CPAP Treatment Saves Lives, Kidney Disease Strong Risk Factor, Ethics of Continued Vaccine Trials: COVID-19 Updates

December 4, 2020 I One-third of children asymptomatic, lung tissue recovers well, adverse outcomes unlikely in COVID-19 positive pregnant women, Type O and Rh negative blood groups at lower risk, immune mechanism that triggers cytokine storm, direct oral anticoagulants show no protection, overdose-related cardiac arrest rates surge, trial underway for nasal spray prophylaxis, protective factors in children, and pregnant women suffer mental health effects. Plus: Wuhan lockdown proves effective, ongoing vaccine trials and advancements, and triple combination therapy trial underway.

 

Research News

In a new perspective paper, published in Science, researchers evaluate the ethics of continuing COVID-19 vaccine trials once an effective and safe candidate is found. Currently, over 180 COVID-19 vaccines are in development and at least 12 are undergoing phase 3 clinical trials. The researchers explain that, given this unprecedented effort, more than one candidate will likely be found safe and effective while many others are still being tested. They recommend continuing with these trials in low risk populations, even once an effective vaccine has been approved, to continue the collection of valuable data and address the need for more than one effective vaccine to meet global demands. They suggest excluding those at high risk from ongoing trials to protect those most vulnerable to the virus and allow them access to approved vaccines first. DOI:10.1126/science.abf5084

Overdose-related cardiac arrest rates have surged amid the pandemic, finds a new study published in JAMA Psychiatry. Researchers used the National Emergency Medical Services (EMS) Information System, which is a large registry of more than 10,000 EMS agencies in 47 states, to examine reported weekly overdose-related cardiac arrests and compared those findings to the weekly average in 2018 and 2019. They discovered a steep increase in overdose-related cardiac arrests during the initial months of the pandemic, nearly double when compared to 2018 and 2019, and overall 2020 values increased by 50%. They compared these findings to a measurement of mobility, which was significantly decreased during this surge, and conclude that social isolation may have sharply accelerated fatal overdose trends. DOI:10.1001/jamapsychiatry.2020.4218

Differences in immune systems and blood vessel health likely protect children from severe COVID-19, according to a review of global COVID-19 literature led by researchers at the Murdoch Children’s Research Institute. Published in the Archives of Disease in Childhood, their research revealed several factors that could offer protection in children including recent immunization with live vaccines (such as the MMR vaccine), recurrent viral infections that improve trained immunity, higher levels of microbiota that help regulate immunity (in the throat, nose, lungs, and stomach), and higher levels of vitamin D. They also linked healthier blood vessels and less chronic inflammation in children to better outcomes of COVID-19, as adults tend to develop damage to the endothelial cells lining the blood vessels and heart with increased age and there was an association between conditions that affect these cells and severe COVID-19 disease. DOI:10.1136/archdischild-2020-320338

Chronic kidney disease is a leading risk factor for COVID-19 hospitalization, finds new research published in PLOS ONE. A team from Geisinger Health System analyzed medical records of nearly 13,000 patients who were tested for COVID-19 within their health system between March and May 2020 and studied the association between specific clinical conditions, such as kidney, cardiovascular, respiratory and metabolic conditions, and COVID-19 hospitalization. They determined that patients with kidney disease were most strongly associated with hospitalization and those with end-stage renal disease were 11 times more likely to be admitted to the hospital than patients with no history of kidney disease. DOI:10.1371/journal.pone.0242182

A case study, published in JACC: Case Reports, documents a 2-month-old infant diagnosed with COVID-19 that experienced reversible myocardial injury and heart failure. The patient was born pre-maturely at 33 weeks and stayed in the neonatal intensive care unit (NICU) for three weeks, including one week of nasal continuous positive airway pressure (CPAP). The infant presented with choking and bluish discoloration of the skin after feeding, with no history of illness or other symptoms. The patient tested positive for COVID-19, after repeated testing, and an ECG showed myocardial injury due to viral infection, resulting in heart failure, with tests ruling out all other possible viral causes for the myocardial injury. Author of the case report and pediatric cardiologist at The Children’s Hospital of Montefiore adds that this young patient’s case mirrors four case reports of acute myocardial injury reported in adult patients with COVID-19. DOI:10.1016/j.jaccas.2020.09.031

