Common Cold May Lessen Severity, ‘Brain Fog’ Really PTSD, Eyeglasses A Fourth Defense Mechanism: COVID-19 Updates

October 9, 2020 | Previous infection with a non-SARS-CoV-2 coronavirus may lessen severity COVID-19. Long term exposure to urban air pollution may have made COVID-19 more deadly for some. 86% of UK residents who tested positive this spring did not have the specific virus symptoms. And a new look at the interrelationship between COVID-19 and cancer. Plus, survey shows patients have concerns about their health and safety at in-office visits, TestBoston trial looks for previous infection, and Israel opens pediatric COVID-19 ward.

 

Research Updates

Early timing of tracheotomy in COVID-19 patients may be important in reducing time of invasive mechanical ventilation, according to a study published in JAMA Otolaryngology. This prospective cohort study assessed 50 patients admitted to the ICU with COVID-19 that required tracheotomy. Findings were that there was less time on invasive mechanical ventilation support with early vs late tracheotomy (mean 18 vs 22.3 days respectively). Postoperative complications were rare, with minor bleeding being the most common (12%). These findings could have implications on ICU availability during the pandemic. DOI:10.1001/jamaoto.2020.3641 

Oncology clinical trials have faced many challenges during the COVID-19 pandemic. Patient enrollment has significantly decreased, and many investigators have concerns that protocol deviations, due to the pandemic, could compromise study quality and integrity. The FDA has given guidance to support continued oncology drug development and clinical trials, including flexible approaches to conducting certain aspects of these trials and allowing sponsors to amend trial processes to prevent hazards without first securing institutional review board approval. The FDA is committed to supporting patient safety and study integrity without halting critical trials for oncology drugs. These guidelines are contextualized in JAMA Oncology. DOI:10.1001/jamaoncol.2020.4975 

Researchers at Emory University have published a study in The Innovation that found long term exposure to urban air pollution may have made COVID-19 more deadly. Key urban air pollutants were analyzed, including fine particle matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), across 3,122 counties in the US from January to July. To examine the association between ambient air pollutants and severity of COVID-19 outcomes, they investigated case-fatality rate and mortality rate. Of the pollutants analyzed, NO2 had the strongest independent correlation with raising a person’s susceptibility to death from COVID-19. A 4.6 parts per billion (ppb) increase of NO2 was associated with 11.3% and 16.2% increases in case-fatality and mortality rate from COVID-19, respectively. They also discovered that just a 4.6 ppb reduction in long-term exposure to NO2 would have prevented 14,672 deaths among those who tested positive for SARS-CoV-2. DOI: 10.1016/j.xinn.2020.100047 

In the largest study to date on COVID-19 among non-hospitalized pregnant women, researchers analyzed the clinical course and outcomes of 594 women who tested positive for SARS-CoV-2 virus during pregnancy. They found the most common early symptoms were cough (20%), sore throat (16%), body aches (12%), and fever (12%). Half of the participants still had symptoms after 3 weeks and 25% had symptoms persisting after 8 weeks or more. The findings from this PRIORITY study (Pregnancy Coronavirus Outcomes Registry) appear in Obstetrics & Gynecology and note that the majority of participants had mild disease and were not hospitalized, but it took a median of 37 days for symptoms to ease. This national study was led by UC San Francisco and UCLA. DOI: 10.1097/AOG.0000000000004178

86% of UK residents who tested positive for COVID-19 between April 26 and June 27 did not have the specific virus symptoms (cough, fever, or loss of taste/smell) according to a new study led by UCL researchers and published in Clinical Epidemiology. Data was used from the Office for National Statistics Coronavirus Infection Survey pilot study and looked at 36,061 people. They found that of those surveyed, 115 tested positive for SARS-CoV-2 (0.32%) and of those who tested positive, only 16 (13.9%) reported specific virus symptoms. The study also included data on people reporting a wider range of symptoms such a fatigue and shortness of breath, and of those who tested positive, 27 (23.5%) were symptomatic and 88 (76.5%) were asymptomatic on the day of the test. The authors did note that several studies have highlighted a lower proportion of SARS-CoV-2 positive individuals are asymptomatic, however, the prevalence of asymptomatic cases varies greatly possibly due to the sampling and settings of the study. DOI: 10.2147/CLEP.S276825 

