August 28, 2020 | Recommendations for COVID-19 rehabilitation, four months of data from Italy’s use of hydroxychloroquine, more data on which comorbidities are most dangerous, Remdesivir data, and more on imaging. Plus, research grants and a convalescent plasma architecture.

CRN Research Updates

An Italian team published a retrospective observational study of 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020 to evaluate the efficacy of hydroxychloroquine in treating COVID-19. 76.3% of the patients received HCQ, and the researchers report a 30% lower risk of death in hospitalized patients receiving HCQ. They published their findings in the European Journal of Internal Medicine. DOI: 10.1016/j.ejim.2020.08.019

However, researchers at Columbia University advise rheumatoid arthritis patients against taking hydroxychloroquine in conjunction with azithromycin. Their retrospective study of patients with rheumatoid arthritis did not consider the drug as a treatment for COVID-19 and they did not include COVID-19 patients in their cohort. The team simply looked at the combination of HCQ and azithromycin for RA patients. In The Lancet Rheumatology, they report findings that the addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality, chest pain or angina, and heart failure. DOI: 10.1016/S2665-9913(20)30276-9

COVID-19 is a multisystem illness that has considerable long-term physical, psychological, cognitive, social and vocational sequelae in survivors. In a report in the Journal of Rehabilitation Medicine, a multidisciplinary team of professionals in the UK outline their comprehensive pragmatic telephone screening tool, the COVID-19 Yorkshire Rehabilitation Screen (C19-YRS), as an integrated rehabilitation pathway. The COVID-19 rehabilitation team is the core troubleshooting forum for managing complex cases with needs spanning multiple domains of the health condition, and the authors recommend that health services dealing with the COVID-19 pandemic adopt a similar telephone screening system and integrated rehabilitation pathway to manage the large number of survivors in a timely and effective manner and to enable the provision of targeted interventions. DOI: 10.2340/16501977-2727

Most adults with systemic lupus erythematosus (SLE) are not at increased risk of hospitalization from COVID-19 due to medications used to dampen their altered immune system, the cause of their disease. Nor are most people with more common types of arthritis, such as rheumatoid, psoriatic and spondyloarthritis, at greater risk of hospitalization from COVID-19, according to a paper in Arthritis and Rheumatology. Although the new studies, led by NYU Grossman School of Medicine researchers, show that for some of those affected the use of steroid medications to reduce inflammation slightly increased the likelihood of needing hospital care, researchers say the results should be reassuring to patients overall. DOI: 10.1002/art.41456

Unfortunately, findings were not as positive for patients who had a combination of high blood pressure, obesity and diabetes. Researchers at Tulane University found these patients were over three times more likely to die from COVID-19. The study, published in the journal Diabetes Care, considered metabolic syndrome, a cluster of at least three of five conditions—hypertension, high blood sugar, obesity, high triglycerides and low HDL cholesterol—that increases risk for cardiovascular disease. DOI: 10.2337/dc20-1714

Mount Sinai scientists have identified two markers of inflammation—IL-6 and TNF-α—that reliably predict the severity of COVID-19 cases and likelihood of survival, providing a foundation for a diagnostic platform and therapeutic targets. Their findings were published in Nature Medicine. The scientists established that the levels of IL-6 and TNF-α in serum, when measured at admission to the hospital, were elevated in patients who fared the worst, a finding that was independent of the patients’ other underlying medical conditions, of demographics such as age and sex, and of other standard clinical biomarkers of disease severity such as low blood oxygen saturation and common markers related to inflammation, iron levels, and blood clotting issues. This study suggests that these cytokines should be monitored in the treatment of COVID-19 patients to help select those who should enter clinical trials and receive specific drugs that can target them, the researchers say. DOI: 10.1038/s41591-020-1051-9

In a paper published in the Journal of General Internal Medicine, researchers from Mount Sinai School of Medicine looked at the characteristics of patients with COVID-19 who returned to the ER or required readmission to the hospital within 14 days of being discharged. Researchers found the most common cause for a patient's early hospital readmission after discharge was for respiratory distress. These patients were also more likely to have other ailments including chronic obstructive pulmonary disease and hypertension. DOI: 10.1007/s11606-020-06120-6

