January 15, 2021 I COVID-19 ICU patients experience higher rates of delirium and coma, ABM recommends women continue breastfeeding after vaccination, guidelines for elective surgery following infection, ACE inhibitors could offer protection, why COVID-19 pneumonia lasts longer, Wuhan study finds lingering symptoms in many, immunosuppressed patients show similar outcomes, and ICU nurses suffer toll on mental health. Plus: Princeton University spin-off launches AI COVID screening tool and poor mental health could impact vaccine effectiveness.

Research News

New research from King’s College London shows that nearly half of intensive care unit (ICU) staff are likely to meet the threshold for post-traumatic stress disorder (PTSD), severe anxiety or problem drinking during the COVID-19 pandemic. The study, published in Occupational Medicine, used information from anonymous web-based surveys in June and July 2020 from over 700 healthcare workers. Over half of the respondents reported good wellbeing, however, 45% met the threshold for severe depression (6%), PTSD (40%), severe anxiety (11%), or problem drinking (7%). Most concerning, 13% of the respondents reported frequent thoughts of being better off dead or hurting themselves in the past two weeks. The researchers note that poor mental health was more pronounced in nurses than in doctors or other healthcare professionals. DOI:10.1093/occmed/kqaa220

The Academy of Breastfeeding Medicine (ABM) does not recommend cessation of breastfeeding for individuals who receive a COVID-19 vaccine. In their new statement, the ABM suggests lactating women discuss the risks and benefits of vaccination with their health care provider, within the context of their risk of contracting COVID-19 and developing severe disease. They acknowledge that no clinical data regarding the safety of COVID-19 vaccines exists and vaccine trials exclude lactating women. They do, however, believe that there is little biological plausibility that the vaccine causes harm to the lactating mother and breastfeeding child, and the antibodies to COVID-19 in the mother’s milk could offer protection to her child. The ABM recommends that phase 3 clinical trials routinely include pregnant and lactating individuals moving forward. These full statements are published in Breastfeeding Medicine. DOI:10.1089/bfm.2020.29171.ams

The make-up of gut microbiome may influence the severity of COVID-19 and immune response to the infection, finds new research published in Gut. Researchers collected blood and stool samples, along with medical records, from 100 patients hospitalized with confirmed COVID-19 and from 78 individuals without the virus. After their analysis, they found that the make-up of the gut microbiome differed significantly between patients with and without COVID-19, regardless of whether they had been treated with medications, including antibiotics. Lower numbers of F. prausnitzii and B. bifidum were particularly associated with infection severity. An analysis of blood samples revealed that the microbiome imbalance found in COVID-19 patients was also linked to raised levels of cytokines and blood markers of tissue damage. DOI:10.1136/gutjnl-2020-323020

Oregon Health & Science University has published protocol to prepare patients for elective surgery following COVID-19 infection, which is believed to be the first of its kind. The researchers sought out to create these guidelines to ensure surgery would be safe for these patients. They looked to data published worldwide about health outcomes of patients who underwent surgery following illness and adopted a set of guidelines based on this research. Some key recommendations include a minimum recovery time for COVID-positive patients, a thorough evaluation to determine whether a patient has returned to their “pre-COVID” baseline health, and guidance for specific tests prior to surgery. The researchers note that this protocol does not account for patients who are suffering from ‘long-COVID’. This protocol is published in Perioperative Medicine. DOI:10.1186/s13741-020-00172-2

A new article published in Lancet Respiratory Medicine calls for hospitals and medical institutions to support and promote the safe return to work for all health care workers disabled from long-COVID. The authors of the paper recommend that multidisciplinary teams at medical institutions be charged with devising back-to-work strategies for health care workers with long-term COVID symptoms, such as gradual introduction into the work force, limiting shifts, mandating frequent breaks, and reducing workloads to prevent fatigue. In addition, the authors are advocating for Congress to acknowledge the health issues and needs of long-hauler health care providers and to create funding to support these individuals. DOI:10.1016/S2213-2600(20)30575-0

Pediatric hospitalizations for COVID-19 in the United States are rising, according to a new study published in JAMA Pediatrics. Researchers examined pediatric hospitalization trends in 22 states between May and November 2020. They found that the average cumulative hospitalization rate per 100,000 children (19 years and younger) was 2.0 at the beginning of the study and increased to 17.2 by the conclusion in November. The researchers report large variations across states, but they noted that several states saw significant growth in 3 months, with Utah experiencing a 5067% increase from 0.3 hospitalizations to 15.5 per 100,000 at the high end. They conclude that these results raise concern about pediatric populations and conversations around continuing in-person education, as this study presents alarming trends in rising hospitalizations. DOI:10.1001/jamapediatrics.2020.5535

