November 6, 2020 I Statin treatment may prevent deaths, COVID-19 worsens tinnitus, delirium early symptom in elderly, monoclonal antibody LY-CoV555 reduces hospitalization, phase 3 trial underway for REGN-COV2 antibody cocktail, remdesivir shows no mortality benefit, pandemic effects on childbirth, seven forms of disease identified, twenty percent experience GI symptoms, osteoporosis drugs may offer protection, and Europe linked to spread. Plus: Skin symptoms reveal ‘long haulers’, autoimmune antibody culprit for blood clots, smartphone app to reach at risk communities, increased discrimination against Asian Americans affecting their health, and smartwatch predicts COVID-19 infection.

Research News

More than 1.7 million New Yorkers have been infected with SARs-CoV-2 and the infection fatality rate of the virus is close to 1%, making it ten times deadlier than the flu, according to new research from the Icahn School of Medicine at Mount Sinai. The study, published in Nature, looked at a dataset of over 10,000 plasma samples from Mount Sinai Health System patients between February and July 2020 who were seen in the emergency department and urgent care and also from patients seen for routine care. Researchers tested for SARS-CoV-2 antibodies weekly and determined seroprevalence to be roughly 22% after the first wave subsided by the end of May. They also noted that seropositive samples were found as early as mid-February, before the first cases had been reported. DOI:10.1038/s41586-020-2912-6

Researchers have identified unique characteristics in the lungs of those suffering from ‘long COVID’. The study, published in eBioMedicine, analyzed the organs of 41 patients who died from COVID-19 at the University Hospital of Trieste, Italy from February to April 2020, examining lung, heart, liver, and kidney samples. The research team, led by King’s College London, found extensive lung damage in most cases and profound disruption of the normal lung structure. Nearly 90% of the patient lung samples showed extensive blood clotting in the lung arteries and veins and several lung cells were abnormally large. Additionally, the samples showed persistence of the viral genome in respiratory cells and in cells lining the blood vessels that persisted for several weeks or months. They believe these findings could explain ‘long COVID’. The study found no obvious signs of SARS-CoV-2 infection or prolonged inflammation in other organs. DOI:10.1016/j.ebiom.2020.103104

COVID-19 may worsen tinnitus, new research has shown published in the Frontiers in Public Health. This study led by Anglia Ruskin University (ARU) researchers involved over 3,100 participants with tinnitus from 48 countries, mostly from the UK and U.S. The research team found that 40% of those displaying COVID-19 symptoms also experienced a worsening of their tinnitus. Most people had the condition prior to contracting the virus, but a small portion reported that their tinnitus was triggered with the onset of COVID-19 symptoms. The study suggests that tinnitus could be a ‘long COVID’ symptom in some cases. DOI:10.3389/fpubh.2020.592878

Treatment with statins may prevent one in five deaths from COVID-19, finds a new study published in the European Heart Journal – Cardiovascular Pharmacotherapy. Moreover, researchers of this study found that continued treatment with statins in patients hospitalized with COVID-19 prevented one in four deaths. This study was carried out through the Network of Lipid and Arteriosclerosis Units of Catalonia and collected information from over 2,100 patients infected with SARS-CoV-2 from 19 hospitals during the first wave of the pandemic. After evaluating one hundred clinical variables per patient, the researchers compared death rates of patients being treated with statins with death rates among those who were not. Additionally, they analyzed the effects of withdrawing statin treatment upon hospital admission. DOI:10.1093/ehjcvp/pvaa128

A new case study, published in Cell, details a unique case of a 71-year-old woman with chronic lymphocytic leukemia who shed infectious SARS-CoV-2 for at least 70 days, while never showing any symptoms. An expert, and lead author, from the National Institute of Allergy and Infectious Diseases (NIAID) was contacted by a study co-author after this patient had several positive tests for the virus over several weeks. The researchers believe that this patient remained infectious for an extended period of time due to her compromised immune system that never triggered a response to the virus. Blood tests also showed that the patient never produced any antibodies. The team adds that this is the longest case of active infection with COVID while remaining asymptomatic to their knowledge. DOI:10.1016/j.cell.2020.10.049