Columbia Engineering researchers demonstrate that RNA terminated by Sofosbuvir is more resistant to the proofreader of SARS-CoV-2 than Remdesivir-terminated RNA. The results of the new study, published in Scientific Reports, support the use of FDA-approved hepatitis C drug EPCLUSA (sofosbuvir/velpatasvir) in combination with other drugs in COVID-19 clinical trials. Other investigators have demonstrated the ability for Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells. Currently, COVID-19 trials with a number of hepatitis C drugs, such as EPCLUSA, and the combination of Sofosbuvir and Daclatasvir are ongoing in several countries. The study notes that recent preprint from UC Berkeley indicates that a combination of Remdesivir and EPCLUSA increase Remdesivir’s efficacy 25-fold in inhibiting SARS-CoV-2, which offers a molecular basis supporting study of EPCLUSA in combination with Remdesivir for COVID-19 clinical trials. DOI: 10.1038/s41598-020-73641-9

Setting up ‘COVID-19’ free hospital areas for surgical patients could reduce the risk of death from lung infections associated with the virus, according to a new global study led by researchers at the University of Birmingham. Experts from over 130 countries examined data from 9171 patients in 55 countries from the start of the pandemic up to the middle of April 2020, and they found that pulmonary complication and death rates were lower, 2.2% vs 4.9% and 0.7% vs 1.7% respectively, for those patients treated in coronavirus free areas. The group has published its findings in the Journal of Clinical Oncology, noting that setting up these areas could prevent 6,000 unnecessary COVID-related deaths after cancer surgery in the UK alone over the next year. DOI: 10.1200/JCO.20.01933

Previous infection with a non-SARS-CoV-2 coronavirus may lessen severity COVID-19. The study, led by researchers at Boston Medical Center, looked at electronic medical record data from COVID-19 patients who had previously tested positive for a coronavirus and discovered that these patients had significantly lower odds of being admitted to the ICU and lower trending odds of requiring mechanical ventilation. However, a previous positive test result for a coronavirus did not prevent someone from getting infected with COVID-19. This provides important insight into the immune response against SARS-CoV-2 and could have significant implications of vaccine development. Research on this is published in the Journal of Clinical InvestigationDOI: 10.1172/JCI143380

New study published online by Cancer Cell represents the most comprehensive scientific survey to date about the interrelationship between COVID-19 and cancer. The report by researchers at Dana-Farber Cancer Institute and other institutions, reveals that while COVID-19 has complicated cancer treatment, it has also benefitted from insights gained over years of cancer research. A variety of drugs used to alleviate cytokine release syndrome in cancer patients, a side effect of some cancer therapies, are being evaluated for effectiveness against cytokine storm in patients with COVID-19. On the negative side, studies have shown a sharp decline in cancer diagnoses and some cancer centers halted enrollment on clinical trials entirely during the height of the pandemic. DOI: 10.1016/j.ccell.2020.09.018

Brain fog’ and other neurological symptoms after COVID-19 may be due to post-traumatic stress disorder (PTSD). A review of data from the SARS and MERS outbreaks showed that survivors had heightened risk for PTSD and symptoms from this may arise in response to invasive measure needed, including intubation and ventilation, to treat some COVID-19 patients. Frontline health-care workers can be similarly affected due to constant stress and fear they face at work. Researchers are still working to understand the direct neurological effects of COVID-19. This co-authored paper was published in The Clinical Neurophychologist. DOI: 10.1080/13854046.2020.1811894 

A research team in China suggests that there is a fourth defensive measure against COVID-19: eyeglasses. Their retrospective study of 276 people who tested positive for SARS-CoV-2 virus found that the proportion of patients who wore eyeglasses more than eight hours per day were significantly lower than the general population. Experts at John Hopkins Medicine reviewed this study and commented that the study looks at the very beginning of the pandemic before universal masking and social distancing became common prevention practices, but that more studies using data from people who previously had COVID-19 and those newly diagnosed would be valuable to confirm the study’s findings. Commentary on the study appears in JAMA Ophthalmology. DOI:10.1001/jamaophthalmol.2020.3909

