Research News

Practicing social distancing has benefits for the individual as well as the larger community, according to new research published in PNAS. Authors of the study used an online, longitudinal study of 2,120 U.S. residents with an average age of 40 years old to determine whether individual differences in social distancing behavior predicted the likelihood that a person would contract COVID-19 during the subsequent months. To assess an individual’s social distancing behavior, the researchers presented participants with virtual depictions of real-world situations and examined how the participants positioned themselves relative to others. They found that an index of social distancing based on the participants’ responses was significantly associated with a reduced likelihood of contracting COVID-19 within the next four months. One standard deviation in the social distancing index was associated with about a 20% decrease in the odds of contracting the virus. DOI:10.1073/pnas.2023131118

Airborne transmission contributed substantially to the COVID-19 outbreak on the Diamond Princess cruise ship, finds a new study published in PNAS. Researchers modeled SARS-CoV-2 transmission aboard the cruise ship, which experienced a large COVID-19 outbreak in early 2020, to evaluate the relative contributions of various transmission pathways. Based on these models, the authors of the study estimated that short-range, long-range, and fomite transmission modes each contributed to 30-35% of overall disease transmission. Airborne transmission contributed to more than half of overall transmission. Both large droplets and small aerosols contributed equally to transmission before passengers were quarantined, while small aerosols dominated transmission post-quarantine. These findings highlight the importance of measures to control small aerosol inhalation in addition to existing precautions that help control large droplet and fomite transmission, according to the authors. DOI:10.1073/pnas.2015482118

In a study published in PNAS, researchers predict that peak SARS-CoV-2 viral load typically coincides with symptom onset. Authors of the study used a mathematical model of SARS-CoV-2 viral load over time based on data from 655 patients in France (age 48-72 years). This model showed a peak viral load at the onset of symptoms, which then declined. Decline after this peak was slower in patients over 65 years old when compared to those patients younger than 65 years. Viral dynamics after hospital admission were significantly associated with mortality independent of age, gender, and chronic pulmonary disease. DOI:10.1073/pnas.2017962118

A team of experts recommends that Parkinson’s Disease (PD) patients receive COVID-19 vaccination with approved vaccines, and they have published these recommendations and commentary in the Journal of Parkinson’s Disease. The authors of the study based this guidance on a review of scientific literature, the unfolding experience with widespread vaccination in the population at large, and input from the International Parkinson and Movement Disorder Society Scientific Issues Committee (IPMDS-SIC). They explain that compared to the general population, the risk of SARS-CoV-2 infection causing serious, life-threatening disease seems higher for people living with PD, especially those with advanced disease. Additionally, the approved mRNA-based vaccines and viral vector vaccines under development are not known or expected to interact with the neurodegenerative process in PD, the authors suggest. They strongly encourage PD patients to visit the International Parkinson and Movement Disorder Society website where recommendations will be updated as new data becomes available. DOI:10.3233/JPD-212573

People with severe mental disorders have a significantly increased risk of dying from COVID-19, according to a study published in the Frontiers of Psychiatry. Researchers analyzed data covering the entire Swedish population over the age of 20 from March to June 2020. Among those citizens with severe mental disorder, 130 individuals died from COVID-19 during that period, which corresponded to 0.1% of the group. Among people who had not been diagnosed with a severe mental disorder, the mortality rate was nearly half of that (0.06%). Severe mental disorders in this study included schizophrenia and bipolar disorder. It did not include depression or anxiety, although these conditions can also be severe. DOI:10.3389/fpsyt.2020.609579

Clinical trials of new COVID-19 treatments often overlook the most vulnerable populations, say researchers from the University of Chicago Medical Center. The team examined 303 active COVID-19 treatment trials involving more than 92,000 patients and used Census data from the 2015 American Community Survey to estimate the proportion of Black and Hispanic individuals who could be potentially recruited from the geographic catchment area of each study’s recruitment hospital. They found that 51% of trials excluded patients with non-severe comorbid diseases, such as diabetes, and 60% of trials excluded pregnant women and/or required using contraception. 47% of lactating women and 95% of children less than 18 years old were also excluded from these trials. The study did not include data on COVID-19 prevention studies, such as those testing vaccine candidates. This study is published in the Journal of General Internal Medicine. DOI:10.1007/s11606-020-06566-8

