April 14, 2020

From the Curator-in-Chief's Desk


Dear Colleagues,

The pandemic of SARS-CoV-2 is unprecedented at many levels. Many scientists are trying to find ways to apply their expertise to tackle the overwhelming issues from fundamental research to applications to diagnostics and treatment.  The “sound bites” touting “everything you need to know about coronavirus” are everywhere, but there are few places to find actual research publications with data. Keeping up with the most relevant research publications is challenging for any investigator, but when hundreds of publications and preprints are appearing every week, the task can be overwhelming. 

The registry is an effort by ASM to provide aggregated access to vetted fundamental research on SARS-CoV-2, and other relevant viruses. The registry experts will highlight relevant preprints and publications that appear every week. The goal is to ensure maximum acceleration of fundamental discoveries which are essential to optimize our chances of defeating the pandemic.

The registry is a resource for all scientists working to address the current challenge and be ready for future epidemics. For those scientists with a strong desire to contribute, but with little or no experience with viruses in general and SARS-CoV-2 in particular, this registry will provide reliable and up-to-date scientific information in selected areas, vetted by experts. 

We welcome your feedback and ideas to make the Registry a useful resource for the scientific community to fight against the pandemic.

Sincerely,

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Lynn Enquist, Ph.D.
Curator-in-Chief
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Harold Varmus, M.D.
Chief Consultant


 

Commentary

by John J. Dennehy, Ph.D., a Professor at Queens College and The Graduate Center of CUNY.
 
As the world struggles to overcome the COVID-19 pandemic, one fact is clear: testing and contact tracing will be a part of the solution. However, difficulties scaling up test capacity remain an issue. Test conductors are beset by logistical problems with every aspect of the workflow, from supply chains to operational coordination.
 
A preprint from a Yale University team suggests a way to alleviate some of these issues, while also increasing test reliability. Wyllie et al. report that tests of saliva for SARS-CoV-2 returned greater detection sensitivity and consistency throughout the course of infection than did patient-matched samples acquired from nasopharyngeal swabs. It is likely that larger sample volumes provided by saliva sampling reduce inconsistencies in sampler technique.
 
The results are significant for 3 reasons:

  1. SARS-CoV-2 test performance is already troubled by false negative results, so greater reliability is clearly indicated.
  2. Nasopharyngeal swabs, considered the gold standard of COVID-19 testing, have been in short supply. Dispensing with swabs will streamline test logistics.
  3. Nasopharyngeal swabbing is usually performed by trained medical personnel. Saliva sampling can be performed at home and submitted by post, alleviating demands on both patients and health care workers.

Further research of both COVID-19 positive and negative participants will reveal if saliva testing is ready for wider application.
 


Commentary

By Linda J Saif, Distinguished University Professor, The Ohio State University, Wooster, Ohio
 
Trinity of COVID-19: Immunity, inflammation and intervention” by Tay, M.Z., et al, Nat Rev Immunol 2020
 
To date many approaches to therapeutic interventions for COVID-19 are empirical or based on only limited knowledge of SARS-CoV-2 infections. Based on increasing numbers of global reports, a clearer understanding of SARS-CoV-2 pathogenesis and pathophysiology is emerging to guide the rational design of targeted interventions. This is the topic of the selected review.
 
This review of the pathophysiology of SARS CoV-2 infections is comprehensive and timely. The authors highlight the temporal sequence of coronavirus replication in respiratory tract cells and induction of healthy immune responses. They then characterize the chronology and potential contribution of dysfunctional immune responses to disease progression, focusing on the observed uncontrolled inflammation and cytokine storm leading to acute respiratory distress syndrome. Important and pertinent aspects of SARS and MERS coronavirus pathogenesis are compared to illuminate related data on SARS CoV-2 infections. A table of relevant interventional clinical trials (March 2020) is included, but more updated versions are available on the WHO web site.
 
Significant conclusions include:

  1. Combined synergistic therapies are needed to inhibit both virus infection and regulate the dysfunctional immune responses.
  2. Studies of healthy versus dysfunctional outcomes and their chronology are critical to elucidate biomarkers of disease severity that will aid in the rational design of targeted interventions and a timeline for their application.
  3. Identification of biomarkers for immune correlates of protection and those related to disease severity are important for the design of safe and efficacious vaccines to circumvent immunopathology and to induce protection, respectively. 

Unknowns that require additional research are how age, sex, genetics, co-morbidities, hypoxia, co-infections, immune landscape, microbiota, drug treatments, etc contribute to SARS-CoV-2 susceptibility, dysfunctional immune responses and disease severity. More information on innate immune responses is needed. A comprehensive, One Health, multi-disciplinary approach is highly relevant to answer these questions. Examples include: How do the coronavirus ancestor host species (bats) cope with SAR-like coronavirus infections to render them innocuous? How do the incidental hosts (cats, felids, ferrets, mink, non-human primates, etc) respond to SARS-CoV as a largely asymptomatic or mild infection? How do the above parameters influence the pathophysiology and severity of the disease and immune responses in humans compared with the animal disease models? Continued studies of the full spectrum of coronavirus disease (enteric, respiratory, systemic, and nervous systems) in naïve and partially immune natural host species are also warranted to delineate the impact of coronavirus infections on multiple organ systems and immune responses and to test potential targeted interventions, including vaccines.