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Dr. Petri explains a Neanderthal connection to COVID-19, and rebound infections

University of Virginia immunologist and COVID-19 researcher Dr. William Petri continues to answer reader questions about COVID-19 and, now, monkeypox. Send your questions to Lynne Anderson at, and she will forward them to Dr. Petri.

I’ve had COVID-19 four times. I’ve had both vaccinations. Is there the likelihood that I will continue to be a magnet for COVID’s new variants?

First off, I am so sorry! You must have a strong constitution get through COVID-19 four times! I hope the 4th is the charm and you are spared future infections.

Your unique susceptibility to COVID is an example of “precision health,” a new area of medicine where we work to treat and prevent disease working with the knowledge that each person is unique, due to a combination of genes and environment, or “nature and nurture.”

One area where genetic differences (“nature”) control susceptibility to COVID-19 is in chromosome 3. Part of chromosome 3 comes from Neanderthals. When humans migrated from Africa about 100,000 years ago, they met and had sex with Neanderthals, perhaps first along the Nile River in Egypt. As a result, people of European and Asian but not African descent share about 1-3% of their genes with Neanderthals. Neanderthal variants or alleles of immune signaling genes in chromosome 3, including CXCR6 and LZTFL1, cause a twofold increased risk. Another genetic pathway that is different is in interferons, which are proteins made by the immune system that interfere with the replication of viruses inside our cells.

There is a UVa connection here, as the late Robert Wagner, who led microbiology and was my mentor, was a pioneer in the study of interferons. Just to close this discussion of “nature” we humans are amazingly and beautifully diverse; any two people are different genetically in over 30 million parts of the genome!

Environmental (“nurture”) factors that affect susceptibility are notably age: Someone age 80 is 10,000-times more likely to die than a child! Reflected in this, almost all the deaths during the current BA.5 wave of omicron are in those age 65 and older.

Finally, men are 1.5 times as likely to die, and coexisting illness such as diabetes and heart disease also increase susceptibility about twofold. As we begin to understand the contributions of nature and nurture to our susceptibility to COVID-19, this will lead to new treatments and preventative strategies. But I am hoping you will sail clear of COVID-19 this fall!

I just read that President Biden has a rebound COVID-19 infection. What does this mean, and how does this happen?

A rebound COVID-19 infection is a relapse with the same virus after an apparent recovery from a primary COVID-19 infection. They occur on average about 10 to 14 days after the initial infection. Fortunately, most rebounds are mild, or as in the case of President Biden. even asymptomatic.

They are of importance, as people remain infectious during a rebound, requiring an additional five days of isolation at home, followed by five days of wearing a mask around other people. Their mild nature is reflected in an only 1/200 chance of ending up in the hospital, as a recent study of 11,000 individuals from Case Western Reserve University showed.

Rebounds gained notice after they occurred in one in six people after Paxlovid and Molnupiravir treatment but are also part of the natural course of untreated infection. Patients who rebound tend to be older and have more other medical illnesses than those who did not.

The post-Paxlovid rebound should not keep one from taking this safe and highly effective anti-viral medicine. Paxlovid has emergency approval from the FDA for the treatment of acute COVID-19 (within five days of a positive viral test) in patients ages 12 years and up who are at high risk for progression to severe COVID-19. Treatment is for five days. Approval is based on a clinical trial of 1361 subjects that showed that Paxlovid reduced hospitalization or death to 0.8% compared to 7% in the placebo group.

It is possible that the virus will evolve resistance to Paxlovid, although there is not evidence of this occurring in these initial clinical trials. Adverse events in a minority (7%) of Paxlovid treated subjects included a metallic taste, diarrhea, nausea, or vomiting.

I don’t see many people wearing masks when I am out doing my errands, such as grocery shopping. Am I being too cautious by wearing a mask?

Nothing wrong with being cautious! The older I get the more cautious I am, mostly from an appreciation of how fragile the human body is. We are not in a good place right now as far as COVID-19. The BA.5 lineage of omicron is causing the sixth wave of the pandemic, each day resulting in about 125,000 new infections and, even though less deadly than delta, is causing 400 deaths.