Early use of therapeutic anticoagulation for critically ill COVID-19 adult patients likely does not improve outcomes and could do more harm than good by increasing risk for major bleeding, finds a new study published in Annals of Internal Medicine. Massachusetts General Hospital researchers with collaborators evaluated the incidence of venous thromboembolism (VTE) as well as the occurrence of major, life threatening bleeding through the use of a simulated randomized clinical trial model. Their model showed that 6.3% of over 3,000 patients developed VTE and 2.8% had major bleeding events. Their results also showed that there was no survival benefit for patients who received therapeutic anticoagulation in the first two days of intensive care admission compared with patients who did not receive early therapeutic anticoagulation. DOI:10.7326/M20-6739

More than half of cancer survivors in the United States reported having additional underlying medical condition associated with severe COVID-19 disease, according to a study published in JNCI: The Journal of the National Cancer Institute. Most cancer survivors reported having more than one of the conditions associated with severe COVID-19 illness and nearly 25% reported more than two conditions. These conditions were more prevalent in survivors of kidney, liver and uterine cancers, as well as Black survivors, those with low socioeconomic status, and public insurance. Older age was associated with a higher prevalence of these medical conditions, however, even in the youngest age group (18-44 years), nearly half of cancer survivors (47.6%) had at least one additional condition linked to severe disease with COVID-19. The researchers say that these findings highlight the need to protect cancer survivors against COVID-19 transmission and prioritize these patients for vaccination. DOI:10.1093/jnci/djab012

Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH) have provided new evidence that critically ill COVID-19 patients who were treated with extracorporeal membrane oxygenation (ECMO) had better odds of survival than those who were not treated with ECMO. The team analyzed observational data from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), which is a multicenter cohort study of patients with COVID-19 admitted to intensive care units (ICU) at 68 hospitals across the United States. Overall, the scientists found that 190 of 5,122 critically ill adults (3%) admitted to the ICU with COVID-19 between March and June 2020 received treatment with ECMO. Among those 190 patients, nearly 70% survived to hospital discharge or at least 60 days following ICU admission, and they report a 45% reduction in death overall from treatment with ECMO. These findings are published in Intensive Care Medicine. DOI:10.1007/s00134-020-06331-9

An interim analysis of data from the Phase 3 COVID-19 vaccine trial from Russia (Gan-COVID-Vac) suggests that a two-dose regimen of the adenovirus-based vaccine offers 91.6% efficacy against symptomatic COVID-19.  These preliminary findings, published in The Lancet, are based on analysis data from nearly 20,000 participants, 75% of whom received the vaccine and 25% received a placebo. Serious adverse events were rare in both the placebo and vaccine groups, 0.4% and 0.2% respectively, and none were considered associated with vaccination. Four deaths were reported in the trial, none of which were considered related to the vaccine. Most reported adverse events were mild, which included flu-like symptoms, pain at the injection site and weakness or low energy. DOI:10.1016/S0140-6736(21)00234-8

Asymptomatic COVID-19 infections may be on the rise globally, a new study finds published in JAMA. The retrospective cohort study was conducted from April 16, 2020 through October 12, 2020 and included over 19 million international travelers who entered China and were tested for SARS-CoV-2. Among those testing positive for the virus, 43.6% were symptomatic at entry, 4.4% were presymptomatic, and 51.9% were asymptomatic upon entry and never developed symptoms of SARS-CoV-2 infection. They found a high and increasing proportion of asymptomatic infections among the SARS-CoV-2-positive international travelers coming into China, which they suggest might signal an increase in asymptomatic infections worldwide. The researchers note that the proportion of symptomatic cases was unchanging over the study’s time period, which suggests that the increase in asymptomatic infections over time was not due to symptomatic individuals being screened out before travel. DOI:10.1001/jama.2020.23942

