Wednesday, April 28, 2021

"Long Covid:" does it exist? What is it?

Hopefully most of you realize that Covid-19 is not “just like the flu.” The death rate is much higher and there are many more complications involving other organ systems, including blood clots. As we (hopefully) dig our way out of the pandemic thanks to vaccinations and see fewer desperately ill patients on ventilators and many fewer deaths, another issue has been getting attention. Many people who have recovered from the worst of the illness, and many who had only mild symptoms or none are complaining of on-going problems.

The medical profession does not yet understand the cause of these symptoms, and there is vigorous debate over whether the complaints are psychosomatic or physical. The NIH plans to fund research into Covid “long-haulers,” but that research is unlikely to answer our questions in the near future.

The issue is two-fold: persisting symptoms in those who were seriously ill and new symptoms in those (often younger people) who had no or only mild symptoms when infected.

It is not surprising that the sickest Covid-19 patients, those hospitalized, remained sub-par for many weeks or months. An Italian study looked at 143 patients 60 days after onset of illness and 36 days after hospital discharge and found that only 12% felt back to normal. Half still complained of fatigue and shortness of breath and a quarter had joint and/or chest pain. A Swedish study found that among patients needing ICU care, over half still had abnormal lung function four months after discharge. A French study contacted 478 patients who had been admitted to a university hospital for Covid, also four months after discharge, and found that half had at least one complaint not present pre-Covid. Those who complained of shortness of breath were offered a chest CT scan and 61% of these showed persisting abnormalities.

We can hope that time will resolve or at least lessen these persisting symptoms.

More difficult to understand are the new complaints in patients who were not seriously ill.

A Swedish group looked at 323 health care workers who had serum evidence of Covid but had not reported symptoms. Compared to their co-workers with no evidence of prior infection, 5 times as many (15% vs 3%) had at least one moderate or severe complaint 8 months or more after their exposure. In Mexico, researchers looked at 115 patients with mild symptoms and a positive PCR who recovered at home with no treatment; 30 days after the positive test, some 60% had persisting fatigue and shortness of breath. In California, of 1400 patients with a positive PCR and minimal symptoms, 27% studied 60 days later reported symptoms. The symptoms in all of these groups included chest pain, cough, shortness of breath, joint pain and impaired thinking (“brain fog).

While skeptics might say these were all due to anxiety, there is evidence of very “real” and very severe illness coming after infection with the coronavirus. In Singapore, where the virus spread rapidly among “guest workers” from other Asian countries, there was mass testing. Researchers there reported a series of strokes in young (mean age 41) men who had positive Covid antibody testing but had never experienced obvious illness. A larger study in the U.S. used electronic medical records to compare patients diagnosed with Covid-19 with a matched group who had been diagnosed with flu or other respiratory illnesses at six months after diagnosis. The Covid patients had 2.5 times as many brain hemorrhages, ischemic strokes and new diagnoses of dementia. They also found higher numbers with insomnia, anxiety, psychosis and substance use disorders.

What is “long Covid?” The only honest answer is that at this point we really do not know. One theory is viral persistence. Another is auto-immunity. Favoring the former are reports that many patients with persistent symptoms report marked improvement after vaccination. Favoring the latter is that women are disproportionately affected, and we know that women have more auto-immune disorders than do men. And yes, some of the symptoms may be psychosomatic. Having a scary illness would tend to make one focus on bodily symptoms.

What can we do?

If you are a physician, I would ask you to maintain some humility and remain open-minded about an illness still under study. Do not dismiss the complaints as being due to anxiety.

If you have persisting symptoms and have not been vaccinated, I would encourage you to get the vaccine, as patients with mild or no symptoms are at risk of reinfection and many of your fellow sufferers have improved after vaccination.

If you have never had Covid, take this as one more reason to get a vaccine as soon as you can.

All of us: stay tuned!

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Tuesday, April 13, 2021

J &J Vaccine "paused." Should you worry?

The news media and our email in-boxes this morning were filled with the news that the CDC had recommended a pause in use of the Janssen/Johnson & Johnson Covid-19 vaccine pending investigation of six reported cases of an unusual illness that occurred following its use. Of the 6.8 million doses given in the U.S. to date, 6 women aged 18 to 48 had developed severe clotting disorders along with low platelets. [Platelets are the body’s first line of defense against bleeding, and you expect low platelet counts to be accompanied by bleeding, not clotting.]

This mirrors the concerns raised earlier in Europe about a similar illness that followed use of the AstraZeneca vaccine, leading many European countries to stop using it or to restrict its use to older people, since there, also, the rare illness was reported in younger people only. In Great Britain, which has given more than 20 million doses of the AZ vaccine, there have been 79 cases of blood clots associated with low platelets. In two papers published in the New England Journal of Medicine, 13 of 16 patients described were women, and their ages ranged from 22 to 54, with most being in their 30’s.

The common thread seems to be that both the AZ and J&J vaccines share similar technology, using harmless adenoviruses to get Covid spike protein code into human cells to produce antibodies. This is different than the mRNA technique used by the Pfizer and Moderna vaccines, which to date have not been linked to this rare disease.

