July 10, 2020 | The mental health burden associated with COVID-19 is considerable among the general population of China, highlighting the demand for interventions. Elsewhere, the National Institute of Standards and Technology has released a new material that can aid in the evaluation and development of diagnostic assays for SARS-CoV-2. This, plus more, are included in this week’s COVID-19 news and research in the diagnostics industry.
A case-series study reports on four children at the Great Ormond Street Hospital for Children (London) with COVID-19 presenting with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. The study, published in JAMA Neurology, concludes that the diagnosis should be considered within the differential diagnosis of splenial lesions. Neurological improvement was seen in all patients in the study, with two making a complete recovery. DOI: 10.1001/jamaneurol.2020.2687
The mental health burden associated with COVID-19 is considerable among the general population of China, highlighting the demand for interventions—especially among infected individuals, people with suspected infection, and people who might have contact with patients with the novel coronavirus. The survey study, published in JAMA Network Open, found that 27.9% of 56,679 respondents had symptoms of depression, 31.6% had symptoms of anxiety, 29.2% had symptoms of insomnia, and 24.4% had symptoms of acute stress during the outbreak. DOI: 10.1001/jamanetworkopen.2020.14053
A clinical-grade wearable developed by researchers at Northwestern University and the Shirley Ryan AbilityLab (Chicago) that streams COVID-19 symptom data to physicians is described in an article in Science Advances. The device sits just below the suprasternal notch (the visible dip at the base of the throat)—an ideal location for monitoring respiratory health. The device has recently been paired with a flexible pulse oximeter to continuously monitor for silent hypoxia to provide a fuller picture of the disease's onset, progression and response to treatment. It has an embedded temperature sensor to measure fever, counts coughs and monitors their intensity, and tracks heart rate via mechanical signatures of blood flow. Testing both in the hospital and the home have generated 3,000 hours of data, which will continue to strengthen the device's machine learning algorithms. The goal is to train the algorithms to distinguish between a COVID-like cough and more benign coughs from allergies, colds or dryness. The team expects to test 500 subjects by the end of the year. It is already actively being tested on pulmonary patients at Northwestern. Sonica Health launched to accelerate manufacturing and deployment. The startup previously partnered with the Biomedical Advanced Research Deployment Authority to focus on chronic obstructive pulmonary disease and the partnership expanded to focus on early detection of respiratory infections in high-risk clinical populations. The pulse oximetry sensor is the result of a collaboration with another Northwestern spinout, Sibel Health. The companies will jointly submit the device and associated algorithms for FDA approval later this month. DOI: 10.1126/sciadv.abd4794
A research review published in The BMJ finds major weaknesses in the evidence base for COVID-19 antibody tests. The evidence is particularly weak for point-of-care tests and does not support their continued use, the researchers say. Findings were based on 40 eligible studies, most (70%) from China. Half of the studies were not peer reviewed and most were found to have a high or unclear risk of bias; only four included outpatients and two evaluated tests at the point of care. Sensitivity results for each study, when pooled together, ranged from 66% to 97.8%, and pooled specificities ranged from 96.6% to 99.7%. Pooled sensitivities were consistently lower for the lateral flow immunoassay, a point-of-care method that is being considered for “immunity passports.” Pooled sensitivities were also lower with commercial test kits compared with non-commercial kits and in the first and second week after symptom onset compared with after the second week. DOI: 10.1136/bmj.m2516
A study in Archives of Disease in Childhood points to a “silent pandemic” of domestic child abuse, with researchers at the Great Ormond Street Hospital for Children reporting new cases of head injury rising 1493% between March 23 and April 23, 2020 relative to the same period in each of the previous three years. Ten children (six boys and four girls), ranging from 17 days to 13 months old, presented for treatment of suspected abusive head trauma in the most recent one-month period. The symptoms prompting a hospital visit included colic in five of the infants; breathing issues and loss of consciousness in four; seizures in two; extensive bruising in five; swollen scalp in five; and marks caused by repeated picking at the skin in one child. The infants' families all lived in areas of significant social and economic deprivation; two of the parents had a history of criminal activity, three had mental health issues, and four had financial worries. DOI: 10.1135/archdischild-2020-319872
