Sore Eyes Significant Symptom, IgA Antibodies Dominate Early Response, Prophylactic Nasal Spray Development: COVID-19 Updates

December 11, 2020 I Dogs detect COVID-19 in sweat, safety evaluation of ventilator sharing, two-thirds lose sense of taste and smell, ethics of human challenge trials, Oxford COVID-19 vaccine trial results, blood vessel damage in children, diabetes and cancer patients at greater risk, transmission from mother to neonate rare, and effects of COVID-19 exposure on healthcare workers. Plus: New oral antiviral could block transmission, metformin may reduce death risk in women, and UC Davis joins Novavax for late-stage COVID-19 vaccine trial.


Research News

Trained dogs might be able to detect people infected with COVID-19 by sniffing their sweat, according to a preliminary proof-to-concept study published in PLOS ONE. The testing was conducted at two sites with a total of six dogs that were trained for one to three weeks to detect COVID-19 positive samples. For the study, 177 participants provided a sweat sample. 95 participants were symptomatic and COVID-19 positive and 82 were asymptomatic and negative for the virus. The success rate per dog to accurately identify the samples ranged from 76% to 100%. The researchers add that these results need to be confirmed in further studies. DOI:10.1371/journal.pone.0243122

Patients with cancer may be at an increased risk for COVID-19 infection and adverse outcomes, especially African Americans, according to a new study published in JAMA Oncology. Researchers from Case Western Reserve University analyzed electronic medical records from over 73 million patients across all 50 U.S states and determined that those patients who had a recent cancer diagnosis were at a significantly increased risk for SARS-CoV-2 infection, with the strongest association for recently diagnosed leukemia. African Americans had a significantly higher risk for infection than White patients, particularly in those with breast cancer. Overall, patients with cancer and COVID-19 had much worse outcomes than patients without cancer and the virus. DOI:10.1001/jamaoncol.2020.6178

The use of statins, angiotensin-converting enzyme inhibitors (ACE inhibitors), and calcium channel blockers may be associated with decreased mortality in patients hospitalized with COVID-19, finds a new study published in JAMA Network Open. The research team studied nearly 65,000 patients treated for COVID-19 across hundreds of U.S hospitals using the Premier Healthcare Database. Overall, the in-hospital mortality rate was 20.3% among these inpatients, with older age (>80 years) being the strongest risk factor for death. They determined that patients taking those cholesterol and blood pressure medications had a decreased risk of mortality, and those given the hydroxychloroquine and azithromycin combination had increased odds of mortality when compared to those not taking this drug combination. The study notes that these findings require future randomized trials for validity. DOI:10.1001/jamanetworkopen.2020.29058

Nearly two-thirds of COVID-19 patients admitted to an Italian hospital reported a loss of smell and taste, according to a new study published in Neurology Clinical Practice. The study included 93 patients (average age of 63) who were admitted to the COVID-19 unit in March of 2020, and 58 of those patients (63%) stated that they lost their sense of taste and smell when interviewed about their symptoms. Moreover, 22% of those patients reported that this was their first symptom with an average duration of 25 to 30 days. The researchers then analyzed bloodwork of these patients and determined that those with compromised sense of smell had lower neutrophil counts, which was 29% less when compared to those with a normal sense of smell. DOI:10.1212/CPJ.0000000000001029

A new paper in JAMA Psychiatry details The Healthy Brain and Child Development (HBCD) Study, which will directly investigate the associations of adverse environments, socioeconomic disadvantage, and impacts of the current pandemic on the development of both brain and behavior throughout early childhood. The study will collect information on several variables, among them SARS-CoV-2 infection during pregnancy or thereafter. The National Institutes of Health (NIH) investigators explain that this will be the most detailed study of early brain development ever conducted, to their knowledge, and will provide invaluable information on the consequences of COVID-19 infection during pregnancy or after the child is born. DOI:10.1001/jamapsychiatry.2020.3803

Community exposure may have driven most healthcare workers’ exposure to COVID-19 early in the pandemic, finds a new study by Northwestern Medicine. The study looked at over 6,500 healthcare workers that included nurses, doctors, non-patient facing administrators and other staff members in the Chicago area and surrounding Illinois. They determined that nurses were the only group with higher risks once community exposure was accounted for, specifically those working with high-flow oxygen therapy and hemodialysis. Other high-risk procedures were not associated with a higher risk of exposure. The researchers credit these findings to the effectiveness of Personal Protective Equipment (PPE), as all participants in this study had adequate access to PPE and other protective measures. This study is published in Open Forum Infectious Diseases. DOI:10.1093/ofid/ofaa582

