The Science of COVID-19: COVID-19 and treatment of adults

Dr. Moti Ramgopal,
the Guyanese doctor who led the clinical trial
on COVID-19 treatment given to US President Donald Trump

Since March this year, I have treated hundreds of cases of patients infected with COVID-19, but three cases in particular have aroused my curiosity about the genetic relationship of COVID-19. Do genes play a role in how severe symptoms will be?
Take the case of JT, age 61, I saw over a month ago with a history of COPD, hypertension and diabetes, who developed fatigue, body aches, cough, shortness of breath, and a temperature of 101.6 degrees Fahrenheit. His COVID test was positive.
His oxygen saturation was 94percent on 3.5 L. Indicators of severe disease are marked tachypnea (respiratory rate, ≥30 breaths per minute), hypoxemia (oxygen saturation, ≤93percent; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, 50percent of the lung field involved within 24 to 48 hours).
Once admitted, he started treatment with decadron, remdesivir, convalescent plasma, vitamin C, zinc and anticoagulants. With a history of diabetes and obesity, iron deteriorated, and he was enrolled into clinical trials and received several investigational drugs as well as Actemra, an immunomodulator.
30 days later, he is currently hospitalized with a tracheostomy tube and a feeding tube.
His brother PT,with diabetes, hypertension, and obesity as well as bladder cancer, was admitted two days prior to his brother’s admission with cough and a positive COVID-19 test.
PT was hospitalized for four days and discharged on oxygen after he clinically improved. PT was readmitted five days later with worsening shortness of breath and he was started on Remdesivir, Decadron, heparin and plasma. PT’s condition improved over the next three days, but then went into cardiac arrest with ventricular arrhythmia and died.
Their 82-year-old mother was infected with COVID as well, but was asymptomatic until she presented three weeks later for thromboembolic event, or a blood clot, involving her right leg. She developed ischemia, an inadequate blood supply, requiring amputation. The family decided on hospice care.

Genetic composition
These three cases question the genetic component of COVID-19. A UK group studying more than 2,200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease.
In June, one such genome wide association study in “The New England Journal of Medicine (NEJM)” found two “hits” linked to respiratory failure in 1,600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a person’s blood type, and a stretch of chromosome three that holds a half-dozen genes.
A gene called IFNAR2 codes for a cell receptor for interferon. A variant of this gene raises the risk of severe COVID 19 by 30 per cent. There are genes which code proteins, that can activate an enzyme that breaks down viral RNA changes in this gene, and this activation allows the virus to flourish.
Also, genes can code for proteins to ramp-up the inflammatory response to lung damage triggered by COVID-19. Genes DPP9 and TYK2 are involved in inflammation and blocking these enzymes may be beneficial. CCR2 is a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data points to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by COVID-19 to enter cells.
The importance of recognizing the genetic impact may influence treatment strategies.
It still unknown why African-American or Hispanic patients had such a higher risk of infection, but this can be related back to pre-existing conditions. However, I would not be surprised if there is a genetic relationship that can be found.
Blood type A is associated with higher risk of respiratory failure. COVID-19 is primarily spread from person to person through respiratory particles, probably of varying sizes, which are released when an infected person coughs, sneezes, or speaks. Because both smaller particles (aerosols) and larger particles (droplets) are concentrated within a few meters, the likelihood of transmission decreases with physical distancing and increased ventilation.
Aerosols can be generated under circumstances, such as talking, singing, or shouting indoors in poorly ventilated environments. In these situations, transmission over longer distances may occur. Respiratory transmission is probably the main mode of transmission, hence masking and physical distancing markedly decrease the chance of transmission. Under laboratory conditions, COVID-19 may persist on cardboard, plastic and stainless steel for days.
Patients can be infectious one to three days before symptom onset, and up to 40-to-50 percent of cases may be attributable to transmission from asymptomatic or presymptomatic people. Just before and soon after symptom onset, patients have high nasopharyngeal viral levels, which then fall over a period of one to two weeks.
A patient maybe positive for weeks to months, but viable virus and contact-tracing assessments suggest that the duration of infectivity is much shorter and isolation can be lifted in most patients 10 days after symptom onset if fever has been absent for at least 24 hours and other symptoms have decreased.