A nasal spray that primes the immune system in the respiratory tract and is in development for COVID-19 shows that it is also effective against the common cold. This is according to a new study published in the European Respiratory Journal. Hunter Medical Research Institute (HMRI) and collaborators demonstrated that treatment with this nasal spray, INNA-X, prior to infection with rhinovirus significantly reduced viral load and inhibited harmful inflammation. INNA-X is developed by the Australian biotech company Ena Respiratory and works by stimulating the innate immune system in the airways. It has also been shown to be highly effective at reducing viral shedding of SARS-CoV-2 and human trials of Ena Respiratory’s clinical candidate INNA-051 will begin soon in Australia. DOI:10.1183/13993003.01584-2020

Intensive care mortality from COVID-19 has continued to fall since the start of the pandemic, according to a meta-analysis of global studies published in Anaesthesia. However, the improvement is slowing and may have plateaued. Authors of the study used data from 52 observational studies including over 43,000 patients worldwide. In a previous review, they found a large drop in ICU mortality from COVID-19 from March to May 2020, and this updated analysis shows that any fall in mortality rate between June and October 2020 appears to have flattened or plateaued. They credit improved management of COVID-19 for dips in mortality rates in the first half of 2020, but project that the several variant viruses that have emerged will transform the trajectory of the pandemic. They are hopeful, however, that vaccination will positively impact the pandemic trajectory and demand on ICU care. DOI:10.1111/anae.15425

A new study in Scientific Reports has found that a subset of COVID-19 patients has an increased bleeding risk. The study included 118 COVID-19 patients and 30 health controls with approximately half of the COVID-19 patients on mechanical ventilation and a quarter of the COVID-19 patients were able to breathe room air. They found that, compared with patients breathing room air, the patients requiring supplemental oxygen had significantly higher levels of plasminogen activator-inhibitor-1 (PAI-1), which is associated with stabilizing blood clots. Those patients with high levels of PAI-1 and tissue-type plasminogen activator (tPA), which is responsible for removing clots, were associated with worse lung function, and high tPA independently correlated with mortality. The levels of either molecule can increase independently of the other, but the research also found a change in one can have consequences on the other, according to the authors of the study. DOI:10.1038/s41598-020-80010-z

Patients treated in the ICU for COVID-19 are twice as likely to die when ICU capacity is strained by the number of COVID-19 patients, finds a new study published in JAMA Network Open. The research team looked at outcomes of over 8,500 COVID-19 patients who were admitted to 88 U.S. Department of Veterans Affairs (VA) hospitals across the country from March through August 2020. The strain on the hospitals’ critical care capacity was measured by comparing the number of critically ill COVID-19 patients to the typical ICU bed count and caseload for each patient’s stay in the hospital. They determined that patients who were admitted during peak times of COVID-19 ICU demand were up to two times more likely to die than those admitted under less strained time periods. DOI:10.1001/jamanetworkopen.2020.34266

An early functional SARS-CoV-2 specific T cell response may prevent severe infection, according to Duke-NUS Medical School researchers. Their study, published in Cell Reports, investigated the changes in virological and immunological parameters in 12 patients with symptomatic acute COVID-19 infection from onset to recovery or death. They found that patients who experienced only mild symptoms were characterized by an early induction of IFN-y secreting SARS-CoV-2 specific T cells. They also determined that the amount of humoral response does not predict the level of severity with COVID-19 infection. The researchers suggest that T cell monitoring be considered in providing a comprehensive understanding of the immune response against SARS-CoV-2. DOI:10.1016/j.celrep.2021.108728

The COVID-19 intensive care unit (ICU) mortality rate in Sweden was lower during the first wave of the pandemic than in many studies from other countries, new research reveals. The study, published in the European Journal of Anaesthesiology, analyzed over 1,500 adult admissions to Swedish ICUs from March through May 2020 with confirmed COVID-19 infection. They found that the 30-day all-cause mortality rate was 27% while mortality within the ICU was 23%. Compared to a recent meta-analysis of 20 studies worldwide that reported an ICU mortality of 42% for patients with completed ICU admissions and discharge data, Sweden’s mortality rate is much lower. Authors of the study believe that process and organizational factors likely contributed to the relatively good outcomes seen in Swedish ICUs as staffing, protective equipment, availability of drugs, medical and technical equipment were considered at an early stage at hospital and regional levels. DOI:10.1097/EJA.0000000000001459