A new paper, published in the Journal of Medicine & Philosophy, discusses the ethics of human challenge trials for COVID-19 vaccines. The author argues that the potential benefits seem to justify the undeniable risks of these trials to its participants. The Rutgers University researcher answers some ethical questions regarding these challenge trials. He explains that, although the research may not have therapeutic value for the participants and could potentially cause harm, the human challenge trials will benefit the greater good and the potential enormous benefits seem to justify the risks to its healthy volunteers. DOI:10.1093/jmp/jhaa028

Healthcare workers are seven times as likely to have severe COVID-19 infection than other non-essential workers, finds an observational study published in Occupational & Environmental Medicine. The study included over 120,000 employees in the UK (49-64 years old) with 29% classified as essential workers in various fields. They determined that those working in healthcare were more than seven times as likely to have severe infection when compared to non-essential workers and those working in social care and transport workers were 2.5 and 2 times more likely to have severe disease, respectively. Researchers of this study emphasize the need for adequate protection against SARS-CoV-2 in these essential workers. DOI:10.1136/oemed-2020-106731

The first full peer-reviewed efficacy results for a COVID-19 vaccine have been published in The Lancet. The interim results of the Oxford COVID-19 vaccine trials find that the vaccine protects against symptomatic COVID-19 disease in 70% of cases, with vaccine efficacy of 62% in those given two full doses and 90% in those given a half dose followed by a full dose. The vaccine was found to be safe, with only three out of 23,745 participants over roughly three months experiencing serious adverse events that could have been related to the vaccine, and all three of those participants have recovered. The vaccine uses a chimpanzee adenovirus viral vector that cannot cause disease in humans and expresses the SARS-CoV-2 spike protein. Past trials have found that the vaccine induces antibody and T cell immune responses. DOI:10.1016/S0140-6736(20)32661-1

Researchers from the Children’s Hospital of Philadelphia (CHOP) have found elevated levels of a biomarker related to blood vessel damage in children with COVID-19, even in those with mild to no symptoms. In this study, published in Blood Advances, they also found that in a cohort of 22 pediatric patients with COVID-19, 86% met the clinical and diagnostic criteria for thrombotic microangiopathy (TMA), which is a syndrome that involves clotting in the small blood vessels. The researchers explain that they do not yet know the implications of this elevated biomarker in children with COVID-19 but suggest further testing and monitoring of children with SARS-CoV-2 to gain a better understanding. They add that these findings show that there is much more to learn about the virus and its short and long-term impacts on health. DOI:10.1182/bloodadvances.2020003471

Sore eyes may be the most significant ocular symptom of COVID-19, finds new research published in BMJ Open Ophthalmology. Anglia Ruskin University (ARU) researchers looked at questionnaire responses from 83 individuals diagnosed with COVID-19 to evaluate reported symptoms. They found that sore eyes were the most commonly reported symptom, with 16% reporting this problem and only 5% stating that they had this condition prior to infection. 81% of the respondents reported ocular issues within two weeks of COVID-19 symptom onset, however 80% of those persons stated that these eye problems lasted less than two weeks. The researchers suggest that sore eyes replace conjunctivitis on the list of possible COVID-19 symptoms, as it is important to differentiate between an ocular symptom and a possible bacterial infection of the eye. DOI:10.1136/bmjophth-2020-000632

A case report of COVID-19 positive identical twins in Italy sheds light on how the virus can cause differences in infection severity. Authors of the report explain that the male identical twins who both tested positive for SARS-CoV-2 had similar presentations and early treatment, however, one twin experienced no complications and the other twin required four days of invasive ventilation. Neither twin had a history of chronic disease, cardiovascular risk factors, or long-term therapy, and they both lived and worked at the same location. The researchers suggest that these differences in clinical illness from the virus could have been from a different infecting dose or virus mutations. This report is published in the Annals of Internal Medicine. DOI:10.7326/L20-1207

