Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19.

OBJECTIVES: To examine the radiological patterns specifically associated with hypoxemic respiratory failure in patients with coronavirus disease (COVID-19). METHODS: We enrolled patients with COVID-19 confirmed by qPCR in this prospective observational cohort study. We explored the association of clinical, radiological, and microbiological data with the development of hypoxemic respiratory failure after COVID-19 onset. Semi-quantitative CT scores and dominant CT patterns were retrospectively determined for each patient. The microbiological evaluation included checking the SARS-CoV-2 viral load by qPCR using nasal swab and serum specimens. RESULTS: Of the 214 eligible patients, 75 developed hypoxemic respiratory failure and 139 did not. The CT score was significantly higher in patients who developed hypoxemic respiratory failure than in those did not (median [interquartile range]: 9 [6-14] vs 0 [0-3]; p < 0.001). The dominant CT patterns were subpleural ground-glass opacities (GGOs) extending beyond the segmental area (n = 44); defined as "extended GGOs." Multivariable analysis showed that hypoxemic respiratory failure was significantly associated with extended GGOs (odds ratio [OR] 29.6; 95% confidence interval [CI], 9.3-120; p < 0.001), and a CT score > 4 (OR 12.7; 95% CI, 5.3-33; p < 0.001). The incidence of RNAemia was significantly higher in patients with extended GGOs (58.3%) than in those without any pulmonary lesion (14.7%; p < 0.001). CONCLUSIONS: Extended GGOs along the subpleural area were strongly associated with hypoxemia and viremia in patients with COVID-19. KEY POINTS: • Extended ground-glass opacities (GGOs) along the subpleural area and a CT score > 4, in the early phase of COVID-19, were independently associated with the development of hypoxemic respiratory failure. • The absence of pulmonary lesions on CT in the early phase of COVID-19 was associated with a lower risk of developing hypoxemic respiratory failure. • Compared to patients with other CT findings, the extended GGOs and a higher CT score were also associated with a higher incidence of RNAemia.

Efficacy and Safety of Nelfinavir in Asymptomatic and Mild COVID-19 Patients: A Multicenter, Randomized Controlled Trial

Background. Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibited the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. To evaluate the efficacy and safety of nelfinavir, we conducted a randomized controlled trial. Methods. Adult patients testing positive for SARS-CoV-2 infection within 3 days were eligible for the study if they had no or mild symptoms of coronavirus disease 2019. Exclusion criteria included the followings: onset of symptoms >= 8 days before enrollment;oxygen saturation of 95% or less on room air;and vaccinated patients. Patients were randomly assigned (1:1) to receive oral nelfinavir 750 mg (x3 times daily) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to clearance of SARS-CoV-2. Saliva was collected every day and viral load was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nelfinavir was administered for 14 days. However, the treatment could be discontinued by the decision of investigator, if patients had 2 consecutive negative test results by qRT-PCR. Clinical course and safety information were collected through day 28. The study is registered with the Japan Registry of Clinical Trials (number, jRCT2071200023). Results. Between July 2020 and October 2021, 123 patients (63 in the nelfinavir group and 60 in the control group) were enrolled into the study and included in the analysis. The median time to viral clearance was 8.0 (95% confidence interval [CI] 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI 7.0 to 10.0) days in the control group without statistically significant difference between the treatment group (hazard ratio 0.815, 95% CI 0.563 to 1.182;P = 0.1870). Adverse events were reported in 47 (74.6%) patients in the nelfinavir group and 20 (33.3%) in the control group. The most common adverse events in the nelfinavir group were diarrhea (49.2%) and nausea (6.3%). Conclusion. Nelfinavir did not reduce the time to viral clearance in this setting.

Evaluation of droplet and aerosol dispersion under high flow nasal cannula with or without surgical mask

Rationale: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), transmit by droplet and aerosol particles. Droplets and aerosol generation during the oxygen delivery methods such as high flow oxygen therapy (HFNC) and noninvasive positive pressure ventilation (NPPV) during COVID-19 respiratory care, may poses a risk of increasing transmission to healthcare workers. We aimed to evaluate droplet and aerosol dispersion associated with oxygen delivery modes, and further to verify the effect of surgical mask (SM) on preventing particle dispersion.Methods: Two experiments were performed at the laboratory of Shin Nippon Air Technologies, Japan, to visualize (Experiment 1) and to quantify (Experiment 2) dispersing particles. Three (Experiment 1) and five (Experiment 2) healthy Japanese male volunteers aged 30-40s and non-smokers, were recruited. For visualization study (Experiment 1), dispersing particles (>5μm) were recorded by ultra-high sensitive video camera 'eye scope'. For quantification study (Experiment 2), two types of micro-particle detection panel 'Type S' which counts particles > 0.5μm or >5μm were used under air-controlled room with down-flow of 0.3m/sec to avoid contamination of dusts and to drop aerosols on Type S panel. Five patterns of oxygen delivery modalities (No device, 5L/min of nasal cannula, 30L/min or 60L/min of HFNC, 10L/min of oxygen mask, and NPPV) with and without SM, while three breathing patterns (rest breathing, speaking, and coughing) were recorded. The differences in continuous numbers between corresponding two groups were analyzed by ratio paired t-test. A P-value <0.05 was considered as statistically significant.Results: Droplets were able to visualize at further than 50cm while speaking, and further than 1m while coughing. Without SM, droplets were more visible with nasal cannula compared to HFNC. SM effectively reduced droplets under each oxygen delivery modes, and they are hard to visualize even in speaking or coughing. In NPPV mode, floating droplets were visible while coughing. Droplets and aerosols were counted 10-times more while coughing compared to speaking. SM significantly reduced both of droplets and aerosol dispersion while speaking or coughing regardless of oxygen delivery mode. Reduction rate of dispersion under HFNC was higher compared to nasal cannula. 60L/min of HFNC did not increase droplets or aerosol dispersion by counts or by distance compared to 30L/min of HFNC. SM effectively reduced over 90% of droplets and over 95% of aerosols during HFNC mode.Conclusions: SM over HFNC mode may be used safely in appropriate infection control setting and recommended for acute hypoxemic respiratory failure in COVID-19 patients.