Antidepressant Prevents Severe Disease, Measles Outbreak Unexpected Outcome, Cytokine Storm Unlikely: COVID-19 Updates

November 20, 2020 I Arthritis drug improves outcomes in elderly, why COVID-19 spares children, increased risk of tracheal complications, E-cigarette users show poor immune response, effects of in-utero exposure, significant rise in depression, UIC launches trials on blood clot prevention, cytokine storm unlikely, and MRS reveals white matter changes. Plus: XPRIZE announces Pandemic Response Challenge, combination therapy advances, and UT opens post-COVID-19 clinic.

 

Research News

Specialized scanning, sometimes referred to as virtual biopsy, was performed on the brains of three COVID-19 patients at Massachusetts General Hospital (MGH) that revealed potential effects of SARS-CoV-2 on the brain. The researchers discovered similar metabolites to patients with white matter abnormalities after hypoxia without COVID-19. One of the patients displayed severe white matter necrosis and cavitation and had particularly pronounced lactate elevation, another sign of brain injury from hypoxia. The authors of this study, published in the American Journal of Neuroradiology, now hope to find answers to explain whether these white matter changes are a result of hypoxia, or if the virus itself is attacking the white matter in the brain. DOI:10.3174/ajnr.A6877

A new paper, published in the Journal of Neurotrauma, details the risks for acute and persistent neurological deficits associated with COVID-19, and the potential for neurodegenerative diseases and psychiatric disorders. The research describes mechanisms of central nervous system penetration and action of the virus and also makes recommendations for the use of blood biomarkers to detect brain injury in combination with existing diagnostic tools to address this urgent need for rapid detection and treatment in COVID-19 patients. DOI:10.1089/neu.2020.7332

Research led at the University of Tennessee Health Science Center (UTHSC) has identified three drugs that can potentially be repurposed for treatment of COVID-19. Based on virtual and in vitro experiments conducted at the UTHSC Regional Biocontainment Laboratory (RBL), the researchers found zuclopenthixol (an antipsychotic drug), nebivolol (an antihypertensive drug), and amodiaquine (an older antimalarial) to be good candidates for future clinical trials. They found these three drugs to act similarly to hydroxychloroquine, in some cases safer, and efficacy may be improved with combination therapy using remdesivir. This research is published in ACS Pharmacology & Translational Science. DOI:10.1021/acsptsci.0c00131

Implicit racial attitudes in a community potentially explain racial disparities in COVID-19 case rates in the United States, according to Texas A&M University researchers. The study, published in PLOS ONE, collected data from several publicly available sources for 817 counties across the U.S. that included information on cumulative COVID-19 deaths and cases from January to August 2020, as well as explicit and implicit racial attitudes that were collected through Harvard University’s Project Implicit. Their results showed that the percent of Black residents in a county was positively associated with COVID-19 cases and deaths in that county and racial attitudes were positively associated with COVID-19. They concluded that implicit racial attitudes help explain disparities. DOI:10.1371/journal.pone.0242044

An observational study of over 2,700 patients, all who were over the age of 80 years old and hospitalized for COVID-19 in 150 Spanish hospitals, examined the risk factors for in-patient mortality from the virus. Researchers found that age, being male and poor preadmission functional status were all associated with a poor prognosis and mortality. The overall mortality rate from this cohort was 46.9 percent and this increased with age from 41.6 percent in patients 80 to 84 years old to 54.2 percent in patients over 95 years old. Comorbidities were not predictive of poor outcomes. This study is published in The Journals of Gerontology. DOI:10.1093/gerona/glaa243

Prolonged prone-positioning of COVID-19 patients may pose a risk for eye damage, a new study reports in JAMA Opthalmology. Researchers from Northwell Health reported two cases of patients with periorbital edema in the prone position that were found to have bilateral optic disc edema and retinal hemorrhage upon further investigation. Authors of the study note that these cases could have been associated with anticoagulation therapy and suggest the use of eye protection and maintaining the patient’s head position above heart level during prone positioning. DOI:10.1001/jamaophthalmol.2020.4988

