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Cell-Free Antibody Test, Ultrasounds Show Cardiac Impact, Acuity Score Predicts Outcomes: COVID-19 Updates

October 30, 2020 I Organs-on-Chips technology to evaluate potential vaccines, COVID-19 associated strokes, recovered patients may be asymptomatic carriers, metabolites identified as biomarkers, frontal lobe involvement in abnormal EEGs, and antibodies detectable for several months. Plus: AI-based algorithm predicts acute kidney injury, PerkinElmer screens for COVID-19 and flu in single test, faster more efficient antibody test by U-M scientists, and NYC outbreak linked to European strains of the virus.

 

Research News

Computed tomography angiogram (CTA) scans could provide earlier detection of COVID-19 in stroke patients, finds new research published in Stroke: Journal of the American Heart Association. The study found that CTA scans in combination with patient-reported COVID-19 symptoms were able to diagnose SARS-CoV-2 with 83% accuracy before a nasal swab test could provide results. This research was conducted retrospectively on 57 patients treated for acute ischemic stroke (AIS) at three hospitals in the Bronx between March and April and received a CTA scan within 24 hours of hospitalization. 30 of the 57 patients included in the study were positive for COVID-19. DOI:10.1161/STROKEAHA.120.030959

New research conducted by the Stroke Research Group at the University of Cambridge finds that stroke occurs in 14 out of every 1,000 COVID-19 patients admitted to the hospital. The study, published in the International Journal of Stroke, analyzed 61 studies with more than 100,000 patients admitted to the hospital with COVID-19. Among those stroke victims, the most common was acute ischemic stroke which occurred in 12 out of every 1,000 cases. Age (average 4.8 years older), pre-existing conditions (particularly high blood pressure), and severity of infection were all found to be risk factors of developing stroke with SARS-CoV-2. The researchers attribute COVID-19 associated strokes to blood coagulation, inflammation in blood vessel linings, and over-reaction of the immune system triggering ‘cytokine storm’. DOI:10.1177/1747493020972922

Nearly 17% of recovered COVID-19 patients could still be asymptomatic carriers of the virus, finds a new study published in the American Journal of Preventative Medicine. The study included 131 patients who met criteria for discontinuing quarantine at least two weeks before their follow-up visit. These criteria, specified by the World Health Organization (WHO), were no fever without fever-reducing medications for three days, improvement in any symptoms related to COVID-19, be more than seven days past onset of symptoms, and test negative for SARS-CoV-2 twice at least 24 hours apart with RT-PCR testing. In these patients, a new RT-PCR test was administered at the time of post-acute care admission and 22 patients tested positive again (16.7%). Researchers also found that persistence of sore throat and rhinitis were associated with those SARS-CoV-2 positive patients. DOI:10.1016/j.amepre.2020.08.014

University of California, Irvine researchers in partnership with the Orange County Health Care Agency have found that 11.5% of Orange County residents have antibodies for COVID-19, compared to the previous estimates of less than 2%. Researchers tested a representative sample of OC residents for this study, call the actOC project. Rates were highest among Latino and low-income residents (17% and 15%, respectively). The study confirms the concerns over inequalities during this pandemic and researchers recommend improved strategies for testing access to all communities. The team plans to follow up with a subset of 200 people who have SARS-CoV-2 antibodies every two weeks for four months to look at their immune response over time. This study is published on the pre-print server site MedRxiv. DOI:10.1101/2020.10.07.20208660

Three specific metabolites have been identified that could act as biomarkers to quickly screen patients for COVID-19 and predict the risk of death from infection. A new study, published in Critical Care Explorations, performed metabolomics profiling on blood samples from 30 patients: 10 with COVID-19, 10 with other infections, and 10 healthy control patients. The research team discovered that concentrations of kynurenine and arginine could distinguish SARS-CoV-2 positive patients from other critically ill or healthy patients with 98% accuracy. Additionally, they found that creatinine and arginine could help predict which severe COVID-19 patients had the greatest risk of dying. The authors of this study hope that along with using these biomarkers to diagnose COVID-19, that replenishing these specific metabolites in patients could act as a secondary therapy. DOI:10.1097/CCE.0000000000000272

One-third of COVID-19 patients given an electroencephalogram (EEG) had abnormal neuroimaging in the frontal lobe of the brain, new research finds led at Baylor College of Medicine and the University of Pittsburgh. The researchers collected more than 80 studies focusing on EEG abnormalities and analyzed the data to provide a clearer view of how COVID-19 affects the brain. The most common findings were slowing or unusual electric discharge in the frontal lobe and some of the alterations found in COVID-19 patients indicated damage that may not be repairable after recovery. The authors of the study pointed out the location of the frontal lobe being directly next to the entry point of the virus, in the nose. They also noted that the average age of those affected was 61 years old and two-thirds were male. This study is published in Seizure: European Journal of Epilepsy. DOI:10.1016/j.seizure.2020.10.014

