A November chill in Covidlandia

Bundle up, and buckle up for this month's tour de force.

The Examined Artist-in-Residence is back with what I consider an outstanding illustration for this month’s edition. Kids of 13 years can do amazing things.

Welcome back to some monthly highlights from a place I call Covidlandia, a forgotten land between black and white, carefree and cautious, pandemic beginning and end. Here I present recent news, scientific discoveries, and medical knowledge that caught my attention and that is of interest to primary care. We are wary of the stories told; instead we follow the data and scientific studies. I try to curate and comment, and realize that one human being cannot possibly keep up with everything. But I try to collect useful, actionable stuff. January, February, March, April, May, June, July, August, September, October, and now November.

Some housekeeping:

• Twitter has become a sad place ruled by algorithms, advertisements, and agendas. I’m liking Bluesky. Consider joining me over there if you once thought Twitter was helpful, too.

• I’m going to keep writing as I always have. But I’m also planning to step up against bad health information as part of an evidence-based, old-school-expertise-driven band of professionals who are declining to bend the knee. If you are concerned by the anti-vaccination, pseudoscientific, agenda-driven voices that make lots of money harnessing people’s resentment and confusion — stick around. Upgraded subscriptions do increase visibility and reach on sites like Substack and beyond.

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It’s been 5 years since the genesis of SARS CoV-2

I’d like to acknowledge Dr. Ben Maser’s article in The Atlantic about the new crop of revisionists and iconoclasts who are ready to tear into our institutions. Drs. Katelyn Jetelina and Kristen Panthagani also published an accurate and constructive review. These profiting populists are riding a wave of understandable resentment and anger about the pandemic. Many people lost jobs, family and friends, felt bullied into vaccinations, found their children falling behind in virtual classrooms. Consider all our little souvenirs of a terrible year. But 2020 was always going to be horrible. We should never forget the many heroes, from the grocery store to the ICU. We should honor our own service and sacrifices. I propose a national day of reflection and remembrance. We shall not forget the ~3,000 who died on 9/11/2001. What about the ~3,000,000 Americans who’ve died of Covid? Don’t forget that restrictions slowed down the death toll, the overflowing hospital morgues, saved millions of lives, bought us time to research a novel virus, produce PPE, and achieve a modern wonder of the world - a vaccine in less than a year that saved an estimated 20 million lives in the first year alone. 20,000,000. Nonetheless, we suffered. It was a collective trauma. But be aware if you feel it — that legacy of bitterness and distrust is now a major political force.

More on this later. Read on.

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State of the states

Covid rates are going to creep up after Thanksgiving. I have seen a decent uptick in my practice this week. Some near and dear to me are affected; maybe myself as I monitor stuff and test. I’m thankful for immunity gains from vaccinations (and prior infections), antivirals, metformin, and nasal saline. A picture is worth a thousand words, so here is the most recent data and forecast from the Pandemic Mitigation Collaborative:

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More support for using Paxlovid when sick

We keep finding benefit to taking antivirals even in 2024 after some personal combination of previous illnesses and vaccinations. I’m keeping my post in defense of Paxlovid up to date with this new one, too.

An authoritative randomized clinical trial published in Clinical Infectious Diseases demonstrated that Paxlovid significantly reduced Covid hospitalizations, deaths, and healthcare resource utilization compared to placebo during the Delta period from July 2021 through December 2021. In the nearly 2,000 patients randomized, those given Paxlovid had an 85.5% reduction in hospitalizations, faster symptom resolution (median 16 vs 19 days), and zero deaths in the Paxlovid group compared to 15 deaths in the placebo group over 6 months.

Yes please.

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Molnupiravir not a bad option

Paxlovid can be contraindicated with some other medications. Outpatient infusion centers offering remdesivir treatment are hard to find. Third line molnupiravir pills have very few drug-drug interactions, but most studies show less efficacy for the results we care about. Molnupiravir also has the theoretical potential to cause mutations in DNA. And yet in some older, complicated, high risk patients I have used it successfully. Maybe it’s better than we give it credit for…

A large-scale study conducted in the Czech Republic during 2022 found that the antiviral drug molnupiravir significantly reduced Covid mortality when administered early in the infection. The research, analyzing data from over 74,500 molnupiravir recipients compared to 1.5 million matched controls, demonstrated that the drug halved the risk of Covid death and lowered all-cause mortality, particularly in patients over 65 years old. The medication proved effective regardless of vaccination status, sex, or hospitalization status, but showed the greatest benefit when started within the first three days of diagnosis. Notably, patients with kidney or liver disease experienced substantial benefits, with the drug reducing their elevated mortality risk by 42%.

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AI suggests a much higher rate of long Covid than human doctors pick up

Long Covid is at once a potential scapegoat for many unexplained symptoms in primary care and a valid, unifying explanation for complex syndromes of brain fog, mood problems, fatigue, and feeling winded. Relying on doctors to diagnose long Covid is problematic, as we have to rule out all sorts of problems first. There is no consensus blood test. But in my practice I include long Covid in the differential diagnosis of many problems, ranging from worsening insomnia to headaches to depression. A new study finds that long Covid incidence is quite high.