A new study, published in JAMA Otolaryngology - Head & Neck Surgery, finds increased frequency of tracheal complications in patients with COVID-19 and severe respiratory failure. Researchers in Italy examined 98 COVID-19 patients who required mechanical ventilation and found that the incidence of full-thickness tracheal lesions or tracheoesophageal fistulas was significantly higher in this group when compared to a matched control group (46.7% and 2.2% respectively). The authors of the study recommend improved efforts to prevent these lesions and their quick detection when they occur to avoid life-threatening complications from mechanical ventilation in COVID-19 patients. DOI:10.1001/jamaoto.2020.4148

Results from a Phase 1/2 randomized clinical trial of the SARS-CoV-2 vaccine candidate, CoronaVac, show that the formulation appears to be safe and induces an antibody response in healthy volunteers aged 18 to 59 years old. The trial involved more than 700 healthy volunteers in China between April and May 2020. These results, published in The Lancet Infectious Disease, also found that these antibody responses could be induced after giving two doses of the vaccine candidate 14 days apart. The antibody levels induced by the vaccine were lower than those found in recovered COVID-19 patients, but researchers believe the vaccine could provide sufficient protection against the virus. A Phase 3 trial will assess CoronaVac’s efficacy. DOI:10.1016/S1473-3099(20)30843-4

Non-COVID-19 related deaths significantly increased during the first three months of the pandemic across several demographics. These findings, published in Public Health, were determined by researchers from the University of Illinois at Urbana-Champaign. Deaths attributed to COVID-19 were removed from the Centers of Disease Control and Prevention (CDC) totals and then compared to the same timeframe in 2019. They found a significant increase in deaths for men between 15 and 59 years old and women between 25 and 44 years old in 2020. The researchers predict these increases may be the result of delaying care for other conditions or undetected COVID-19 deaths. Interestingly, death rates for females between the ages of 5 and 14 years old decreased, possibly as a result of less accidental deaths that historically occur at a higher rate in that age group. DOI:10.1016/j.puhe.2020.10.004

Black and Hispanic patients accounted for more than half of all inpatient deaths from COVID-19 from January to July 2020, according to a new study published in Circulation. Researchers from the Stanford University School of Medicine and Duke University examined a sample of over 7,800 patients hospitalized with COVID-19 who were enrolled in the American Heart Association’s (AHA) COVID-19 Cardiovascular Disease Registry. They found the overall mortality rate for this patient sample was 18.4 percent, with 53 percent of all deaths occurring in Black and Hispanic patients. Researchers also found that Black and Hispanic patients were significantly younger than white and Asian patients and had more underlying health conditions. An author of the study notes that more of the variations in mortality seem to be explained by where care was given rather than solely by race or ethnicity. DOI:10.1161/CIRCULATIONAHA.120.052278

Young adults who are overweight or obese are at a higher risk for severe COVID-19, finds a new study from UT Southwestern. Researchers analyzed data from more than 7,600 patients across 88 hospitals in the U.S. who were enrolled in the AHA COVID-19 Cardiovascular Disease Registry. They found that when looking at hospitalized COVID-19 patients under 50 years old, 85% were either overweight or obese. In comparison, 54% of patients over age 70 were overweight or obese. Among those younger patients, those with severe obesity had a 36% higher risk of dying from the virus when compared to individuals with a normal weight. This study is published in Circulation. DOI:10.1161/CIRCULATIONAHA.120.051936

In a new perspective paper, published in Science, researchers highlight the importance of comprehensive safety testing of COVID-19 vaccines based on vaccine development in the past. The authors explain that it is critical for developers to understand a vaccine’s mechanism of action to ensure that the vaccine will provide the optimal immune response against COVID-19 and avoid nonproductive or counterproductive responses of the immune system. They point out that another historical lesson in vaccine development is that if serious adverse events occur during clinical trials, it is imperative to conduct additional clinical testing or put a pause on that trial. The researchers recognize the urgency for effective COVID-19 vaccines in the paper, but they emphasize the obligation to protect the public health through rigorous testing for safety and efficacy. DOI:10.1126/science.abf0357

E-cigarette users could be at the highest risk of a poor immune response to COVID-19, a new study published in the American Journal of Respiratory Cell and Molecular Biology has concluded. Researchers from the University of North Carolina School of Medicine found that vaping changes the expression of genes, production of proteins in respiratory cells, and alters virus-specific antibody production. After testing immune responses to a model of influenza infection, they observed more changes to the immune response in e-cigarette users than in smokers and believe these findings are applicable to the SARS-CoV-2 virus, as well as other respiratory viruses. DOI:10.1165/rcmb.2020-0164OC