Researchers from Brigham and Women’s Hospital have found that the COVID-19 pandemic seems to be worsening depression, anxiety, and post-traumatic stress disorder (PTSD) in pregnant and postpartum women. The researchers launched the Perinatal Experiences and COVID-19 Effects Study (PEACE) to assess the mental health in this group of women and surveyed over 1,100 individuals who were pregnant or had recently given birth. They found that 36.4% reported clinically significant levels of depression, 22.7% reported generalized anxiety, and 10.3% reported symptoms above the clinical threshold for PTSD. Prior to the pandemic, rates of perinatal depression were generally considered to be 15-20%. These findings are published in Psychiatry Research. DOI:10.1016/j.psychres.2020.113552

Direct oral anticoagulant (DOAC) use does not appear to protect against developing severe COVID-19, finds a new study conducted by Karolinska Institutet. The study, published in The Journal of Internal Medicine, included over 100,000 Swedish patients (45 to 84 years old) with atrial fibrillation being treated with DOACs and a control group including over 350,000 individuals with cardiac disease but not being treated with those anticoagulants. The researchers examined hospitalization rates, intensive care admission, and deaths from COVID-19 in both groups and found no reduction in these risks from the use of DOACs. They point out that these findings do not suggest that other types of anticoagulants are ineffective for the treatment of COVID-19. DOI:10.1111/joim.13205

In a new study, published in the Journal of Experimental Medicine, researchers from Brazil pinpoint an immune mechanism that triggers cytokine storm seen in severe COVID-19. The research team demonstrated for the first time that in COVID-19 patients an immune mechanism, known as the inflammasome, plays an important role in the activation of the inflammatory process that can lead to organ damage and death. The authors suggest that their findings support the use of inflammasome activation as a marker for disease prognosis, identifying high-risk patients at an early stage, and as a potential therapeutic target in severe COVID-19. They report that there are drugs already approved for human use that are capable of inhibiting inflammasome activation and these drugs should be investigated in the context of SARS-CoV-2 infection. DOI:10.1084/jem.20201707

University of Alberta researchers found that more than one-third of children with COVID-19 are asymptomatic. The team analyzed results from 2,463 children who were tested for the virus between March and September and, of those children, 1,987 tested positive for COVID-19 with 35.9% experiencing no symptoms. Researchers of this study, published in CMAJ, also determined cough, runny nose and sore throat to be the three most common symptoms in COVID-19 positive children (25%, 19%, and 16%, respectively), however, these symptoms were actually more prominent in children who tested negative. They suggest that these findings highlight the importance of mask-wearing and social distancing even when feeling well, and COVID-19 questionnaires and self-reported symptoms of sore throat and runny nose are not good indicators for whether or not a child may be a SARS-CoV-2 carrier. DOI:10.1503/cmaj.202065

A mass screening of more than 10 million Wuhan residents, after the city’s strict lockdown period from January to April, found 300 asymptomatic cases of COVID-19. Interestingly, none of these cases identified were infectious. Researchers of the study, published in Nature Communications, explain that these findings could be due to stringent protocols for mask-wearing, social distancing, and lockdown restrictions which weakened the virulence of COVID-19 and decreased the viral load in these asymptomatic cases identified. The team cautions that this research should not be applied to locations with a high level of virus transmission, but rather exemplifies that COVID-19 safety measures proved effective in Wuhan, China. DOI:10.1038/s41467-020-19802-w

Cancer survivors likely have a higher risk of severe COVID-19 outcomes, according to London School of Hygiene & Tropical Medicine researchers. The research team analyzed medical records from 1990 to 2014 of more than 630,000 patients in the UK, which included 100,000 survivors of cancer. When comparing the rates of influenza hospitalization and death between cancer survivors and those with no history of cancer, they found that the risk of these outcomes was greater than nine times higher in survivors from lymphomas, leukemia, and multiple myeloma. Given that influenza and COVID-19 are both epidemic respiratory viruses with broadly similar risk factors, the researchers concluded that these findings suggest that cancer survivors are also likely to have an increased risk for poor COVID-19 outcomes. They acknowledge that it is not certain that risk factors for severe influenza will have the same associations with COVID-19. This study is published in EClinicalMedicine. DOI:10.1016/j.eclinm.2020.100656

Early use of CPAP may save the lives of some COVID-19 patients, according to a new study published in BMJ Respiratory Open. A team from Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust (WWL) and Lancaster University found that using CPAP in the first days of hospitalization appeared to have saved between 10 to 20% of patients’ lives. They found that early use of CPAP potentially reduces lung damage and allows the patient to recover from inflammatory effects – and this treatment could be used outside of the intensive care unit and reduce the need for invasive ventilation techniques. The researchers note that this was a pilot study with a small sample size, however, they are seeing continued success with this treatment measure. DOI:10.1136/bmjresp-2020-000692