An augmented immune response may explain the severe disease progression in patients with hypertension, however, angiotensin-converting enzyme (ACE) inhibitors could offer protection. This is according to a new study published in Nature Biotechnology. Scientists analyzed individual cells from the respiratory systems of COVID-19 patients who were also taking medication for high blood pressure. They found that the medications did not increase the risk of severe COVID-19, but patients taking ACE inhibitors actually displayed a lower risk that was comparable to COVID-19 patients without cardiovascular (CV) disease. The team then analyzed cells from the nasopharynx of 32 COVID-19 patients and 16 non-infected controls and found an augmented immune response in CV patients associated with risk for severe disease, however ACE inhibitors appeared to prevent this augmented response of the immune system following infection with SARS-CoV-2. DOI:10.1038/s41587-020-00796-1

Northwestern Medicine investigators have unveiled why COVID-19 pneumonia lasts longer and causes more damage than other pneumonias in a new study published in Nature. The scientists analyzed immune cells from the lungs of COVID-19 pneumonia patients and compared them to cells from patients with pneumonia from other viruses or bacteria. They discovered that, instead of rapidly infecting large regions of the lung, SARS-CoV-2 invades multiple small areas of the lungs. It then hijacks the lungs’ own immune cells and uses them to spread across the lung over a period of several days to weeks, leaving damage behind. The research team also identified macrophages and T cells as critical targets to treat severe SARS-CoV-2 pneumonia and lessen its damage. Their findings suggest that macrophages can be infected with the virus and contribute to spreading the infection though the lung. They plan to test an experimental drug to treat these targets in patients suffering from COVID-19 pneumonia. DOI:10.1038/s41586-020-03148-w

Cardiovascular deaths not related to COVID-19 increased after the onset of the COVID-19 pandemic, specifically in states most affected by the virus. Beth Israel Deaconess Medical Center (BIDMC) researchers evaluated the rate of U.S. deaths due to cardiovascular causes in mid-March to June 2020, compared to the immediately preceding 11 weeks prior to the pandemic and to the same time period from the prior year. They discovered that deaths due to ischemic heart diseases and hypertensive diseases increased by 11% and 17%, respectively, compared to the previous year. The increase in deaths was concentrated in states that experienced a high number of COVID-19 cases, specifically New York, New Jersey, Michigan, and Illinois. New York City saw the largest relative rise in deaths due to ischemic heart diseases (139%). Massachusetts, which experienced a surge in cases during the spring, was an exception and did not see similar spikes in cardiac deaths. Researchers credit these findings to avoidance of hospitals, delayed elective procedures, and strain on hospitals during the early phase of the pandemic. This study is published in the Journal of the American College of Cardiology (JACC). DOI:10.1016/j.jacc.2020.10.055

Vanderbilt University Medical Center (VUMC) researchers have found that myocarditis in athletes recovering from COVID-19 is much less common than previously reported in other studies. The study, called COVID-19 Myocardial Pathology Evaluation in Athletes with Cardiac Magnetic Resonance (COMPETE CMR), evaluated 59 Vanderbilt athletes and compared them to a healthy control group and an athlete control group. They determined the degree of myocarditis found by cardiac MRI in the athletes was only 3%. The researchers add that traditional screening tests did not detect the athletes with myocarditis and none of those athletes had experienced symptoms of COVID-19, highlighting the importance of considering cardiac MRI in addition to other screening measures. The Vanderbilt team also explains that many of the athletes showed scarring in the heart muscle, which is benign scarring due to athletic remodeling, and without the knowledge of this common scarring in healthy athletes, clinicians could attribute this finding to COVID-19. This research is published in Circulation. DOI:10.1161/CIRCULATIONAHA.120.052573

Patients with severe COVID-19 requiring intensive care were at a significantly higher risk of delirium and coma than typically seen in patients with acute respiratory failure, according to new research led by VUMC. The observational study, published in The Lancet Respiratory Medicine, tracked the incidence of brain dysfunction in over 2,000 COVID-19 patients admitted before late April 2020 to 69 intensive care units across 14 countries. 82% of those patients were in a coma for a median of 10 days, and 55% of the patients were delirious for a median of three days. Researchers state that this is double of what is typically seen in non-COVID ICU patients, citing a previous study led by VUMC. Upon further investigation, researchers determined that patients receiving benzodiazepine sedative infusions were at a higher risk (59%) of developing delirium, and patients who received family visitation (virtual or in-person) had a lower risk of delirium (30%). The researchers voice concern over these findings, which they explain are largely avoidable, and call for lighter sedation, frequent awakening and breathing trials, mobilization, and safe visitations. DOI:10.1016/S2213-2600(20)30552-X

