Intubation timing as determinant of outcome in patients with acute respiratory distress syndrome by SARS-CoV-2 infection.

PURPOSE: To determine whether time-to-intubation was associated with higher ICU mortality in patients with COVID-19 on mechanical ventilation due to respiratory insufficiency. MATERIALS AND METHODS: We conducted an observational, prospective, single-center study of patients with confirmed SARS-CoV-2 infection hospitalized with moderate to severe ARDS, connected to mechanical ventilation in the ICU between March 17 and July 31, 2020. We examined their general and clinical characteristics. Time-to-intubation was the time from hospital admission to endotracheal intubation. RESULTS: We included 183 consecutive patients; 28% were female, and median age was 62 years old. Eighty-eight patients (48%) were intubated before 48 h (early) and ninety-five (52%) after 48 h (late). Patients intubated early had similar admission PaO2/FiO2 ratio (123 vs 99; p = 0.179) but were younger (59 vs 64; p = 0.013) and had higher body mass index (30 vs 28; p = 0.006) compared to patients intubated late. Mortality was higher in patients intubated late (18% versus 43%), with admission PaO2/FiO2 ratio < 100 mmHg (OR 5.2; p = 0.011), of older age (OR 1.1; p = 0.001), and with previous use of ACE inhibitors (OR 4.8; p = 0.026). CONCLUSIONS: In COVID-19 patients, late intubation, Pafi <100, older age, and previous ACE inhibitors use were associated with increased ICU mortality.

Clinical Prediction Tool to Assess the Likelihood of a Positive SARS-Cov-2 (COVID-19) Polymerase Chain Reaction Test in Patients with Flu-like Symptoms.

INTRODUCTION: The clinical presentation of coronavirus disease 2019 (COVID-19) overlaps with many other common cold and influenza viruses. Identifying patients with a higher probability of infection becomes crucial in settings with limited access to testing. We developed a prediction instrument to assess the likelihood of a positive polymerase chain reaction (PCR) test, based solely on clinical variables that can be determined within the time frame of an emergency department (ED) patient encounter. METHODS: We derived and prospectively validated a model to predict SARS-CoV-2 PCR positivity in patients visiting the ED with symptoms consistent with the disease. RESULTS: Our model was based on 617 ED visits. In the derivation cohort, the median age was 36 years, 43% were men, and 9% had a positive result. The median time to testing from the onset of initial symptoms was four days (interquartile range [IQR]: 2-5 days, range 0-23 days), and 91% of all patients were discharged home. The final model based on a multivariable logistic regression included a history of close contact (adjusted odds ratio [AOR] 2.47, 95% confidence interval [CI], 1.29-4.7); fever (AOR 3.63, 95% CI, 1.931-6.85); anosmia or dysgeusia (AOR 9.7, 95% CI, 2.72-34.5); headache (AOR 1.95, 95% CI, 1.06-3.58), myalgia (AOR 2.6, 95% CI, 1.39-4.89); and dry cough (AOR 1.93, 95% CI, 1.02-3.64). The area under the curve (AUC) from the derivation cohort was 0.79 (95% CI, 0.73-0.85) and AUC 0.7 (95% CI, 0.61-0.75) in the validation cohort (N = 379). CONCLUSION: We developed and validated a clinical tool to predict SARS-CoV-2 PCR positivity in patients presenting to the ED to assist with patient disposition in environments where COVID-19 tests or timely results are not readily available.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.