A new study, published in Nature Communications, details how children in a Melbourne family developed a COVID-19 immune response after chronic exposure from their parents without ever testing positive for the virus or displaying any symptoms. Researchers at the Murdoch Children’s Research Institute followed the immune response of the two parents, both with symptomatic COVID-19, and their three school-aged children by testing samples every two to three days. All three children mounted an immune response against COVID-19 and the youngest child developed the strongest antibody response. Authors of the study suggest that the children’s immune systems effectively blocked the virus from replicating in their cells. DOI:10.1038/s41467-020-19545-8

Measles outbreaks are likely to occur in 2021 as an unexpected outcome of the COVID-19 pandemic, a new article published in The Lancet warns. The lead author, from the Murdoch Children’s Research Institute and Chair of the World Health Organization’s SAGE Working Group on measles and rubella vaccines, states that estimates show nearly 94 million children will miss scheduled measles vaccine doses by the end of October 2020 due to delayed vaccination campaigns in 26 countries. These missed vaccinations in children will make future measles outbreaks inevitable. In addition to this, economic impacts will lead to childhood malnutrition in many cases, which worsens the severity of measles and leads to poorer outcomes. The article outlines immediate actions needed to mitigate this potential crisis. DOI:10.1016/S0140-6736(20)32394-1 

A national survey of over 1,000 Americans between the ages of 18-35 years old reveals significant symptoms of depression in 80 percent of respondents. The results of this survey showed that most participants who reported an increase in feelings of loneliness also reported increased drinking, drug use, anxiety, depression, and a decrease in feelings of connectedness. Overall, nearly half of all respondents reported a great degree of loneliness. Authors of this analysis, published in the Journal of Psychoactive Drugs, state that a response to this mental health crisis is crucial amid the pandemic and addiction epidemic in the U.S. DOI:10.1080/02791072.2020.1836435

Diaphragmatic weakness and fibrosis may be associated with severe COVID-19, a new study finds published in JAMA Internal Medicine. Researchers analyzed diaphragm muscle specimens from 26 patients who died from severe COVID-19 in three intensive care units in the Netherlands, and diaphragm specimens from eight critically ill patients who died from other causes as a control group. The team discovered angiotensin-converting enzyme 2 (ACE-2) in the specimens from both groups. Evidence of SARS-CoV-2 viral RNA was present in only four COVID-19 patient samples, however, epimysial and perimysial fibrosis was two times higher in the COVID-19 diaphragm specimens studied when compared to the control group. The authors conclude that persistent shortness of breath and fatigue may be related to a weakened diaphragm in those patients who survive severe COVID-19. DOI:10.1001/jamainternmed.2020.6278

Health care workers, especially nurses, are most at risk for COVID-19 when compared to non-health care workers, according to Rutgers University researchers. The study, published in BMC Infectious Diseases, evaluated 546 health care workers with direct patient exposure and 283 non-health care workers with no direct patient contact. Baseline results show that at the start of the study in March, 40 health care workers and only one non-health care worker tested positive for COVID-19. Of the 40 infected health care workers, 25 were nurses, and those caring for five or more patients with suspected for confirmed infection of the virus were more likely to test positive themselves. Intensive care nurses had the lowest rates of infection, possibly due to more consistent use of personal protective equipment. DOI:10.1186/s12879-020-05587-2

A new study, published in Transboundary and Emerging Diseases, has found that roughly 95 percent of current entries in GISAID, the world’s largest COVID-19 genome database, is missing relevant patient information that is critical to understanding the virus and its mutations. In response to this finding, the researchers have developed a standardized data collection template that allows entry of key patient information without identifying that individual. The authors explain that de-identified patient data associated with the virus genome sequences is urgently needed in order to identify whether disease outcomes are related to virus mutations or other factors such as age, gender and comorbidities. This study was led by Australia’s national science agency CSIRO. DOI:10.1111/tbed.13892