Rutgers University researchers report the first case of COVID-19 triggering a recurrence of Guillain-Barré Syndrome (GBS), according to a case report published in Pathogens. The patient was a 54-year-old male who had suffered from the syndrome twice and had a third occurrence after testing positive for SARS-CoV-2. The researchers then examined close to 1,200 hospital patients diagnosed with COVID-19 who were admitted between March and May of 2020 and found this to be the only case where the virus triggered a recurrence of GBS. They explain that most people recover from this condition that causes progressive muscle weakness, but roughly 5% of people experience a recurrence and recommend that patients with a history of GBS who develop COVID-19 be closely monitored for several weeks. DOI:10.3390/pathogens9110965

COVID-19 patients may develop a wide range of symptoms that evolve over time. This prolonged infection, or ‘long COVID’, was further investigated by researchers in Geneva by reviewing COVID-19 symptom evolution and persistence in an outpatient setting from the first day of diagnosis through day 30 to 45. They determined that these patients developed an array of symptoms that evolved over time. Fatigue, dyspnea, and loss of taste or smell were the most prominent symptoms that persisted. The researchers believe that public health messages about these persistent symptoms could encourage some to comply with recommended measures to slow the spread and avoid infection. This research is published in the Annals of Internal Medicine. DOI:10.7326/M20-5926

A new study, published in CMAJ, analyzed the risk of developing COVID-19 complications using a large patient database from the United States. Across this health database, researchers identified over 70,000 patients who had a COVID-19-related health visit between March and April, and more than half of those patients required hospital admission and 5% required intensive care. They found that the most common complications associated with COVID-19 were pneumonia (27.6%), respiratory failure (22.6%), kidney failure (11.8%), and sepsis or systemic inflammation (10.4%). There was a relatively low risk associated with a range of other lung and cardiovascular conditions, and there appeared to be no increased risk of developing stroke from SARS-CoV-2 infection. DOI:10.1503/cmaj.201686

IgA antibodies dominate the early neutralizing antibody response to SARS-CoV-2, finds a new study published in Science Translational Medicine. Researchers studied samples from over 150 COVID-19 patients with mild to severe symptoms and found that IgA concentrations were higher than IgG and IgM concentrations in the first 3 to 4 weeks after symptom onset and then waned, however, IgA antibodies persisted in saliva for several more weeks. In a separate study, the researchers cloned antibodies taken from recovered COVID-19 patients and discovered that the dimeric form of IgA was fifteen times better at neutralizing the SARS-CoV-2 virus then the monomeric form. Based on these findings, they suggest vaccine development that induces an IgA response and IgA-based tests to detect infection at early stages. DOI:10.1126/scitranslmed.abd2223

Preterm birth and stillbirth rates have remained unchanged during the COVID-19 pandemic, finds new research at Children’s Hospital of Philadelphia. The research team used data from a patient cohort, known as GeoBirth, that includes over 100,000 births at two Penn Medicine hospitals in Philadelphia since 2008. Each preterm birth is examined by one of two independent and blind reviewers and classified as either a spontaneous preterm birth or a medically indicated preterm birth. After analyzing close to 3,000 live births from March through June in 2020, their data did not show any significant change in preterm or stillbirth rates when compared to the same time period in 2018 and 2019. This study is published in JAMA. DOI:10.1001/jama.2020.20991

In a five-month longitudinal study, researchers followed 254 COVID-19 patients who had varying degrees of severity with infection and investigated antibody responses in these patients. They found that IgA and IgM antibodies to SARS-CoV-2 disappeared rather quickly and IgG antibodies lasted longer, however, they documented a slow decline in this antibody class as well, even in those who recovered from severe COVID-19 disease. Interestingly, they detected a higher ratio of antibodies that react to the viral spike protein complex in those patients with mild infection compared to those with severe symptoms, concluding that this finding could explain why these individuals never developed severe infection. The authors of this study, published in Science Immunology, also suggest that their findings may indicate an underestimation of how many people have previously been infected with COVID-19 and raise the question of how long a vaccine will offer protection against the virus. DOI:10.1126/scitranslmed.abe024