A study published in the British Journal of Dermatology provides evidence in support of the link between “COVID toes”—red sores or lesions on the feet and hands in children and young adults—and COVID-19. Investigators in Spain found that the SARS-CoV-2 virus was present in skin biopsies in children with symptoms of COVID toes, despite negative results from traditional tests. Analyses detected the virus in skin's blood vessel endothelial cells, as well as in the sweat glands. Electron microscopy in one biopsy also found evidence of viral particles within endothelial cells. DOI: 10.1111/bjd.19327
A prospective, survey-based study published in JAMA Otolaryngology - Head & Neck Surgery has found that smell and taste impairment completely resolved in 48.7% of 202 mildly symptomatic adult patients with COVID-19 at four weeks from the onset. Another 40.7% reported an improvement in the severity and 10.6% reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection. The study was conducted at Treviso Regional Hospital (Italy) between March 19 and March 22, 2020. DOI: 10.1001/jamaoto.2020.1379
A study involving 16 COVID-19 patients with oxygen levels as low as 50%, without shortness of breath or dyspnea, found that several pathophysiological mechanisms account for most (if not all) cases of “silent” or “happy” hypoxemia. This understanding of the condition could prevent unnecessary intubation and ventilation in patients. The researchers, from Hines Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, note that assessing a patient's oxygen level with a pulse oximeter is remarkably accurate when oxygen readings are high but can markedly exaggerate the severity of low levels of oxygen. The brain also does not respond until oxygen falls to very low levels, which is typically when patients become short of breath. In addition, more than half of the patients had low levels of carbon dioxide, which may diminish the impact of an extremely low oxygen level. It’s possible that the coronavirus is exerting a peculiar action on how the body senses low levels of oxygen, which could be linked to the lack of smell experienced by two-thirds of COVID-19 patients. Results published online in the American Journal of Respiratory and Critical Care Medicine. DOI: 10.1164/rccm.202006-2157CP
Testing of oropharyngeal secretions (OS) may reduce the number of false negative results from nasal swab testing of patients who have seemingly recovered from COVID-19, according to a study that published in the Journal of Dental Research. The first-of-its-kind prospective study by researchers at Huazhong University (China) included 75 ready-for-discharge COVID-19 patients who tested negative using two consecutive nucleic acid amplification testing (NAAT) of viral samples retrieved with nasopharyngeal swabs (NPS). Because potential false-negatives were detected in that cohort, NAAT results of paired OS and NPS samples collected from 50 additional COVID-19 recruits during their recovery stage were used in a second prospective study to compare the diagnostic values of the two viral RNA sampling methods. OS obtained from two subjects in the first study yielded positive results for SARS-CoV-2 nucleic acid; in the second study, OS samples were significantly more sensitive for detection of the virus than NPS samples, missed 14% versus 59% of positive cases. DOI: 10.1177/0022034520940292
Neurological complications of COVID-19 can include delirium, brain inflammation, stroke and nerve damage, according to a study led by University College London and University College London Hospitals (UCLH) researchers and published in Brain. One rare and sometimes fatal inflammatory condition, known as acute disseminated encephalomyelitis (ADEM), appears to be increasing in prevalence due to the pandemic. Some patients in the study did not experience severe respiratory symptoms, and the neurological disorder was the first and main presentation of the virus. The study provides a detailed account of neurological symptoms of 43 people (aged 16-85) treated at the National Hospital for Neurology and Neurosurgery at UCLH who had either confirmed or suspected COVID-19. Among these were 10 cases of transient encephalopathies (temporary brain dysfunction) with delirium, 12 cases of brain inflammation, eight cases of strokes, and eight others with nerve damage (mainly Guillain-Barré syndrome). Most of those with brain inflammation conditions were diagnosed with ADEM. DOI: 10.1093/brain/awaa240
