Question of COVID-19 contagion window

A small study at Zhongnan Hospital of Wuhan University, China, demonstrated the persistence of the novel coronavirus, COVID-19, and difficulty in determining when people infected with the virus are no longer contagious. The team studied four patients, all medical professionals, who were exposed to the virus between Jan. 1 and Feb. 15, 2020, and evaluated with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid to ascertain when it was safe for them to return to work. For hospital discharge or release from quarantine, they required a normal temperature lasting longer than three days, resolved respiratory symptoms, substantially improved chest CT and two consecutively negative RT-PCR tests administered at least one day apart. The RT-PCR tests were performed using kits from Shanghai Biogerm Medical Technology Co., Ltd., which were recommended by the Chinese Center for Disease Control and Prevention. Both internal and negative controls were performed with each batch of tests. Following two negative RT-PCR test results and release from hospital or quarantine, all four patients were asked to continue home quarantine for five days. Doctors repeated the throat swab RT-PCR tests five to 13 days later and all were positive. Over the next four to five days, the patients had three more RT-PCR tests and all were positive. An additional test with a kit from a different manufacturer produced the same results. “These findings suggest that at least a proportion of recovered patients still may be virus carriers….Current criteria for hospital discharge or discontinuation of quarantine and continued patient management may need to be reevaluated,” the authors wrote. The research letter was published online Feb. 27, 2020, in the Journal of the American Medical Association.

A paper-based, portable coronavirus test

Researchers at Purdue University have developed a hand-held paper-based, point-of-care (POC) platform that quickly and accurately detects MERS-CoV, a strain of coronavirus that first emerged in the Middle East in 2017, even in small samples. The test result can be read directly from the fully portable device. Because it is not specific to any virus, the device could be used to detect the new coronavirus strain, COVID-19. However, producing the devices at scale remains a logistical and costly problem, as the process requires hand-cutting and assembling the paper components. In a study published Feb. 26, 2020, in the journal ACS Omega, the team of biomedical engineers designed a novel two-dimensional paper network (2DPN) that automates the flow of a signal enhancement solution to improve the limit-of-detection of nucleic acid samples labeled with fluorescein isothiocyanate and biotin. The team improved on earlier 2DPN models by decreasing the number of fluidic inputs and detection time and incorporating dry storage for all necessary reagents. The device retains activity after 28 days of dry storage and provides accurate signal enhancement 40 minutes after a sample is applied. “The proof-of-concept for a fully dried, deployable 2DPN shows promise for detecting many other pathogens beyond MERS-CoV and can be employed with other nucleic acid amplification techniques,” the authors wrote. “These results are promising for future applications of this technology at the POC.”

Finding the next pandemic threat early on

Even as public health officials are scrambling, with a decreasing likelihood of success, to prevent COVID-19 from becoming a pandemic, basic researchers are hunting for ways to identify future pandemic threats. Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a platform to rapidly test which coronaviruses were capable of infecting human cells. Beyond SARS, MERS and COVID-19, there are thousands of coronaviruses that infect more than a dozen animal species. To date, there has been no good method to determine which of these strains were capable of infecting humans. The NIAID team developed a platform that could rapidly screen strains, and showed that “several other lineage B coronaviruses are capable of entering human cells through an unknown receptor and that lineage B spike proteins can recombine to gain entry with a known host receptor. Taken together with the latest outbreak…, these findings underscore the importance of continued surveillance of coronaviruses at the sequence and functional levels in order to better prepare for the next emerging virus.” They reported their results in the Feb. 24, 2020, online issue of Nature Microbiology.

Finding the silent majority

Scientists at Stanford University have developed a method to systematically identify silencer regions, expanding the understanding of functions of the noncoding genome. Noncoding regions make up 98% of the entire genome, and the more those regions are studied, the more functions are identified for what was once dismissed as being junk DNA. However, much as the coding genome receives a disproportionate amount of attention, regulatory regions that increase protein production have received disproportionate attention within the noncoding genome. In their work, the team developed a high-throughput screening method and used it to identify more than 5,000 candidate silencer elements for specific genes. In addition to characterizing their genomic locations and epigenetic signatures, they demonstrated that “deletion of silencers linked to drug transporter genes led to transcriptional upregulation of these genes and promoted chemotherapy resistance, suggesting that genetic variation in silencer regions may impact both biology and personalized medicine.” They reported their findings in the Feb. 24, 2020, online issue of Nature Genetics.

Anatomy study reveals schizophrenia subtypes

Researchers at the University of Pennsylvania have used structural MRI measurements in more than 300 schizophrenic individuals and more than 350 controls to identify two distinct subgroups of patients based on changes to grey matter, white matter and cerebrospinal fluid. Schizophrenia is a heterogenous disorder, and understanding its subtypes is likely to be a necessary prerequisite to improving treatment. Schizophrenia is thought to be accompanied by loss of neuronal grey matter throughout the brain, but in their study, the authors saw that pattern in only about 65% of patients. The others had a distinct pattern characterized by increased volume in certain midbrain structures, including the basal ganglia, and no loss of tissue elsewhere. In individuals with loss of grey matter, loss was greater with increasing duration of their illness, which, the authors wrote, “are more consistent with mechanisms associated with early neurodevelopmental disruption, inflammation, and cortical dysfunction” than the brain volume increases seen in other patients, which did not appear to be greater in patients with longer illness. The team published its results in the Feb. 26, 2020, online issue of Brain.