COVID-19 Update: March 6, 2020

Published on March 6, 2020

Dr. Sarah Zaidi has provided an updated analysis of the COVID-19 spread, testing methodologies, and on questions over the potential mutation of the virus.

As with our previous COVID-19 reports, this report was not produced by SGH, and as such solely reflects the analysis and interpretation of data by Dr. Zaidi. The report is for informational purposes only and does not constitute investment advice.

COVID-19 is a ‘SUPER’ flu or FLU++. While it can spread through a community, it kills a selective group of people (elderly, immunocompromised, and those with underlying conditions).

Broad environmental conditions in the U.S. are not similar to conditions in China, and COVID-19 will likely pass as weather warms up. However, if the virus is introduced in closed systems that house at-risk communities, then it will be a killer.

The true mortality impact of COVID-19 will only be known after the epidemic has passed.

One issue of concern based on news report of emergence of two strains of SARS-CoV-2, L-type or S-type, is whether the virus has mutated or has the potential to mutate.

Population genetic analyses of the SARS-CoV-2 genomes indicate that the virus evolved into two major types, with the L-type being more prevalent (70%) than the S-type (30%) which was found to be the ancestral version.

In the early stages of the epidemic in Wuhan, the L-type was more prevalent, but because of the severe restrictions placed in Hubei, that strain could have faced more severe selection pressure. On the other hand, the S-type, which is evolutionarily older and less aggressive, may have experienced different selective pressure.

It is not clear whether the L-type is more virulent than the S-type or whether L-type evolved from the S-type in humans, or in the intermediate hosts.

As of today, the cases of novel coronavirus (SARS-COV-2) have surpassed 100,000 and there have been 3,410 deaths. After China, South Korea (6,593 cases), Iran (4,747 cases) and Italy (3,858 cases) have the highest reported number of people with COVID-19.

In the U.S there have been 233 reported COVID-19 cases, with California (53) and Washington (70) states having the highest numbers, and a few cases (1-5 each) across Oregon, Arizona, Illinois, Wisconsin, New York, Maine, Massachusetts, Rhode Island, North Carolina, Georgia, Florida, and most recently Maryland.

The governor of California has declared a state of emergency and offered testing in 20 locations. According to the CDC, person-to-person or community spread is noted for 20 cases.

In the United States, there have been 14 reported deaths, most of them in a nursing home in the Seattle area. The U.S. Congress has pledged $8.3 billion in funding as an initial response, and Vice President Mike Pence has stated that 1.5 million tests would be available for diagnosing COVID-19.

Cigna health insurance has announced that it will waive all copays and cost-share fees for members who are tested for COVID-19 infection per their doctors’ instructions. As the U.S. prepares to detect more cases, the numbers of new infections in China, according to the government, are declining.

The quick sequencing of the SARS-CoV-2 genome resulted in the first diagnostic protocol for COVID-19 using swabbed samples from a patient’s nose and throat. The initial test was developed on the genetic similarity between SARS and SARS-CoV-2 and detects the presence of an gene. Once a sample is taken it takes 24-48 hours to get results, in comparison to 1 hour to generate flu results.

The U.S. CDC has not adopted the WHO’s recommended diagnostic, but has developed its own assay that looks for three sequences in the N gene, screening for a third gene encoding a protein that forms the viral nucleocapsid (a kind of shell around the viral genetic material). While the principles of testing are the same, it is the genetic targets that vary, and it is not clear why the CDC took this decision, and whether this type of testing has greater analytical sensitivity than the other. It takes 48-72 hours to get results from the CDC test.

There are numerous companies working on commercial test kits for rapid diagnosis given the epidemic. Sherlock Biosciences (Cambridge, MA) is using CRISPR technology, which is based on using paper strips to detect the presence of the virus and would take 1 hour to deliver results. Anglo-French biotech company Novacyte has released a real-time PCR (polymerase chain reaction) diagnostic kit for COVID, which will deliver results in 2 hours.

It is however not yet clear how long a person needs to be infected before testing positive, or whether someone who is infected could be identified by the test before displaying symptoms.

Recent data from China, based on 1,000 patients, suggest the primary screening tool for COVID-19 should be chest CT as it is a more reliable, practical, and rapid method to diagnose and assess COVID-19 disease in epidemic areas. In comparing oral swabs with chest CTs, the results show that 601 patients (59%) had positive RT-PCR results and 888 (88%) had positive chest CT. In patients with negative oral swab detection, 75% (308 of 413 patients) had positive chest CT.

The analysis of serial oral swabs showed that the interval between the initial negative to positive RT-PCR results was 4 to 8 days. In high-risk cases, chest CT should be used to immediately detect the presence of COVID-19.

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