Among 147 cases of confirmed COVID-19 in King County, Washington, receiving emergency medical services between Feb. 1 and March 18, 2020, 29.3% had no symptoms of fever, cough, or shortness of breath, according to a study from Seattle-based researchers that published in JAMA Open Network. Fever, tachypnea, or hypoxia were present, respectively, in 51.2%, 32.1% and 53.6% of patients. As of June 1, mortality among the study cohort was 52.4%. Most were older and had multiple chronic health conditions. Findings suggest that the conventional description of febrile respiratory illness may not adequately identify COVID-19 in the prehospital emergency setting. DOI: 10.1001/jamanetworkopen.2020.14549
Johns Hopkins researchers examined the characteristics of SARS-CoV-2 antibodies among 11,066 patients to determine the clinical validity and utility of SARS-CoV-2 antibodies. Of those, 115 patients were hospitalized and investigated for COVID-19 and a clinical record review was performed to classify them into either a COVID-19 case group or a non-COVID-19 control group and then compared to a laboratory control group. The researchers surmised that antibodies to SARS-CoV-2 demonstrate infection when measured at least 14 days after symptom onset, associate with clinical severity, and provide valuable diagnostic support in patients who test negative by nucleic acid amplification test on nasopharyngeal swabs but remain clinically suspicious for COVID-19. Results published in the Annals of Internal Medicine. DOI: /10.7326/M20-2889
Cleveland Clinic researchers report in JAMA Network Open that they have found a significant increase in patients experiencing stress cardiomyopathy (aka broken heart syndrome) during the COVID-19 pandemic. Patients typically experience symptoms such as chest pain and shortness of breath, but usually do not have acutely blocked coronary arteries. The left ventricle of the heart, however, may show enlargement. Other symptoms include irregular heartbeat, fainting, low blood pressure and cardiogenic shock. For the study, cardiologists looked at 258 patients coming into Cleveland Clinic and Cleveland Clinic Akron General with acute coronary syndrome (ACS) between March 1 and April 30, 2020 and compared them with four control groups of ACS patients prior to the pandemic. Diagnosis of stress cardiomyopathy rose from a pre-pandemic level of 1.7% to 7.8% among the 258 patients, who also had a longer length of hospital stay than those hospitalized in the pre-pandemic period. All patients diagnosed with stress cardiomyopathy tested negative for COVID-19. DOI: 10.1001/jamanetworkopen.2020.14780
Researchers from the University of Houston and Medistar Corporation report in Materials Today Physics that they have designed a "catch and kill" nickel foam air filter that can trap the virus responsible for COVID-19, killing it instantly. In testing at the Galveston National Laboratory, run by the University of Texas Medical Branch, they found 99.8% of SARS-CoV-2 was killed in a single pass through the filter when heated to 392 degrees Fahrenheit. It is reportedly compatible with conventional heating, ventilation and air conditioning systems. High-priority venues—including hospitals and healthcare facilities—would be in the initial roll-out of the device. DOI: 10.1016/j.mtphys.2020.100249
A pair of studies appearing in the Clinical Journal of the American Society of Nephrology have found that most kidney transplant recipients with COVID-19 do not need to be hospitalized, and that patients on dialysis who develop COVID-19 may have symptoms that are different from other patients with the infectious disease. Researchers for the first study, who are clinicians at Columbia University Medical Center, describe their experience with 41 patients with confirmed or suspected cases COVID-19, 32% of whom required hospitalization. These patients were more likely to have shortness of breath and higher levels of a blood marker for impaired kidney function. Notably, there was also wide variation in the amount of time it took patients to improve. The other study, led by an investigator from Tongren Hospital of Wuhan University, looked at 49 hospitalized dialysis patients and 52 hospitalized patients without kidney failure with confirmed COVID-19. Among patients on dialysis, most common symptoms were fatigue and anorexia, with fever and cough being less common. Common complications including shock, acute respiratory distress syndrome, arrhythmia, and acute cardiac injury were also significantly higher in patients on dialysis; also, 14% of patients on hemodialysis died versus 4% of controls. DOI: 10.2215/CJN.05170420 (story one) and DOI: 10.2215/CJN.04160320 (story two).
