February 12, 2021 | Several promising COVID-19 treatments, majority of Los Angeles healthcare workers not confident about vaccine, patients with dementia at increased risk, pregnancy and vaccination, and AI model predicts risk of death. Plus: old drugs may be repurposed to treat COVID-19, NIH enrolling participants for Phase III clinical trial, New Yorkers more likely to take vaccine than before.

Research News

Breastfeeding women with COVID-19 do not pass along the SARS-CoV-2 virus in their milk but do transfer milk-borne antibodies that are able to neutralize the virus, a multi-institutional team of researchers led by the University of Idaho reported. The team analyzed 37 milk samples submitted by 18 women diagnosed with COVID-19. None of the milk samples were found to contain the virus, but nearly two-thirds of the samples did contain two antibodies specific to the virus. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness. The results were published in mBio. DOI: 10.1128/mBio.03192-20

Researchers from Brazil applied an ultrasound examination protocol covering 12 lung regions in 180 COVID-19 patients undergoing treatment at HC. The results showed that the higher the lung ultrasound score, the greater the risk of admission to an intensive care unit (ICU), intubation, and death. They argue that lung ultrasound is a good predictor of the need for intensive care with endotracheal intubation and the risk of death for COVID-19 patients admitted to the emergency room. The authors call it, “a simple, cheap way to estimate the prognosis for patients infected by the virus.” Their findings are published in the Annals of Intensive Care. DOI: 10.1186/s13613-020-00799-w

A team from Massachusetts General Hospital (MGH) has created a tool to guide frontline clinicians through diagnostic evaluations of patients they suspect have COVID-19 so that they'll know when it's safe to discontinue precautions. The tool was developed and validated in a study published in Clinical Infectious Diseases. CORAL (COvid Risk cALculator) is a clinical decision support system that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to Infectious Diseases (ID) physician review. In Clinical Infectious Diseases, they report that CORAL significantly reduced the average time to end isolation precautions. DOI: 10.1093/cid/ciab111

To determine the factors that affect the generation of airborne droplets during acts of breathing researchers conducted two studies. The first evaluated the breath of 194 healthy human volunteers. The second measured the exhaled breath from two species of nonhuman primates (NHPs) following experimental infection with of SARS-CoV-2. Analysis of the exhalations of the human group revealed high variability with aerosol particle production varying by three orders of magnitude between subjects and fewer than 20% of participants exhaling 80% of the total particle production. There was a significant correlation between exhaled aerosol, age, and BMI with higher BMI-years having higher aerosol exhalations. Among the NHPs, exhaled breath particle production began to increase starting about three days after infection, peaking around day seven before dropping back near baseline. Particle size shifted similarly, growing larger and receding. Identification of the high variability of airway droplet generation and the pattern of viral load shedding in aerosol droplets has uncovered new insights to approach controlling COVID-19 transmission. More information is available in PNAS. DOI: 10.1073/pnas.2021830118

Until now the African green monkey was the only nonhuman primate used to study airborne transmission of the SARS-CoV-2 virus. According to new research published online this week, three nonhuman primate species were evaluated as potential models and any of these species may be useful in the testing of vaccines and treatments for COVID-19. The research team at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) exposed cynomolgus macaques, rhesus macaques, and African green monkeys to SARS-CoV-2 using a model system invented at USAMRIID that generates a controlled dosage of highly respirable airborne particles within a sealed chamber. The animals were monitored, and their cases documented. All three species developed disease that resembled mild acute respiratory disease in human patients. Identification of additional animal models allows for continuing evaluation of vaccine and therapeutic candidates and helps to facilitate a more rapid deployment of new medical products to mitigate the COVID-19 pandemic. Read about it in PLoS ONE. DOI: 10.1371/journal.pone.0246366  