Delirium accompanied by fever may be an early symptom of COVID-19, according to a new study published in the Journal of Clinical Immunology and Immunotherapy and conducted by researchers at the Universitat Oberta de Catalunya (OUC). The scientific research review concludes that along with loss of taste and smell and headaches, delirium or state of confusion accompanied by high fever should be considering an early marker for the disease, especially in the elderly population. The researchers attribute the cause of delirium to systemic inflammation and hypoxia, which in turn causes neuronal tissue inflammation and damage to areas such as the hippocampus. DOI:10.24966/CIIT-8844/1000039

Black and Latinx hospital workers are at the highest risk of COVID-19 infection, even those without patient care responsibilities, shows a new study led by Rutgers University and published in Open Forum Infectious Diseases. Researchers screened just over 3,900 employees and clinicians at a New Jersey hospital between April and June for the virus and SARS-CoV-2 antibodies. They found that Black and Latinx workers were twice as likely to test positive for the virus or antibodies when compared to white employees. Phlebotomists had the highest positive test rate, followed by maintenance and housekeeping staff, dining and food staff, and support roles. Surprisingly, physicians, nurses, and emergency medical technicians had much lower infection rates. The authors of the study attribute these findings to less access to PPE or less enforcement of safety protocols. DOI:10.1093/ofid/ofaa534

Racial and ethnic minorities with rheumatic disease and COVID-19 have higher risks of requiring hospitalization and mechanical ventilation, finds an analysis published in Arthritis & Rheumatology. The analysis included data on all U.S. patients with rheumatic disease and COVID-19 entered into the COVID-19 Global Rheumatology Alliance physician registry from March to August 2020. Over 1,300 patients were included, with 36% requiring hospital admission, 26% required mechanical ventilation, and 6% died. Compared to white patients, Black, Latin American, and Asian patients all had an increased prevalence of being hospitalized. Latin Americans also were three times more likely to need mechanical ventilation. The study did find, however, that there were no differences in mortality rates based on race or ethnicity. DOI:10.1002/art.41567

Some medications used to treat osteoporosis may provide a protective effect against SARS-CoV-2, according to a new study published in Aging. The study analyzed data from more than 2,000 patients with osteoporosis, osteoarthritis, and fibromyalgia who are being followed at the Hospital del Mar after a low incidence of COVID-19 infection was perceived by specialists. Researchers found that some of the main treatments for osteoporosis, specifically denosumab, zoledronate and calcium, provide a significant reduction in incidence of COVID-19 (30 to 40%) in patients taking those medications. Researchers of this study point out that this data shows these medications are safe for patients in the wake of COVID-19 and may even lower incidence of acquiring the virus, but more research needs to be done on determining their efficacy related to preventing COVID-19. DOI:10.18632/aging.104117

A new study led at Brigham and Women’s Hospital has uncovered a subset of recovered COVID-19 patients that sustain antibodies for several months post-infection. The research team recruited and enrolled 92 participants in the Boston area who had recovered from the virus between March and June 2020. They collected and analyzed blood samples monthly, measuring a range of antibodies which included IgG. They found that in a subset of these individuals (roughly 20%), virus-specific IgG production remained stable or enhanced over the course of three to four months, compared to the other recovered patients that had declining levels of this antibody. These “sustainers” also had symptoms for a significantly shorter period of time when compared to the other participants (10 days vs 16 days, respectively). The authors of this study, published in Cell, noted that one limitation to this research was that most of the volunteers were adult white females. DOI:10.1016/j.cell.2020.10.051

