October 23, 2020 | Tocilizumab lowers in-hospital deaths, a global survey finds mixed responses to vaccine views and in the US they are driven partially by politics, and Monell Chemical Senses Center finds loss of smell more prevalent than we thought. Plus: the UK plans to develop a COVID-19 (SARS-CoV-2) human challenge study model, Texas launches a state-wide antibody study, and a call to action for the upcoming flu season.

Research Updates

A global survey published in Nature Medicine of 13,426 people in 19 countries found that 71.5% of participants reported that they would be very or somewhat likely to take a COVID-19 vaccine, and 61.4% reported that they would accept their employer’s recommendation to do so. Differences in acceptance rates ranged from almost 90% (in China) to less than 55% (in Russia). Respondents reporting higher levels of trust in information from government sources were more likely to accept a vaccine and take their employer’s advice to do so. DOI: 10.1038/s41591-020-1124-9. A separate study, published in JAMA Network Open, identified vaccine-related attributes (eg, vaccine efficacy, adverse effects, and protection duration) and political factors (eg, US Food and Drug Administration approval process, national origin of vaccine, and endorsements) as factors influencing whether or not US adults would take a COVID-19 vaccine. DOI:10.1001/jamanetworkopen.2020.25594

Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a major contributing factor in skilled nursing facility (SNF) outbreaks, say a team of Brown researchers in a Research Letter published in JAMA Internal Medicine. Using data from a multi-state care provider, the team reviewed data from 350 SNFs between March and July. They observed high asymptomatic and presymptomatic SARS-CoV-2 infection rates in a large multistate sample of SNFs, demonstrating the importance of universal testing for identifying and isolating cases. DOI: 10.1001/jamainternmed.2020.5664

Monell Chemical Senses Center researchers scanned the published literature on COVID-19 and SARS-CoV-2 infections looking for data on loss of smell among patients. They identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 tested with objective methods, 28 with subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements and 44% with subjective measurements. The researchers conclude that there is a much higher prevalence of olfactory loss in COVID-19 than previously believed. DOI: 10.1093/chemse/bjaa064

In a multicenter cohort study of 3,924 patients, the risk of in-hospital death was estimated to be lower with tocilizumab treatment in the first 2 days of intensive care unit admission compared with no early use of tocilizumab. The results were published in JAMA Internal Medicine. Patients treated with tocilizumab were younger (median age, 58 vs 63 years) and had a higher prevalence of hypoxemia on ICU admission than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. The findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed, the authors write. DOI: 10.1001/jamainternmed.2020.6252

An international team profiled the lung and colon transcriptomes and lung proteomes of nine patients who died of COVID-19 during the first wave of the pandemic in Wuhan, China, and published their findings in PNAS. They found little virus present in lung tissue at the time of death suggests that these patients may have died of sequelae related to COVID-19 pneumonia (i.e., the host inflammatory response) rather than an ongoing, fulminant active viral infection. Although there is no obvious pathogenesis in the colon tissue based on histological examination, there is a dramatic change in the transcriptome in the colon tissues in the fatal cases when compared to healthy controls. These findings inform the treatment choices of COVID-19 patients, the authors write. DOI: 10.1073/pnas.2018030117

The Temple University COVID-19 Research Group used logistic regression and principal component analysis to determine the predictive criteria for COVID-19 cytokine storm. They analyzed the early hospitalization records for 513 patients who were positive for COVID-19 and showed ground-glass opacity by chest high-resolution CT. They developed new predictive criteria of COVID-19 cytokine storm based on inflammation, cell death and tissue damage, and prerenal electrolyte imbalance. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyperimmune response and possibly decrease mortality, the authors write in the Annals of the Rheumatic Diseases. DOI: 10.1136/annrheumdis-2020-218323

Researchers at Johns Hopkins Bloomberg School of Public Health found that male sex, older age, and hospitalization for COVID-19 are associated with increased antibody responses across the serological assays. In studying convalescent plasma collected from 126 patients with molecular confirmed SARS–CoV-2 infection, they found substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses. Their results were published in the Journal of Clinical Investigation. DOI: 10.1172/JCI142004

UK researchers looked at papers describing mental health problems in healthcare workers in past pandemics to begin to predict some of the problems facing current healthcare workers. They found that almost a quarter of health-care workers (23.4%) experienced PTSD symptoms during the most intense 'acute' phase of previous pandemic outbreaks—with 11.9% of carers still experiencing symptoms a year on. They also looked at data about elevated levels of mental distress and found that more than a third of health workers (34.1%) experienced symptoms such as anxiety or depression during the acute phase, dropping to 17.9% after six months. This figure however increased again to 29.3% after 12 months or longer. The published their findings in the European Journal of Psychotraumatology. DOI: 10.1080/20008198.2020.1810903