COVID-19 racial disparities in the United States are associated with social factors like income, education and internet access, finds Rutgers University researchers. The study, published in the Journal of Racial and Ethnic Health Disparities, investigated the association between COVID-19 cases and deaths in over 2,000 U.S. counties from January to October 2020 and social determinants of health. The researchers found that a 1 percentage point increase in a county’s percent of Black residents, uninsured adults, low birthweight infants, adults without a high school diploma, incarceration rate and households without internet increased that county’s COVID-19 death rates during that time period. Counties that were the most socioeconomically deprived had a 67 percent increase in the COVID-19 death rate. DOI:10.1007/s40615-020-00952-y

More than a third of Americans are unlikely or hesitant to get a COVID-19 vaccine, a new study reports that is published in Vaccine. University of California, Davis (UC Davis) researchers polled over 800 English-speaking adults nationwide and found that 14.8 percent of respondents were unlikely to get vaccinated and 23 percent were unsure. Authors of the study indicated that demographic characteristics, vaccine knowledge, perceived vulnerability to COVID-19, risk factors for COVID-19, and politics likely contributed to vaccination hesitancy. The study was conducted earlier in the pandemic (June 2020) over the course of two days. DOI:10.1016/j.vaccine.2021.01.010

BioNTech-Pfizer’s COVID-19 vaccine is largely effective against the B.1.1.7 variant, according to a new study published in Science. Researchers collected blood samples from 40 individuals who had received the BioNTech-Pfizer vaccine during clinical trials and tested SARS-CoV-2 pseudoviruses with the blood sera from those patients. They found that the sera had slightly reduced but largely preserved neutralizing titers against the B.1.1.7 lineage pseudovirus. The researchers suggest that these findings mean that the UK variant will not escape protection provided from this COVID-19 vaccine, but they include that the non-replicating pseudovirus system they used may be a potential limitation to their study. DOI:10.1126/science.abg6105

A large survey of health care workers found that community and demographic factors, such as contact with a confirmed or suspected COVID-19 case outside of the workplace and Black race, were stronger predictors of COVID-19 infection than occupational exposure. The survey was conducted from April to June 2020 within the Emory University Medical health care system to quantify occupational, community, and demographic risk factors for SARS-CoV-2 seropositivity. The researchers then found an overall SARS-CoV-2 seroprevalence of 3.8% among the health care workers after the initial surge of the pandemic. After adjusting for possible bias due to voluntary participation in testing, Black race was still a stronger predictor of infection than workplace exposure. This study is published in Annals of Internal Medicine. DOI:10.7326/M20-7145

Maternal antibodies to SARS-CoV-2 likely provide neonatal protection against COVID-19, a new study finds that is published in JAMA Pediatrics. The study included over 1,400 women who delivered at Pennsylvania Hospital in Philadelphia and antibodies were measured in maternal and cord blood sera. SARS-CoV-2 IgG or IgM antibodies were detected in 83 of the mothers at time of delivery, and IgG antibodies were detected in cord blood from 72 of those 83 newborns. However, IgM antibodies were not detected in any cord blood specimen. The researchers conclude that maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic or symptomatic infection during pregnancy, and these findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from COVID-19. DOI:10.1001/jamapediatrics.2021.0038

A new study conducted by the University of Michigan shows that the more disadvantaged a county’s population was prior to the pandemic, the higher the toll of COVID-19 last spring and summer. The researchers measured the level of disadvantage on a standard scale called the Social Vulnerability Index (SVI), which tracked closely with the number of cases and deaths per 100,00 residents in each county. The ten-point SVI score combines many measures of social disadvantage of a county’s population, with higher scores meaning a greater disadvantage. For every point higher on the scale, counties had a 14% higher incidence of COVID-19 cases and 14% more deaths per 100,000 people. The researchers translated these findings to 87 excess COVID-19 cases per 100,000 people, and 3 excess COVID-19 deaths per 100,000 people, for every step up the SVI scale. This study is published in JAMA Network Open. DOI:10.1001/jamanetworkopen.2020.36462