Lung tissue of patients who suffered from severe COVID-19 recovers well in most cases, finds new research published in Clinical Infectious Diseases. The study, carried out by the Radboud University Medical Center, followed up with three groups of patients who were treated in the ICU, admitted to a general nursing floor, or were referred by a general practitioner for persistent symptoms from COVID-19. After three months, an extensive health assessment revealed the lung tissue of patients with severe disease was recovering well and showed similarities to acute pneumonia or acute respiratory distress syndrome (ARDS) recovery. Interestingly, they also found that those patients referred by a GP showed the worst recovery, even though hardly any anomalies were found in the lungs. The researchers emphasize that these findings warrant further research into explanations and treatment options for those with persistent symptoms. DOI:10.1093/cid/ciaa1750

In a new paper, part of the Pandemic Respiratory Infection Emergency Triage (PRIEST) study and funded by the National Institutes of Health Research (NIHR), researchers collected data from over 22,000 patients presenting to 70 emergency departments across the UK with suspected COVID-19 infection between March and May 2020. They then studied differences in symptoms and outcomes based on age, sex, and ethnicity and found that adults admitted to the hospital with confirmed COVID-19 were twice as likely to die or receive organ support than adults who did not have the virus, showing worse outcomes from COVID-19 than similar presentations. Children younger than 16 years of age had much better outcomes when compared to adult patients and men showed worse outcomes when compared to women. Racial disparities were also seen in Black and Asian adult patients, as they tended to be younger, more likely to require oxygen support, and more likely to test positive for COVID-19 when compared to White patients. These findings are published in PLOS ONE. DOI:10.1371/journal.pone.0240206

Preliminary results from the Predi-COVID study in Luxembourg have been published in the British Medical Journal Open, and researchers from the study are seeing encouraging participation rates. Predi-COVID aims to identify clinical, epidemiological, and socio-demographic characteristics, as well as specific biomarkers from both the virus and the patient. The research team has also launched an ancillary study, called Predi-COVID-H, which includes household members of COVID-19 positive patients to study transmission of the virus in this high-risk population. Preliminary findings show that most of the enrolled participants experienced few or mild symptoms. The most prevalent symptoms included fever (26.2%), cough (23.3%), rhinitis (12.2%), and sore throat (10.8%). Common comorbidities and risk factors included smoking (18.1%), asthma (5.4%), diabetes (4.7%), chronic heart disease (3.6%), and obesity (3.3%). Researchers are also exploring “vocal biomarkers” for easy remote monitoring of patients from their homes. DOI:10.1136/bmjopen-2020-041834

Researcher’s from Children’s Hospital of Philadelphia, along with six other large children’s health systems through PEDSnet, have reported that of more than 135,000 pediatric patients tested for SARS-CoV-2, only 4% tested positive for the virus and infections were typically mild, however, risk and severity may be higher in children from ethnic minorities, adolescents, patients without private insurance, and those with underlying medical conditions. The most severe disease was seen in 7% of children with those risk factors. The study, published in JAMA Pediatrics, found that patients who were Black, older than 12 years of age, and had a history of public insurance were 1.5 to 3 times more likely to develop severe COVID-19, and patients with long-term medical conditions were roughly 6 times as likely. DOI:10.1001/jamapediatrics.2020.5052

Type O and Rh negative blood groups may be associated with a slightly lower risk for SARS-CoV-2 infection, finds a new study published in Annals of Internal Medicine. Researchers from ICES in Toronto conducted a population-based study on over 225,000 individuals who had an ABO blood group test from January 2007 to December 2019 and also had a SARS-CoV-2 test to determine whether ABO and Rh blood groups were linked to risk for infection and severity of COVID-19. The authors of the study included that further investigation using universal screening would be needed to verify if type O and Rh negative individuals do indeed have a lower risk. DOI:10.7326/M20-4511

A systematic review and meta-analysis of three human coronaviruses, published in The Lancet Microbe, finds that people infected with SARS-CoV-2 are most infectious within the first five days of symptom onset and highlights the importance of rapid isolation. No live SARS-CoV-2 virus was found in any type of sample collected beyond nine days of symptom onset, although viral genetic material was detected in respiratory or stool samples for several weeks. These findings are in line with contact tracing studies and current recommendations by many countries to self-isolate for ten days. These findings also suggest that repeat testing for SARS-CoV-2 may not be needed to deem that a patient is no longer infectious, as this could remain positive for much longer and does not indicate infectiousness. DOI:10.1016/S2666-5247(20)30172-5