Canadian researchers analyzed plasma at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. They observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. They also observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, the results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. The results were published in mBio. DOI: 10.1128/mBio.02590-20

A Chinese team reports preliminary results from a vaccine candidate, BBIBP-CorV, based on inactivated SARS-CoV-2 virus that is safe and induces an immune response in healthy volunteers, they say in Lancet Infectious Diseases. The Phase 1/2 randomized controlled trial of an inactivated SARS-CoV-2 vaccine candidate was carried out in China between 29 April and 30 July 2020 and involved more than 600 healthy volunteers. The study detected antibody responses in all recipients by day 42 after vaccination and provides some data for participants aged over 60 years. DOI: 10.1016/S1473-3099(20)30831-8

The correlation between elevated interleukin 6 (IL‐6) concentrations and the risk of respiratory failure in COVID‐19 patients, makes IL-6 a promising biomarker of advanced disease. Researchers at McMaster University and SQI Diagnostics have created a surface coating that repels every component of blood and other complex fluids such as urine, but is dotted with microscopic islands of molecules that attract IL-6, making it possible to detect and measure IL-6 with unprecedented accuracy and sensitivity, at concentrations as low as 0.5 picograms per mL—or one half of one trillionth of a gram per mL—making it far more sensitive than existing technology. They published the technology in Small and are working to adapt it to the Toronto company's existing testing platforms in the hope of moving it into clinical use as soon as possible. DOI: 10.1002/smll.202003844

Researchers at Oregon Health & Science University and Oregon State University reviewed 77 studies reporting SARS-CoV-2 viral shedding dynamics. SARS-COV-2 RNA shedding can be prolonged, yet high heterogeneity exists, they report in Infection Control & Hospital Epidemiology. The overall pooled median duration of RNA shedding from respiratory sources was 18.4 days, with viral RNA shedding 19.8 days among severely ill patients and 17.2 days in mild/moderate illness. DOI: 10.1017/ice.2020.1273

Industry Updates

Open Orphan (ORPH) has signed a contract by hVIVO, a subsidiary of Open Orphan, with the UK Government to develop a COVID-19 (SARS-CoV-2) human challenge study model. The model development involves the manufacture of the challenge virus and the first-in-human characterization study for this virus. The contract starts immediately and could be worth approximately £10 million to hVIVO depending upon the final number of volunteers that are included in the characterization study. In addition, the Government has secured the first three slots to test vaccines using hVIVO's COVID-19 challenge study, which we expect start in 2021, each slot reservation has been secured at a cost of £2.5m each bringing the total value of these slot reservations to £7.5m. The study, which is expected to complete in May 2021 and will require regulatory and ethical approval, enables identification of the most appropriate dose of the challenge virus for use in future human challenge studies which play a vital role in helping to develop vaccines and antivirals for infectious diseases such as COVID-19. Press release.

Researchers at The University of Texas Health Science Center at Houston (UTHealth) are partnering with the Texas Department of State Health Services (DSHS) to launch the Texas Coronavirus Antibody Response Survey (Texas CARES). Texas CARES will determine the proportion of people throughout Texas who have COVID-19 antibodies, indicating a past infection and presumably some degree of immune protection. The survey team is looking to enroll a diverse population of 100,000 participants to gather more insight on why some individuals infected with the virus are asymptomatic and if that affects their antibody response. Those who have tested positive, negative, or have never been tested for COVID-19 are eligible to enroll in the assessment. Press release.

The National Institutes of Health has launched an adaptive Phase 3 clinical trial to evaluate the safety and efficacy of three immune modulator drugs in hospitalized adults with COVID-19. The trial, known as ACTIV-1 Immune Modulators (IM), aims to determine if modulating that immune response can reduce the need for ventilators and shorten hospital stays, and will determine if the therapeutics are able to restore balance to an overactive immune system. ACTIV-1 IM is a randomized, placebo-controlled trial that uses an adaptive master protocol, and will begin by testing three agents from a pool of over 130 immune modulators initially reviewed based on several factors, including their relevance to COVID-19, strong evidence for use against inflammatory reaction and cytokine storm, and availability for large-scale clinical studies. Press release.

The National Foundation for Infectious Diseases (NFID) issued a new Call to Action report detailing the risks of co-infection with influenza (flu) and COVID-19 in adults with chronic health conditions, and the importance of flu vaccination during the 2020-2021 season. The goals of the report, The Dangers of Influenza and COVID-19 in Adults with Chronic Health Conditions, have been supported by more than 35 leading medical organizations, including the American College of Cardiology, American College of Emergency Physicians, American Diabetes Association, and American Lung Association, who are now urging their stakeholders to prioritize flu vaccination for these high-risk populations. Call to Action.