1 in 3 adults are experiencing anxiety and depression related to COVID-19, particularly women, younger adults, and those of lower socioeconomic status, according to researchers at Duke-NUS Medical School in Singapore. The study, published in PLOS ONE, analyzed 68 studies conducted during the pandemic, which encompassed over 288,000 individuals from 19 countries, to assess risk factors associated with anxiety and depression among the general population. They found that women were more likely to experience psychological distress than men and that adults younger than 35 years old were also at a higher risk for anxiety and depression. Living in rural areas, lower education, lower income or unemployment, and being at a high risk for COVID-19 were other factors linked to psychological distress amid the pandemic. The researchers did find that having stronger family and social support and using positive coping strategies reduced this risk. DOI:10.1371/journal.pone.0244630

In a study published in JAMA Network Open, researchers found a 60% decrease in oncology clinical trials of drugs and biologic therapies during the ongoing pandemic. Researchers aggregated all Phase 1 through 4 oncology trials that launched during the 8 consecutive months of October through May over 5 successive years (40 months) and defined the pandemic period to be from January 2020 through May 2020 and the 35-month period preceding January 2020 was considered the pre-pandemic period. After analysis, their results showed a 60% decrease in oncology trials launched during the pandemic period compared with the pre-pandemic period. Authors of the study suggest that these findings show that the COVID-19 pandemic could be associated with longer term indirect effects on population morbidity and mortality in many ways, such as stalled drug development. DOI:10.1001/jamanetworkopen.2020.36353

Industry News

Electronic health records can be a valuable predictor of probability of death from COVID-19. This is according to a study conducted by Massachusetts General Hospital researchers. The study, published in npj Digital Medicine, describes how artificial intelligence (AI) technology was able to identify factors such as age, history of pneumonia, gender, race and comorbidities like diabetes and cancer as predictors of poor outcomes in COVID-19 patients. The team developed a set of models to forecast the most severe COVID-19 outcomes based on past medical records and to help understand the differences in risk factors across different age groups. They determined age to be the most important predictor of mortality. A history of pneumonia, uncontrolled diabetes and cancer were also identified as significant risk factors. The researchers found that race altered the odds of mortality only in the oldest cohort of patients, as African Americans were associated with a higher chance of death in that age group. Source

Vaxart has announced positive preliminary data from the Phase 1 clinical trial evaluating its oral COVID-19 tablet vaccine candidate. This first oral COVID-19 tablet vaccine to be evaluated in human subjects met its primary and secondary endpoints of safety and immunogenicity, respectively. Results show that the vaccine, VXA-COV2-1, was generally safe and well-tolerated. It induced a robust immune response, specifically a CD8+T cell response that was higher than reported for other vaccines. VXA-COV-1 is a room temperature stable tablet and is designed to be protective not only against the prevalent SARS-CoV-2 strain, but also against emerging variants carrying mutations in the Spike (S) protein by inducing a response to both the S and more stable N protein of the virus. Press Release

The Goethe Coronavirus Fund has reached their goal of 5 million euros in donations from over 2,000 contributors. The fund provided researchers at Goethe University and Frankfurt University Hospital with start-up support and more than 40 projects are now being funded, including the coronavirus crisis hotline and studies on the psychological consequences of the pandemic. The latest project supported by the Coronavirus Fund is dedicated to the work situation of healthcare workers and doctors in COVID-19 care in Hessian hospitals who are under particular strain, and the results will be used to make recommendations and concrete options for managers and healthcare workers for workplace health promotion. Press Release

125,000 lives could be saved by the end of 2021 if 50% or more of the U.S. population initiates COVID-19 vaccination by March 1, 2021. This is according to a team from Lehigh University. The researchers utilized data from experts and trained forecasters and combined their predictions into a single consensus forecast. The research team also predicts 87% of U.S. samples sent for genomic sequencing in the first two weeks of February that have an S-gene dropout (which is present in B.1.1.7 samples) will be positively identified as the B.1.1.7 variant. Currently, approximately 22% of samples are being identified as the B.1.1.7 variant, according to the Lehigh University team. Report