A global network study including more than 34,000 patients hospitalized with COVID-19 found that these patients were more likely male, younger, and (in both the US and Spain) had fewer comorbidities and lower medication use than those hospitalized with influenza. Many of the COVID-19 patients hospitalized did have other health conditions, such as hypertension (24-70%), diabetes (13-43%), and asthma (4-15%), but despite this, when compared to patients hospitalized with influenza in recent years, those with COVID-19 were seen to generally be healthier. COPD, CV disease and dementia were all more common among hospitalized influenza patients. This study initiated by the Observational Health Data Sciences and Informatics (OHDSI) community was published in Nature Communications. DOI: 10.1038/s41467-020-18849-z 

Individuals with rare inherited immune disorders, or primary immunodeficiency (PID), infected with SARS-CoV-2 were found to have similar outcomes to the general population. Research led by the Garvan Institute of Medical Research and KU Leuven, followed outcomes of 94 PID patients with COVID-19 and reported higher admission rates to the ICU and average age lower in those patients, however the mortality rate (9.6%) was within the range of global data for those not affected by PID (1-20%). More than half the patients surveyed (56%) had a deficiency in their ability to produce antibodies, and these patients had a similar outcome to the rest of the cohort. Findings also revealed that patients with gene defects that resulted in the body being unable to respond to the pro-inflammatory effects of interleukin 6 (IL-6), developed little or no disease when infected with SARS-CoV-2. This suggests that certain forms of immune suppression, which reduce the function of IL-6, are protective against the pathological effects of cytokine storm frequently observed in COVID-19 patients. The researchers published the findings in Journal of Allergy and Clinical Immunology. DOI: 10.1016/j.jaci.2020.09.010

In some patients who have died with severe COVID-19 and respiratory failure, a jelly formed and filled the lungs that resembled the lungs of someone who had drowned. A new study by a group of researchers at Umea University have established what the active agent in the jelly is: hyaluronan. Hyaluronan is normally found in the human body and acts as a useful characteristic in the connective tissue and aides in the early stages of wound healing. Identifying this substance paves way to treatment options such as using a drug called Hymecromone (used to slow down the production of hyaluronan in other diseases such as gallbladder attacks) and cortisone. Cortisone reduces the production of this jelly-like substance as shown in a preliminary study when using the drug Dexamethasone in severely ill COVID-19 patients. This new research is published in the Journal of Biological Chemistry. DOI: 10.1074/jbc.AC120.015967

Three international cardiovascular (CV) outcomes trials are currently underway examining the cardioprotective effects of different influenza vaccine formulations and may provide insight to developing and evaluating vaccine strategies for COVID-19. CVD patients or those at risk for CVD with COVID-19 have an increased case fatality ratio, including 6% for hypertension, 7.3% for diabetes and 10.5% for CVD. Comparatively, overall case fatality ratio is around 2.3%. Influenza has the best evidence of a safe vaccine option for cardiovascular risk reduction to date and may further help prevent CV complications of COVID-19. This review is published in the Journal or the American College of Cardiology. DOI: 10.1016/j.jacc.2020.08.028 

Findings from the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial conducted at 176 UK hospitals does not support the use of lopinavir-ritonavir to treat patients admitted with the virus. Results published in The Lancet, reported that using lopinavir-ritonavir to treat patients does not reduce deaths within 28 days of treatment beginning. 23% who received the anti-viral medication died within 28 days when compared to 22% mortality rate of those given usual care. The WHO has halted lopinavir-ritonavir treatment groups involved in its SOLIDARITY trial, as they reported their interim results were in line with these findings. DOI: 10.1016/S0140-6736(20)32013-4

The Blagosklonny Research Team reviews in Aging-US the reasons why COVID-19 vulnerability is an age-dependent syndrome, linking it to other age-related diseases. The authors contend that at its deepest level, aging is driven by inappropriately high cellular functioning. They go on to highlight that an anti-aging intervention, such as rapamycin (an anti-inflammatory agent), may slow aging and therefore potentially decrease COVID-19 vulnerability. Cytokine storm and hyper-inflammation is the main cause of the death in COVID-19 pneumonia and this agent may inhibit hyperfunctions, cellular senescence and decrease secretion of cytokines in those patients, according to this research. DOI: 10.18632/aging.103493 

