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medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.21.21268197


Understanding who is at risk of progression to severe COVID-19 is key to effective treatment. We studied correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of SARS-CoV-2 infection. Several laboratory parameters identified study participants at greater risk of severe disease, including a high neutrophil-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test and whole blood transcriptome profiles. Sotrovimab treatment in these groups was associated with normalization of NLR and the transcriptomic profile, and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provided the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identified a 10-gene signature with similar predictive accuracy. In summary, we identified markers of risk for disease progression and demonstrated that normalization of these parameters occurs with antibody treatment of established infection.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.11.03.21265533


Importance: Older patients and those with underlying comorbidities infected with SARS-CoV-2 may be at increased risk of hospitalization and death from COVID-19. Sotrovimab is a neutralizing antibody designed for treatment of high-risk patients to prevent COVID-19 progression. Objective: To evaluate the efficacy and safety of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease. Design: Randomized, double-blind, multicenter, placebo-controlled, phase 3 study. Setting: 57 centers in 5 countries. Participants: Nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for disease progression. Intervention: Patients were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with COVID-19 progression, defined as all-cause hospitalization longer than 24 hours for acute illness management or death through day 29. Key secondary outcomes included the proportion of patients with COVID-19 progression, defined as emergency room visit, hospitalization of any duration, or death, and proportion of patients developing severe/critical respiratory COVID-19 requiring supplemental oxygen. Results: Among 1057 patients randomized (sotrovimab, 528; placebo, 529), all-cause hospitalization longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) by 79% (95% CI, 50% to 91%; P

Severe Acute Respiratory Syndrome , Acute Disease , Death , COVID-19
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.04.09.20059402


Conventional epidemiological models require estimates of important parameters including incubation time and case fatality rate that may be unavailable in the early stage of an epidemic. For the ongoing SARS-COV-2 epidemic, with no previous population exposure, alternative prediction methods less reliant on assumptions may prove more effective in the near-term. We present three methods used to provide early estimates of likely SARS-COV-2 epidemic progression. During the first stage of the epidemic, growth rate charts revealed the UK, Italy and Spain as outliers, with differentially increasing growth of deaths over cases. A novel data-driven time-series model was then used to near-cast 7-day future cases and deaths with much greater precision. Finally, an epidemio-statistical model was used to bridge from near-casting to forecasting the future course of the global epidemic. By applying multiple approaches to global SARS-COV-2 data, coupled with mixed-effects methods, countries further ahead in the epidemic provide valuable information for those behind. Using current daily global data, we note convergence in near-term predictions for Italy signifying an appropriate call on the future course of the global epidemic. For the UK and elsewhere, prediction of peak and eventual time to resolution is now possible.