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

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.

'One Year Later' - SARS-CoV-2-Specific Immunity in Mild Cases of COVID-19 (preprint)

Background: Duration and quality of immunity to SARS-CoV-2 have significant implications for the management of COVID-19 pandemic. Here, we present a comprehensive set of immunological data from a cohort of individuals (n=43), 12 months after mild COVID-19 disease and in the absence of virus re-exposure.Methods: Serum and PBMC were collected from mild-COVID-19 convalescents 12 months after the COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15). Serum titers of SARS-CoV-2-specific immunoglobulins were quantified by ELISA and virus neutralisation activity was assessed using SARS-CoV-2-Spike pseudovirus particles. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped with an activation-induced marker assay.Findings: In the absence of re-exposure to SARS-CoV-2 Spike- and RBD-specific antibodies were present in 90% of COVID-19 convalescents 12 months post-infection. RBD-specific IgG + memory B cells were maintained in 88.9% of patients, while 62% of patients had serum neutralising activity. Functionally mature memory CD4 + and CD8 + T cells were maintained at frequencies previously reported for earlier time points post-COVID-19, indicating substantial maintenance of durable T cell responses. Interpretations: Immunity to SARS-CoV-2 persists for 12 months in mild COVID-19 convalescent patients that retain high Spike-specific antibody titres, virus neutralisation capacity and circulating RBD-specific memory B cells. Significantly, T cell immunity remained stable 12 months post-infection. This study offers vital information on the duration of natural COVID-19 immunity and its potential protective effect against SARS-CoV-2 reinfection and clinical disease, with clear implications for the ongoing management of the global pandemic. Funding Statement: This work was funded by project grants from The Hospital Research Foundation and Women’s and Children’s Foundation, Adelaide, Australia. This work has been supported by NIH contract 75N9301900065 (A.S, D.W).Declaration of Interests: A.S. is currently a consultant for Gritstone, Flow Pharma, Arcturus, Epitogenesis, Oxfordimmunotech, Caprion and Avalia. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.Authors PGV, CMH, MGM, AELY, HB, ZAM, ZAD, AA, DA, JG, CF, SO, EMM, DJL, GM, EJG, BAJR, DS, CKL, MRB, DW, RAB, SCB and BGB declare no conflict of interest.Ethics Approval Statement: Study protocols were approved by the Central Adelaide Clinical Human Research Ethics Committee (#13050) and the Women’s and Children’s Health Network Human research ethics (protocol HREC/19/WCHN/65), Adelaide, Australia.

A Systematic Review of COVID - 19 Induced Myocarditis - Symptomatology, Prognosis, and Clinical Findings (preprint)

Objective: With the advent of a novel coronavirus in December 2019, several case studies have reported its adversity on cardiac cells. We conducted a systematic review that describes the symptomatology, prognosis, and clinical findings of patients with COVID-19-related myocarditis. Methods: Search engines including PubMed, Google Scholar, Cochrane Central, and Web of Science were queried for SARS-CoV-2 or COVID 19 and myocarditis. PRISMA guidelines were employed, and peer-reviewed journals in English related to COVID-19 were included. Results: This systematic review included 22 studies and 37 patients. Eight patients (36%) were confirmed myocarditis, while the rest were possible myocarditis. Most patients had elevated cardiac biomarkers, including troponin, CRP, CK, CK-MB, and NT-pro BNP. Electrocardiogram results noted tachycardia (47%), left ventricular hypertrophy (50%), ST-segment alterations (41%), and T wave inversion (18%). Echocardiography presented reduced LVEF (77%), left ventricle abnormalities (34%), right ventricle aberrations (12%), and pericardial effusion (71%). Further, CMR showed reduced myocardial edema (75%), non-ischemic patterns (50%), and hypokinesis (26%). The mortality was significant at 25%. Conclusions: Mortality associated with COVID-19 myocarditis appears significant but underestimated. Further studies are warranted to evaluate and quantify patients actual prognosis and outcomes with COVID-19 myocarditis.