High body mass index (BMI) and high low-density lipoprotein (LDL) cholesterol may pose an increased risk of getting COVID-19, according to new research led at Queen Mary University of London. The study, published in Frontiers of Genetics, used a novel approach called “Mendelian Randomization” which looked at individual genetic information to analyze the effects of cardiovascular risk factors on the risk of COVID-19 infection. Researchers found that high blood pressure and diabetes did not elevate risk of contracting the virus but suggest the use of BMI and LDL cholesterol in risk assessment along with other know factors, such as age and ethnicity. DOI:10.3389/fgene.2020.586308

Acute kidney injury (AKI) is common during hospitalization with COVID-19 in U.S. veterans and is associated with a higher risk of death, finds a new study published in CJASN. An analysis of data from 5,216 U.S. veterans hospitalized with COVID-19 from March to July 2020 also found that this risk is especially high for Black veterans, with AKI being associated with a 6.7-times higher risk of death among this group. Among all veterans, 32% had AKI and 47% did not fully recover their kidney function by the time they were discharged from the hospital. DOI:10.2215/CJN.09610620

Vanderbilt University Medical Center researchers have uncovered why COVID-19 seems to spare children. The research team identified an enzyme, called TMPRSS2, that allows the virus to gain entry into airway epithelial cells and is found at lower levels in children. In the study, published in the Journal of Clinical Investigation, the researchers obtained and analyzed human lung specimens collected from donors of different ages and found that the expression of TMPRSS2 went up significantly with age. The team also analyzed autopsy samples for three patients who died from COVID-19 and found the virus in three types of cells that express the enzyme. Drugs that block TMPRSS2, which have been approved for the treatment of prostate cancer, are currently being tested clinically as a potential treatment for COVID-19. DOI:10.1172/JCI140766

A national study, published in JAMA, finds that hydroxychloroquine is not an effective treatment for hospitalized COVID-19 patients. The Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease (ORCHID) study enrolled 479 patients between April and June 2020 and found that hydroxychloroquine did not significantly improve clinical outcomes of patients hospitalized for respiratory illness related to COVID-19, when compared to an inactive placebo. One month after starting the study, 10.4 percent of patients treated with the drug and 10.6 percent of patients treated with placebo had died. The National Heart, Lung, and Blood Institute (NHLBI), who funded the study, halted it in June 2020 after determining that hydroxychloroquine was not likely to benefit hospitalized COVID-19 patients. DOI:10.1001/jama.2020.22240

High-doses of blood thinners in COVID-19 patients may be ineffective and potentially harmful, according to a new study by George Washington University researchers. The research team evaluated 402 hospitalized patients diagnosed with COVID-19 and clinical outcomes were compared between 152 patients treated with high-dose blood thinners and 250 patients treated with the standard low dose. They found that higher doses of blood thinners were potentially harmful and had no clear benefits in those patients. The authors caution against an aggressive blood thinner regimen unless there is clear clinical evidence to do so, and they add that the benefits remain unknown. This study is published in Thrombosis Research. DOI:10.1016/j.thromres.2020.10.031

The rheumatoid arthritis drug baricitinib could improve outcomes in elderly COVID-19 patients, a new study published in Science Advances finds. Researchers studied 83 patients hospitalized with COVID-19 pneumonia in Italy and Spain who were treated with baricitinib in addition to standard care and 83 patients in a matched control group who received standard care only, with a median age of 81 years old among both groups. They found a 71 percent reduction in mortality for the group receiving baricitinib. Additionally, the international research team grew organoids to investigate how the drug may combat COVID-19 and found that it may work by reducing organ damage caused by inflammation and blocking the virus from entering human cells. DOI:10.1126/sciadv.abe4724

Sleep apnea may be a risk factor for COVID-19, finds a new study published in Sleep Medicine and Disorders International Journal. University of Turku researchers focused on 28 patients admitted to Turku University Hospital in Southwest Finland for COVID-19. Their comparison revealed that 29 percent of patients admitted had a prior sleep apnea diagnosis, compared to only 3.1 percent of the Southwest Finland population seeking treatment for sleep apnea. The authors of this study explain that although the number of patients studied was low, the proportion of sleep apnea patients was high and justifies the consideration of sleep apnea as a risk factor for the virus. DOI:10.15406/smdij.2020.04.00075

