At Least Five Disease Variants, Pandemic Impact on Life Span, Role of Past Coronavirus Infection on Immunity: COVID-19 Updates
January 22, 2021 | A modeling platform validated in New York predicts the spread of COVID-19 in small towns and cities, Americans have lost more than a year of life expectancy, the role of antibodies from previous infections, and wastewater sequencing to track SARS-CoV-2 variants. Plus: new modeling tools to prioritize vaccine distribution and more efforts on drug repositioning.
Research Updates
Georgia State University biology researchers have found that infecting the nasal passages of mice with the virus that causes COVID-19 led to a rapid, escalating attack on the brain that triggered severe illness, even after the lungs were successfully clearing themselves of the virus. Onset of severe disease in infected mice correlated with peak viral levels in the brain. Their findings were published in Viruses. DOI: 10.3390/v13010132
An NYU team used an agent‐based modeling platform to simulate the spreading of COVID‐19 in small towns and cities, with a single‐individual resolution. The platform is validated on real data from New Rochelle, NY—one of the first outbreaks registered in the United States. The model incorporates detailed elements of the spreading within a statistically realistic population and accounts for the burden of other illnesses with symptoms similar to COVID‐19. The model suggests that prioritizing vaccination of high‐risk individuals has a marginal effect on the count of COVID‐19 deaths. A much more significant improvement is registered when a quarter of the town is vaccinated. Importantly, the benefits of the restrictive measures in place during the first wave greatly surpass those from any of these selective vaccination scenarios. The model has limitations, the authors note. The published the model in Advanced Theory and Simulations. DOI: 10.1002/adts.202000277
The results of a study led by Northern Arizona University and the Translational Genomics Research Institute (TGen) and published in Cell Reports Medicine suggest the immune systems of people infected with COVID-19 may rely on antibodies created during infections from earlier coronaviruses to help fight the disease. The team studied cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. They found that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes and that these cross-reactive antibodies preferentially bind endemic homologs. The findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses. DOI: 10.1016/j.xcrm.2020.100189
Metatranscriptomic sequencing of wastewater can be used to profile the viral genetic diversity across infected communities. Researchers sequenced RNA directly from sewage collected by municipal utility districts in the San Francisco Bay Area to generate complete and nearly complete SARS-CoV-2 genomes. The major consensus SARS-CoV-2 genotypes detected in the sewage were identical to clinical genomes from the region. The study proves, the authors say, that epidemiological surveillance through wastewater sequencing can aid in tracking exact viral strains in an epidemic context. Their results are published in mBio. DOI: 10.1128/mBio.02703-20
A German research team used RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Their findings stratify the COVID-19 disease, which is caused by the SARS-CoV-2 coronavirus, into at least five different variants that differ in how the immune system responds to the infection. Further, the stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Their findings are published in Genome Medicine. DOI: 10.1186/s13073-020-00823-5
A team of researchers from the Canadian Institute for Advanced Research call for an exploration of the COVID-19 pandemic’s potential to affect the human microbiome in both infected and uninfected individuals in PNAS. There is currently little direct evidence of interaction between the SARS-CoV-2 pathogen and the human microbiome, but the authors suggest that host microbial populations may affect susceptibility to initial infection, subsequent pathogenesis, and clinical outcomes, underscoring the need for detailed studies of microbiota changes during SARS-CoV-2 infection. In addition, control measures used to prevent COVID-19 transmission, though necessary, may affect the human microbiome. DOI: 10.1073/pnas.2010217118
A team from Houston Methodist Research Institute used EMR data to determine if males have a higher likelihood of SARS-CoV-2 susceptibility than females, and if among the hospitalized COVID-19 patients, male sex is independently associated with COVID-19 severity and poor in-hospital outcomes. While evidence from China and Europe has suggested that mortality from COVID-19 infection is higher in men than women, evidence from US populations is lacking. The team looked at data from 96,473 individuals who had COVID-19 tests. About 15,000 tested positive, about 4,800 were hospitalized, and 452 died. The overall SARS-CoV-2 positivity among all tested individuals was 15.5%, and was higher in males than females. This sex difference held after adjusting for age, race, ethnicity, marital status, insurance type, median income, BMI, smoking and 17 comorbidities. A higher proportion of males (vs. females) experienced pulmonary (ARDS, hypoxic respiratory failure) and extra-pulmonary (acute renal injury) complications during their hospital course. After adjustment, length of stay (LOS), need for mechanical ventilation, and in-hospital mortality were significantly higher in males as compared to females. The findings were published in PLOS. DOI: 10.1371/journal.pone.0245556
