November 13, 2020 | Italian insights into re-infection, Oxford studies increased rates of psychiatric diagnoses, a model for how today’s nonpharmaceutical interventions will impact future flu seasons, exploring the relationship between ethnicity and clinical outcomes, and tracking COVID-19 research over time. Plus, a recommended vaccine distribution framework and new funding for Canadian treatments and vaccines.

Research Updates

A research team out of Rome explored patients who have recovered from COVID-19 with documented negative real-time polymerase chain reaction (RT-PCR) results, but later have subsequent positive RT-PCR test results for SARS-CoV-2 in the absence of any symptoms suggestive of new infection. They report that 18% of patients with COVID-19 in their institution became RT-PCR positive for SARS-CoV-2 RNA after clinical recovery and previous negative results, but only 1 in 32 who retested positive had replicating virus. The work highlights that many patients who recovered from COVID-19 may be still positive (albeit at lower levels) for SARS-CoV-2 RNA, but only a minority of the patients may carry a replicating SARS-CoV-2 in the respiratory tract, the authors write in JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2020.7570

A Vanderbilt University team conducted a randomized clinical trial comparing the effects of hydroxychloroquine versus placebo on patients' clinical status at 14 days (home, requiring noninvasive or invasive ventilation or extracorporeal membrane oxygenation, hospitalized, died) among adults hospitalized with COVID-19. The trial included 479 hospitalized adults with respiratory symptoms from COVID-19 and was published in JAMA. The distribution of the day 14 clinical status score (measured using a 7-category ordinal scale) was not significantly different for patients randomized to receive hydroxychloroquine compared with placebo. DOI: 10.1001/jama.2020.22240

A University of Oxford team conducted an electronic health record network cohort study to assess whether a diagnosis of COVID-19 (compared with other health events) was associated with increased rates of subsequent psychiatric diagnoses. The researchers used the TriNetX Analytics Network, a global federated network that captures anonymized data from electronic health records in 54 health-care organizations. They found that in patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events. The association was greatest for new diagnoses of anxiety disorders, insomnia, and dementia. The incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18.1%. The results are published in The Lancet Psychiatry. DOI: 10.1016/S2215-0366(20)30462-4

A Princeton team modeled the impact of COVID-19 nonpharmaceutical interventions (NPIs) on the future dynamics of endemic infections like flu and RSV. They project large future outbreaks of both diseases may occur following a period of extended NPIs. These outbreaks, which may reach peak numbers in the winter, could increase the burden to healthcare systems. The researchers used an epidemiological model based on historic RSV data and observations of the recent decline in RSV cases to examine the possible impact of COVID-19 NPIs on future RSV outbreaks in the United States and Mexico. They found that even relatively short periods of NPI measures could lead to large future RSV outbreaks. These outbreaks were often delayed following the end of the NPI period, with peak cases projected to occur in many locations in winter 2021-22. They published their model in PNAS. DOI: 10.1073/pnas.2013182117

Researchers at the University of Michigan interviewed 488 COVID-19 patients by phone around 60 days after their hospitalization and categorized their health statuses. They've published their findings in the Annals of Internal Medicine. More than 39% of the patients interviewed said they hadn't gotten back to normal activities yet, two months after leaving the hospital. Twelve percent of the patients said they couldn't carry out basic care for themselves anymore, or as well as before. Nearly 23% said they became short of breath just climbing a flight of stairs. One-third had ongoing COVID-like symptoms, including many who still had problems with taste or smell. The patients listed many financial and emotional impacts as well. DOI: 10.7326/M20-5661

Researchers from St. James’ Hospital in Dublin, Ireland, examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). Their results were published in PLOS One. Of 128 participants, more than half reported persistent fatigue at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. DOI: 10.1371/journal.pone.0240784

Using nasal swab tests before surgery to detect COVID-19 in patients with no symptoms is linked to lower rate of serious breathing complications, report researchers at the University of Birmingham. They published their findings in the British Journal of Surgery and recommend routine pre-operative swab testing as part of a broader strategy to reduce COVID-19 exposure for patients undergoing surgery. To help, they launched a 'toolkit' that will help healthcare chiefs use such testing, 'COVID-free' hospital zones and other measures to 're-boot' surgery safely and prevent further delays. DOI: 10.1093/bjs/znaa051

Dexamethasone, a widely used corticosteroid, has recently been reported as the first drug to increase the survival chances of patients with severe COVID-19. Therapeutic agents, including dexamethasone, are mostly transported through the body by binding to serum albumin. In a paper published in the Journal of the International Union of Crystallography, a team from the University of Virginia—using the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE's Argonne National Laboratory—determined the structure of serum albumin in complex with dexamethasone. Dexamethasone binds to drug site 7, which is also the binding site for commonly used nonsteroidal anti-inflammatory drugs and testosterone, suggesting potentially problematic binding competition. DOI: 10.1107/S2052252520012944

Researchers from the Universities of Leicester and Nottingham performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19 in the UK and the US. 18,728,893 patients from 50 studies were included. Individuals from Black and Asian ethnicities had a higher risk of COVID-19 infection compared to White individuals. Individuals of Asian ethnicity may also be at higher risk of ICU admission and death. They published their findings in eClinicalMedicine. DOI: 10.1016/j.eclinm.2020.100630

