Head-to-head performance comparison of self-collected nasal versus professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test.

In 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen-detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies are necessary for SARS-CoV-2 Ag-RDT nasal sampling to demonstrate comparability of performance with nasopharyngeal (NP) sampling. We conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio™ Ag-RDT (distributed by Abbott). We calculated positive and negative percent agreement between the sampling methods as well as sensitivity and specificity for both sampling techniques compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR). A SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0-94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5-99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2-92.3%) and 88.9% (40/45; CI 76.5-95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1-99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log10 SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7-99.8%) for both, NMT and NP sampling. For the Panbio supervised NMT self-sampling yields comparable results to NP sampling. This suggests that nasal self-sampling could be used for to enable scaled-up population testing.Clinical Trial DRKS00021220.

Design of clinical trials evaluating ruxolitinib, a jak1/jak2 inhibitor, for treatment of covid-19–associated cytokine storm

Recent insight into the pathophysiology of severe coronavirus disease 2019 (COVID-19) has implicated hyperactivation of the immune response, resulting in a “cytokine storm,” which can lead to excessive immune-cell infiltration of the lungs, alveolar damage, decreased lung function, and death. Several cytokines implicated in the COVID-19–associated cytokine storm predominantly signal through the Janus kinase (JAK)/signal transducer and activator of transcription pathway. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 that has been explored in small studies of patients with COVID-19–associated cytokine storm. Early clinical data from these trials, combined with a body of preclinical and clinical evidence in other inflammatory conditions, support exploration of the efficacy and safety of ruxolitinib in these patients in larger, well-controlled trials. Here we describe the designs of three such ongoing clinical trials. RUXCOVID is a phase 3 randomized, double-blind, multicenter study of ruxolitinib 5 mg twice daily (BID) vs placebo (both plus standard of care) in patients with COVID-19–associated cytokine storm. 369-DEVENT is a phase 3, randomized, double-blind, placebo-controlled, multicenter study of ruxolitinib 5 or 15 mg BID vs placebo (all plus standard of care) in patients with COVID-19–associated acute respiratory distress syndrome who require mechanical ventilation. Patients with severe COVID-19–associated cytokine storm who are ineligible for these trials can receive ruxolitinib through an Expanded Access Program (EAP) in the United States and similar programs outside of the United States. RUXCOVID and 369-DEVENT will provide insight into the efficacy and safety of ruxolitinib in hospitalized patients prior to or during ventilator use. If these trials are successful, ruxolitinib could improve outcomes for patients with COVID-19 as well as lessen the overall burden on the health care system. © 2020, Delaware Academy of Medicine. All rights reserved.

RUXCOVID: A phase 3, randomized, placebo-controlled study evaluating the efficacy andsafety of ruxolitinib in patients with COVID-19-associatedcytokine storm

Background: Severe COVID-19 can result in pneumonia, with many patients (pts) requiring hospitalization andoxygen support. Severe COVID-19 may also be complicated by acute respiratory distress syndrome, sepsis andseptic shock, and/or multiorgan failure. Many of these pts have features consistent with cytokine release syndrome(CRS) and its associated hyperinflammation. Given their immunomodulatory effects, Janus kinase (JAK) inhibitorshave been suggested as a potential therapeutic option in pts with severe COVID-19. Ruxolitinib-a potentJAK1/JAK2 inhibitor approved for treating myelofibrosis, polycythemia vera, and steroid-refractory acute graft-vs.-host disease (GvHD;US only)-has been associated with reduced levels of inflammatory cytokines in disorderswhere cytokine dysregulation plays a role, including GvHD and secondary hemophagocytic lymphohistiocytosis.Additionally, findings from a small, randomized, phase 2 study (N = 43;Cao Y et al., J Allergy Clin Immunol 2020)showed that treatment with ruxolitinib plus standard of care (SOC) reduced CRS-associated hyperinflammation inpts with severe COVID-19 vs placebo plus SOC, with significant improvement seen in chest computed tomography(CT) features. Although no statistically significant differences were observed, ruxolitinib-treated pts also had anumerically shorter median time to clinical improvement, a lower proportion requiring intensive care/mechanicalventilation, and reduced mortality, with ruxolitinib having a favorable safety profile. Methods: RUXCOVID ( NCT04362137 ) is a global, randomized (2:1), double-blind, placebo-controlled, 29-day, phase 3 study evaluating the efficacy and safety of ruxolitinib plus SOC compared with placebo plus SOC in pts withCOVID-19. Pts are eligible for the study if they are ≥ 12 years old, have confirmed COVID-19, are hospitalized, andmeet ≥ 1 of the following: pulmonary infiltrates (by chest x-ray or CT scan), respiratory frequency ≥ 30 breaths/min, requirement of supplemental oxygen, oxygen saturation (SpO ) ≤ 94% on room air, or arterial oxygen partialpressure (PaO )/fraction of inspired oxygen (FiO ) < 300 mm Hg (1 mm Hg = 0.133 kPa). Pts with a need forintensive care or intubation are not eligible. Pts will be randomized to ruxolitinib 5 mg twice daily or placebo andtreated for 14 days. Pts may be treated for an additional 14 days if no improvement occurs and the potential benefitoutweighs the potential risk per investigator assessment. The primary endpoint is the proportion of pts who die, develop respiratory failure (require mechanical ventilation), or require intensive care by day 29. Secondaryendpoints include improvement in clinical status, in-hospital outcomes, change in National Early Warning Score, change in SpO :FiO ratio, mortality rate, change in inflammatory biomarkers, and safety. Target enrollment is 402pts. Sponsored by Novartis Pharmaceuticals and Incyte.