Researchers from Italy have determined that SARS-CoV-2 transmission from mother to newborn is rare, provided that appropriate droplet and contact precautions are taken. This study, published in JAMA Pediatrics, included 62 neonates born to 61 mothers with COVID-19 who were roomed-in with appropriate precautions in place. None of the newborns tested positive for the virus and 95% of those newborns were breastfed. After a 3-week follow-up, only 1 of the newborns was diagnosed with COVID-19 infection. Researchers of this study suggest that these findings provide support of newborns rooming-in with their mothers, even if COVID-19 positive, provided that all precautions are in place. DOI:10.1001/jamapediatrics.2020.5086

Black patients hospitalized with COVID-19 have a lower risk of severe disease and death when compared to White patients, according to a new study published in JAMA Network Open. A team of researchers at NYU Langone Health investigated electronic health records from over 9,000 patients tested for COVID-19 in their health system and compiled self-reported race and ethnicity data along with several other health and socioeconomic factors. They found that, even after adjusting for age, sex, insurance status, and comorbidity, Black patients had a lower risk of death from COVID-19 when compared to White patients. Hispanic and Asian patients had similar outcomes to White patients after adjusting for these factors. The researchers note that Black populations are more likely to be uninsured or underinsured than White populations and consequently may die outside of the hospital due to poor access to care. They also added that another limitation to this study was that most of the Black patients were female (62%) and the male sex is a known predictor of poor outcomes for hospitalized COVID-19 patients. DOI:10.1001/jamanetworkopen.2020.26881

An assessment score used to measure a patient’s severity of illness, the National Early Warning Score (NEWS), can effectively be applied to assess COVID-19 patients, finds a research team led at the University of Portsmouth. The Portsmouth Academic Consortium for Investigating COVID-19 (PACIFIC-19) team has provided research that shows the NEWS is just as accurate at predicting adverse clinical outcomes in COVID-19 patients as it is in other hospitalized patients. The score takes commonly measured vital signs and converts them to a single value. Recently the World Health Organization (WHO) has recommended the use of NEWS for close monitoring of clinical deterioration in patients infected with SARS-CoV-2. This research is published in Resuscitation. DOI:10.1016/j.resuscitation.2020.10.039

Individuals with type 1 and type 2 diabetes who become infected with COVID-19 are three times more likely to require hospitalization or experience severe disease compared to those without diabetes, finds a new study published in Diabetes Care. Vanderbilt University Medical Center researchers looked at electronic health records from over 6,000 patients across their clinical sites who tested positive for COVID-19 from March to August and compared the impact of the virus on those with type 1 diabetes, patients with type 2 diabetes, and patients with no history of diabetes. Their findings have led to a plea for policymakers to prioritize those with diabetes for COVID-19 vaccination. DOI:10.2337/dc20-2260

Researchers from the University of Texas have found that alcohol consumption and binge drinking increased with each week of lockdown from the COVID-19 pandemic. The study used data from an online survey completed by nearly 2,000 adults that coincided with the first U.S. state-wide stay-at-home order beginning in March and found that heavy alcohol consumption among binge drinkers rose 19% for every week in lockdown. Overall, 32% of participants reported binge drinking during this time period. Non-binge drinkers, however, consumed about the same amount of alcohol than before the stay-at-home orders. The researchers highlight the need for new intervention and prevention strategies for people in isolation who are at risk for binge drinking. These findings are published in the American Journal of Drug and Alcohol Abuse. DOI:10.1080/00952990.2020.1832508

Boston Children’s Hospital emergency department (ED) saw a sharp decline in asthma-related visits during the COVID-19 lockdown in the spring. This study, published in the Annals of American Thoracic Society, examined medical records of children ages 2-22 years old who visited the hospital’s ED for asthma treatment between January and May in 2018, 2019 and 2020. They discovered a sudden drop in ED visits occurred shortly after schools closed and stay-at-home orders went into effect. The rate of ED visits decreased 80% and 82% the week after lockdown in 2020 when compared to 2018 and 2019, respectively. This decrease continued through May. The researchers believe that these findings contribute to the growing research that shows the pandemic is not leading to increased asthma exacerbations in children and that social distancing has decreased these exacerbations significantly. DOI:10.1513/AnnalsATS.202007-765RL

