Association of Lung Fibrotic Changes and Cardiological Dysfunction with Hypertension in Long COVID-19 cohort

Abstract

Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID and its comorbidities have not been established. Methods. Between May and September 2020 we included 312 patients with post-COVID-19 from 21 primary care centers if they had any persistent symptoms for at least three months from the first onset of the disease. On the 6 months follow up, their lung function was assessed by CT and spirometry, whereas cardiac function was assessed by electrocardiogram (ECG), Holter ECG, Echocardiography, and 24-hour blood pressure monitoring. A six-minute test (6MWT) was conducted on 308 participants during the follow-up visit. All participants were given a questionnaire with items on demographic information, current complaints, comorbidities, and medications, and Chalder Fatigue Scale (CFS) questionnaire. Statistical analysis was done using R vs. 4.1.2. Two-group comparison of continuous variables was performed using a T-test for normally distributed data, and the Mann-Whitney Wilcoxon test, ANOVA, and Kruskal-Wallis tests were applied for multiple comparisons following with Tukey and Dunn tests as post-hoc methods. Hochberg p-value adjustment was used to reduce the false discovery rate during multiple comparisons. Categorical variables were analyzed with Fishers Exact test. Results. Of 312 persons investigated, there was no significant gender difference between post-COVID-19 clinical manifestations except for memory dysfunction and anxiety, more prevalent among female participants. Chalder Fatigue Score was predominant in female participants (243, 78%). 39 (12.5%) participants reported having type 2 diabetes mellitus, and 158 (50.64%) had hypertension. Among the tested parameters, those positively correlated with comorbid conditions include age, BMI, D-dimers, NT-proBNP, C-reactive protein, neutrophils, fasting glucose, and HbA1c; hypertension also shows three associations that were not found in patients when examining the role of diabetes: increased hemoglobin, fibrinogen, and ferritin. 24-hour blood pressure monitoring revealed significantly higher systolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP in participants with hypertension and subjects with type 2 diabetes. Left ventricular diastolic dysfunction is more frequently present in patients with hypertension. Chest CT was conducted on 227 (72.8%) participants 5.8+/-0.9 months after the onset of COVID-19. The most common registered CT abnormality was chronic bronchitis (198, 87.2%), followed by fibrotic changes in (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Immunological test results showed that SARS-CoV19 IgG antibodies were present in 241 subjects (77.2%), and SARS-CoV19 IgM antibodies were present in 9 subjects (2.88%). Conclusions. Our study provides valuable clues for long-term post-sequelae in a cohort of the Long COVID-19 subjects. We demonstrated a strong association of signs of cardiac dysfunction, lung fibrotic changes, increased hemoglobin, fibrinogen, and ferritin with hypertension but not with other comorbidities. Our results are of importance for understanding the Long Covid-19 syndrome.