covariates, including those pertaining to the time courses of 6 head motions, white matter, and cerebrospinal fluid. Finally, we also performed temporal lowpass filtering (0.01–0.1 Hz).
Subsequently, we calculated the average voxel-wised FC using the Pearson’s correlation coefficient (r) between the blood-oxygen-level-dependent time series of each voxel. We also applied Fisher’s z transformation to improve the normality of the data [40 (link), 41 (link)]. Finally, we acquired 90 FC maps for each participant by applying the AAL atlas [39 (link)] to segment the participants’ images (Fig. 1A).

The current study comprised 3,184 patients with a diagnosis of COVID-19 who were referred to a teaching hospital of Ilam University of Medical Sciences, Ilam, Iran, within November 2020 to February 2022, including 1,734 recovered and 1450 deceased patients. A COVID-19 infection was deemed for all patients as a result of a positive SARS-CoV-2 laboratory test with real-time reverse transcription polymerase chain reaction (rtReal time-PCR) from the nasopharyngeal swabs. Peripheral blood samples from each patient were taken to isolate deoxyribonucleic acid (DNA) and conduct additional genetic studies.
The samples were collected in the three peaks (Alpha, Delta, and Omicron BA.5) from 14,472 positive patients based on the inclusion criteria, namely (1) patients who were willing to participate in the study and had signed a written consent form, (2) all patients who were Iranian with one ethnicity, and (3) patients who did not have any underlying comorbidities diseases, such as kidney, heart, and pulmonary diseases, hypertension, diabetes, obesity, cancer, viral infections (e.g., human immunodeficiency virus and hepatitis B and C viruses), and pregnancy.
All clinical data of patients such as real-time PCR cycle threshold (Ct) values, 25-hydroxyvitamin D, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count (CBC), lipid profile (cholesterol, high density lipoprotein, and low density lipoprotein), liver enzymes (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), creatinine and uric acid were extracted from patient files, and these tests were performed when the patient entered the hospital.
According to the World Health Organization guidelines, adult COVID-19 patients were divided into three clinical course categories, mild, moderate, and severe. In this study, subjects with mild/moderate and severe/critical symptoms were considered recovered and deceased patients, respectively.
Patients with mild symptoms include those who have a fever, fatigue, cough, headache, myalgia, and fatigue but do not have dyspnea or pneumonia; patients with moderate symptoms include those who have blood oxygen saturation levels above 93% on room air and evidence of pneumonia based on imaging showing up to 50% lung involvement; patients with severe symptoms include those who have blood oxygen saturation levels below 93% on room air and need supportive oxygen therapy.