Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study (preprint)

Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors

Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome (preprint)

Background The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. Methods Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. Results Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time. Discussion The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Post-COVID Syndrome. A Case Series and Comprehensive Review (preprint)

The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8 to 55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143 to 258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2 to 1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.