ABSTRACT
The emergence of new SARSCoV-2 variants can affect vaccine efficacy, laboratory diagnosis and therapies already available, triggering interest in the search for antiviral agents for SARSCoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARSCoV-2. Methods. This retrospective study evaluated the dynamic and viral clearance of SARSCoV-2 in hospitalized adult participants (PTs) with COVID-19 pneumonia who received RBV aerosol within a compassionate use study. Was also assessed the impact of RBV on the clinical outcome and the mutational profile of SARSCoV-2. Results. The median RNA values measured in nine PTs included in the study de-creased from baseline to discharge (at BL, threshold cycle (Ct)=22.4, IQR 19.84-5.07; at discharge, Ct=27.92, IQR 26.43-36.11). Seven/9 PTs experienced a clinical improvement, while two PTs deceased during hos-pitalization. In PTs with a favorable outcome the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within day 14th from discharge. A mutational pattern after RBV was detected in 3/5 PTs in whom was available whole genome sequencing. Conclusions. RBV may limit SARSCOV-2 replication resulting in a favorable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARSCoV-2.
Subject(s)
COVID-19 , Pneumonia , InfectionsABSTRACT
Objective To identify predictors of 30-day survival in elderly patients with COVID-19. Methods Retrospective cohort study including COVID-19 patients≥65 years old hospitalized in 6 European sites (January 2020-May 2021). Demographics, comorbidities, clinical characteristics and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validationina cohort including elderly patients from a major COVID-19 center in Israel was performed. Discrimination was evaluated by the area under the receiver operating characteristic curve (AUC)in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. Results Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). Intensive care unit (ICU) admission rate was 7.6% (228/3010).The model predicting survival included independent functional status (OR 4.87, 95%CI 3.93-6.03), SpO2/FiO2 ratio>235 (OR 3.75, 95%CI 3.04-4.63), C-reactive protein<14 mg/dl (OR 2.41, 95%CI 1.91-3.04), creatinine<1.3 (OR 2.02, 95%CI 1.62-2.52) mg/dl and absence of fever (OR 1.34, 95%CI 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC 0.79, 95%CI 0.77–0.81, p<0.001) and validation cohort (AUC 0.79, 95%CI 0.76–0.81, p<0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665)across four risk groups according to scorequartiles in the derivation cohort. Similar proportions were observed in the validation set.. Conclusions The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including ICU admission/exclusion.
ABSTRACT
Ribavirin is an inosine monophosphate dehydrogenase inhibitor with demonstrated activity against coronaviruses, including SARS-CoV-2. Two hospitalized patients with COVID-19 (confirmed by positive tests for SARS-CoV-2) received treatment with ribavirin for inhalation solution (ribavirin aerosol) as part of a compassionate use program. Patient 1 was a 33-year-old male with an unremarkable medical history. Patient 2 was a 29-year-old male who was an active smoker. Both patients were managed according to international and Italian treatment guidelines for COVID-19. In addition, therapy with ribavirin aerosol 100 mg/mL was administered for 30 minutes twice daily for 6 days (ie, 12 doses) in both patients. In order to address concerns about a possible increase in viral dispersal with the use of a nebulizer, healthcare providers remained outside the patient room during ribavirin aerosol administration. Pretreatment chest computed tomography scans showed pseudonodular areas in the upper right lobe with associated ground glass opacities (Patient 1) and multiple areas of parenchymal consolidation in both lower lobes with associated ground glass opacities (Patient 2) that were almost completely resolved on imaging at the end of ribavirin treatment. No adverse reactions to ribavirin treatment were observed in either patient. Both patients recovered fully, and 2 sequential nasopharyngeal swabs obtained after hospital discharge tested negative for SARS-CoV-2. Ribavirin aerosol appears to be efficacious in the treatment of patients with COVID-19. The compassionate use study of ribavirin aerosol is ongoing and will provide additional data across a broader patient population.
Subject(s)
COVID-19ABSTRACT
The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients.Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs.The primary outcome was the time to nasopharyngeal swab negativization.A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization.Of 280 patients included, 59 (21.1%) patients were treated with steroids.Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p=0.023) or ≤100 mmHg (16.9% vs 12.7%; p=0.027), and length of hospitalization (20 vs 14 days; p<0.001).Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p=0.985).According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 >200 mmHg, and a lymphocyte count at admission >1.0*109/L. SARS-CoV-2 clearance was not associated with corticosteroid use.Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with early use of corticosteroids