The oral antiviral drug, Molnupiravir (MK-4482/EIDD-2801), could potentially block SARS-CoV-2 transmission within 24 hours, finds new research led at Georgia State University. The study, published in Nature Microbiology, used a ferret model to test the effect of the drug on suppressing the spread of the virus. They found that the infected ferrets with SARS-CoV-2 and treated with Molnupiravir did not transmit the virus to any other ferrets co-housed with them. In contrast, those ferrets treated with placebo infected all other ferrets in close contact. The researchers believe that the ferrets are a relevant transmission model because they rapidly spread SARS-CoV-2 but do not generally develop severe disease, which resembles the spread of COVID-19 in young adults. This drug is now in advanced Phase 2/3 clinical trials for the treatment of COVID-19. DOI:10.1038/s41564-020-00835-2

Metformin may reduce COVID-19 death risks in women, a large observational study led by the University of Minnesota Medical School and UnitedHealth Group has determined. The team analyzed roughly 6,000 hospitalized COVID-19 patients with type 2 diabetes or obesity and found that women in this patient cohort who had recently filled a metformin prescription prior to hospitalization had a 21 to 24% reduction in mortality risk when compared to similar women not taking the drug. They found no significant reduction in mortality among men in the group. The researchers believe that a reduction in inflammation may have reduced this risk in women, as metformin reduces inflammation proteins like TNF-alpha that may make COVID-19 worse. An investigational drug application has been approved by the Food and Drug Administration (FDA), and a pilot study to further investigate these findings will begin enrolling participants this month. This research is published in The Lancet Healthy Longevity. DOI:10.1016/S2666-7568(20)30033-7

Researchers from Geisinger Health System collaborated with Bucknell University and Kitware, a New York-based software research and development company, to develop a simulation study to evaluate the safety of ventilator sharing where resources may be limited. They created a whole-body physiological simulation of 287 COVID-19 patients that could be successfully managed using a single ventilator and then used their software, Kitware’s Pulse Physiology Engine software, to calculate outcomes for all possible patient pairings to project success of a shared ventilator. They found that patients with similar levels of lung function and oxygen saturation index were the most likely to have positive outcomes when paired to one ventilator. The researchers of this study, published in PLOS ONE, urge that this approach should be considered last resort, however, ventilatory sharing could be a viable option in regions with limited resources. DOI:10.1371/journal.pone.0242532

Social distancing and advice to stay at home may have reduced cardiac events in those over 70 years old, finds a new study published in the Journal of Internal Medicine. Researchers from Sweden used aggregated mobility data from map services from mobile devices to track location data and mapped it against admissions to the country’s 29 emergency cardiac angiography units. They found that on days when the location data revealed people were staying close to home, the proportion of patients going for emergency heart treatments dropped from an average of 63 patients a day in prior years to an average of 55 patients a day during the first wave of the pandemic (March to May 2020). The researchers conclude that the Swedish public health authorities advising those over 70 to stay home may have prevented exposure to known heart attack triggers such as stress, vigorous physical activity, air pollution, and exposure to viruses. DOI:10.1111/joim.13206

In a systematic review of 52 observational studies, researchers have determined that Black and Hispanic populations are disproportionally impacted by COVID-19 due to a higher risk of being exposed to the virus, not from underlying health conditions. This study, published in the Annals of Internal Medicine, found that inequalities in housing, transportation, and occupation are likely causing a heightened risk of being exposed to COVID-19 and underlying health conditions did not appear to be a driving factor for higher rates of hospitalizations and deaths in these populations. They explain that, for example, several outbreaks in Oregon have affected workers in food processing and agriculture, with a labor pool comprised of mainly Latino workers, and that efforts need to be made to reduce exposure to COVID-19 in these vulnerable populations. DOI:10.7326/M20-6306

People with rare autoimmune rheumatic diseases, such as lupus, could be at a higher risk of dying during the COVID-19 pandemic, finds a new study led by researchers from the University of Nottingham. The team examined electronic health records of 170,000 people in England with rare autoimmune rheumatic diseases during the first two months of the pandemic and found that 1.1% of people with these diseases died. They hope to determine whether these deaths were related to COVID-19 infection or from a disruption in healthcare services in future research. Their results also showed that this population had a greater risk of dying at a younger age during the pandemic when compared to the general population. This study is published in Rheumatology. DOI:10.1093/rheumatology/keaa855