Canada’s National Advisory Committee on Immunization (NACI) recommends prioritizing key populations for early COVID-19 vaccination, such as people at risk for developing severe disease, those at risk for transmitting the virus and essential workers. The Public Healthy Agency of Canada (PHAC) requested NACI to offer guidance on which populations should be prioritized for early doses of a COVID-19 vaccine, as vaccine supply will likely be limited at first. NACI is an independent external group of 15 experts that advise PHAC on the use of current vaccines or newly approved ones in Canada. The hope is for a safe and effective vaccine in early 2021. This preliminary guidance is published in Canadian Medical Association Journal. DOI:10.1503/cmaj.202353

Researchers at the University of Huddersfield and University of Minho in Portugal have carried out one of the largest analyses of its kind on 27,000 virus genomes from around the world to map out the dispersal of SARS-CoV-2. They discovered that the spread of the virus to America and other parts of the world was largely linked to Europe, not China. They did find that the virus originated in China, likely transmitted from horseshoe bats to humans. Their research also suggests that travel restrictions across Britain and Europe were implemented too late. The group’s findings are published in Microorganisms. DOI:10.3390/microorganisms8111678

Nearly 20% of COVID-19 patients present with gastrointestinal symptoms, according to a new study published in Abdominal Radiology. The researchers reviewed 36 studies published through July to determine these findings. GI symptoms varied widely but researchers found that 18% of COVID-19 patients presented with these symptoms and 16% of cases only showed gastrointestinal symptoms with the virus. Researchers also determined potential signs for radiologists to look for which included inflammation of the small and large bowel, air within the bowl wall and bowel perforation. They noted that these signs are quite rare and would indicate advanced disease. DOI:10.1007/s00261-020-02739-5

An autoimmune antibody may be the cause of COVID-19 blood clots, according to new research published in Science Translational Medicine. The study led at Michigan Medicine identified this blood-clotting antibody in about half of hospitalized COVID-19 patients that is typically seen in patients with the autoimmune disease antiphospholipid syndrome. These patients with severe COVID-19 also had high levels of super-activated neutrophils, which destruct white blood cells. Researchers studied the activated neutrophils and those antibodies found in COVID-19 patients on mouse models and discovered a very high level of clotting in those animals. The team now aims to determine if blocking these antibodies in severely ill patients proves better outcomes and for how long these antibodies remain in circulation after recovery. DOI:10.1126/science.abd3876

Seven different “forms of disease” have been identified in mild COVID-19 cases, finds a team of Medical University of Vienna scientists. The study, published in Allergy, involved 109 convalescent individuals and 98 health individuals for their control group. Researchers were able to determine seven different groups of symptoms, which distinguished systemic from organ-specific forms of disease. The scientists also found that the virus leaves behind detectable changes in the blood that is similar to a fingerprint. The number of granulocytes were significantly lower in the COVID-19 group and regulatory cells were greatly diminished, which the study emphasizes could lead to autoimmunity. Essentially, their findings show that the immune system “doubles up” when fighting COVID-19 even several weeks after infection. They hope to implement these findings for development of a highly effective vaccine. DOI:10.1111/all.14647

In a recent paper published in the Annals of Internal Medicine, authors from the University of Pennsylvania and NYU School of Medicine suggest that evidence should take priority in shifting standards of care for SARS-CoV-2 patients over the use of COVID-19 vaccines and drugs granted emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA). They explain that evidence supporting EUAs varies widely and clinicians are not obligated to offer unproven interventions, but rather use available evidence to determine appropriate treatments for COVID-19 patients. DOI:10.7326/M20-6703

Shorter hospital stays and increased protection protocols do not pose an increased risk for mothers and their babies, finds a study conducted by Cedars-Sinai. The study, which is published in the American Journal of Obstetrics & Gynecology, reviewed data from over 1,900 deliveries that compared patients who gave birth prior to the pandemic in January and February and those who delivered in March and April when increased infection control protocols were put into place. They found that shorter stays and increased safety protocols had no impact on the rate of cesarean deliveries or adverse maternal and neonatal outcomes. The researchers of this study add that there may be value in exploring whether there are benefits, after the COVID-19 pandemic, of a shorter hospital stay for childbirth and limiting visitors. DOI:10.1016/j.ajogmf.2020.100234

