Moti Ramgopal, Dr.
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 COVID-19 infected patients, but three cases in particular have sparked my curiosity about the genetic relationship of COVID-19. Do genes play a role in the severity of symptoms?
Take the case of JT, 61, I saw over a month ago with a history of COPD, hypertension, and diabetes, which developed fatigue, body aches, cough, shortness of breath, and a temperature of 101.6 degrees Fahrenheit. His COVID test was positive.
Its oxygen saturation was 94 percent at 3.5 L. Indicators of severe disease marked tachypnea (respiratory rate, ≥30 breaths per minute), hypoxemia (oxygen saturation, ≤93percent; ratio of arterial oxygen partial pressure to fraction of oxygen have to inspire, 50 percent of the lung field in question within 24 to 48 hours).
After admission, he began treatment with decadron, remdesivir, convalescent plasma, vitamin C, zinc and anticoagulants. With a history of diabetes and obesity, iron declined, he was enrolled in clinical trials and received several investigational drugs as well as Actemra, an immunomodulator.
30 days later, he currently has a tracheostomy tube and a feeding tube.
His brother PT, with diabetes, hypertension, and obesity along with bladder cancer, was admitted two days before his brother received a cough and a positive COVID-19 test.
PT was hospitalized for four days and discharged on oxygen after he had recovered clinically. PT was re-admitted five days later with worsening breathlessness and was started on Remdesivir, Decadron, heparin and plasma. The condition of PT improved over the next three days, but he then underwent cardiac arrest with ventricular arrhythmia and died.
Their 82-year-old mother was also infected with COVID, but was unresponsive until she presented three weeks later for a thromboembolic event, or blood clot, involving her right leg. He developed ischemia, an inadequate blood supply, which needed to be shed. The family decided on hospice care.
These three cases call into question the genetic component of COVID-19. A UK group studying more than 2,200 COVID-19 patients has identified common gene variants associated with the most serious causes of the disease.
In June, one such genome-wide association study in “The New England Journal of Medicine (NEJM)” found two “seizures” associated with respiratory failure in 1,600 COVID-19 patients from Italy and Spain: a marker of within the ABO gene, which determines a person’s blood type, and a piece of chromosome three that holds half a dozen genes.
A gene called interferon cell receptor IFNAR2 codes. A variant of this gene increases the risk of severe COVID 19 by 30 percent. There are genes that code for proteins, which can activate an enzyme that breaks down viral RNA changes in this gene, and this activation allows the virus to thrive.
Also, coding genes to proteins can ramp the inflammatory response to COVID-19-induced lung damage. DPP9 and TYK2 genes are involved in inflammation and blocking these enzymes may be beneficial. CCR2 is a gene encoding a receptor for cytokine proteins that plays a role in inflammation. But other data point 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 effect can influence treatment strategies.
It is still unknown why African-American or Hispanic patients had such a higher risk of infection, but this may be linked back to pre-existing conditions. However, I would not be surprised if there is a detectable genetic relationship.
Blood type A is associated with an increased risk of respiratory failure. COVID-19 is mainly spread from person to person by respiratory particles, probably of various sizes, which are released when an infected person coughs, sneezes, or talks. Because smaller particles (aerosols) and larger particles (droplets) are concentrated within a few meters, the probability of transmission decreases with physical distance and increased ventilation.
Aerosols can be produced under circumstances, such as talking, singing, or shouting indoors in poorly ventilated environments. In these situations, transfer over longer distances can occur. Respiratory transmission is probably the main mode of transmission, so masking and physical distance significantly reduce the chance of transmission. Under laboratory conditions, COVID-19 can remain on cardboard, plastic and stainless steel for days.
Patients can be infectious one to three days before the onset of symptoms, and up to 40-to-50 percent of cases can be attributed to asymptomatic or precymptomatic transmission. Just before and shortly after the onset of symptoms, patients have elevated nasopharyngeal viral levels, which then subside over the course of a week to two weeks.
A patient may be positive for weeks to months, but virus assessments and viable contact tracking suggest that the duration of infection is much shorter and isolation can be raised in most patients 10 days after symptom onset if the fever has been absent for at least 24 hours and other symptoms have lessened.
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