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CORONAVIRUS, Part II: What is to be done?

We live in evolutionary competition with microbes—bacteria and viruses. There is no guarantee that we will be the survivors.

(To read Rich Kessin’s first article on the coronavirus pandemic, click HERE.)

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We live in evolutionary competition with microbes—bacteria and viruses. There is no guarantee that we will be the survivors.

The aphorism from Joshua Lederberg, a founder of molecular biology, is remarkable for its humility and for the challenge it defines. Before the germ theory of disease, which appeared in the second half of the 19th century, medicine was helpless against infection. We have since become good at preventing and treating many infections, so it is galling that we remain stymied in our battle with COVID19.

The natural world creates new viral genomes by mutation or exchange between two viruses. Some of these viruses escape the surveillance of human immune systems and spread as epidemics or pandemics. What the natural world can mount in the way of threats is greater than anything we could build ourselves, but when a new disease appears, we have an innate tendency to blame other humans, as if nature could not be so clever. Thus, President Trump and Secretary of State Pompeo have been blaming the Chinese. It they had constructed a new genome out of other viruses, those sequences would have been found in the new virus. Chinese virologists did not make SARS-CoV2. (Editor’s note: The author clarifies that SARS-Cov2 is the name of the virus; Covid-19 is the name of the disease and the year it appeared.)

The genome of SARS-CoV2 is almost 30,000 nucleotides long and is arranged in a code that can be translated into the proteins of SARS-CoV2. On January 9, Chinese virologists deposited the nucleotide sequence in GenBank, the NIH sponsored resource for the world’s scientific and medical communities. It had taken them 10 days to sequence and analyze the genome and it is all described in Nature, the British science magazine. From that sequence, skilled virologists can make vaccines and begin other studies. Two and a half months into the pandemic, the flow of scientific reports on COVID19 has become a reassuring flood.

That the Wuhan Institute of Virology deposited the sequence so fast is not the act of people hiding information. Perhaps the suspicious functionaries of the Chinese government, who chastised Dr. Li Wenliang after he described the disease knew nothing about GenBank. Perhaps (purely my guess) the critical sequence information slipped by them, like a fastball low and away.

How did the pandemic develop? Imagine a person with COVID19 who infects between two and three other people. Thus R naught is 2-3 and the very infectious virus creates exponential growth. Social distancing, hand washing, testing and tracing reduce R naught, as does just staying home. A good vaccine could reduce it to nearly zero, but vaccines are months away.

Coronavirus invading a cell: Transmission electron microscopic image of an isolate from the first U.S. case of COVID-19. The spherical extracellular viral particles contain cross-sections through the viral genome, seen as black dots, which are about to enter the cell. This is a cell that has been immobilized (fixed) with a chemical and then sliced very thinly before viewing. Courtesy of the CDC.

The COVID19 coronavirus produces many copies of itself that exit a lung cell in little blisters. The two images show virus infecting cells and new virus coming out. If replication of the virus is not slowed, the inflammation and cellular destruction that result cause the blood vessels around the alveoli of the lungs to leak. Plasma and the defensive cells of the immune system fill these air sacs. Breathing becomes difficult without supplemental oxygen and often a ventilator. People recover from ventilation but it is often a long haul.

Between now and the appearance of new vaccines, the best we can do, beyond testing and isolation, is to find drugs that slow the virus infection and protect front-line medical staff. There will probably be a new surge of virus in the fall and it would be criminal to ask nurses, doctors and others to return to emergency rooms without much better protection than they have had. At this writing that supply is not assured.

Drugs that slow viruses similar to SARS-CoV2 exist and are entering clinical trials quickly. Some, like hydroxyquinoline, don’t work and have been abandoned. Remdesiver blocks the production of the RNA genomes for new viruses. More trials are necessary according to Dr. Anthony Fauci, for whom this is familiar territory from the battle against HIV. Tests of dosage and early use in the course of an infection may make Remdesiver more effective.  Another drug, baricitinib, blocks the cytokine storms and inflammation that occur days after infection. The NIH is beginning a clinical trial that asks whether the two drugs have additive benefits.  Many such experimental treatments with other drugs are being done around the world (See ClinicalTrials.gov).

Prof. Arturo Casadevall of the Johns Hopkins Bloomberg School of Public Health speaks of layered defenses. What he has in mind is the convalescent antisera of people who have recovered from COVID19. Dr. Francis Collins, director of the NIH, has noted that almost all patients who have recovered from COVID19 have circulating antibodies to the virus. This approach to stopping the virus by supplying antibodies to the circulation has entered clinical trials in the United Kingdom and will soon be in double-blind trials in the United States. Anecdotal evidence (a scientific oxymoron) says that Italian patients benefitted from convalescent serum.

It is good to use a layered defense, trying all strategies because there will be a COVID25, a pandemic flu strain, or a respiratory form of Ebolavirus in our future. In this pandemic we have not performed brilliantly up to now. Science and organization count and we should reinforce them with a regenerated CDC.

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Richard Kessin is Professor Emeritus of Pathology and Cell Biology at the Columbia University Irving Medical Center. He lives in Norfolk, Conn., and can be reached at Richard.Kessin@gmail.com.

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