The manufacturers of currently available vaccines excluded pregnant and lactating women from clinical trials leaving pregnant women without the necessary evidence to make an informed decision about vaccination. While useful impact and outcome data can now be collected by the US Centers for Disease Control and Prevention and the FDA from women who receive a COVID-19 vaccination while pregnant, right now pregnant women and their providers are trying to make a decision without supporting evidence. In 2016 a task force, the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC), was established to develop recommendations for safely and ethically including pregnant and lactating women in clinical research to ensure that pregnant women have the same ability to make informed decisions about their medical care as the non-pregnant do. Recommendations from PRGLAC specified key activities that could be implemented to improve the lack of pregnant women in clinical vaccine trials. Proactive protocol planning for inclusion of pregnant people could be implemented. Use of existing registries, usable data sources, and federally funded research networks with specific expertise in this area could accelerate research. And the specific development of models to estimate the effects of pregnancy on pharmacokinetic and pharmacodynamic testing would assist in advancing this line of research. Viewpoint in JAMA. DOI: 10.1001/jama.2021.1865  

A recent research letter in JAMA assessed prevalence and outcome of SARS CoV-2 infection among migrant workers in Singapore. Following a surge of 244 COVID-19 cases among migrant workers living in dormitories, a national task force was created to coordinate Singapore’s outbreak response. In addition to a nearly two-month national lockdown that confined workers to their dormitories, medical posts were deployed on-site and capacity for testing and screening increased. Workers with a positive PCR test result were admitted to healthcare facilities for isolation and treatment. The study revealed that, of the almost completely male group of migrant workers, 95.1% had at least one SARS-CoV-2 test administered. There were 111,280 residents with a positive PCR or serology result, for an overall infection prevalence of 56.1%, comprising 24,197 clinical cases (21.7% of infected) and 87,083 subclinical cases (78.3% of infected). The outbreak among the migrant workers was characterized by a high prevalence of infection, low morbidity with few ICU admissions, and low mortality. The study highlights how severely infection prevalence could have been underestimated if only those patients presenting with symptoms were tested and counted as many infections are subclinical and identified during mass screening. DOI: 10.1001/jama.2020.24071  

Scientists from the UNC School of Medicine and UNC Gillings School of Global Public Health have found that an experimental drug, EIDD-2801, halts SARS-CoV-2 replication and prevents infection of human cells in a new in vivo lab model containing human lung tissue. Researchers found that EIDD-2801 reduced virus replication after two days of treatment with a more than 25,000-fold reduction in number of infectious particles in human lung tissue when treatment was initiated 24 hours post-exposure. Researchers also tested the ability of EIDD-2801 to prevent SARS-CoV-2 infection and found that pre-exposure prophylaxis with EIDD-2801 inhibited SARS-CoV-2 replication, reducing virus titers in human lung tissues of lung-only mice by over 100,000-fold in two independent experiments. The results were published in Nature. DOI: 10.1038/s41586-021-03312

The American College of Physicians (ACP) addressed emerging evidence regarding the effectiveness of remdesivir in hospitalized patients with COVID-19 as well as whether benefits and harms vary by symptom duration, disease severity, and treatment duration and updated Practice Points to target patients who will most benefit from the use of remdesivir. Updated Practice Points suggest considering remdesivir for five days to treat hospitalized COVID-19 patients who do not require mechanical ventilation orECMO. New Practice Points further suggest considering the extension of remdesivir to 10 days to treat hospitalized patients with COVID-19 who require mechanical ventilation or ECMO within a 5-day course but avoiding remdesivir to treat hospitalized COVID-19 patients who are already on mechanical ventilation or ECMO. The ACP's updated Practice Points were published in Annals of Internal Medicine. DOI: 10.7326/M20-8101

A recent survey indicates that the majority of healthcare workers in the Los Angeles area do not feel confident about the COVID-19 vaccine. Less than half of the participants in the survey feel that a novel coronavirus vaccine can protect them from COVID-19, and around one third do not trust the science behind the vaccines. Most participants indicated that they will delay vaccination once available with about half waiting to see how it affects other first. Participants who identify as Asian (23.9%) or Latino (26.2%) reported being less likely to accept vaccination immediately upon availability compared with other racial and ethnic groups. Health care workers age 50 or older are more likely than their younger coworkers to accept vaccination right away. The survey, published in Annals of Internal Medicine, identified three primary influences for the respondent’s feelings about the COVID-19 vaccine. They were most influenced by the rapid development of the vaccine, the novel nature of SARS CoV-2 science, and the political climate in which the research and regulation were conducted. DOI: 10.7326/M20-7580