New research published in Anaesthesia shows that during the first wave of the pandemic, the proportion of cesarean section deliveries carried out under general anesthesia nearly halved, dropping from 7.7% in 2019 to 3.7% in 2020 during the same period of time. Authors of the study concluded that this decline was related to changes in decision-making recommendations for anesthetic guidelines and the presence of an on-site experienced anesthetic consultant in the delivery suite due to COVID-19 safety protocols. The authors also noted that regional anesthesia has been recognized as a safer option over general anesthesia for a long time. The reasons for this decline in general anesthesia use should be considered, as well as better equipping trainees to provide regional anesthesia in order to continue this trend and benefit both women and their babies. DOI:10.1111/anae.15313

University of Cambridge scientists have developed a new model to provide better insights into COVID-19 infection rates in those under 65 years old. The researchers integrated age-specific COVID-19 death data from 45 countries with 22 national-level seroprevalence studies and report that their model can be used at a country-wide level to predict a person’s likelihood of COVID-19 death from infection, depending on their age. The team excluded data on those over 65 years old due to vast differences in reported deaths in the elderly population across different countries. They also explain that even after excluding data from those over 65, the model shows that COVID-19 death rates cannot be compared between some countries because of widespread comorbidities that affect severity of SARS-CoV-2 infection. The researchers do, however, believe this model will prove to be beneficial when applied at a sub-national scale or where large seroprevalence studies are unavailable. This study is published in Nature. DOI:10.1038/s41586-020-2918-0

A new paper written by Washington State University researchers reports that discrimination against Asian and Asian-Americans has increased since the beginning of the pandemic—and it is affecting their health negatively. The researchers surveyed over 400 people and 30% reported an increase in discrimination since the pandemic began and 40% reported more health issues. The reports of racial discriminations ranged from microaggressions to more direct actions. The survey results also revealed that those who experienced discrimination but had more social support experienced less depressive symptoms. This research is published in Stigma and Health. DOI:10.1037/sah0000275

COVID-19 may spread faster and more widely throughout U.S. households than previous estimates, based on new research led by Vanderbilt University Medical Center (VUMC). This study, published in the Morbidity and Mortality Weekly Report, found that 51% of individuals living in the same home as someone with COVID-19 also became infected, and at least 75% of the those secondary infections occurred within five days of the first infected person experiencing symptoms. These preliminary findings are based on an ongoing study in Nashville, Tennessee, and Marshfield, Wisconsin. The study also found that less than half of household members experienced symptoms when they first tested positive, and many reported no symptoms throughout a daily follow-up period of seven days. DOI:10.15585/mmwr.mm6944e1

Researchers from Florida Atlantic University with collaborators have concluded that remdesivir, which has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA), has shown decreased mean recovery time but no mortality benefit after reviewing the totality of available evidence. This commentary was published in Contemporary Clinical Trials Communications, ahead of the World Health Organization (WHO) publishing the largest randomized trial showing no benefit on reducing hospital stays or mortality when given the drug. According to the researchers, Dexamethasone is the only drug with FDA approval based on a large, randomized trial showing a mortality benefit. The authors suggest coordinated efforts on preventative strategies as our first line of defense against COVID-19 this fall and winter. DOI:10.1016/j.conctc.2020.100663

German researchers have developed a two-step antibody testing approach that provides more accurate results, close to 100% specificity and more than 95% sensitivity, and utilized these tests to detect antibody frequency in Bavaria children. The study, published in Med, screened 12,000 children (1-18 years old) for SARS-CoV-2 antibody positivity and detected a frequency of 0.87%. When compared to the incidence of COVID-19 positive cases in children reported by the Bavarian Health and Food Safety Authority, the antibody positive frequency found by researchers was six times higher. These findings indicate the importance of large-scale antibody testing for SARS-CoV-2. The study also showed 47% of the antibody-positive children were asymptomatic and in children with virus-positive family members, 35% had antibodies. DOI:10.1016/j.medj.2020.10.003

