Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience from the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score (preprint)

Background: Sepsis patients with a concomitant Coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of sepsis patients with a concomitant COVID-19 to determine clinical characteristics, laboratory and radiological findings, and predictors of mortality. We developed a risk score for the estimation of sepsis risk in patients with COVID-19.Methods: In the present study, we conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus.Findings: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), haemoptysis, peripheral oxygen saturation (SpO2) < 92%, blood pressure (BP) (systolic BP< 90mmHg and diastolic BP <60mmHg), Glasgow coma scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated Creatinine > 1.5 mg/dl. By assigning odds ratio weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased blood pressure, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to haemoptysis.Interpretation: The HOPE Sepsis Score including 9 parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.Funding Statement: Non-conditioned grant (FUNDACIÓN INTERHOSPITALARIA PARA LA INVESTIGACIÓN CARDIOVASCULAR, FIC. Madrid, Spain)Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The study was approved by the Ethics Committee in all involved centres.

Post-COVID-19 Syndrome: Prospective Evaluation of Clinical and Functional Outcomes and Systematic Review (preprint)

Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. However, long-term clinical, functional, and metabolic consequences are still unknown. This study sought to identify clinical sequelae and its potential intrinsic mechanism among COVID-19 survivors in the follow-up. Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up, an outpatient asymptomatic control group was also evaluated. They underwent serial testing with cardio-pulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis and quality of life questionaries.Results: Patients with dyspnea (n=41, 58.6%), compared with asymptomatic (n=29, 41.4%), had a higher proportion of females (73.2% vs. 51.7%; p= 0.065), with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in transthoracic echocardiogram and pulmonary function test, in either group. Patients who referred dyspnea had a significant decline in predicted peak O2 consumption (77.8 [64-92.5] vs. 99 [88-105]: p<0.00; p<0.001), total distance in the 6-minute walking test (535 [467-600] vs. 611 [550-650] meters; p= 0.001), and quality of life (KCCQ-23 60.1±18.6 vs. 82.8±11.3; p<0.001). Additionally, abnormalities in CPET were suggestive of a ventilation/perfusion characterized by impaired ventilatory efficiency (VE/VCO2 slope 32 [28.1-37.4] vs. 29.4 [26.9-31.4]; p= 0.022) and low O2 pulse (9.2 [7.3-11.3] vs. 10.6 [8.7-13.2]; p= 0.013). Interpretation: In this study >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest potential ventilation/perfusion mismatch.Funding Statement: The present study was partially granted by Gerencia Regional de Salud de Castilla y León under grant number GRS COVID 111/A/20 and Grant from the Spanish Society of Cardiology: SEC/FEC-INVCLI 20/030Declaration of Interests: None.Ethics Approval Statement: The institutional local ethics committees approved the study protocol (CASVE PI-20-1894) and all patients provided written informed consent before inclusion.

COVID-19 anosmia and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry (preprint)

Olfactory and gustatory dysfunctions (OGD) are a frequent symptom of Coronavirus disease 2019 (COVID-19). It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2 could be due to olfactory bulb invasion, conversely studies suggest it could be a good prognostic factor. The aim of the current study was to investigate the prognosis value of OGD in COVID-19.These symptoms were recorded on admission from a cohort study of 5868 patients with confirmed or highly suspected COVID-19 infection included in the multicenter international HOPE Registry (NCT04334291).There was statistical relation in multivariate analysis for OGD in gender, more frequent in female 12.41% vs 8.67% in male, related to age, more frequent under 65 years, presence of hypertension, dyslipidemia, diabetes, smoke, renal insufficiency, lung, heart, cancer and neurological disease. We did not find statistical differences in pregnant (p=0.505), patient suffering cognitive (p=0.484), liver (p=0.1) or immune disease (p=0.32). There was inverse relation (protective) between OGD and prone positioning (0.005) and death (<0.0001), but no with ICU (0.165) or mechanical ventilation (0.292). On univariable logistic regression OGD was found to be inversely related to death in COVID-19 patients. The Odds Ratio was 0.26 (0.15-0.44) (p<0.001) and Z was -5.05.The presence of anosmia is fundamental in the diagnosis of SARS.CoV-2 infection, but also could be important when classifying patients and in therapeutic decisions. Even more knowing that it is an early symptom of the disease. Knowing that other situations as being Afro-American or Latino-American, Hypertension, renal insufficiency, or increase of C-reactive protein (CRP) imply a worse prognosis we can make a clinical score to estimate the vital prognosis of the patient.The exact pathogenesis of SARS-CoV-2 that causes olfactory and gustative disorders remains unknown but seems related to the prognosis. This point is fundamental, insomuch as could be a plausible way to find a treatment. 

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19 (preprint)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). Methods: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary endpoint was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. Results: A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease with complete resolution among survivors. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c < 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein > 88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia < 1000 cells/ml (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Conclusion: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.