In a randomized, open-label, phase 3 trial of Remdesivir for 584 patients with moderate COVID-19, the day 11 clinical status distribution measured on a 7-point ordinal scale was significantly better for those randomized to a 5-day course of remdesivir (median length of treatment, 5 days) compared with those randomized to standard care. However, the difference for those randomized to a 10-day course (median length of treatment, 6 days) compared with standard care was not significantly different. The findings were published in JAMA. DOI: 10.1001/jama.2020.16349

Physicists at the University of Göttingen, together with pathologists and lung specialists at the Medical University of Hannover, have developed a three-dimensional imaging technique that enables high resolution and three-dimensional representation of damaged lung tissue following severe Covid-19. Using a special X-ray microscopy technique, they were able to image changes caused by the coronavirus in the structure of alveoli (the tiny air sacs in the lung) and the vasculature. The results of the study were published in the research journal eLife. DOI: 10.7554/eLife.60408

Self-collected saliva and deep nasal swabs collected by healthcare providers are equally effective for detecting SARS-CoV-2, the virus that causes COVID-19, according to a new study conducted by ARUP Laboratories and University of Utah Health. The study, published in the Journal of Clinical Microbiology, represents one of the largest prospective specimen type comparisons to date. But specimens self-collected from the front of the nose are less effective than deep nasal swabs for virus detection. DOI: 10.1128/JCM.01824-20 

Researchers at the Gladstone Institutes have catalogued the T cells of people who have recovered from mild cases of COVID-19. Their analysis, published in Cell Reports Medicine, sheds light on what a successful immune response to SARS-CoV-2 might entail, and has implications for vaccine development. While antibodies against SARS-CoV-2 appear to wane rapidly after an infection, their results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19. DOI: 10.1016/j.xcrm.2020.100081

Researchers from the Washington University School of Medicine in St. Louis report a vaccine that targets the SARS-CoV-2 virus, can be given in one dose via the nose and is effective in preventing infection in mice susceptible to the novel coronavirus. They published their findings in Cell. The vaccine candidate has not yet been studied in humans. DOI: 10.1016/j.cell.2020.08.026 

CRN Industry Updates

Dr. Christopher Basler, professor and director of the Center for Microbial Pathogenesis in the Institute for Biomedical Sciences at Georgia State University, has received a $100,000 COVID-19 Fast Grant to study enzymes that are critical for the replication of SARS-CoV-2, the virus that causes COVID-19. Basler is exploring several small molecule inhibitors that would block formation of membranes needed for SARS-CoV-2 infection. These include enzymes such as VPS34, long chain fatty acyl-coA synthetase and fatty acid synthase. Drugs that affect cell membranes and lipids are being pursued as treatments for other medical conditions, including cancer, diabetes and obesity. Early data from the Basler lab suggest such drugs might be effective to slow SARS-CoV-2. Press release.

KPMG has built the technology architecture for a solution that can match patients in clinical trials for convalescent plasma therapy to recovered patients willing to donate their antibodies. KPMG's solution has been designed to make the plasma donation process easier and more efficient by automating the complex tasks and logistics associated with the data collection, qualification and matching process by performing statistical analytics, and using artificial intelligence (AI) and virtualized data. It is designed to integrate third-party data from blood banks, hospitals and diagnostic labs, and work with data backbones and existing technology applications that are already in place, such as IT infrastructure owned by governments and hospitals. Press release.

Vanderbilt University Medical Center (VUMC) has been awarded a one-year, $34-million grant by the National Center for Advancing Translational Sciences, part of the National Institutes of Health, to conduct a nationwide study of "convalescent plasma" as a treatment for COVID-19. The randomized, controlled trial will test whether infusions of plasma, the liquid part of blood collected from COVID-19 survivors, can help other hospitalized patients with COVID-19. The study will recruit 1,000 participants in approximately 51 sites across the country. The goal is to complete enrollment by October 31, and report results by November. Press release.