A new AI-based score, called the COVID-19 Acuity Score (CoVA), predicts which patients are most likely to develop complications and require hospitalization. A team of experts from Massachusetts General Hospital (MGH) along with machine learning designed this score based on input from information on 9,381 adult patients treated at MGH’s clinics and emergency department between March and May 2020. The model was then tested in another 2,205 patients and demonstrated accuracy in predicting which patients would require hospitalization, experience critical disease or death. The top five predictors for CoVA were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status and respiratory rate. This study is published in The Journal of Infectious Diseases. DOI:10.1093/infdis/jiaa663

Researchers at Icahn School of Medicine at Mount Sinai have shown the cardiac impact of COVID-19 through ultrasounds. The study, published in the Journal of the American College of Cardiology, looked at transthoracic electrocardiographic (TTE) and electrocardiographic (ECG) scans from 305 hospitalized adult patients with COVID-19 between March and May 2020 (median age 63 years old). 190 (62.6%) of those patients had evidence of myocardial injury – 118 patients had heart damage upon admission and 72 patients developed cardiac injury during hospitalization. Patients with myocardial injury had more EKG and TTE abnormalities and higher inflammatory biomarkers than those patients without cardiac injury. Furthermore, researchers looked at troponin levels in these patients and 31.7% showed troponin elevation who also had myocardial injury and EKG abnormalities, giving these patients the worse prognosis. Researchers added that follow-up for these patients will be critical. DOI:10.1016/j.jacc.2020.08.069

New research led at NYU Grossman School of Medicine traces the origins of New York City’s SARS-CoV-2 outbreak and shows that the virus first appeared in late February and closely matches strains from Europe or other states in the U.S. rather than those from China. The study, published in Genome Research, collected viral genetic information on 864 nasal swabs from COVID-19 positive individuals in New York between March 12 and May 10. The researchers then compared the gene sequences of the virus from those samples to the original strain isolated last winter from Wuhan, China patients. This revealed not only that these strains did not closely match those from China, but that the virus stemmed from at least 109 different sources rather than from a single infected person. Authors of the study also noted that 95% of New Yorkers with COVID-19 had a strain with a mutation, making it easier to transmit to others. DOI:10.1101/gr.266676.120

A group of doctors is calling on the UK government to divert funding spent on a privatized test and trace system to local services for better management of the COVID-19 pandemic. The authors of the paper, published in the Journal of the Royal Society of Medicine, say that the government has overlooked the importance of clinical insight and distributing funds to local primary care and public health services would allow for clinical interpretation with more accurate diagnosis and protocol. Authors also state that current PCR tests have a 29% false negative rate and do not distinguish between current infection and previous exposure to the virus without infectiousness. This results in some false reassurance and unnecessary isolation that could be avoided with clinical expertise. DOI:10.1177/0141076820967906

A UK cohort study, called COVID-19 Social Study, aims to monitor depressive symptoms and severity among at-risk groups during the pandemic. This ongoing study was established on March 21 and data analysis was conducted in May 2020 comprising over 50,000 adults. 33.3% of participants from this sample were in the lowest socioeconomic position (SEP), 22.1% were classified as essential workers, and 12% were Black, Asian, or of a racial minority. Based on participant responses, researchers found that those with low SEP were the most at-risk to experience severe depressive symptoms, as well as those participants with psychosocial and health-related risk factors. These findings are published in JAMA Network Open. DOI:10.1001/jamanetworkopen.2020.26064

COVID-19 antibodies are detectable for up to seven months after infection, a new Portuguese study has found. The research team monitored antibody levels in over 300 COVID-19 hospital patients and healthcare workers and over 200 volunteers who had contracted the virus. Through use of in-house serology testing, they found that 90% of their study subjects had neutralizing antibodies for 40 days up to seven months after contracting SARS-CoV-2. Age did not affect the production of these antibodies, but those with severe disease had higher antibody levels during the acute phase. Men produced more antibodies than women in the first three weeks after symptom onset, however these levels evened out after this early stage. This research is published in the European Journal of Immunology. DOI:10.1002/eji.202048970

A study conducted at Tongji Hospital of Huazhong University of Science and Technology enrolled over 35,000 individuals who had no known history of COVID-19 to screen for antibodies against SARS-CoV-2. Participants were over 18 years old (median age 36) and the serological tests screened for IgM and IgG antibodies. Overall, researchers of this study found a seropositivity rate of 3.9%. This rate was highest among those living in urban districts, in women compared to men, and significantly higher in participants over the age of 60 years old (9.2%). The authors points out several limitations to these findings, such as few participants over the age of 60 and the possibility that low levels of SARS-CoV-2 antibodies may be undetected in population-based studies. This research is published in JAMA Network Open. DOI:10.1001/jamanetworkopen.2020.25717

Researchers have developed a new method that assesses the immune properties of nucleic acid nanoparticles (NANPS) prior to clinical testing. The protocol uses human white blood cells to assess for inflammatory properties of any given NANP design intended to deliver therapeutic nucleic acids. The research, published in Nature Protocols, demonstrated a step-by-step process when using freshly drawn and isolated blood from 100 healthy donors. The process has been validated for more than 60 NANP designs across several labs. The authors note that this protocol is reproduceable and more predictive of cytokine storm than animal models. Article