University of Southern California and Princeton researchers project that, due to the pandemic deaths in 2020, life expectancy at birth for Americans will shorten by 1.13 years to 77.48 years, according to their study published in the Proceedings of the National Academy of Sciences. That is the largest single-year decline in life expectancy in at least 40 years and is the lowest life expectancy estimated since 2003. The declines in life expectancy impact all races, but are likely even starker among minority populations. For Blacks, the researchers project their life expectancy would shorten by 2.10 years to 72.78 years, and for Latinos, by 3.05 years to 78.77 years. Whites projected decline is 0.68 years to a life expectancy of 77.84 years. DOI: 10.1073/pnas.2014746118
Use of the diabetes drug metformin before a diagnosis of COVID-19 is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. The team conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between the end of February and the end of June at the University of Alabama at Birmingham Hospital. The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans and in subjects with obesity, hypertension, and diabetes, but metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19. The findings raise the possibility that metformin may provide a protective approach in this high-risk population. The findings were published in Frontiers in Endocrinology. DOI: 10.3389/fendo.2020.600439
Industry Updates
Two Korean companies—Syntekabio, an AI and NGS-based drug development company, and Hanmi Science, a manufacturer of biologics, chemical entities, and drugs—have entered into a strategic collaboration to co-develop breakthrough COVID-19 treatments using drug repositioning technologies. Under the new agreement, Syntekabio and Hanmi Science will investigate the potential efficacy of existing drug candidates against COVID-19, as well as other diseases, utilizing Syntekabio’s proprietary AI drug discovery platform: the DeepMatcher. The drug repositioning and indication expansion research will see the two companies undertaking clinical development activities while also managing regulatory affairs. Data derived from the research will be used to enable the development of a digital therapeutics platform for clinical practice. Furthermore, Syntekabio and Hanmi Science will work together to drive clinical development of Syntekabio’s proprietary COVID-19 treatment: the Zafirlukast-sulfinpyrazone combination therapy. Press release.
Jubilant Therapeutics and The Wistar Institute are partnering to evaluate the ability of Peptidyl Arginine Deiminase 4 (PAD4) inhibitors provided by Jubilant Therapeutics to block neutrophil extracellular trap (NET) formation in the context of COVID-19 related cytokine storms. PAD4 is an enzyme that catalyzes conversion of arginine to citrulline in proteins, including histones and is highly expressed in neutrophils. Histone citrullination has been implicated in Neutrophil Extracellular Trap (NET) formation and accumulating evidence suggests that NETs may be linked to the severity of COVID-19, as their formation is a result of pro-inflammatory cytokine release syndrome (CRS), or cytokine storms, produced by the body's immune response to the SARS-CoV-2 virus. Cytokine storms are implicated in the development of acute respiratory distress syndrome (ARDS), which is the leading cause of death in patients infected with COVID-19. Press release.
Researchers at the University of Wisconsin School of Medicine and Public Health and UW Health have developed a tool that incorporates a person's age and socioeconomic status to prioritize vaccine distribution among people who otherwise share similar risks due to their jobs. The tool helps identify those who are at greater risk of severe complications or death from COVID-19. While the UW-Madison tool was designed with the first phase of eligible recipients in mind, it could be used as vaccine distribution expands to larger populations. As the eligible population increases, the gap between initial supply and demand could grow, making such prioritization tools even more helpful. Press release.
A new UK national research project to study the effects of emerging mutations in SARS-CoV-2 is being launched with £2.5 million of funding from UK Research and Innovation (UKRI). The 'G2P-UK' National Virology Consortium (genome-to-phenome) will study how mutations in the virus affect key outcomes such as how transmissible it is, the severity of COVID-19 it causes, and the effectiveness of vaccines and treatments. The Consortium will bring together leading virologists from 10 research institutions within the UK to work alongside the COVID-19 Genomics UK (COG-UK) consortium, which plays a world-leading role in virus genome sequencing, and Public Health England to boost the UK's capacity to study newly identified virus variants and rapidly inform government policy. Press release.