A retrospective analysis of patient electronic health records (EHRs) finds that patients with dementia are at increased risk for COVID‐19 compared to patients without dementia. A study led by Case Western Reserve University researchers found that patients with dementia are at significantly increased risk for COVID‐19 compared to patients without dementia, and the risk nearly doubles for African Americans with dementia. Patients with dementia and COVID-19 also had worse outcomes. The researchers used modern informatics techniques to analyze a large de-identified database of patient EHRs. While they don’t know exactly why COVID-19 risk is greater for people with dementia, they hypothesize that patients with dementia might be more susceptible to COVID-19 because certain viruses can reach the brain more easily due to blood-brain barrier damage. Dementia may also interfere with a person’s ability to wear a mask, perform frequent hand hygiene, or physically distance. The study, published in, Alzheimer's & Dementia: The Journal of the Alzheimer's Association, highlights another vulnerable group and the need to protect patients with dementia from COVID-19. DOI: 10.1002/alz.12296

Treatment strategies gleaned from the field of neuroimmunology may offer hope for patients suffering from long-COVID. Researchers propose managing some of the symptoms of long-COVID related to chronic, low-grade inflammation, such as depression and other mental health problems, with insights gained from large-scale studies of chronic fatigue syndrome, fibromyalgia, depression, and other mental health disorders that show immune abnormalities. Current treatment strategies could include anti-inflammatory medications, addressing stress levels and increased social support, physical exercise, and an adjusted diet. These findings are published in Oxford Open Immunology. DOI: 10.1093/oxfimm/iqab004

A recent study, accepted for publication in Diabetologia, found that the additional COVID-19 mortality risk associated with type 2 diabetes increases the younger someone is when comparing patients with type 2 diabetes to similarly aged patients without. This finding impacts middle-aged patients especially, elevating their age-related COVID-19 risk. A 40-year-old patient with diabetes gains around 20 years of mortality risk, making their COVID-19 mortality risk equivalent to that of a 60-year-old person without diabetes. Because the additional COVID-19 mortality risk associated with diabetes is markedly higher in the younger than in older people a 70-year-old with diabetes only gains around eight years of additional mortality risk, giving them a COVID-age of around 78 years. These numbers could provide better assessment of COVID-19 risk and better guidance for vaccine prioritization. DOI: 10.1007/s00125-021-05404-8

Seroprevalence data is thought to better reflect the rate of infection as it shows the levels of antibodies in the blood, whether an individual showed symptoms of COVID-19 or not. In a study published in The Lancet Child & Adolescent Health, researchers used that data to determine what role young children play in spreading the SARS CoV-2 virus. During the first French national lockdown from mid-March to mid-May of 2020, when most daycare centers and schools were closed, a small number operated at reduced capacity to care for children of critical workers. The team compared 197 daycare staff and children with 164 control adults. Seroprevalence rates of COVID-19 antibodies did not differ significantly from those of the comparator group. Of 327 children, 14 were seropositive and came from 13 daycare centers, suggesting that there was no child-child transmission. The seropositive children were more likely to have had contact with a confirmed adult household case of COVID-19 than seronegative children, while the reverse could not be said for the seropositive adults. Results suggest that young children are more likely to contract COVID-19 at home and are not primary spreaders of the virus. DOI: 10.1016/S2352-4642(21)00024-9

Pregnant women are at increased risk of preterm birth or pregnancy loss if they develop a severe case of COVID-19 and need effective guidance in choosing whether to receive a COVID-19 vaccination. Because pregnant women were excluded from the clinical trials during the testing of the COVID-19 vaccine that guidance is reliant upon the vaccine lessons of history. A recent JAMA article outlines how available safety data, the basic science of mRNA vaccines, and the long history of successfully administering most other vaccines in pregnant women can help set the stage for healthcare professionals to counsel patients on the benefits of COVID-19 vaccination. DOI:10.1001/jama.2021.1658