Is there any similar disease unrelated to vaccines? There are two. A condition called TTP (thrombotic thrombocytopenic purpura) occurs at a rate of about 3 people per million per year, is commoner in women and has an average age of onset of 41. While this disease has clotting, the clots occur in very tiny vessels, unlike the vaccine-associated illness. Much more similar is HIT (heparin-induced thrombocytopenia). This disease, caused by an immune reaction to the blood-thinner heparin, occurs in some 2% of patients receiving heparin and is commoner in women, but tends to occur in older individuals, being very rare in people under 40. This does cause the type of clotting now being reported. Our best guess at this point is that the vaccine-associated illness is caused by an immune reaction like HIT, albeit to what is still unknown.

What are the important things you should know?

1. This is a rare side-effect if it is indeed a side effect, occurring in 1 to 4 people per million.
2. There is no reason to believe that it would happen with the Pfizer or Moderna vaccines.
3. It has so far only been reported in younger vaccine recipients, predominantly women.

What should you do?

1. If you have a chance to get the Pfizer or Moderna vaccine, get it!
2. If you are over 65 and have the choice of the J&J or AZ vaccine or no vaccine, I would personally take the vaccine.
3. If you have recently had the J&J or AZ vaccine, relax. You are VERY unlikely to have this illness happen to you.

Remember that all medications have side effects. It is your doctor’s job, working with you, to decide if the benefits exceed the risks of any medication you may take.

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Sunday, April 4, 2021

You can teach an old dog new tricks!

Colchicine is one of the longest-used remedies in the modern medical armamentarium. It was mentioned in the Ebers Papyrus, dating from Egypt in 1500 BC, and its use to treat gout was described by the ancient Greeks. It is derived from the autumn crocus, scientifically named Colchicum autumnale. The active ingredient was isolated in the early 1800’s and it has been widely used to treat gout ever since.

When I was a pup, the dictum was to treat an acute gout attack by taking one colchicine tablet every hour until either the gout was resolved or the diarrhea was so bad that the patient did not care about the gout. In the intervening years we have learned a much more civilized approach. Lower doses work just as well and have much less GI side effects.

Readers of Prescription for Bankruptcy know that colchicine is also a sordid example of pharmaceutical company greed, with this ancient remedy manipulated into becoming a high cost branded product.

My focus here, however, is to note that this “one trick pony,” which 50 years ago was considered as useful only to treat gout has become a hot new product, with a rapidly expanding portfolio of uses.

Amazingly for a product of this lineage, the exact mechanism of action of colchicine is still being studied, but it clearly has strong anti-inflammatory properties, and works to reduce the effects of the body’s white blood cells. It is this anti-inflammatory property that is being exploited to treat a broad and growing range of diseases. The first new use was to treat a rare disease, Familial Mediterranean Fever, a disease whose victims suffer repeated attacks of fever, joint and abdominal pain, and many of whom go on to develop chronic kidney failure. Two trials published in 1974 showed that colchicine could dramatically reduce the frequency of acute attacks, and it was later shown that it largely prevented the kidney disease.

A variety of rare skin diseases characterized by local inflammation also respond to colchicine. More recently, colchicine has shown the ability to reduce recurrences of pericarditis, a non-fatal but very painful inflammation of the sac surrounding the heart.

As most of you know, the leading cause of death in the U.S. and most western countries is coronary disease. While we tend to simplistically think of heart attacks as caused by build up of cholesterol deposits in the coronary arteries, inflammation has long been felt to play a part. It is thus not surprising that several trials have looked at the effect of colchicine on heart attack. Two large trials, one in patients who had recently suffered an acute heart attack and one in patients with stable coronary disease found that daily low-dose colchicine reduced the risk of heart attacks, stroke, coronary surgery and cardiovascular death. Before we anoint colchicine the Fountain of Youth, it must be noted that overall death rates were not reduced, and may have even been a bit higher, in the colchicine group than in those taking placebos.

Finally, it would be remiss in 2021 not to note the potential role of colchicine in the fight against Covid-19. You may be aware that cortisone-type drugs, which have an anti-inflammatory effect, have been proven to improve outcomes in very sick Covid-19 patients, so a trial of colchicine was obvious. A small trial done in Brazil at the beginning of the year gave colchicine or placebo for 10 days to 72 patients hospitalized with Covid-19. Those given colchicine had shorter time in the hospital and less need for oxygen. While the small size of the trial prevented conclusions about the effect on survival, the only two deaths were in the placebo group.

A much larger trial was conducted by a group from Montreal. They studied 4159 patients not sick enough initially to be hospitalized. Half were given 0.5 mg of colchicine 3 times daily for three days and then once daily for another 27 days. Since this was a less sick group, the absolute numbers were not high in either group, but the patients given colchicine had reduced rates of needing to end up in the hospital, require a ventilator or die.

Just because a drug has been around for a long time, it can still be very useful, and there are always new things to learn about it.

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