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New Variants That Evade Immunity Are On The Move
Virologists have been watching the rise of the BQ.1.1 variant for the past several weeks, and it appears to be one the most immune evasive SARS-CoV-2 variants yet seen. A new report from Germany compared resistance to monoclonal antibodies for many of the most troublesome new variants (mutation map of spike protein below) and, unlike the others assayed, showed that BQ.1.1 demonstrates resistance to all available monoclonal antibodies. That certainly reinforces this variant’s immune escape properties.
How To Interpret This Chart
The left column lists the names of monoclonal antibodies. A list of common viral variants is across the top.
Green boxes: antibody still very effective.
Yellow boxes: less effective.
Light brown: even less effective.
Maroon boxes: antibodies have almost no affect on the virus.
Notice that variant BQ.1.1,which is now moving across the country, is quite immune to all the drugs available!
It’s Not The Bats: The Emergence Of Covid
A recent publication in Science concludes that multiple transmissions from wildlife at a market in Wuhan probably led to the SARS-CoV-2 emergence. Although the most probable reservoir animal was Rhinolophus bats, this pandemic, like most zoonotic spillovers likely involved intermediate animals. The wholesale market in Wuhan sold many animals susceptible to coronavirus, including raccoon dogs, foxes, and mink. Wild animals harbor various pathogens, including potentially pandemic-causing coronaviruses. The more species in the wild or on farms having the virus, the more it has time to mutate and become infectious to humans.
After comprehensive geographical studies, epidemiological evidence showed that early cases were centered around the Wuhan market and the surrounding neighborhoods. The study pretty much eliminates the hypothesis that the virus escaped from the Wuhan Institute Of Virology.
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).