Researchers in Denmark have developed a machine learning (ML) model that can predict the risk of death at the time of a COVID-19 diagnosis with 90% accuracy. Computer scientists from the University of Copenhagen trained a machine learning model on a Danish dataset to predict the risk of an adverse outcome at diagnosis, hospitalization, pre-ICU admission, and post-ICU admission. Their ML model was further trained with additional data input, such as physiological parameters, comorbidities, temporal features, and lab results to test its performance as well as reveal links to primary motivators of disease progression. A limited set of demographic variables of age, gender and BMI—BMI being a primary hallmark of adverse outcome—can predict an adverse outcome (hospitalization, ICU admission, death) as early as diagnosis. Unsurprisingly, comorbidities such as hypertension and diabetes are driving factors of adverse outcomes. Prognostic indicators like CRP levels and markers for organ damage gain significance as the patient moves through the hospital system. Altogether the results indicate that the outcome of a COVID-19 diagnosis can be largely predicted with the relatively limited values of age, gender, and comorbidities, essentially long-hand for frailty. The research is published in Scientific Reports. DOI: 10.1038/s41598-021-81844-x

An anticancer drug has shown promise as a treatment for severe COVID-19 patients in a small clinical trial by shortening recovery time and reducing mortality. Bevacizumab, a humanized anti-VEGF monoclonal antibody previously used in oncology at higher doses, improved the oxygen-support status of 92% of patients. The study followed two groups of 26 participants each with the experimental group receiving a single 7.5 mg/kg dose of the anti-vascular endothelial growth factor (VEGF) bevacizumab. The researchers hypothesize that the VEGF expression induced by hypoxia caused by COVID-19 infection could be blocked, thereby improving oxygen perfusion and anti-inflammatory response, and leading to reduction of clinical symptoms. After the single dose of bevacizumab, 17 of 26 patients were able to be discharged. Six patients receiving ventilator support discontinued it and of those six, four were discharged. Chest imaging revealed a reduction in the total lesion areas and lesion ratios and an absence of consolidation lesions. Patients also showed a rapid improvement in PaO₂/FiO₂ ratios, rapid reduction in fever, increases in peripheral blood lymphocytes, and profound decreases in C-reactive protein (CRP). There were no deaths in the treatment group. Research was published in Nature Communications DOI: 10.1038/s41467-021-21085-8

An experimental antiviral drug may hasten recovery for COVID-19 outpatients and benefit public health according to a clinical study published in Lancet Respiratory Medicine. Patients who received a single dose of peginterferon lambda were more than four times more likely to clear the virus than a control group. Interferon lambda is produced in response to viral infection and has the ability to activate several cellular pathways against the virus. SARS CoV-2 prevents the body from producing interferons allowing it to evade this arm of the immune system. DOI: 10.1016/S2213-2600(20)30566-X 

A common gout drug may reduce the need for oxygen therapy and length of hospital stay in COVID-19 patients according to the results of a small clinical trial. Colchicine, a drug used to treat gout and other systemic inflammatory conditions, was added to the standard treatment of a subset of 75 hospitalized COVID-19 patients with moderate to severe infection. Others received placebo. Average time on oxygen therapy was four days and average hospital stay was seven days for the treated group, compared with 6.5 days of oxygen therapy and an average hospital stay of nine days for the placebo group. While the mechanism of action remains unknown, colchicine is not associated with severe side effects, and the researchers suggest it may be worth adding to the standard treatment. Research is published in RMD Open. DOI: 10.1136/rmdopen-2020-001455 

A study published in the CMAJ (Canadian Medical Association Journal) found that those on long-term dialysis are almost four times more likely to die from COVID-19 and should be prioritized for vaccination. According to data covering a period from March to August, researchers found that among long-term dialysis patients diagnosed with COVID-19, 28.3% died and 62.6% were hospitalized. However, long-term dialysis patients who remained uninfected during that period had a death rate of 5.8% and a hospitalization rate of 27%. Vaccination and reduction of risk factors for SARS CoV-2 infection are key, as well as patient education about their increased risk for infection and higher mortality. DOI: 10.1503/cmaj.202601