The frequency of blood pressure and cholesterol assessments has dropped by about 50% and 37%, respectively, amid COVID-19 pandemic. The study published in JAMA Network Open and led by researchers at John Hopkins Bloomberg School of Public Health, found that despite an unprecedented surge in telemedicine use, primary care consultations dropped by 21.4 percent from the second quarters of 2018 and 2019 to the first full quarter following the start of the pandemic. These findings raise serious concerns on the prevention of heart attacks and strokes. DOI: 10.1001/jamanetworkopen.2020.21476

Face mask wearing not shown to have any harmful effects on patients with chronic obstructive pulmonary disease (COPD), according to a study published in the Annals of the American Thoracic Society. After concern was raised about potential adverse effects on gas exchange under a facial covering, researchers found that the effects are minimal even in those with severe COPD. Dyspnea, or shortness of breath, may be experienced with increased exertion, but the solution to this would be to slow down. Benefits greatly outweigh any risks when it comes to COPD patients wearing face masks and should be done along with hand washing and social distancing to reduce the risk of infection of COVID-19. DOI: 10.1513/AnnalsATS.202007-812RL

Researchers from the University of Iowa Health have found that people with Parkinson's disease (PD) have a 30% higher risk of dying from COVID-19 compared to individuals without this neurodegenerative condition, as reported in Movement Disorders. The reason may be the increased risk of developing pneumonia when infected with COVID, and pneumonia is the leading cause of death in PD patients. These findings should be considered when forming a plan of care for PD patients, the authors say, and utilizing telehealth visits may be beneficial. They’re also confident that a diagnosis of PD should be considered an independent risk factor for death from COVID-19. DOI: 10.1002/mds.28325

COVID-19 pandemic is taking a heavy toll on mental health, even on those not directly impacted by the virus, according to a study published in Frontiers of Psychiatry. Researchers in Australia surveyed nearly 1300 adults that included a representative distribution of the population and found that participants experienced twice as much depression and anxiety despite low rates of infection and fatalities in the country. Of the 36 participants that received a COVID-19 diagnosis or had a close contact diagnosed, none reported a link to mental health impact. Financial distress and disruptions to work and social activities were significantly associated with symptoms of depression and anxiety. Working from home was not associated with any negative effects. Higher rates of mental health symptoms were reported in those who were younger, identified as female or had a pre-existing mental health condition. DOI: 10.3389/fpsyt.2020.579985

A paper published by the Journal of General Internal Medicine suggests that an effective vaccine for COVID-19 may not be available to the general public in the U.S. and Canada until September/October 2021, based on a survey conducted with 28 vaccinology experts. The soonest predicted date was June 2021 and the latest July 2022; but for those at the highest risk from the virus, availability could be as early as March/April 2021. One-third of the experts also believe that vaccine development could face many potential setbacks, including a boxed warning from the FDA to highlight serious or life-threatening adverse reactions on the first widely deployed vaccine and inefficacy or negative effects reported from the first large trial. DOI: 10.1007/s11606-020-06244-9

The use of hydroxychloroquine in organ transplant patients with COVID-19 infection was found to increase risk of death by 10 times when compared to not using the treatment. The study conducted out of the University of Michigan and published in Transplantation looked at the outcomes of both solid organ transplant patients and non-transplant patients based on their treatments. It also highlighted the racial inequalities in the U.S. Researchers found the severity of COVID-19 infection in organ transplant and non-transplant patients to be similar, only with organ transplant patients needing more kidney support through renal replacement therapy. In contrast, when looking at the demographics of their patients, they found that two-thirds of their COVID-19 positive patients who had received a solid organ transplant were black, when typically black patients only account for one-tenth of the recipients at the University of Michigan Transplant Center. DOI: 10.1097/TP.0000000000003447