Children are at a low risk of severe COVID-19, finds a new study published in the New England Journal of Medicine. Swedish researchers conducted a registry study of children aged one to sixteen years old to identify how many were treated in an intensive care unit for COVID-19 or multi-inflammatory syndrome in children (MIS-C) in that age group. They found 15 children, out of nearly 2 million, with COVID-19 or MIS-C were treated in intensive care units in Sweden, which is the equivalent of 0.77 per 100,000 children. The researchers of the study explain that preschools and primary schools remained open between March and June 2020 in Sweden, which is when the registry data was examined, and their findings show a very low incidence of severe infection with SARS-CoV-2 in children despite this. DOI:10.1056/NEJMc2026670

In a new study of over 1,700 patients hospitalized in Wuhan, China with COVID-19, researchers found that 76% of those patients reported at least one symptom six months after initial infection. The most common symptoms to persist were fatigue or muscle weakness (63%), difficulty sleeping (26%), and anxiety or depression (23%). The researchers conducted face-to-face interviews with the COVID-19 patients, all who were discharged from Jin Yin-tan Hospital in Wuhan between January and May 2020, to evaluate their symptoms and quality of life. The patients also underwent physical examinations, lab tests, and a six-minute walking test to measure endurance. Those with more severe disease commonly had reduced lung function and performed worse in the walking test. The researchers suggest that those patients with severe COVID-19 infection receive post-discharge care and that long-term research be conducted to better understand the lasting effects of the virus. This study is published in The Lancet. DOI:10.1016/S0140-6736(20)32656-8

Thousands of Wuhan residents were infected with asymptomatic cases of COVID-19 after the infection was declared to be under control in China. Researchers tested more than 60,000 healthy individuals for SARS-CoV-2 antibodies and studied the prevalence of IgG and IgM antibodies in the blood samples, which were collected between March and May 2020. The percentage of people with positive SARS-CoV-2 antibodies was approximately 1.68%. This number was significantly higher than in other regions of China where antibody positivity rate was 0.38% on average. According to the IgM positivity rate (0.46%) in Wuhan, the researchers estimate that thousands of people had asymptomatic cases between March and May 2020, although there were not clinically reported cases of COVID-19. The researchers warn that avirulent SARS-CoV-2 strains could still cause symptoms in those who are extremely susceptible, and it may also revert to a highly virulent strain. These findings are published in PLOS Neglected Tropical Diseases. DOI:10.1371/journal.pntd.0008975

Hospitalized COVID-19 patients on chronic immunosuppressive medications have similar outcomes to non-immunosuppressed patients, finds a new study led by John Hopkins Bloomberg School of Public Health researchers. The study, published in Clinical Infectious Diseases, analyzed records of over 2,000 COVID-19 patients hospitalized between March and August 2020 in the John Hopkins medical system. Their analysis revealed that immunosuppressed COVID-19 patients, who accounted for 5% of the study cohort, did not have worse COVID-19 outcomes when compared to those who were not immunosuppressed. Outcomes measured included a longer length of stay in the hospital, death in the hospital, and use of mechanical ventilation. The John Hopkins team is now following up with an analysis of a much larger set of data of nationwide COVID-19 cases to confirm these findings. DOI:10.1093/cid/ciaa1488

Industry News

Poor mental health could impact COVID-19 vaccine effectiveness, according to Ohio State University researchers. They reviewed 49 previous vaccine studies dating back 30 years that document how stress, depression, and poor health behaviors can negatively affect the body’s immune response to vaccination. These impaired immune responses included interference with the development of antibodies against the pathogen, more rapid decline in antibody protection that does develop, and worsening of the vaccination’s side effects. The researchers say that, fortunately, improving health habits even in the short term can positively influence how the body responds to vaccination. This study is published as preprint and has been accepted for publication in Perspectives on Psychological Science. Article

Researchers evaluating the investigational drug, vadadustat, for its effectiveness in preventing acute respiratory distress syndrome (ARDS) in COVID-19 patients have been awarded $5.1 million in funding from the U.S. Department of Defense (DoD) to expand the Phase II clinical trial at The University of Texas Health Science Center at Houston. (UTHealth). Vadadustat is an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) designed to mimic the physiologic effect of altitude on oxygen availability. Stabilization of HIF can help reduce alveolar inflammation, a key problem that COVID-19 patients are facing when they develop ARDS. The award was given through the DoD’s Peer Reviewed Medical Research Program as a COVID Clinical Trial Award. Press Release

