Clinical Characteristics and Outcomes of Covid-19 Patients With Underlying Dementia: Results From a Large Multicenter Propensity-matched Brazilian Cohort Study (preprint)

Background  Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia.  Methods  This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events.  Results  Among 8,947 eligible patients, 405 (4.5%) had a diagnosis of dementia and were matched with 1,151 patients without dementia. Compared to a group of similar demographics and comorbidities, patients with dementia presented a lower duration of symptoms (5.0 vs. 7.0 days; p<0.001) and frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia. Fever and delirium were more frequent in patients with dementia than the control group. Patients with dementia also received more palliative care than the control group. Dementia was associated with lower admission (32.7% vs. 47.1%, p<0.001) and length of stay (7 vs. 9 days, p<0.026) in the ICU, frequency of sepsis (17% vs. 24%, p=0.005), KRT (6.4% vs. 13%, p<0.001), and IVM (4.6% vs. 9.8%, p=0.002). We did not find differences in hospital mortality among those with and without dementia.  Conclusion  Clinical manifestations of COVID-19 differ in older patients with and without dementia in the hospital, with delirium being highly prevalent among those with dementia. Our findings indicate that dementia alone might not explain higher short-term mortality after severe COVID-19. Clinicians should include other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of COVID-19 in the hospital.

COVID-19 outcomes in people living with HIV: peering through the waves (preprint)

Background: HIV infection remains a public health concern, especially in low- and middle-income countries. Data regarding exposure of COVID-19 in HIV infected patients remains scarce. We evaluated clinical characteristics and outcomes of COVID-19 patients infected with HIV, and compared with a paired sample without HIV infection. Methods: This is a substudy of a large Brazilian cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records to collect variables of interest and primary outcomes: intensive care admission, mechanical ventilation and death. COVID-19 patients infected with HIV were compared to COVID-19 patients without concomitant diagnosis of HIV infection using the Chi-Square Test and Fisher's exact test for categorical variables and the Wilcoxon test for numerical variables. Both groups were matched for age, sex, number of comorbidities and hospital of origin using the technique of propensity score matching (up to 4:1).Results: Throughout the study, 17,101 COVID-19 patients were hospitalized, 130 (0.76%) of these infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with predominance of females in both periods. People living with HIV (PLHIV) and their controls showed similar prevalence for the admission in the ICU and mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs 17.7%; p=0.049), but there was no difference in mortality between groups in 2021 (25.0% vs 25.1%; p>0.999). Conclusion: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, indicating that measures such as large-scale immunization programs have successfully contributed to reducing the excess mortality seen in PLHIV.

Hypernatremia increases mortality in patients admitted by COVID-19: A Retrospective longitudinal study with 1000 patients (preprint)

Coronavirus disease 2019 (COVID-19) pandemic spread rapidly and this scenario is concerning worldwide. In hospitalized patients, dysnatremia (hyponatremia and/or hypernatremia) is the most common electrolyte disturbance, being reported in 30–40% of cases and associated with a poor prognosis. This retrospective longitudinal study aimed to evaluate the association of dysnatremia with mortality in hospitalized patients infected with COVID-19. We analyzed data from hospital records of 1000 patients with COVID-19 (median age, 62.5 years; 57.1% men), including 109 (10.9%) deaths. Kaplan-Meier survival curves and Cox proportional hazard models with Hazard Ratio (HR) with 95% confidence intervals (95%CI) were applied to confirm the association between dysnatremia (hyponatremia and/or hypernatremia) and death. Hypernatremia was detected in 83 (76.1%) of the patients who died, with a cumulative reduction in survival (p < 0.01) and an increased risk for death by 2.4 fold (95%CI 1.4–2.9). In the multivariable analysis, hypernatremia was the main factor associated with increased mortality (HR:1.50; 95%CI:1.23–1.81). Other factors also associated with death were long length of stay (LOS) (HR:1.54; 95%CI:1.21–1.78), old age (HR:1.63; 95%CI:1.28–1.88), and kidney disease (HR:1.77; 95%CI:1.21–3.30). Hypernatremia during hospitalization is an important risk factor for poor prognosis and an increased risk (2.4) of mortality. LOS, old age, and kidney disease could also be used for risk stratification in patients with COVID-19.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients (preprint)