The SARS-CoV-2 viral load detected in hospitalized patients with COVID-19 associated pneumonia predicts risk of adverse outcomes, finds a new study published in the Annals of the American Thoracic Society. Researchers looked at medical records from 314 patients who came to the NYU Langone Health emergency department and were diagnosed with COVID-19 and viral pneumonia requiring hospitalization. They found that high viral load was a strong predictor of poor outcomes, even after considering the patients’ underlying conditions. They also determined that patients with comorbidities were more likely to have a high SARS-CoV-2 load upon admission, and therefore experience increased risk for poor outcomes. DOI:10.1513/AnnalsATS.202008-931RL  

New research shows that myocarditis caused by COVID-19 may not be as common as suspected. The study, published in Cardiovascular Pathology, collected data from 277 autopsies to analyze cardiovascular pathology findings from COVID-19 deaths in nine countries. Researchers of this analysis determined that the rate of myocarditis in these patients was between 1.4 and 7.2%, compared to previously reported rates of COVID-19 myocarditis ranging from 60% among middle-aged and elderly recovered patients to 14% among recovered athletes. The authors pointed out that these findings do not mean that SARS-CoV-2 does not have a significant impact on cardiovascular health, explaining that these complications are likely due to endothelial cell activation, cytokine storms, or electrolyte imbalances. DOI:10.1016/j.carpath.2020.107300

COVID-19 patients given the monoclonal antibody LY-CoV555 were less likely to be hospitalized or require emergency medical care, according to a new study published in The New England Journal of Medicine. The Phase 2 clinical trial from Cedars-Sinai tested three different doses of LY-CoV555 and found that the 2,800-milligram dosage level provided a reduction in viral load and reduced hospitalization and emergency care rates. Hospitalization rates were 1.6% in the group of patients treated with the monoclonal antibody, compared to 6.3% in the placebo group. This reduction in hospitalizations was seen across all demographic groups, including those in high-risk categories. DOI:10.1056/NEJMoa2029849

A new study, published in Nature Medicine, reveals that sensor data from wearable devices may predict COVID-19 infection along with self-reported symptoms. Scripps Research Institute examined data from the first six weeks of the DETECT study, which launched in March and uses a mobile app to collect smartwatch and activity tracker data from participants, and also collects self-reported symptoms and diagnostic test results. The research team reviewed sensor data from those who reported COVID-19 symptoms and tested positive for the virus to pinpoint specific changes in heart rate, sleep and activity levels. Using this health data from wearable devices, the study showed approximately 80% accuracy in predicting whether a person who reported symptoms was likely to have COVID-19. DOI:10.1038/s41591-020-1123-x

Industry News

Parexel has announced a strategic collaboration with Synexa Life Sciences and Drawbridge Health. This will significantly improve the clinical trial experience for patients participating in pivotal COVID-19 clinical trials. There is currently urgent need for accurate serology testing by improved methods of blood collection that minimize exposure to COVID-19. Parexel, Synexa and Drawbridge Health will provide the necessary tools for drug developers, clinicians, and health experts to assess and quantify population exposure, immunity and COVID-19 reinfection risk. Press Release

The European Medicines Agency (EMA) has implemented two extra transparency measures for COVID-19 vaccines and therapeutics by publishing both the clinical data in support of the authorization on remdesivir and scientific advice and guidance from EMA’s pandemic Task Force (COVID-ETF) on treatments. The Agency had to suspend publication of clinical data in 2018 due to relocation from London to Amsterdam, and currently remains suspended from pandemic-related constraints. The EMA has decided to exceptionally publish clinical data for COVID-19 medicines based on public interest. The data package is available on EMA’s clinical data website and includes the clinical overview, summaries, and final reports from clinical studies and clinical data from the compassionate use program. Press Release