Novaerus, a WellAir company that delivers clean air solutions to help prevent the spread of infectious outbreaks, has announced that the U.S. Food and Drug Administration (FDA) cleared the Novaerus Defend 1050 (NV 1050) as a 510(k) Class II Medical Device to inactivate and filter out micro-organisms, including viruses and bacteria, for medical purposes. The Defend 1050 demonstrated a 99.99% reduction of the MS2 bacteriophage RNA virus, an accepted surrogate for SARS-CoV-2. The system is currently used in hospitals and healthcare settings in over 60 countries and meets relevant performance criteria in the FDA Guidance, which provides non-binding recommendations that may reduce the risk of viral exposure for patients and healthcare providers during the current public health emergency. Press Release

In the first publication from the COVID-19 Host Genome Structural Variant Consortium, their study identifies structural variants (SV) with possible roles in pathogenesis and clinical outcomes using Bionano’s Saphyr System. The new study reports the analysis of the genomes of 37 patients admitted to the ICU at Augusta University with severe COVID-19. Of the SVs revealed by Saphyr, the most compelling finding was the duplication of the STK26 gene. The study found significant upregulation of STK26 in all severely ill patients tested but not in asymptomatic COVID-19 patients, implying the duplication to be a potential novel, prognostic biomarker for the severe immune response seen in critically ill patients with COVID-19. Press Release

Syntegra and the National Institutes of Health (NIH) have signed a partnership to validate Syntegra’s synthetic data technology to advance the understanding and care for COVID-19. Syntegra’s synthetic data engine is already a key component of the National COVID Cohort Collaborative (N3C). The synthetic database represents over 2.7 million screened individuals and includes over 413,000 COVID-19 positive patients with over 2.6 billion rows of data. The Bill and Melinda Gates Foundation, through their COVID-19 Therapeutic Accelerator, is supporting this new collaboration between Syntegra and the NIH. The partnership will play a vital role for researchers around the world to advance treatments and vaccines, while providing a better insight into how and why SARS-CoV-2 affects individuals in vastly different ways. Press Release

NeuTigers, an artificial intelligence (AI) company spun out of Princeton University, has launched CovidDeep, a clinically validated technology that uses physiological sensors data to detect potential SARS-CoV-2 infection with over 90% accuracy. The screening tool uses advanced algorithms of machine learning to detect physiological patterns even before they are felt by the patients with real-time analysis. Users answer a questionnaire regarding symptoms and health history and input their health sensor’s data. Data is entered by connecting CovidDeep to a wearable device, an Empatica E4 Wristband, as well as inputting blood pressure and oxygen readings using any off-the-shelf device. CovidDeep analyzes this data in approximately two minutes and provides a prediction as to whether someone is likely to be negative or positive for COVID-19. This screening tool is now available globally. Press Release

CohBar has announced a preclinical collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) to evaluate the potential of CB5064 Analogs for the treatment of COVID-19 associated acute respiratory distress syndrome (ARDS). Under a Non-Clinical Evaluation Agreement (NCEA), the NIAID will be responsible for any study conducted and will be provided with CohBar’s CB5064 Analogs to test preclinical models of COVID-19, such as the golden Syrian hamster SARS-CoV-2 model. This model has been used to assess other COVID-19 therapeutics and demonstrates clinical features and immune responses that are similar to mild-to-moderate COVID-19 infection seen in human patients. CohBar’s CB5064 Analog program has shown positive results in models of acute lung injury, which included reduced levels of fluid accumulation, neutrophil infiltration, and cytokine secretion. Press Release

The American Lung Association is calling for applications for its second round of research funding opportunities for COVID-19 and future respiratory virus treatments. This COVID-19 and Respiratory Virus Research Award is part of the Lung Association’s recently expanded awards and grants program through its COVID-19 Action Initiative. The award is funded at $100,000 a year for two years and letters of intent for this second application cycle are due February 18, 2021. Press Release

A data scientist from the University of Tennessee Health Science Center (UTHSC) will be joining in the national COVID-19 data research effort, N3C. The N3C includes clinicians and researchers from over 60 institutions working to turn data from thousands of medical records from COVID-19 patients into treatments and predictive analytical tools to help address the pandemic. Dr. Madlock-Brown is the co-lead for the Social Determinants of Health (SDoH) team that aims to identify questions that either validate current research or answer new questions for local policy around COVID-19, the impact of groups experiencing resource challenges, and the impact of the pandemic on inequalities. Press Release