Existing public health monitoring systems in the U.K. could improve understanding of the risk factors associated with severe COVID-19, according to research published in Microbial Genomics. The authors describe how national surveillance systems can be linked with the UK Biobank (UKB) and this pooled data could then be used to understand how genetics and other epidemiological factors impact the risk of developing severe infection. To facilitate their research, they linked UKB with Public Health England's Second-Generation Surveillance System (SGSS) that holds data collected in clinical diagnostic laboratories in England. Their new computerized system will provide weekly linkage of test results to UKB and other cohorts. DOI: 10.1099/mgen.0.000397
Using data covering a longer period than previously reported, researchers report in The Journals of Gerontology that ApoE e4e4 genotype is associated with COVID-19 test positivity at genome-wide significance in the UK Biobank. Similarly, the e4e4 genotype was associated with a four-fold increase in mortality after testing positive for COVID-19. The findings demonstrate that risks for COVID-19 mortality are not simply related to advanced chronological age or the comorbidities commonly seen in aging. DOI: 10.1093/gerona/glaa169
A review published in The Lancet Neurology and led by University of Liverpool researchers has shown that cases of brain complications linked to COVID-19 are occurring across the globe. Strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease. The review found almost 1,000 patients with COVID-19-associated brain, spinal cord and nerve disease. One particularly concerning complication linked to COVID-19 is encephalitis. DOI: 10.1016/S1474-4422(20)30221-0
Updates from Industry
NIST has released a new material that can aid in the evaluation and development of diagnostic assays for SARS-CoV-2. This material consists of two synthetic RNA fragments from the SARS-CoV-2 genome that include the targets of many molecular diagnostic tests. The RNA fragments are characterized for concentration using digital PCR and can be used to assess the limits of detection for assays and to calibrate other in-house or commercial SARS-CoV-2 controls. We are offering a unit of this material at no cost to research institutions, testing laboratories and commercial vendors of assays/controls and are requesting feedback on its utility and suitability. More information.
LabCorp has launched LabCorp At Home COVID-19 Test Collection Service, the first seamless digital service aimed at helping doctors protect patients by testing them for COVID-19 before surgeries and other important treatments. The service received Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) on July 1, 2020. The service enables a doctor to directly order a LabCorp At Home COVID-19 test collection kit for their patient through a digital interface with LabCorp. Once the order is placed, LabCorp will send the COVID-19 kit to the patient, who will perform the sample collection using a nasal swab and send it back to LabCorp via FedEx. LabCorp will then deliver the patient’s test results to the healthcare provider’s electronic medical record (EMR) and the patient’s LabCorp Patient Portal, making the process seamless for the doctor and patient. The result provides the doctor the information needed to make the appropriate clinical decision prior to proceeding with surgery or other treatment. LabCorp is piloting the service with select providers initially, and plans to make the service available to more health systems, hospitals, and surgical centers through the providers’ EMRs in coming weeks. Press release.
The Korea Institute of Machinery & Materials (KIMM) reports that it has developed a remote specimen collection robot that collects samples from the upper airway of people presenting symptoms, eliminating the need for direct contact between medical personnel and patients. The robot system is composed of a master device controlled by medical personnel and a slave robot, equipped with a disposable swab that retrieves samples from the nose and mouth of patients. It also supports video and audio communication between patients and physicians. Press release.
The newest release of Logical Observation Identifiers Names and Codes (LOINC) by the Regenstrief Institute adds 1,231 new standardized terms, including about 150 codes related to the coronavirus. The codes are crucial to facilitating tracking of the virus by allowing records to be seamlessly exchanged between health systems and public health entities around the world. LOINC has users in 179 countries. The new LOINC release also includes hundreds of new terms for laboratory and clinical test results as well as survey and questionnaire responses, including surveys related to critical issues such as food security and other social determinants of health. The LOINC codes are free and available for download. Press release.