COVID-19 IN YOUNG AND MIDDLE-AGED ADULTS. PREDICTORS OF POOR OUTCOME AND CLINICAL DIFFERENCES. (preprint)

ABSTRACT Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. Objective: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore potential differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. Methods: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of “poor outcome” including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen therapies and/or death. Results: We identified 513 patients <65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, chest pain, anosmia, low oxygen saturation, high LDH and lymphocyte count <800/mL. Conclusions: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are more common and protective. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.

Short-term Neuropsychiatric Outcomes and Quality of Life in COVID-19 Survivors (preprint)

Background: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms, and QoL in COVID-19 survivors shortly after hospital discharge. Methods: This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed-up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity, and QoL (mental and physical components) was administered by telephone. Findings: Of the 229 screened patients, 179 were included in the final analysis. Among survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%), and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety were 29.6%, depression (26.8%), and post-traumatic stress disorder (25.1%) respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients, respectively. Delirium and stress-related symptoms increased approximately 4-fold the odds of developing neurocognitive impairment. Female gender and neurocognitive impairment diagnosis were related with an increase of 2.5 and 4.56-fold odds respectively of psychiatric morbidity. Interpretation: Hospitalized COVID-19 survivors showed a high prevalence of neurocognitive impairment, psychiatric morbidity, and poor QoL in the short-term. It is uncertain if these impacts persist over the long-term.

SARS-CoV-2-RNA viremia is associated to hypercytokinemia and critical illness in COVID-19 (preprint)

BackgroundSevere COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues. Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis-like disease observed in severe COVID-19 is currently unknown. MethodsWe determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution. ResultsThe presence of SARS-CoV-2-RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 - 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 - 0.88], <0.001). Conclusionssystemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.