Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone.

BACKGROUND: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. METHODS: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. RESULTS: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. CONCLUSIONS: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

A randomized placebo-controlled trial of convalescent plasma for adults hospitalized with COVID-19 pneumonia.

Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72-2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46-1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.

Detection of SARS-CoV-2 in exhaled breath from non-hospitalized COVID-19-infected individuals.

The diagnosis of COVID-19 is based on detection of SARS-CoV-2 in oro-/nasopharyngel swabs, but due to discomfort and minor risk during the swab procedure, detection of SARS-CoV-2 has been investigated in other biological matrixes. In this proof-of-concept study, individuals with confirmed SARS-CoV-2 infection performed a daily air sample for five days. Air samples were obtained through a non-invasive electrostatic air sampler. Detection of SARS-CoV-2 RNA was determined with qRT-PCR. The association of positive samples with different exposures was evaluated through mixed-effect models. We obtained 665 air samples from 111 included participants with confirmed SARS-CoV-2 infection. Overall, 52 individuals (46.8%) had at least one positive air sample, and 129 (19.4%) air samples were positive for SARS-CoV-2. Participants with symptoms or a symptom duration ≤ four days had significantly higher odds of having a positive air sample. Cycle threshold values were significantly lower in samples obtained ≤ 4 days from symptom onset. Neither variant of SARS-CoV-2 nor method of air sampling were associated with a positive air sample. We demonstrate that SARS-CoV-2 is detectable in human breath by electrostatic air sampling with the highest detection rate closest to symptom onset. We suggest further evaluation of the air sampling technique to increase sensitivity.