The Phase 2 trial of the UK’s COVID-19 vaccine candidate finds that it is safe and induces an immune response in both healthy young people (18 to 55 years old) and healthy older adults (56 years and over). The trial found that the vaccine candidate provoked a T cell response within 14 days of the first dose of vaccination and an antibody response within 28 days of the booster dose in all healthy age groups. Phase 3 trials are underway to confirm these results and to include evaluation of efficacy in older adults with underlying health conditions. These findings are published in The Lancet. DOI:10.1016/S0140-6736(20)32466-1

UT Southwestern researchers have found that 95% of women who tested positive for COVID-19 during pregnancy had no adverse outcomes and the virus was transmitted to the fetus in just 3% of the cases. The research team followed over 3,000 expectant mothers at Parkland Health and Hospital System, 252 of whom tested positive for the virus during pregnancy (75% Hispanic, 18% Black, and 4% White). Only 6 of those women developed severe or critical COVID-19 pneumonia and preterm birth was the only adverse outcome seen in these critically ill women, while none were seen in those who were asymptomatic or experienced mild symptoms. One author of the study, published in JAMA Network Open, emphasizes that five percent of expectant mothers developing severe disease from COVID-19 is still a major concern, however, this estimation is lower than previous reports from the Centers of Disease Control (CDC). DOI:10.1001/jamanetworkopen.2020.29256

Children’s Hospital Los Angeles has conducted the largest pediatric genomic COVID-19 study to date, and their findings are published in Open Forum Infectious Diseases. The team sequenced every single COVID-19 positive sample that they received to accumulate the largest collection of clinically correlated pediatric genomic data published. They also investigated how subgroups of the virus, or clades, could affect children differently and found that a particular grouping of mutations, called clade 20C, was more commonly seen in pediatric patients with severe COVID-19 symptoms. This finding requires further investigation but highlights the importance of examining genetics of the virus, according to an author of this study. DOI:10.1093/ofid/ofaa551

Industry News

Drawbridge Health partners with University of Cambridge researchers for the use of the OneDraw Blood Collection Device for remote blood sample collection in a large-scale surveillance study currently being conducted to assess the prevalence of previous infection with COVID-19. The study, launched in July 2020, has recruited 4,000 participants and aims to quantify the proportion of people previously infected with the virus in the Fenland cohort, which is broadly representative of the population of Cambridgeshire. The OneDraw device allows study participants to collect blood samples at home, without the need for face-to-face interaction. Based on positive user feedback and demonstrated testing suitability, Drawbridge Health and the University of Cambridge are now developing a collaboration in metabolic health, including the evaluation of nutritional biomarkers. Press Release

Octapharma will present results of their study on the use of high-dose Octagam 10% [Immune Globulin Intravenous (Human)] for severe COVID-19 patients at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. Octapharma’s intravenous immunoglobin (IVIg) portfolio will also be featured in a study design poster focused on primary infection prophylaxis in patients with chronic lymphocytic leukemia during ASH. The poster reports on a randomized open label study that enrolled 33 patients experiencing hypoxia and were at risk of needing mechanical ventilation and found that IVIg, combined with the standard of care (SOC), significantly improved hypoxia and reduced hospital length of stay in patients with COVID-19 when compared to those receiving SOC alone. The research team believes the use of IVIg for prophylaxis of severe disease, especially in immunocompromised patients, is a promising therapeutic possibility for COVID-19 and a larger trial is planned. Press Release

Rutgers University is leading a clinical trial, called Triple Combination Antiviral Coronavirus Therapy (TriACT), to assess the combination of nitazoxanide, ribavirin and hydroxychloroquine to treat adults infected with SARS-CoV-2 who are asymptomatic or experience mild symptoms. The trial seeks to determine if this triple combination therapy will reduce viral load and chances of developing moderate-to-severe symptoms. Experimental studies found this combination to be highly effective in suppressing viral replication. Press Release

