January 22, 2021| The UK’s patient stratification score doesn’t hold up to scrutiny, Fauci and others encourage doctors to equip themselves to argue for vaccines, and NIH launches a study of “Long COVID”. Plus: Siemens, with German funding, sets up more COVID-19 treatment facilities for South Africa.

Research Updates

Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. A team from the Barcelona Institute of Global Health conducted a small, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. DOI: 10.1016/j.eclinm.2020.100720

In a special article for the Annals of Internal Medicine, Anthony S. Fauci and others encourage physicians to be ready with facts to encourage their patients to vaccinate. They provide an overview of the seven COVID-19 vaccines furthest along in development in the United States. For each vaccine candidate, the authors describe the platform used, the current stage of development, and the clinical trial results that have been reported or when results are expected. DOI: 10.7326/M21-0111

A German research team used RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Their findings stratify the COVID-19 disease, which is caused by the SARS-CoV-2 coronavirus, into at least five different variants that differ in how the immune system responds to the infection. Further, the stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Their findings are published in Genome Medicine. DOI: 10.1186/s13073-020-00823-5

The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but new results published in BMC Medicine show a baseline model of ‘NEWS2 + age’ had poor-to-moderate discrimination for severe COVID-19 infection at 14 days. Risk stratification was improved, the authors note, by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. DOI: 10.1186/s12916-020-01893-3

Adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical covid-19 is no better than standard care alone in improving clinical outcomes at 15 days, finds a new trial published by The BMJ. The randomized trial enrolled 129 patients, but the data monitoring committee recommended stopping the trial early because 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15. DOI: 10.1136/bmj.n84

The spread of COVID-19 in Brazil overwhelmed the health systems in all the country's regions between mid-February and mid-August 2020, particularly in areas where they were already fragile. A collaborative retrospective study conducted by the Barcelona Institute for Global Health (ISGlobal), an institution supported by the "la Caixa" Foundation, the University of Sao Paulo, the Catholic University of Rio de Janeiro, the D'Or Institute of Research and Education and the Oswaldo Cruz Foundation, looked at nationwide data for all patients over the age of 20 with COVID-19. The findings, published in The Lancet Respiratory Medicine, reveal that a large percentage of COVID-19 patients that were hospitalized in Brazil required intensive care and respiratory support, and many did not survive. DOI: 10.1016/S2213-2600(20)30560-9

Rush University Medical Center is launching INSPIRE (Innovative Support for Patients with SARS COV-2 Infections Registry), a CDC-funded study to track 3,600 individuals with new COVID-19 symptoms who have been diagnosed with the disease in the preceding four weeks and 1,200 people without COVID-19 to assess the long-term outcomes of infections with SARS CoV-2, the virus that causes COVID-19, on various age groups over a two-year period. Collaborating institutions include University of Washington, Yale New Haven Health, the University of Texas Health Science Center at Houston, the University of Texas Southwestern Medical Center, UCLA, the University of California, San Francisco, and Thomas Jefferson University. ClinicalTrials.gov Listing

Use of the diabetes drug metformin before a diagnosis of COVID-19 is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. The team conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between the end of February and the end of June at the University of Alabama at Birmingham Hospital. The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans and in subjects with obesity, hypertension, and diabetes, but metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19. The findings raise the possibility that metformin may provide a protective approach in this high-risk population. The findings were published in Frontiers in Endocrinology. DOI: 10.3389/fendo.2020.600439

COVID-19 patients who require admission to an intensive care unit (ICU) for invasive ventilation are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). Researchers from the University of Cambridge compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array, and determined the lung microbiome composition using 16S RNA analysis in a subset of samples. They published their findings in Critical Care, finding COVID-19 patients were significantly more likely to develop VAP than patients without COVID, but believe this is not fully explained by the prolonged duration of ventilation. DOI: 10.1186/s13054-021-03460-5

Industry Updates

Siemens South Africa (www.new.Siemens.com/za/en.html) has joined forces with Deutsche Gesellschaft für Internationale Zusammenarbeit GmbH (GIZ), the German Federal Ministry for Economic Cooperation and Development, and the Eastern Cape Department of Health to provide a separate modular hospital solution to the Cecilia Makiwane Hospital in East London in the fight against Covid-19. Further Siemens project partners include Solidarity Fund, Siemens Healthineers, Siemens Caring Hands and Aspen Pharmacare. A financial grant of up to €3.5 million has been contributed by Deutsche Gesellschaft für Internationale Zusammenarbeit on behalf of the German Federal Ministry for Economic Cooperation and Development. Press release.