Despite COVID-19 lockdown restrictions, diagnoses of sexually transmitted infections (STIs) have increased in Milan, Italy, according to new research presented at the 29^th European Academy of Dermatology and Venereology (EADV) Congress, EADV Virtual. The study was conducted in two STI centers in Milan and compared the number of confirmed diagnoses of the most common STIs in patients with symptoms during the March and April lockdown of this year to the same time period in 2019. Specifically, gonorrhea, secondary syphilis and mycoplasma genitalium (MG) increased while non-acute cases, such as genital warts and Molluscum Contagiosum, fell. The researchers note that these findings show the importance of ongoing screening for STIs throughout the pandemic. Press Release

A new analysis of skin symptoms related to COVID-19 reveals a subset of patients, called ‘long-haulers’, who experience prolonged symptoms (more than 60 days). This research, presented at the EADV Virtual, analyzed data from 990 cases from 39 countries that showed patients presenting with a broad range of dermatologic manifestations, but most notable was pernio/chilblains (“COVID toes”). COVID toes often appeared one to four weeks after initial infection and persisted for as long as 150 days. These findings reveal the multi-organ inflammation that can occur with COVID-19 and demonstrate the importance of further research into dermatological symptoms related to the virus. Press Release

Norwegian researchers from the University of Bergen are collecting sperm to study how COVID-19 affects the next generation’s immune system. The research team plans to study sperm samples currently collected, already receiving 50 samples from COVID-19 patients between 30 and 40 years old, and having donors return in 12 months to re-test samples. The researchers are specifically looking at the messenger-RNA and believe they will find epigenetic changes that may impact recommendations on procreating. Press Release

University Hospitals (UH) and Case Western Reserve University (CWRU) announced that UH Cleveland Medical Center has been selected to conduct the Phase 3 clinical trial of COVID-19 vaccine candidate AZD1222, sponsored by AstraZeneca. AZD1222 uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus and contains genetic material of the SARS-CoV-2 spike protein. After vaccination, the surface spike protein is produced to prime the immune system to fight COVID-19. The study, funded by the National Institute of Allergy and Infectious Disease (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), will enroll non-pregnant participants over 18 years old and aims to represent diverse groups. Press Release

The Association of Black Cardiologists has awarded a University of Cincinnati (UC) cardiologist with $25,000 to launch a smartphone app that provides COVID-19 information and education on cardiovascular (CV) disease targeting African American communities. The UC physician hopes to bring this mobile health-based technology into these communities that are disproportionately affected by COVID-19 and CV disease. The Ohio Department of Health reported that Black residents accounted for only 14% of the population in the state but 16.7% of COVID-19 cases and 17.1% of deaths from the virus were among these Black residents. Press Release

A yearlong study, conducted by the Medical College of Georgia (MCG), aims to determine the percentage of frontline workers positive for COVID-19 and whether the antibodies produced by those SARS-CoV-2 positive workers are protective against reinfection. This study is among four others funded by NIAID, totaling $1.9 million, called the SARS2 SeroPrevalance and Respiratory Tract Assessment (SPARTA) study. MCG researchers hope to find which specific antibodies produced by these frontline workers are the most effective at neutralizing the virus and identify variants that may explain the wide range of immune responses. Press Release

University of Illinois Chicago (UIC) researchers are now enrolling asymptomatic individuals who have been in close contact with someone who has tested positive for COVID-19 for a phase 3 clinical trial to test the monoclonal antibody cocktail, REGN-COV2. The randomized, double-blind, placebo-controlled phase 3 trial aims to enroll at least 25 participants, half of whom will receive the monoclonal antibody combination and the other half given a placebo multivitamin infusion. The researchers hope to find another layer of protection for individuals exposed to COVID-19, even if a vaccine becomes available. Press Release