A Cleveland Clinic-led study suggests that melatonin, a hormone that regulates the sleep-wake cycle and is commonly used as an over-the-counter sleep aid, may be a viable treatment option for COVID-19. The findings are published in PLOS Biology. Analysis of patient data from Cleveland Clinic's COVID-19 registry also revealed that melatonin usage was associated with a nearly 30% reduced likelihood of testing positive for SARS-CoV-2 (the virus that causes COVID-19) after adjusting for age, race, smoking history and various disease comorbidities. Notably, the reduced likelihood of testing positive for the virus increased from 30 to 52% for African Americans when adjusted for the same variables. DOI: 10.1371/journal.pbio.3000970

Researchers at Karolinska Institutet in Sweden have explored all COVID-19 research published during the initial phase of the pandemic. To obtain an overview of the more than 60,000 publications on COVID-19 in PubMed, the team used a machine learning technique that enables them to map key areas of a research field and track the development over time. The present study, published in the Journal of Medical Internet Research, includes 16,670 scientific papers on COVID-19 published from 14 February to 1 June 2020, divided into 14 different topics. The most common research topics were health care response, clinical manifestations, and psychosocial impact. Some topics, like health care response, declined over time, while others, such as clinical manifestations and protective measures, showed a growing trend of publications. Protective measures, immunology, and clinical manifestations were the research topics published in journals with the highest average scientific ranking. The countries that accounted for the majority of publications (the USA, China, Italy and the UK) were also amongst the ones hardest hit by the pandemic. DOI: 10.2196/21559

Mount Sinai researchers have developed machine learning models that analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 to predict the likelihood of critical events and mortality within clinically relevant time windows. They share their newest models in the Journal of Medical Internet Research. They used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. The models could aid clinical practitioners at Mount Sinai and across the world in the care and management of COVID-19 patients, they write. DOI: 10.2196/24018

In a single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, a team from Brigham and Women’s Hospital investigated whether inflammatory biomarker levels predict respiratory decline in patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. DOI: 10.1016/j.xcrm.2020.100144

Researchers in the United Arab Emirates implemented a pilot microbiologic screening program in Al Zahra Hospital, identifying presymptomatic COVID-19 in nearly 1 in 10 patients with cancer. The program identified a high rate of COVID-19 among patients with cancer, with 32 of 109 (29.4%) patients developing COVID-19 during the study period. In comparison, the cumulative prevalence of COVID-19 in the UAE was 496.3 per 100 000 residents as of June 29, 2020. Most infections were identified in the presymptomatic phase. In the absence of this microbiologic screening, such patients would have proceeded with anticancer therapy unaware of their COVID-19 infection, which may have increased their complication risk. They published their results in JAMA Oncology. DOI: 10.1001/jamaoncol.2020.5745

A cross-sectional study from researchers from the RAND Corporation conducted a claims-based analysis of 6.8 million commercially insured individuals found that during the initial phase of the COVID-19 epidemic in March and April of 2020, patients significantly reduced use of preventive and elective care and increased use of telemedicine but not enough to offset reductions in in-person care. Racial/ethnic and income disparities were seen in changes in use of in-person care and telemedicine. The findings were published in JAMA Network Open. DOI: 10.1001/jamanetworkopen.2020.24984

University College London researchers found that having COVID-19 at the onset of a stroke was also associated with more than double the mortality rate of other stroke patients, according to the findings published in the Journal of Neurology, Neurosurgery & Psychiatry. The researchers also found evidence that people of Asian descent might be more likely to experience COVID-19-associated ischaemic strokes (those caused by blockage of blood vessels supplying the brain) than those in other groups in the UK. Their work was published in BMJ. DOI: 10.1136/jnnp-2020-324927

In PLOS Biology, two Penn State researchers recommend that samples from COVID-19 vaccine clinical trials be used to assess the likelihood that the vaccines being tested will drive resistance evolution and determine viral titer to assess transmissibility. For example, blood samples can be used to assess the redundancy of immune protection generated by candidate vaccines by measuring the types and amounts of antibodies and T-cells that are present. DOI: 10.1371/journal.pbio.3001000

Industry Updates

Baylor College of Medicine today released a curriculum for teachers that specifically focuses on the COVID-19 pandemic. The curriculum, which includes lesson plans and activities for students in grades K-12, is available for free through BioEdOnline. The COVID-19 curriculum is written by scientists and educators and reviewed by Baylor infectious diseases experts. The program is called COVID HACKS (Healthy Actions, Community, Knowledge and Science). In total, there will be about 30 lesson plans. The lesson plans address questions such as: What are viruses? How big are they? What do they look like? What is COVID-19? What are the symptoms of the infection? How can social distancing slow the spread of viruses? Why 6 feet? Why are face masks important? What are vaccines and how can they protect us? Press release.

The Standing Committee on Vaccination (STIKO), the German Ethics Council and the German National Academy of Sciences Leopoldina have issued a joint position paper on ethical, legal and practical framework conditions for a COVID-19 vaccine. They present a framework for making decisions on vaccine prioritization around four concrete vaccination goals: prevention of severe courses of COVID-19 (hospitalization) and deaths; protection of persons with an especially high work-related risk of exposure to SARS-CoV-2 (occupational indication); prevention of transmission and protection in environments with a high proportion of vulnerable individuals and in those with a high outbreak potential; maintenance of essential state functions and public life. Press release.

Researchers from the University of Ottawa and The Ottawa Hospital have been awarded $1,050,000 million from the Canada Foundation for Innovation to support facilities for manufacturing innovative treatments and vaccines for COVID-19. The funding will support new equipment and infrastructure at The Ottawa Hospital's Biotherapeutics Manufacturing Centre (BMC). Press release.