Two independent clinical studies have shown the effectiveness of the monoclonal antibody eculizumab and the experimental drug AMY-101 in significantly reducing the inflammatory response and accelerating recovery from severe COVID-19. The two drugs were administered separately in each study as the researchers set out to compare the compounds’ therapeutic effects. Both compounds evoked a strong anti-inflammatory response that led to a quicker recovery of respiratory function in the patients. Due to AMY-101 performing slightly better and being more affordable, the two research groups plan to conduct a Phase III trial with severe COVID-19 patients to assess the drug’s efficacy on a wider scale. The results of this study are published in Clinical Immunology. DOI:10.1016/j.clim.2020.108598

A new paper by Michigan Medicine researchers, published in Chest, outlines 20 evidence-based best practices for mechanical ventilation in patients with acute respiratory failure and acute respiratory distress syndrome, that have implications for patients with severe COVID-19. Some best practices that have emerged include prone position, lung protective ventilation to avoid over-inflating the lungs, and frequently checking to see whether a patient is ready to come off the ventilator. The team plans to prioritize these 20 best practices that they have identified to better support healthcare providers in caring for these patients, adding that implementing even three to four of these evidence-based practices yields better outcomes when compared to none. DOI:10.1016/j.chest.2020.06.080  

Most COVID-19 patients with moderate-to-severe disease have a suppressed viral immune response rather than cytokine storm, new research has found conducted by St. Jude Children’s Hospital and Washington University School of Medicine. The study, published in Science Advances, included 168 adults with COVID-19, 26 adults with the flu and 16 healthy participants. Researchers aimed to understand the immune response by measuring a variety of immune cells and factors, including 35 different cytokines. Only 4 percent of the COVID-19 patients met the study definition of cytokine storm. Their analysis revealed that the antiviral immune response was significantly suppressed in COVID-19 patients compared to the flu patients. Researchers emphasize that these findings indicate most COVID-19 patients are not candidates for steroid treatment, such as dexamethasone, and testing to measure cytokines to identify good candidates for immunosuppressive therapy is needed. DOI:10.1126/sciadv.abe3024

The antidepressant fluvoxamine may prevent severe COVID-19 infection, based on a small clinical trial conducted by the Washington University School of Medicine. The trial compared fluvoxamine with a placebo in 152 adult outpatients infected with SARS-CoV-2 and found that none of the participants who received the antidepressant drug saw worsened disease requiring hospitalization or development of serious breathing difficulties after 15 days. In comparison, six of the patients receiving placebo did go on to develop these complications. This drug was tested based on research from the University of Virginia School of Medicine which showed that fluvoxamine reduced the production of cytokines. The authors of this study, published in JAMA, add that this clinical trial had several limitations and further research is needed. They plan to launch a larger trial in the next few weeks. DOI:10.1001/jama.2020.22760

The COVID-19 pandemic could affect the next generation from in-utero exposure, according to a new analysis by University of Southern California researchers. The researchers looked back at the 1918 flu pandemic and previous coronaviruses, such as SARS and MERS, to gain insight on potential impacts on those born during the current pandemic. The authors noted potential long-term health impacts, such as earlier adult mortality, as seen with the 1918 flu pandemic, as well as increased risk of preterm delivery and low birth weight that occurred during the 2002 SARS and 2009 H1N1 influenza outbreaks. The study, published in the Journal of Developmental Origins of Health and Disease, suggests that preliminary findings showing increased rates of preterm birth and higher risk of stillbirth in mothers with severe disease should be followed up with analysis of child growth and development and lifelong study of health. DOI:10.1017/S204017442000104X

Industry News

XPRIZE and Cognizant have announced a Pandemic Response Challenge that aims to safely reopen societies and restart economies through the power of data and artificial intelligence. Based on technology and AI models developed by Cognizant, and using data compiled by the Oxford COVID-19 Government Response Tracker, competing teams will build data-driven AI models that predict local COVID-19 transmission rates and prescribe intervention and measures to minimize infection rates, as well as negative economic impacts. This four-month competition will award a total prize of $500K at its conclusion. Press Release