Background: Acute kidney injury (AKI) is frequently associated with COVID-19 and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalized COVID-19 patients. Methods: This study is part of the multicentre cohort, the Brazilian COVID-19 Registry. A total of 5,212 adult COVID-19 patients were included between March/2020 and September/2020. We evaluated four categories of predictor variables: (1) demographic data; (2) comorbidities and conditions at admission; (3) laboratory exams within 24 h; and (4) the need for mechanical ventilation at any time during hospitalization. Variable selection was performed using generalized additive models (GAM) and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. The accuracy was assessed using the area under the receiver operating characteristic curve (AUCROC). Risk groups were proposed based on predicted probabilities: non-high (up to 14.9%), high (15.0 to 49.9%), and very high risk ([≥] 50.0%). Results: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalization. The validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. Thirty-two variables were tested and four important predictors of the need for KRT during hospitalization were identified using GAM: need for mechanical ventilation, male gender, higher creatinine at admission, and diabetes. The MMCD score had excellent discrimination in derivation (AUROC = 0.929; 95% CI 0.918-0.939) and validation (AUROC = 0.927; 95% CI 0.911-0.941) cohorts an good overall performance in both cohorts (Brier score: 0.057 and 0.056, respectively). The score is implemented in a freely available online risk calculator (https://www.mmcdscore.com/). Conclusion: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalized COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

Frequency and burden of neurological manifestations in hospitalized patients with COVID-19: findings from a large Brazilian cohort (preprint)

Background: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection in the Brazilian population and its association with patient outcomes, such as in-hospital mortality. Methods This study is part of the Brazilian COVID-19 Registry, a multicentric COVID-19 cohort, including data from 37 Brazilian hospitals. For the analysis, patients were grouped according to the presence of self-reported vs. clinically-diagnosed neurological manifestations and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital, and whether or not patients ha neurological underlying disease. Results From 7,232 hospitalized patients with COVID-19, 27.8% presented self-reported neurological manifestations, 9.9% were diagnosed with a clinically-defined neurological syndrome and 1.2% did not show any neurological symptoms. In patients with self-reported symptoms, the most common ones were headache (19.3%), ageusia (10.4%) and anosmia (7.4%). Meanwhile, in the group with clinically-defined neurological syndromes, acute encephalopathy was the most common diagnosis (10.5%), followed by coma (0.6%1) and seizures (0.4%). Men and younger patients were more likely to self-report neurological symptoms, while women and older patients were more likely to develop a neurological syndrome. Patients with clinically-defined neurological syndromes presented a higher prevalence of comorbidities, as well as lower oxygen saturation and blood pressure at hospital admission. In the paired analysis, it was observed that patients with clinically-defined neurological syndromes were more likely to require ICU admission (46.9 vs. 37.9%), mechanical ventilation (33.4 vs. 28.2%), to develop acute heart failure (5.1 vs. 3.0%, p=0.037) and to die (40.7 vs. 32.3%, p<0.001) when compared to controls. Conclusion Neurological manifestations are an important cause of morbidity in COVID-19 patients. More specifically, patients with clinically defined neurological syndromes presented a poorer prognosis for the disease when compared to matched controls.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry (preprint)

Background: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. The study aims to compare clinical characteristics and outcomes of COVID-19 patients with and without hypothyroidism. Methods: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis, including data collected from 37 hospitals. Matching for age, sex, number of comorbidities and hospital was performed to select the patients without hypothyroidism for the paired analysis. Results: From 7,762 COVID-19 patients, 526 had previously diagnosed hypothyroidism (50%) and 526 were selected as matched controls. The median age was 70 (interquartile range 59.0-80.0) years-old and 68.3% were females. The prevalence of underlying comorbidities were similar between groups, except for coronary and chronic kidney diseases, that had a higher prevalence in the hypothyroidism group (9.7% vs. 5.7%, p=0.015 and 9.9% vs. 4.8%, p=0.001, respectively). At hospital presentation, patients with hypothyroidism had a lower frequency of respiratory rate > 24 breaths per minute (36.1% vs 42.0%; p=0.050) and need of mechanical ventilation (4.0% vs 7.4%; p=0.016). D-dimer levels were slightly lower in hypothyroid patients (2.3 times higher than the reference value vs 2.9 times higher; p=0.037). In-hospital management was similar between groups, but hospital length-of-stay (8 vs 9 days; p=0.029) and mechanical ventilation requirement (25.4% vs. 33.1%; p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs. 27.0%; p=0.062). Conclusion: In this large Brazilian COVID-19 Registry, patients with hypothyroidism had a lower requirement of mechanical ventilation, and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis, and should not be considered among the comorbidities that indicate a risk factor for COVID-19 severity.