Vaccination against tuberculosis with the bacilli Calmette-Guerin (BCG) vaccine can slow the spread and severity of COVID-19, according to researchers from St. Petersburg State University. The Russian researchers analyzed statistical data that showed mortality rates and transmission rates to be lower in countries where national vaccine immunization programs included the BCG vaccine. They explain that the BCG vaccine has properties that are uncharacteristic for most adjuvants, as it acts as an immune response-modulating agent and reduces the risk of some autoimmune diseases and, since COVID-19 can cause autoimmune complications, the properties of BCG are beneficial. Earlier studies have shown similar findings. This research is published in Juvenis Scientia. Article

Industry News

The University of Louisville (UofL) has received funding from the U.S. Department of Defense to develop and test a nasal spray to prevent COVID-19 and other serious viral respiratory infections. The nasal spray uses Q-Griffithsin, which is a drug compound developed and co-owned by UofL. This one-year project to develop the prophylactic spray will include a Phase 1 clinical trial, and researchers anticipate that this spray could be used to protect healthcare workers, military personnel living in close quarters, other essential workers, and vulnerable populations for whom a vaccine may not offer full protection. Press Release

Longenesis has announced the release of its product Curator, which is a platform that enables biomedical data sharing to a wide scientific audience without compromising the privacy of patients. The company has already collaborated with more than 20 clinical institutions, patient organizations, biobanks, genomic sequencers, and digital health startups across several countries. The new platform provides an opportunity for clinical investigators to showcase the scope of data that could be used for research while protecting patient privacy. Of note, the Latvian Biomedical Research and Study Center (BMC) is one collaborator that aims to accelerate COVID-19 research and has established a cohort of over 500 COVID-19 patients that includes various types of samples and detailed characterization of each clinical case. Press Release

UC Davis Health will launch a Stage 3 clinical trial with the NIH and Novavax to test an experimental COVID-19 vaccine, called NVX-CoV2373. This vaccine has a subunit from the spike protein in SARS-CoV-2 that is combined with an adjuvant. This combination triggers an immune response to the spike protein and creates antibodies to fight it. It can be stored in a liquid state and allows for distribution using standard vaccine channels, unlike some other vaccines that require subzero temperatures. In November, the U.S. Food and Drug Administration (FDA) approved fast-track authorization for this vaccine. Press Release

A study led by researchers at the University of Oxford finds that healthcare workers who contracted COVID-19 could have immunity that lasts several months. The researchers tested over 12,000 healthcare workers in England routinely for infection with SARS-CoV-2 and for antibodies against the virus. They found that those workers who tested positive for antibodies at the beginning of the study were protected against reinfection for at least six months. Out of more than 1,400 antibody-positive participants in the study, only three subsequently tested positive for COVID-19 and none of them had any symptoms. These findings are published as a pre-print on medRxiv. Press Release

The NIH, under the Rapid Acceleration of Diagnostics-Underserved Populations Initiative (RADx-UP), has awarded a $1.6 million grant to fund a new research project to study whether interventions that have been effective at engaging high-risk populations in HIV/AIDS testing can be adapted to mitigate COVID-19. The project involves a randomized trial with over 580 residents of Essex County in New Jersey, who are medically or socially vulnerable to COVID-19. The researchers will identify factors that promote compliance with testing and precautionary measures such as hand washing, social distancing and self-quarantining. A social work professor from the University of Illinois Urbana-Champaign is partnering with the New Jersey Community Research Initiative for this project. Press Release

A new online tool, funded by the NIH, allows organizations to find the best COVID-19 testing strategy to meet their specific needs. This COVID-19 Testing Impact Calculator is a free resource that computes how different approaches to testing and precautionary measures, such as mask-wearing and social distancing, can help flatten the curve in the spread of the virus in schools, businesses and other organizations. This is the first online tool in the country to provide clear guidance on risk-reducing measures and testing to aid in safely remaining open. Press Release

Purdue University has collaborated with other organizations to accelerate global research on COVID-19 through access to high-quality, real-time multi-center patient datasets. Researchers are testing predictions of artificial intelligence (AI) drug discovery platforms on patient datasets across a network of health care institutions and using the technology to find trends and data connections to better understand and treat COVID-19, specifically the impact existing drugs have on the virus. They hope to identify patterns in patient responses to drugs, rank predictions from the platform for drug repurposing, and evaluate patient responses over time. The National Science Foundation has funded this Records Evaluation for COVID-19 Emergency Research (RECovER) initiative. Press Release

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