The University of Tennessee Health Science Center and Regional One Health have partnered to establish a post-COVID-19 clinic that will provide specialized outpatient follow-up care to individuals who have contracted the virus and experience long-term symptoms post-recovery. The clinic will also be available to individuals with asymptomatic COVID-19 who would like education about ongoing research and potential residual effects. This outpatient clinic, along with the inpatient COVID unit at Regional One Health, will establish a place for longitudinal follow up and care for COVID-19 patients. Press Release

The University of Illinois Chicago (UIC) will conduct three COVID-19 clinical trials to study blood clot prevention. The trials will assess the safety and effectiveness of different anticoagulants to treat adults diagnosed with COVID-19 and are part of the antithrombotics arm of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV). All three trials are collectively known as the ACTIV-4 antithrombotics studies, and are coordinated by the National Heart, Lung, and Blood Institute and funded by Operation Warp Speed. Press Release

New research presented at the 46th Argentine Congress of Cardiology (SAC) links social isolation during the pandemic to increased incidence of high blood pressure among patients admitted to the emergency department. The study compared patients admitted to the Favaloro Foundation University Hospital ED during the three-month social isolation period beginning in March to patients admitted during the same timeframe in 2019 and the three months prior to the pandemic lockdown. Researchers found a 37 percent increase in the likelihood of having elevated blood pressure, even after accounting for several factors such as age and gender. Authors of the study, led by the European Society of Cardiology, explained numerous reasons for these findings, but one emphasized the psychological stress inevitably caused by the pandemic has led to lasting effects on mental and physical health. Press Release

Crystal IS and Boston University research have demonstrated the efficacy of Crystal IS’ Klaran UVC (Ultraviolet) LED technology to effectively inactivate SARS-CoV-2. They found this technology to inactivate 99 percent of the virus in five seconds. Klaran UVC LEDs are currently being used for air disinfection by several partners, including Healthe Air, which provides continuous disinfection and clean airflow in work and retails settings. Press Release

Hypertension and type 2 diabetes may increase the risk of experiencing neurological complications with COVID-19, new research has found being presented at the annual meeting of the Radiological Society of North America (RSNA). The researchers looked at a sample of over 1,300 COVID-19 patients and, of those patients, 81 required a head CT or MRI due to altered mental state or focal neurological deficits. Out of the patients requiring brain scans, roughly one in five had critical findings, such as strokes or hemorrhage. Half of the patients had pre-existing histories of high blood pressure or type 2 diabetes. Also, the study found that two-thirds of the patients with critical results were African American. The research team has plans to initiate a larger prospective study on neurological manifestations related to COVID-19. Press Release

New research led by Case Western Reserve University and Cleveland Clinic will study how the immune system responds to COVID-19 from the start of infection to years after recovery. This research has been funded by the National Cancer Institute (NCI) totaling $2.6 million as part of the NCI’s Serological Sciences Network (SeroNet), which has awarded only 13 grants nationally. Researchers plan to follow household contacts of known COVID-19 cases to determine immune responses to early viral exposure over a 28-day period and then track how this impacts sustained immunity to SARS-CoV-2 over several years. Additionally, the research team will explore differences in immune responses in patients with pre-existing conditions and those who develop conditions, such as heart disease, from COVID-19 infection. Press Release

The Governance Lab (GovLab) at the NYU Tandon School of Engineering has released recommendations for the re-use of data in response to the COVID-19 crisis. The guidance and a new Responsible Data Re-Use framework stem from The Data Assembly initiative in New York City. The GovLab co-hosted four months of remote deliberations with civil rights organizations, key data holders, and policymakers and this newly published release is the product of this combined effort to guide New York decision-makers on potential costs and benefits of re-using data while considering the sometimes contradictory needs of various stakeholders. Press Release

A new study being presented at this year’s virtual American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting examined the charts of 275 patients admitted to the hospital with COVID-19 and any history of allergic disease and found similar outcomes for COVID-19 patients with allergies and those without. When looking at ICU admission, 43% of those with allergic disease were admitted versus 45% without, and 79% of those with allergies needed supplemental oxygen versus 74% of those without allergic disease. The study also found that more patients with allergies had chronic obstructive pulmonary disease (COPD), but after statistically controlling for the presence of COPD and its association with more severe COVID-19, the researchers found a trend suggesting possible protection in those with pre-existing allergic disease but not asthma. Press Release

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