What are the risk factors of hospital length of stay in the novel coronavirus pneumonia (COVID-19) patients? A survival analysis in southwest China.

BACKGROUND: The global epidemic of novel coronavirus pneumonia (COVID-19) has resulted in substantial healthcare resource consumption. Since patients' hospital length of stay (LoS) is at stake in the process, an investigation of COVID-19 patients' LoS and its risk factors becomes urgent for a better understanding of regional capabilities to cope with COVID-19 outbreaks. METHODS: First, we obtained retrospective data of confirmed COVID-19 patients in Sichuan province via National Notifiable Diseases Reporting System (NNDRS) and field surveys, including their demographic, epidemiological, clinical characteristics and LoS. Then we estimated the relationship between LoS and the possibly determinant factors, including demographic characteristics of confirmed patients, individual treatment behavior, local medical resources and hospital grade. The Kaplan-Meier method and the Cox Proportional Hazards Model were applied for single factor and multi-factor survival analysis. RESULTS: From January 16, 2020 to March 4, 2020, 538 human cases of COVID-19 infection were laboratory-confirmed, and were hospitalized for treatment, including 271 (50%) patients aged ≥ 45, 285 (53%) males, and 450 patients (84%) with mild symptoms. The median LoS was 19 (interquartile range (IQR): 14-23, range: 3-41) days. Univariate analysis showed that age and clinical grade were strongly related to LoS (P<0.01). Adjusted multivariate analysis showed that the longer LoS was associated with those aged ≥ 45 (Hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.60-0.91), admission to provincial hospital (HR: 0.73, 95% CI: 0.54-0.99), and severe illness (HR: 0.66, 95% CI: 0.48-0.90). By contrast, the shorter LoS was linked with residential areas with more than 5.5 healthcare workers per 1,000 population (HR: 1.32, 95% CI: 1.05-1.65). Neither gender factor nor time interval from illness onset to diagnosis showed significant impact on LoS. CONCLUSIONS: Understanding COVID-19 patients' hospital LoS and its risk factors is critical for governments' efficient allocation of resources in respective regions. In areas with older and more vulnerable population and in want of primary medical resources, early reserving and strengthening of the construction of multi-level medical institutions are strongly suggested to cope with COVID-19 outbreaks.

Immunometabolic signatures predict risk of progression to sepsis in COVID-19.

Viral sepsis has been proposed as an accurate term to describe all multisystemic dysregulations and clinical findings in severe and critically ill COVID-19 patients. The adoption of this term may help the implementation of more accurate strategies of early diagnosis, prognosis, and in-hospital treatment. We accurately quantified 110 metabolites using targeted metabolomics, and 13 cytokines/chemokines in plasma samples of 121 COVID-19 patients with different levels of severity, and 37 non-COVID-19 individuals. Analyses revealed an integrated host-dependent dysregulation of inflammatory cytokines, neutrophil activation chemokines, glycolysis, mitochondrial metabolism, amino acid metabolism, polyamine synthesis, and lipid metabolism typical of sepsis processes distinctive of a mild disease. Dysregulated metabolites and cytokines/chemokines showed differential correlation patterns in mild and critically ill patients, indicating a crosstalk between metabolism and hyperinflammation. Using multivariate analysis, powerful models for diagnosis and prognosis of COVID-19 induced sepsis were generated, as well as for mortality prediction among septic patients. A metabolite panel made of kynurenine/tryptophan ratio, IL-6, LysoPC a C18:2, and phenylalanine discriminated non-COVID-19 from sepsis patients with an area under the curve (AUC (95%CI)) of 0.991 (0.986-0.995), with sensitivity of 0.978 (0.963-0.992) and specificity of 0.920 (0.890-0.949). The panel that included C10:2, IL-6, NLR, and C5 discriminated mild patients from sepsis patients with an AUC (95%CI) of 0.965 (0.952-0.977), with sensitivity of 0.993(0.984-1.000) and specificity of 0.851 (0.815-0.887). The panel with citric acid, LysoPC a C28:1, neutrophil-lymphocyte ratio (NLR) and kynurenine/tryptophan ratio discriminated severe patients from sepsis patients with an AUC (95%CI) of 0.829 (0.800-0.858), with sensitivity of 0.738 (0.695-0.781) and specificity of 0.781 (0.735-0.827). Septic patients who survived were different from those that did not survive with a model consisting of hippuric acid, along with the presence of Type II diabetes, with an AUC (95%CI) of 0.831 (0.788-0.874), with sensitivity of 0.765 (0.697-0.832) and specificity of 0.817 (0.770-0.865).

Targeted metabolomics identifies high performing diagnostic and prognostic biomarkers for COVID-19.

Research exploring the development and outcome of COVID-19 infections has led to the need to find better diagnostic and prognostic biomarkers. This cross-sectional study used targeted metabolomics to identify potential COVID-19 biomarkers that predicted the course of the illness by assessing 110 endogenous plasma metabolites from individuals admitted to a local hospital for diagnosis/treatment. Patients were classified into four groups (≈ 40 each) according to standard polymerase chain reaction (PCR) COVID-19 testing and disease course: PCR-/controls (i.e., non-COVID controls), PCR+/not-hospitalized, PCR+/hospitalized, and PCR+/intubated. Blood samples were collected within 2 days of admission/PCR testing. Metabolite concentration data, demographic data and clinical data were used to propose biomarkers and develop optimal regression models for the diagnosis and prognosis of COVID-19. The area under the receiver operating characteristic curve (AUC; 95% CI) was used to assess each models' predictive value. A panel that included the kynurenine: tryptophan ratio, lysoPC a C26:0, and pyruvic acid discriminated non-COVID controls from PCR+/not-hospitalized (AUC = 0.947; 95% CI 0.931-0.962). A second panel consisting of C10:2, butyric acid, and pyruvic acid distinguished PCR+/not-hospitalized from PCR+/hospitalized and PCR+/intubated (AUC = 0.975; 95% CI 0.968-0.983). Only lysoPC a C28:0 differentiated PCR+/hospitalized from PCR+/intubated patients (AUC = 0.770; 95% CI 0.736-0.803). If additional studies with targeted metabolomics confirm the diagnostic value of these plasma biomarkers, such panels could eventually be of clinical use in medical practice.

The immunodominant and neutralization linear epitopes for SARS-CoV-2.

Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses.