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Part 1 - Prepared By Dr. Howard Topoff
What Causes Long Covid?
Three Leading Hypotheses
Mild or moderate COVID-19 lasts about two weeks for most people. But in some people, long-term effects of COVID-19 can cause lingering health problems and wreak havoc for months. This condition can affect anyone – old and young, otherwise healthy people and those battling other conditions. It has been seen in those who were hospitalized with COVID-19, patients with very mild symptoms and even some people who had virtually NO symptoms. Studies indicate that about 10% of people infected with COVID-19 will experience long-haul symptoms - the most common being:
• Symptoms that get worse after physical or mental effort.
• Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough.
Hypothesis 1: Cells and tissues that control blood flow are damaged and the blood’s tendency to clot is amplified. Scientists think damage to tiny blood vessels and minuscule clots are the culprit to deteriorated lung function.
Hypothesis 2: The coronavirus keeps hurting people by stubbornly enduring in the body, even after acute infection passes. Studies have shown the virus is capable of persistence in a wide range of body sites, especially nerves and other tissues. Many people, post Covid positive testing, harbor viral RNA in their body, including in the brain, muscle, gut, and lungs. Many organs even had evidence of replicating virus.
Hypothesis 3: The immune system is perturbed, even 8 months after people first tested positive. It was assumed that immune cells galvanized to fight off infection would have calmed down over that time span. So, it was a surprise that these immune cells did not recover. In some people, white blood cells that typically recruit other cells to sites of infection were highly activated, which may explain why the patients’ levels of interferons, proteins the body makes to fight invaders, were sky high 8 months after infection. The participants also had a dearth of inactivated T cells and B cells, a population of cells that normally putters about awaiting instruction to counter pathogens. Collectively this signaled chronic inflammation, which can cause a host of health problems.
Of course, some combination of these three processes may be at work in cases of long Covid. When the pandemic started mid January 2020, we had a lot to learn about the coronavirus that causes Covid. Two and a half years later, we still have many questions. You can read a more detailed account of the causes of long Covid in Science Magazine at:
To Boost Or Not To Boost
Excerpts from Ground Truths
The reluctance for Americans to get a booster shot has been striking. The United States currently ranks 73rd among countries for its uptake of boosters at 33% of its population. All peer, rich countries around the world are at least double that rate. Some of the problem can be blamed on delays, confusion, and poor messaging, which got boosters off on the wrong footing. All the anti-science, anti-vax, mis- and disinformation hasn’t helped at all, and has never been effectively countered.
Very strong evidence supporting boosters dates back to October 2021, when the results of the only large (~10,000 participant) (1st) booster randomized trial were released and later published, with a 95% reduction of symptomatic infections across all age groups, through the Delta wave, durable at that level for at least 4 months. There were no safety concerns or myocarditis.
However, since the Omicron wave (BA.1, BA.2, BA.2.12.1, BA.4/5) there has generally been less protection against infection and transmission from boosters and vaccines, down to levels of 30 to 40% in the first 2 months, and less durable. That’s been a disappointment that has further detracted from enthusiasm for boosters.
With this background, it is understandable that even the new BA.5 bivalent boosters, which nicely match up with the current circulating variants (BA.5 88%, BA.4.6 10%) would not be highly alluring, as reflected in recent headlines.
Boosters provide substantive and unequivocal benefit for protection from severe Covid and help reduce Long Covid (magnitude uncertain), and still, despite the challenges of Omicron, have some early (~2 months) effect for reducing infection and transmission. We don’t know yet if the BA.5 bivalent booster is any better than the BA.1 or the original booster. Based on the evolution of the virus through Omicron and its subvariants, it appears unlikely the new vaccine will have a major or important impact on reducing infection or transmission.
It would be far easier to take a nasal spray repetitively, with expectation of much less side effects, than shots. Certainly encouraging data from CanSino’s newly approved inhaled vaccine vs Omicron is a solid precursor for the many programs that are in advanced clinical trials.
The right question is about the future. We can’t go on getting boosters every 4 to 6 months and the premise of an “annual” shot is that the virus exhibits seasonality like flu, which certainly isn’t the case.
We have a new variant to be concerned about: BA.2.75.2, a daughter of BA.2.75 ,with three new spike mutations that are troubling. This variant has the most immune escape investigators at the Karolinska Institute have yet seen, and that has been replicated by Yunlong Cao’s group in Peking. Given these observations, our current variant-chasing strategy to catch up to BA.5 will not likely help us counter BA.2.75.2. That underscores the need for variant-proof efforts.
In summary, there’s ample evidence that a 3rd shot or 4th shot (1st or 2nd booster) will help provide important protection, and that is especially vital for people age 50+, with ample support for the recommendation for all age 12 and older to get boosters. The right question is about the 5th booster, for which there are no clinical data yet, but will likely extend a high level of protection against severe Covid. But 4 or 6 months isn’t going to cut it as a public health protection policy, as there will be further attrition of interest and uptake for boosters as we go forward. Fortunately, we’re declining in cases and will likely experience a fairly quiescent phase (further descent, no surge) with respect to infections and hospitalizations for the next couple of months until BA.2.75.2 gets legs (or an alternative BA.2 derivative).
From The Washington Post
When should I get the omicron booster? Will I need covid shots forever?
The new shots are here, but many people remain confused about when to get them
Even though the number of daily reported cases fell again this week, the virus is still spreading. About 30,000 people are hospitalized with covid across the United States and 410 Americans on average die each day from the virus.
“I feel that there’s probably a tepid response to the boosters right now because everything looks relatively quiet on the covid front in the U.S.,” said Peter Chin-Hong, an infectious-disease specialist at University of California at San Francisco. “But, once cases start going up, I bet there’ll be people coming out of the woodwork to go and get it.”
Bob Wachter, professor and chair of the department of medicine at the University of California at San Francisco, said that “timing the market” and waiting for case numbers to rise before you get a booster shot usually doesn’t work.
Wachter said that even if you’re not concerned about contracting a severe case of covid-19, you still need to contend with the possibility of long covid. “It just makes all the sense in the world” to boost your protection against the long-term consequences of the disease, he said. “The best protection against long covid is not getting covid.”
“Everybody in America over the age of 12 should get it,” said Ashish Jha, the White House coronavirus response coordinator in an interview.
Many Americans still have a “decent amount of protection” against serious illness, Jha said, but if you got your booster shot last year or early this year, “you don’t have that much protection against infection anymore.”
“You’re doing it for your family and your friends,” Jha said. “And you’re doing something that’s free and incredibly safe. It just feels like a no-brainer.”
What are the side effects of the booster shots?
The CDC doesn’t expect side effects for the updated booster shot to differ from those associated with the current vaccines, which include redness and swelling where the shot was administered, as well as occasional fatigue, headache and muscle soreness. Wachter said there’s a reasonable chance that “you’ll feel crummy for a day or two” after getting the booster shot. But there’s no way of telling whether you’ll have side effects this time around.
What if I just had covid?
The CDC says people who recently had a covid-19 infection should consider waiting three months from their first symptoms, or positive test, before getting a booster shot.
Chin-Hong said those who have contracted the virus in the past few months are walking around with a “force field” for now. But all of that could change if there’s a new variant, and people should keep an eye on the number of coronavirus cases in their community.
Stephanie Langel, an immunologist at Duke University, said that as a 34-year-old healthy adult, she’s not at risk for a severe case of covid-19, but she’s planning to get the booster because she wants the broader protection it confers.
What if I just had rebound-covid after taking Paxlovid?
If you took Paxlovid, an antiviral drug used to treat coronavirus infections, and tested positive again in a rebound infection, you should start counting three months from the second onset of symptoms.
What if I recently got the monkeypox vaccine?
According to the CDC, young men who recently got the monkeypox vaccine, called Jynneos, might want to wait four weeks before getting any coronavirus vaccine. The delay is intended to reduce the risk of inflammation of the heart muscle, a rare complication from mRNA coronavirus vaccines that can affect young men.
How do I know I’m getting the right shot? Should I ask to see the label?
Some experts are concerned the bivalent booster shots look too similar to the vials of primary vaccines from Pfizer-BioNTech and Moderna, which are still in circulation for adults and teenagers who haven’t gotten the vaccine yet. The Pfizer-BioNTech bivalent shot is available for anyone 12 and older. The equivalent booster from Moderna can be taken by anyone 18 and older. The CDC said you can get either booster shot, regardless of your first set of vaccinations.
Michael R. Cohen, the founder of the Institute for Safe Medication Practices, a watchdog organization devoted to preventing medication errors, said that in the two weeks since the FDA approved the new booster shots, they’ve received more than a dozen voluntary reports of practitioners mixing up the original vaccines and the boosters.
CVS, Kaiser Permanente and Walgreens — three national distributors of the vaccine — told The Washington Post the companies have policies in place to ensure people get the correct shots. CVS is using different colored baskets to separate vaccines and checklists to ensure the staff is administering the correct shot.
Spokespeople for both CVS and Walgreens said people are welcome to ask to see the label of the vaccine before the shot is administered. William Schaffner, professor of preventive medicine at Vanderbilt University Medical Care, said health-care providers should not take it personally if patients ask to see a label. Schaffner suggested broaching the topic about confusion around the old vaccine and the updated booster shots.
Just say, “Do you mind double-checking? I’d be so much more reassured,” he said.
How long until a booster starts working? And how long will the protection last?
The CDC says it takes two weeks for the booster to take full effect. But some experts, like Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, said at least some of the protection from the booster shot should start kicking in within days.
But we don’t know how long the updated booster will provide protection against infection, and a new variant could change how much protection this booster offers. It’s too early to say to what degree and at what rate.
Can I get a flu shot at the same time?
Yes. You can get the flu vaccine and a coronavirus vaccine or booster at the same time. But some experts said that to get maximum flu protection, you should get the coronavirus booster now and your flu shot in late October or early November. That way, you’re most prepared for the worst of the flu season in January or February.
“If you get vaccinated now and the peak influenza activity isn’t until the end of January or February, you’ll have lost a lot of your protection by then,” Osterholm said.
Jha, the White House coronavirus coordinator, said he got his coronavirus booster and flu shot at the same time on Friday. He doesn’t want people “overthinking it.”
“For a majority of people, it’s so much more important that they get the vaccine than the exact date they get it,” Jha said.
Are we going to need booster shots forever?
Jha said that it’s hard to predict the future with this virus, but he expects people will probably need another booster in the fall of 2023 as well, “based on everything we know.” In the next few years, Jha said he believes most Americans will only need a booster once a year.
“I can imagine a time down the road — two, three, four, five years down the road — where we decide that we don’t need annual shots,” Jha said.
President Biden has took a course of Paxlovid, after testing positive for COVID-19. The antiviral medicine is recommended for early treatment by the Centers for Disease Control and Prevention.
Paxlovid, which combines two different antiviral drugs, has been found to be highly effective at reducing the risks of hospitalization and death for COVID-19 patients with mild or moderate symptoms. It's linked to a quicker recovery and a return to good health. But in some cases, patients report a "Paxlovid rebound" in which the disease returns.
What kind of regimen is the president on?
Paxlovid comes in pill form, in contrast to remdesivir, the intravenous antiviral drug that former president Trump was given when he contracted COVID-19 and was cared for at Walter Reed National Military Medical Center.
The standard Paxlovid regimen is to take three pills twice a day, for five days. It's not authorized for extended use. The FDA recommends the drug for people with mild-to-moderate coronavirus cases who "are at high risk for progression to severe COVID-19, including hospitalization or death."
Early symptoms for Biden, 79, included "an occasional dry cough," along with a runny nose and fatigue, Dr. Kevin O'Connor, the president's physician, said on Thursday.
What about the Paxlovid rebound?
Paxlovid has been hailed as an important tool to prevent COVID-19's worst effects, and for many people, the main challenge has been getting their hands on the medicine. But it's also been linked to a resurgent COVID-19 infection after the course of pills is finished, known as the "Paxlovid rebound.”
Some people who've taken the medicine say that it quickly eased their symptoms — but that they again tested positive and COVID-19 symptoms returned, anytime from two to eight days after their initial recovery, the CDC said in May.
Dr. Anthony Fauci recently experienced the rebound. And while some people say the second round of symptoms is less severe, Fauci said that for him, the rebound case was worse.
If Biden has a similar experience, it could further delay his return to normal duties.
What are the side effects?
The Food and Drug Administration issued an emergency use authorization for Paxlovid to treat COVID-19 patients last December.
"It leaves a terrible taste in your mouth and also gives some people (me) diarrhea," NPR's Joe Palca reported in May, after being prescribed the medicine.
Both of those reactions, including the taste disorder, dysgeusia, are recognized as potential adverse side effects for the medicine, along with hypertension. Paxlovid can also interact with statins and other drugs, as well as St. John's wort and other supplements, according to the FDA.
How does Paxlovid work?
The medicine is made by Pfizer, and is a combination of two other antiviral drugs, nirmatrelvir and ritonavir.
Nirmatrelvir is a protease inhibitor that "has demonstrated antiviral activity against all coronaviruses that are known to infect humans," according to the National Institutes of Health. Ritonavir previously has been used against HIV; for COVID-19 patients, it serves as a booster to help ensure enough nirmatrelvir is present in the body to be effective.
It's crucial to start on the medicine as soon as a case is diagnosed.
"Paxlovid must be taken within five days after symptoms begin," the Food and Drug Administration said earlier this month. Speed is such an important factor that the FDA has authorized licensed pharmacists to prescribe the drug for people who recently tested positive.