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.

Background Inactivated SARS-CoV-2 vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. Methods This prospective cohort study included 193 participants with five different immunocompromising conditions and 67 controls, receiving two doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Chile. Neutralizing antibodies (NAb) positivity, total anti-SARS-CoV-2 IgG antibodies (TAb) concentration, and T cell response were determined. Results NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% (p<0.0001) and 5.7% (p<0.0001) in the solid organ transplant (SOT) group, 41.5% (p<0.0001) and 19.2% (p<0.0001) in the autoimmune rheumatic diseases group, 43.3% (p=0.0002) and 21.4% (p=0.0013) in the cancer patients with solid tumors group, 45.5% (p<0.0001) and 28.7% (p=0.0006) in the HIV infected group, 64.3% (p=n.s.) and 56.6% (p=n.s.) in the hematopoietic stem cell transplantation (HSCT) group, respectively. TAb seropositivity was also lower for the SOT (20.6%, p<0.0001), rheumatic diseases (61%, p=0.0001) and HIV groups (70.9%, p=0.0032), compared to control group (92.3%). On the other hand, the number of IFN-y Spot Forming T Cells specific for SARS-CoV-2 tended to be lower but did not differ significantly between groups. Conclusions Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest a boosting vaccination strategy should be considered in these vulnerable patients.

Tracheal and lung sounds measurements for clinical applications depends on their intrasubject repeatability. Our objectives were to characterize tracheal and lung sounds and to investigate the temporal variability in normal adults. Tracheal sounds were studied in 7 subjects and lung sounds in 10 adults. Acoustic measurements were done in five occasions over a month for tracheal sounds and on seven occasions over a year for lung sounds. Sounds were recorded using contact sensors on the suprasternal notch and on the posterior right lower lobe. Subjects breathed through a pneumotachograph at flows of 0.9-1.1 l/s. Signals were low-pass filtered, amplified and Fourier analysis was applied to sounds within a target flow range. We measured the frequencies below which 25% (F25), 50% (F median), 75% (F75) and 99% (SEF99) of the spectral power between 100 and 2000 Hz. There were no differences between the measurements obtained at different days comparing each subject (P = ns, ANOVA). Our results show that the spectral pattern of tracheal and lung sounds are stable with low intrasubject variability.

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: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified 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. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: 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 found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

We conclude that sinusoidal and complex wheezes occur in patients with AB, that a positive response to bronchodilator is significantly more common in those with classic SW and that lung sounds analysis is a reproducible, safe and non-invasive method for assessing wheeze in infants.