Currently we are at medium levels of COVID transmission in Central Virginia. Based on this, if you are at high risk for severe illness, it makes sense to me to wear a mask and take other precautions, get tested if you are ill, and be sure you have received every booster that you are eligible for. I can tell from your question that you are doing all those things, and I congratulate you for it.

Dr. Petri mentioned the need for yearly boosters as the ever-evolving strains become endemic. Any idea when we will get formal approval for yearly shots? Many thanks for all the great work.

Pfizer and Moderna are expected to have the BA.5 booster available as early as September. For this reason, the CDC is not moving forward with a second booster shot for lower risk individuals under age 50. The plan instead is for everyone to receive an BA.5 omicron booster as part of a two-part, or bivalent, vaccine booster. The bivalent booster will offer added protection against both BA.5 and the original Wuhan strain.

As you know, everyone ages five and older is eligible for a single booster five months after receiving the two-dose original vaccine. I hope someone reading this who has not gotten their booster will do so, as the booster protects you not just from infection but from having such severe COVID-19!

My father is 97 years old, wears a pacemaker, and has congestive heart failure. He had the two-shot Moderna vaccine last autumn, but contracted COVID-19 early this year and recovered. He has had no boosters because his physician advised him that it might cause him to have a heart attack. He suffered no ill effects from his Moderna shots, so I question whether the boosters would be harmful to him. Should he get boosted?

I am so glad that you are monitoring your father’s health. As a physician, I always am glad to see family at the bedside, as it really is a team effort to keep our loved ones healthy. I, like you, don’t understand the advice your father has been given, as the rare (in 1/100,000 young men) side effect of the mRNA vaccines is a self-limited inflammation of the heart, and not a heart attack. I wonder if you could accompany him on his next visit to his physician to get more information.

I’ve got two COVID-19 vaccinations and one booster shot at the end of last year. In my case the booster shot triggered Guillain-Barré Syndrome. I am suffering for seven months. I’ve never had COVID-19, but it can happen any time. I don’t dare to take a second booster shot. What about a Paxlovid and/or molnupiravir oral antiviral treatment in case of a COVID-19 infection in my situation?

How terrible that you are suffering from Guillain-Barré. You are correct to think of antiviral treatments for COVID-19 should you become infected despite three doses of the vaccine. Paxlovid is more effective as a treatment than molnupiravir, but not everyone can take Paxlovid because it interacts with other medications. Molnupiravir thus has an important if secondary role in treatment.

Guillain-Barré has been shown to occur in one of 100,000 recipients of the mRNA vaccines, which is about the same as the background rate of this paralytic illness in the community. So you might have not have gotten Guillain-Barré from the vaccine, but you are wise not to chance further vaccinations.

I read that monkeypox is becoming a major health problem. What can we do to slow this disease? And how do I know if I am at risk?

The good news is that monkeypox is not easily transmitted, as it requires contact with body fluids or the skin lesions from an infected person. Huge differences from COVID-19 include that monkeypox is not spread by breathing and that one is not infectious until symptoms begin. Bad news includes that almost all cases are tragically in men who have sex with men, and that the number of cases is increasing dramatically every day, with 3,500 cases since the first detection in the U.S. in May 2022. The WHO took the extraordinary step of declaring monkeypox a “public health emergency of international concern” and, closer to home, Mayor Eric Adams of New York City has just declared monkeypox a public health emergency.

Symptoms start about a week after exposure, with flu-like symptoms or swollen lymph nodes. The “pox” is a rash that is fluid-filled vesicles or bumps and usually starts on the face and spreads to the trunk and extremities. Vaccination after exposure may be effective, and there are licensed monkeypox vaccines available in the U.S. The related smallpox vaccine provided at least partial protection from monkeypox, and monkeypox has become more common as smallpox vaccination ended with global eradication.


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