RedHill BioPharma announced that the independent Data Safety Monitoring Board (DSMB) for the global Phase 2/3 study of opaganib in patients with severe COVID-19 unanimously recommended to continue the study. This is following a pre-scheduled futility review of unblinded efficacy data from the first 135 patients treated in the study and safety data from the first 175 patients. The positive DSMB futility review, which is suggestive that the global Phase 2/3 study is progressing as expected, adds to the positive top-line safety and efficacy data from the U.S. Phase 2 study of the drug. A blind resizing of the ongoing study is planned, to approximately 460 patients. Top-line data and potential global emergency use authorization (EUA) applications are expected in the second quarter of 2021. Press Release

The Institute for Health Metrics and Evaluation (IHME) at the University of Washington has released its latest COVID-19 forecasts to include two new virus variants. The forecasts show the possibility of a spring spike in deaths with these new variants, and researchers say that mask-wearing and continued social distancing will remain critical despite vaccine rollout. They estimate that the United States will see approximately 654,000 total deaths by May 1 and a resurgence of the virus in the spring in some states, assuming widespread transmission of the B.1.351 variant from South Africa and mobility returning to pre-pandemic levels in the vaccinated. Without the transmission of B.1.351, the forecast in the U.S. drops to 595,000 deaths by May 1, which is an increase of about 26,000 from last week’s predictions. They say that this increase is driven by taking into account that some states are not re-imposing social distancing mandates even as daily death rates rise. Press Release

RedHill Biopharma announced a manufacturing agreement with Cosmo Pharmaceuticals to further expand manufacturing capacity for opaganib to address prospective demand in anticipation of potential global emergency use authorizations. The global Phase 2/3 study of opaganib in severe COVID-19 pneumonia is ongoing, but preliminary data from a non-powered U.S. Phase 2 study showed that the drug was safe and demonstrated improvement in reducing oxygen requirement by the end of treatment on Day 14. Opaganib is a novel, orally-administered sphingosine kinase-2 (SK2) inhibitor that targets a human cell component involved in viral replication that is unrelated to mutations in the viral spike protein, which could be a potential treatment for emerging new strains of SARS-CoV-2. Press Release

In a study presented at the 57^th Annual Meeting of The Society of Thoracic Surgeons, researchers showed that the pandemic has resulted in a substantial decline in overall heart surgeries and an unexplained increase in deaths following coronary artery bypass grafting (CABG). The researchers examined data from over 700,000 adult cardiac surgery patients and more than 20 million COVID-19 patients. They determined that there was a 53% decrease nationwide in all adult cardiac surgery volum0e when compared to 2019 and 65% fewer elective cases in the United States. There was also a 40% decrease in non-elective cases. The researchers found that the Mid-Atlantic area (New York, New Jersey, and Pennsylvania), was among the most affected by the COVID crisis and experienced a significant decrease of 71% in overall case volume, as well as increased deaths following CABG. Their data did not directly address the cause of increased morality, but many surgeons say that they currently are limited to operating on only the most urgent coronary bypass cases and patients tend to be sicker. Press Release

Rutgers University researchers have been awarded $1.6 million from the National Institutes of Health (NIH) to help identify risk factors for severe illness in children from COVID-19. The two-year grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH will support the development of a national network of networks to ensure that children from around the country are included in the study. The project is designed to incorporate a variety of scientific perspectives and integrate a spectrum of multidimensional data to develop approaches that allow clinicians and public health professionals to identify which children are at the highest risk for developing serious illness following infection of SARS-CoV-2. Called the COVID-19 Network of Networks Expanding Clinical Translational approaches to Predict Severe Illness in Children (CONNECT to Predict SIck Children), the collection of data will be funneled to Rutgers for analysis using machine learning and model-based methods to develop and refine predictive models for at-risk children. Press Release

A new study led by the University of Stirling has launched to explore the experiences of those individuals suffering from ‘long COVID’ and aims to improve the support and care available to those patients. The two-year study, funded by the Scottish Government’s Chief Scientist Office, will look at those suffering from prolonged symptoms through their lived experiences. Researchers will conduct and analyze detailed interviews with those living with long COVID and collect information on their symptoms, how their lives have been impacted, services they have used, and the support and care needs that they have. Ultimately, they plan to present information that can be used to train doctors, nurses, and other healthcare workers to improve the care of these patients. Press Release