Because povidone iodine (PI) solutions at concentrations as low as 0.5% can rapidly inactivate SARS-CoV-2 in vitro with contact times as short as 15 seconds, researchers tested whether nasopharyngeal application could reduce the viral load of non-severe COVID-19 outpatients and their subsequent ability to spread the infection. A group of 24 outpatients who had recently tested highly positive for SARS CoV-2 RNA were divided into two groups. One group was administered four successive mouthwashes and gargles of 1% PI each, followed by a nasal rinse of each nostril using the same solution, which was then followed by the application of a dab of 10% PI ointment to each nare with massage to facilitate spread for five days. All patients but one had a negative SARS CoV-2 titer by day three. Because nasopharyngeal decolonization may slow the spread of COVID-19 by reducing the viral load of infectious SARS CoV-2 researchers believe this topic merits a larger clinical study. Find out more in JAMA Otolaryngology - Head & Neck Surgery. DOI: 10.1001/jamaoto.2020.5490

Industry News

A University of Arizona Health Sciences study that is examining COVID-19 immunity and re-infection among frontline workers is expanding to include some Arizona college students while broadening its research focus to include COVID-19 vaccination effectiveness. Serologic and cellular immune response testing will be performed on pre- and post-vaccination blood samples. Different vaccine exposures, including different vaccine types and adherence to recommended vaccine doses and timing, will be examined. The AZ HEROES team invites all eligible college students to sign up for the study. Press release.

Clinicians at UCI Health have seen success with a system for delivering monoclonal antibodies to COVID-19 positive patients that manages the challenges of allocating healthcare workers and finding the space through the creation of a closed loop system that sees patients through doctor referral. With six chairs and a dedicated staff in an infusion clinic, the COVID-19 positive patients are kept separate from other patients, and if the monoclonal antibodies are successful—only about three percent of the first 86 patients to receive monoclonal antibody treatment at UCI later had to be admitted to the emergency department—COVID patients never have to touch the emergency department or hospital setting, helping the community and preserving hospital beds. UCI has seen a significant improvement in COVID-19 hospitalizations with monoclonal antibodies. Press Release

New Yorkers' acceptance of the COVID-19 vaccine has increased significantly according to a survey conducted by the City University of New York Graduate School of Public Health and Health Policy (CUNY SPH). Last September, 55% of residents reported they would take the vaccine when it became available. This January, 64% reported they would take it, and this increase persists across racial and ethnic groups. However, more than half (54%) of New York City respondents believe the state is not doing a good job of managing the vaccine rollout. Press Release

A large international study is underway with hopes of identifying drugs that may be repurposed as treatments against the COVID-19 pandemic, especially in low and middle-income countries where the resources to continue admitting patients to hospital at the current rate simply do exist. McMaster University researchers are leading a large international study with research clinic Cardresearch and the Pontifical Catholic University of Minas Gerais in Brazil and the University of Stellenbosch in South Africa on an ongoing clinical trial funded in part by the Bill and Melinda Gates Foundation and Fastgrants. the Together COVID-19 trial will evaluate the effectiveness of ivermectin, metformin and fluvoxamine on preventing COVID-19 disease progression. Ivermectin is typically used to treat parasitic infections. Metformin is better known as a treatment for diabetes. And fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and anxiety disorders. In Brazil there is particular interest in ivermectin. Costing less than $5 per treatment, ivermectin is on the WHO’s list of essential medicines. Some small clinical trials have indicated a benefit for COVID-19 patients treated with ivermectin during the early stage. Press Release

An NIH trial has begun enrolling participants for an international randomized, controlled Phase III clinical trial to evaluate the safety and efficacy of an investigational long-acting antibody combination for treating people hospitalized with COVID-19. This trial is part of a larger framework, ACTIV-3, and has an adaptive design that allows researchers to add additional sub-studies of new experimental agents. A new sub-study is evaluating AZD7442, an investigational long-acting antibody combination developed by AstraZeneca. In 2020, researchers at Vanderbilt University Medical Center isolated antibodies from two patients who had recovered from COVID-19, and these antibodies, licensed to AstraZeneca, formed the basis for the synthetic antibodies in AZD7442. The AZD7442 study will run concurrently with two other sub-studies, one to evaluate VIR-7831, a SARS-CoV-2 experimental monoclonal antibody and another evaluating a combination of BRII-196 and BRII-198, two investigational SARS-CoV-2 neutralizing monoclonal antibodies. Press Release