Marinomed Biotech announces that Swansea University Medical Center will conduct a clinical trial with Carragelose nasal and throat spray to assess its efficacy in reducing the rate, severity, and duration of COVID-19 in healthcare professionals. The trial will recruit 480 healthcare workers caring for COVID-19 patients in hopes to confirm in vitro findings that the nasal spray works effectively as a COVID-19 prophylaxis and offers protection for vulnerable healthcare professionals. The Carragelose nasal spray is marketed as Boots Dual Defence in the UK. Press Release

Infinity BiologiX (IBX) has announced the launch of its vaccine storage program that will support both the ultra-low temperature storage and distribution of the COVID-19 vaccine. IBX’s vaccine storage program recognizes the need for effective vaccine management practices and incorporates three integral assets to cover each step of the supply chain process to include: ultra-low temperature dedicated storage units, shipment and sample management, and inventory and lot management with specialized distribution logistics that will be essential for vaccine programs requiring multi-doses per individual with a few weeks spread in between each one. Press Release

A Penn State researcher has received funding from the National Institutes of Health (NIH) to study whether vitamin D supplementation helps prevent or lessen severity of COVID-19. The researcher’s team will use mouse and hamster models to test the effects of vitamin D supplementation and if it reduces inflammation in the lungs and limits viral replication to protect against severe COVID-19 infection. The researcher hopes that their findings can contribute to responsible guidance on vitamin D supplementation and its effectiveness in alleviated this disease. Press Release

Thirteen countries in Africa and an international network of research institutions will launch the largest COVID-19 clinical trial in mild-to-moderate outpatients in Africa, called ANTICOV. The clinical trial aims to identify treatments for mild to moderate cases of COVID-19 early on to prevent spikes in hospitalization. The trial will be carried out at 19 sites across 13 countries by the ANTICOV consortium, which includes 26 African and global research and development organizations and is coordinated by the Drugs for Neglected Diseases Initiative (DNDi). ANTICOV will initially focus on testing the safety and efficacy of drugs where large-scale randomized clinical trials could provide missing data in mild-to-moderately ill patients, including the HIV antiretroviral combination lopinavir/ritonavir and the malaria drug hydroxychloroquine, which remain the standard of care for COVID-19 in many African countries. Press Release

Maryland-based Altimmune Inc. has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration to commence a Phase 1 clinical study of its single-dose intranasal COVID-19 vaccine candidate, AdCOVID. The vaccine candidate underwent extensive preclinical testing at the University of Alabama at Birmingham (UAB) and is set to begin clinical testing this month. The UAB preclinical study for Altimmune showed that AdCOVID stimulated a broad immune response as well as local immunity. The researchers note that this vaccine could potentially stop SARS-CoV-2 from entering the lungs, as the nasal mucosa is the first-line barrier to entry of the virus. It could also be particularly beneficial for children, as many studies have found the nasal cavity to be a reservoir for the coronavirus. Press Release

City of Hope has announced the initiation of a Phase 1 clinical trial that will test one of its investigational SARS-CoV-2 vaccines, COH04S1. The investigational vaccine aims to stimulate the immune system to produce antibodies and spur abundant T cells that are believed to provide lasting protection against the virus and could prevent future outbreaks. The goal of the trial is to test the vaccine’s safety and how well it is tolerated. Press Release

New data from Oxford Immunotec (OI) and Public Health England demonstrates that SARS-CoV-2 reactive T cells are associated with lasting protection from COVID-19 and can be detected and measured using OI’s T-SPOT technology. The cohort study of nearly 3,000 essential workers in the UK, part of the EDSAB-HOME Study, investigated both serology and T cell responses and found: none of the participants with a high T cell response developed symptomatic COVID-19 infection in the follow-up period of the study, SARS-CoV-2 responsive T cell numbers are associated with protection from COVID-19, those with low T cell responses were at risk of developing SARS-CoV-2 (20 confirmed infections), and the T-SPOT Discovery SARS-CoV-2 test detected confirmed COVID-19 infection that was not positive in antibody testing. Further follow-up is planned as case numbers rise which may offer additional insights into disease risk. Press Release

Texas Heart Institute has been selected to participate in a global stem cell study for the treatment of COVID-19 patients who develop ARDS. The study, which is sponsored by the Australian regenerative medicine company Mesoblast, will commence this month. Participating ICU patients with ARDS related to COVID-19 will be randomized to receive intravenous infusions of allogenic mesenchymal stromal cell-based therapy or placebo, in addition to maximal support. Previous use of this therapy under emergency compassionate use at New York’s Mount Sinai yielded positive results in COVID-19 patients. Press Release

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