SARS-CoV-2: Investigating the Novel Virus Causing COVID-19
Multiple avenues of research are underway to curb the COVID-19 pandemic
Michelle Dotzert is the creative services manager for Lab Manager. She holds a PhD in Kinesiology (specializing in exercise biochemistry) from the University of Western Ontario. Her research examined the...
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As director of scientific affairs, Dr. Stan Naides oversees scientific communications, publications, and research for EUROIMMUN US, a PerkinElmer company, and is based at the US headquarters in Mountain Lakes, NJ. Dr. Naides was most recently at Quest Diagnostics Nichols Institute as medical director, Immunology R&D. Dr. Naides is a board-certified internist with subspecialty certification in Rheumatology.
Q: Why is SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2) causing so much heightened concern compared to the seasonal flu?
A: SARS-CoV-2 is new. What that means is that no one has any immunity to it. This is important at the individual level, but also at the community level. It means that everyone is susceptible individually, and everyone can pass it on to others. It is therefore highly transmissible. Because we see influenza each year, and the flu virus proteins our immune system targets often recycle or reappear as slightly changed over the years, many of us have some level of immunity from previous infections that partially protects against infection or ameliorates the impact of infection. More importantly, an influenza vaccine is available each year that is optimized to immunize against that year’s prevalent strains. While both SARS-CoV-2 and influenza are especially risky to the elderly and those with comorbid health conditions, SARS-CoV-2 has a mortality rate in hospitalized patients about 20 times higher than this year’s seasonal flu (about two percent versus 0.1 percent). Given the potential for widespread infection, there is heightened concern that hospital system capacity will be exceeded, and the very people on the frontlines—the health care providers, and first responders—are at increased risk of exposure and risk of becoming unavailable through quarantine or illness to provide care.
“Since this is a new virus, the most pressing avenue of research is a better understanding of the disease caused by this virus, its clinical course, its complications, and how best to medically manage patients.”
Q: How is the virus thought to have emerged? How is this different from the seasonal flu?
A: It appears that the SARS-CoV-2 virus most closely resembles bat coronaviruses. It is thought to have come from a bat or an intermediate host and was then transmitted to humans. Influenza is a bird virus that typically passes through pigs to humans. With passage through pigs, the influenza virus is usually attenuated or weakened in its pathological effect on humans. Both are RNA viruses that have poor proofreading mechanisms when making progeny viruses, allowing misreads of the parental viral nucleic acid sequence and selection of progeny virus better adapted to the next host species.
Q: What are some different avenues of research involving SARS-CoV-2?
A: Since this is a new virus, the most pressing avenue of research is a better understanding of the disease caused by this virus, its clinical course, its complications, and how best to medically manage patients. Understanding the epidemiology of COVID-19, the public health threat, the dynamics and mechanisms of spread in the community, and the extent of the community viral burden is another critical avenue of research. A better understanding of the virology of this infection and the immune response to it is yet another critical avenue of research: What is the structure of this virus? How do its proteins function and interact with cellular machinery? What cell types can the virus enter? How does the immune response eliminate the virus? How long can the virus persist? How long can it be shed?
It will be important to follow the virus’s evolution—do mutations lead to changes in virus behavior or immune response? Understanding changes in viral sequences and viral mutations will be necessary as we develop medications to treat and vaccines to prevent SARS-CoV-2 infection.
Q: What are some of the immediate and long-term goals of this research?
A: As noted above, the most pressing avenue of research is a better understanding of the disease caused by this virus, its clinical course, its complications, and how best to medically manage patients. Understanding the epidemiology of COVID-19, public health threat, the dynamics and mechanisms of spread in the community, and the extent of the community viral burden is another critical avenue of research. Long term goals are development of preventive vaccines and specific anti-viral drugs to treat sick patients.
Q: What are some key pieces of laboratory equipment or technologies that make it possible to study these viruses?
“Understanding changes in viral sequences and viral mutations will be necessary as we develop medications to treat and vaccines to prevent SARS-COV-2 infection.”
A: Key to studying the virus are molecular methods (including polymerase chain reaction, PCR), cell culture methods (to grow virus to study virus-cell interactions), and immunological methods. Epidemiological and clinical studies would benefit from high throughput platforms for RNA extraction and real time PCR, as well as high throughput platforms for enzyme-linked immunosorbent assays (ELISAs). Cell culture, hybridoma, and recombinant protein technologies will be employed to generate protein targets for ELISAs. Recombinant RNA/DNA technologies will allow manipulation of viral genome and proteins in experimental laboratory systems to study virus behavior in cell culture.
Q: How does a laboratory become certified to work with SARS-CoV-2 and other viruses?
A: Clinical diagnostic laboratories are required to be certified under the Clinical Laboratory Improvement Act (CLIA). CLIA certified laboratories may develop laboratory developed tests (LDTs) following defined test validation guidelines. The FDA recently announced a policy to allow CLIA laboratories to develop serological tests for SARS-COV-2 as LDTs without submitting and receiving an Emergency Use Authorization (EUA). However, laboratories developing molecular assays for SARS-COV-2 are still required to submit their validation data to the FDA for a fast-tracked EUA for the molecular testing.
Q: What are some important considerations for laboratory managers and personnel working with SARS-CoV-2?
A: First and foremost, all personnel, both managers and technologists, must ensure personnel safety and virus containment. Clinical laboratories should prepare samples and perform molecular diagnostic testing under biosafety level 2 (BSL2) conditions. Laboratories growing and/or culturing virus will require BSL3 conditions. These conditions include appropriate personal protective equipment, laminar flow hoods appropriate to each safety level required, and laboratory engineering that ensures safe air handling. Proper waste management should be observed within the laboratory and beyond. Personnel working with SARS-CoV-2 materials should be surveyed regularly for signs of illness. Contingency plans should be available for medical evaluation and care of ill individuals. With good laboratory practice, it is more likely that personnel who become SARS-CoV-2 positive were infected through community transmission rather than from laboratory procedures; management should have backup contingencies to replace personnel who become absent due to illness, quarantine, or home commitments and who are critical for SARS-CoV-2 testing. Such contingencies are also required to maintain routine laboratory functions during a pandemic.