A scientist from Seattle Children’s Research Institute has developed an innovative way to test for COVID-19 antibodies by using a technique called immunoprecipitation detected by flow cytometry (IP-FCM). Instead of relying on live cells and viruses, IP-FCM uses lab-made proteins and commonly available instruments in commercial labs. This cell-free test can determine immunity overnight as opposed to standard tests that take roughly three days to provide results. 24 participants’ blood samples were tested using IP-FCM, and the test found that 92% of the participants had antibodies to COVID-19 at an average of one month post-infection. These results were validated with 30 control samples. Another interesting find was that those who spiked a fever had higher levels of antibodies. This work is published in The Journal of Infectious Diseases. DOI:10.1093/infdis/jiaa508

A new study, published in Neurology, shows that immune response may be the underlying cause of neural damage in COVID-19 patients, not the virus itself. This study from the University of Gothenburg examined cerebrospinal fluid (CSF) samples from six hospitalized COVID-19 patients that showed signs of brain impairment. The samples were analyzed for biomarkers that reflect the brain’s response to the virus, and every patient exhibited markedly elevated levels of neopterin and beta-2-microglobulin (inflammation markers), suggesting substantial brain immune cell activation. In contrast, no impact was observed on markers for damage to the blood-brain barrier, local antibody productions or raised white blood-cell count, indicating that the virus was likely not present in the CSF samples. DOI:10.1212/WNL.0000000000010977

Asymptomatic children with COVID-19 may carry less viral load than symptomatic children, a new study finds that is published in the Journal of Clinical Microbiology. The study included 339 asymptomatic and 478 symptomatic children (0-17 years old) that were matched by age groups from nine children’s hospitals across the US and Canada. All children were screened using a PCR test. The analysis revealed that even when looking at asymptomatic patients with the highest viral loads (children with diabetes or those in recent close contact with an infected person), the median viral loads were still significantly lower than in the symptomatic group. The authors raise the question of timing and test sensitivity, noting that the PCR test may have missed the peak of the virus in asymptomatic children and that the levels of the virus would have not been detected using a rapid antigen test for many of the asymptomatic children. DOI:10.1128/JCM.02593-20

A team of researchers at Duke University have developed a lab-grown lung model that mimics the air sacs of human lungs. This model has allowed them to observe how SARS-CoV-2 infection attacks the lung cells on a molecular level. Dubbed mini-lungs, these lung organoids are purely human without any helper cells that would interfere with accurate findings. The team plans to next examine a new strain of SARS-CoV-2, called D614G, that has emerged in Italy. A description of this development and early experiments with COVID-19 are published in the journal Cell Stem Cell. DOI:10.1016/j.stem.2020.10.005

A new COVID-19 antibody testing method developed by University of Michigan (U-M) scientists, called “lab on a chip”, can identify COVID-19 antibodies faster and more efficiently than the current ELISA technology. U-M researchers along with Hackensack Meridian Center for Discovery and Innovation (CDI) have demonstrated that this device takes only 15 minutes with just a finger prick’s worth of blood to detect the presence and amount of neutralizing antibodies. This new tool could have particular value for the validation of convalescent plasma as a treatment for COVID-19. These findings are published in Biosensors and Bioelectronics. DOI:10.1016/j.bios.2020.112572

 

Industry News

Emulate announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the FDA to enable agency-wide studies at FDA to use Organs-on-Chips technology to better understand COVID-19 and evaluate safety of potential vaccines. The CRADA studies will use the Human Emulation System from Emulate - comprised of Organ-Chips, instrumentation and software apps – which is able to recreate the natural physiology of human tissues and organs in several research areas. These research areas include a Lung-Chip, Brain-Chip, Intestine-Chip and Liver-Chip. The Lung-Chip will be used to evaluate COVID-19 vaccines and understand the human immune response against SARS-CoV-2. Press Release

PerkinElmer’s PKamp Respiratory SARS-CoV-2 RT-PCR Panel Assay has received the CE-IVD mark for in vitro diagnostic use in more than 30 countries. This multi-analyte assay allows laboratories to conserve resources and simultaneously screen individuals for COVID-19 and the flu in a single test. This PKamp test can detect smaller amounts of viral material in samples, which is critical to detect and differentiate between the two viruses. Press Release

A new model using an artificial intelligence-based algorithm predicts acute kidney injury (AKI) requiring dialysis in COVID-19 patients. Using data from more than 3,000 hospitalized COVID-19 patients, researchers at the Icahn School of Medicine at Mount Sinai trained a model based on machine learning to predict AKI that requires dialysis. This model demonstrated high accuracy and features that were important for prediction, including blood levels of creatinine and potassium, age, heart rate, and oxygen saturation. This research is being presented online during the American Society of Nephrology (ASN) Kidney Week 2020 Reimagined. Press Release

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