Researchers out of the University of Tennessee Health Science Center, along with MD Anderson Cancer Center of Houston, have found that some antibodies are more protective than others when it comes to COVID-19. A test procedure developed 25 years ago to study Ebolavirus was applied to the infection of and subsequent immunity produced against the COVID-19 virus, specifically looking for neutralizing antibodies that can prevent reinfection. The findings were published in JCI Insight. Current available assays that detect antibodies against COVID-19 only provide a positive or negative result, which does not equal immunity from reinfection. Further research is needed to determine how much neutralizing antibodies are needed to prevent infection or reinfection. DOI: 10.1172/jci.insight.142386

A meta-analysis performed out of the Medical University of Vienna and published in the Research and Practice in Thrombosis and Haemostasis has found that nearly half of all patients hospitalized with COVID-19 developed deep vein thrombosis when routinely screened using ultrasound. Overall risk of developing venous thromboembolism (VTE) was also significantly higher. Overall, VTE risk was 14%, although thromboprophylaxis regimens were frequently used. The highest rate was found in intensive care unit patients with 23% suffering from VTE, while patients in a general ward suffered VTE in 8% of the cases. Risk for a pulmonary embolism was 10% to 18% in patients requiring intensive care. DOI: 10.1002/rth2.12439

 

Industry Updates

A recent survey conducted by SubjectWell and Reify Health found that 51% of patients have concerns about their health and safety at in-office visits. In direct response to this feedback, the 268 clinical trial site partners polled reported 96% increase in sanitation procedures and 91% and 93%, respectively, have implemented protocols to keep infected patients and infected staff at home. The joint survey shows importance to ease concerns to continue clinical trials amid COVID-19 pandemic. Press Release

Clinicians and researchers from Brigham and Women’s Hospital, the Broad Institute of MIT and Harvard, and the MGB Center for COVID Innovation are launching TestBoston, a large-scale research study to detect active COVID-19 cases and evidence of previous infection. Over the course of six months, participants will be sent monthly at-home test kits for viral and antibody testing. The study aims to detect when clusters of COVID-19 are on the rise again throughout the fall and winter in the greater Boston area and learn more about whether prior infection provides any protection against subsequent re-infection. TestBoston will invite participation of patients who have been seen at any Brigham site within the past year and live within a 45-mile radius of Boston. Press Release

UK government funding, awarded from the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI), will help researchers develop an innovative online program to improve and personalize care for dementia patients in care homes, which have been hit hard by the COVID-19 pandemic. The study will draw on the most successful elements of their Improving Wellbeing and Health for People with Dementia (WHELD) program, one of the few staff training programs that is proven to improve lives for people with dementia in care homes. These patients may experience increased anxiety and depression, as they might not be able to see loved ones and see staff in full PPE without fully understanding the reasons for these changes. This in turn is expected to lead to poorer physical health and well-being. The program will be made available to 160 care homes within four weeks and the team will evaluate outcomes before implementing a national care home roll-out. Press Release

Eleven academic institutions and their community partners across California have received a $4.1 million grant from NIH for a statewide community-engaged approach to addressing COVID-19 among those communities at risk. Investigators at UCLA will lead the coalition, called STOP COVID-19 CA, and plan to run in-depth virtual focus groups with multiethnic communities to identify barriers and challenges to inclusive vaccine development and vaccination. Another project would assess racial and ethnic attitudes among high-risk veterans that might prevent them from accepting a potential vaccine. The NIH grant is for one year and began Sept. 9, 2020. Press Release 

Children tested for COVID-19 using a polymerase chain reaction (PCR) test prior to receiving anesthesia saves extensive personal protective equipment (PPE). The research presented by the American Society of Anesthesiologists at the ANESTHESIOLOGY® 2020 annual meeting showed a reduction of 70% in wearing expanded PPE when using PCR testing instead of a verbal screening. This links the importance of universal testing to experience similar PPE and safety benefits in other treatment centers. Press Release 

Israel’s Sheba Medical Center has opened one of the first pediatric COVID-19 wards in the world. Children who test positive for COVID-19 are often placed in general virus wards that lack bright décor and kid-friendly activities needed to help both a child’s psychological and physical wellbeing. Sheba has designed a children’s facility with playrooms, entertainment, and even access to teachers and clowns in hazmat suits. Most importantly, the new ward can accommodate twelve children and their parents, meaning that a child will always have family by their side. Press Release

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