Massachusetts General Hospital (MGH) researchers have developed a new AI tool that analyzes electronic medical records to identify signs of long Covid, suggesting that about 23% of the population has experienced the condition—a much higher estimate than the previously accepted 7%. The AI tool works by identifying unexplained long Covid symptoms in patients who had Covid-19 at least two months prior, using data from nearly 300,000 patients across 14 MGH hospitals and 20 community health centers. The tool proved to be more accurate than existing diagnostic codes and showed less bias toward populations with better healthcare access, potentially offering a more precise and equitable approach to diagnosing long Covid. While the study had some limitations, including incomplete electronic medical record data and uncertainty about initial infection timing, researchers believe this tool could transform the diagnostic process for long Covid and improve treatment approaches.

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A good summary of some emerging long Covid treatments

The struggle continues, both to help patients with chronic long Covid and to increase awareness and decrease denialism. Here are some ideas that a few zeitgeist doctors are using for treatment in addition to brief explanations of their proposed mechanisms:

• Low-dose naltrexone — anti-inflammatory properties and opiate receptor upregulation. May help some with brain fog, pain, sleep issues, and fatigue.

• SSRIs (selective serotonin reuptake inhibitors) and antidepressants — address lower serotonin levels found in long Covid patients, helping some with concentration issues, brain fog, and depression.

• Low-dose Abilify (aripiprazole) — functions as an anti-inflammatory agent when used in low doses, perhaps helping with cognitive issues.

• Modafinil — targets inflammatory cytokine pathways and affects neurotransmitters, may help with fatigue and neurocognitive deficits.

• Metformin — operates through anti-inflammatory effects and may reduce viral persistence, working best when taken during acute Covid phase rather than after developing long Covid. It’s part of my self treatment, and actually has shown antiviral effects on it’s own in terms of lowering viral loads.

• Antihistamines (including famotidine) — block histamine receptors to reduce mast cell-related inflammation, sometimes helping with symptoms like brain fog, breathing difficulties, and elevated heart rate.

Effectiveness will vary significantly between patients, and all treatments should be taken under medical supervision due to potential risks and interactions.​​​​​​​​​​​​​​​​ This is an example of off label prescribing. Thanks for the link, KB :)

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Also, Dr. Daniel Griffin throws down a monster dunk with this very helpful, evidence-based, long Covid review. Here is a referenced table of therapeutics that are being tried, mostly overlapping those cited above.

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Two more studies confirm that recent vaccination is tied to a lower risk of long Covid

The VENUS study from Japan, published in the journal Vaccine, analyzed data from 84,464 Covid patients to investigate how the timing of Covid-19 vaccination affects the development of long Covid. The researchers divided participants into three groups based on when they got infected relative to their most recent vaccination: distant (≥365 days), intermediate (150-364 days), and recent (14-149 days). Despite having the oldest average age and highest rate of pre-existing conditions, the recent group (infected within 14-149 days of vaccination) had significantly lower risks of developing 28 out of 36 studied post-Covid conditions over an 8-month follow-up period. To note just two of those conditions: the recent group experienced a 45% reduction in fatigue (HR 0.55) and 42% reduction in pain (HR 0.58). The study concludes that Covid-19 vaccination can effectively reduce the risk of long Covid when administered within 5 months before infection, with this protective effect being particularly pronounced in older adults.

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A second study of 936 essential workers in six US cities, published in The Journal of Infectious Diseases, found that 24% developed long Covid symptoms after infection during the Omicron wave, with vaccinated individuals making up 83% of the total participants. Those who received a third mRNA vaccine dose showed significantly reduced odds of developing various long Covid symptoms compared to unvaccinated participants, with reductions of 63% for gastrointestinal symptoms, 44% for neurologic symptoms, and 52% for other symptoms. The researchers concluded that Covid-19 vaccination, particularly a third dose, served as an important tool for preventing post-Covid condition during Omicron variant predominance.

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Evidence that last year’s updated shots helped

A study published in Clinical Infectious Diseases, conducted in Singapore from November 2023 to January 2024 during a JN.1 variant wave, analyzed data from over 3 million boosted adults to assess the effectiveness of updated Covid-19 vaccines. The results showed that receiving an updated XBB.1.5 booster within the previous 8-120 days reduced the risk of JN.1 infection by 41%, emergency department visits by 50%, and hospitalizations by 42% compared to those boosted with older vaccines more than a year ago. The study concluded that annual updated Covid-19 boosters provide significant protection against emerging variants like JN.1, both for previously infected and uninfected individuals.

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Interesting case report

Here’s one example from my little practice of 3-4,000 patients. I saw a 68 year old male with chronic lymphocytic leukemia, IgA immunoglobulin deficiency, coronary artery disease, only 2 Covid shots ever, who came down with his first case of Covid about 6 months ago. After discussing options, risks, benefits, unknowns, he decided to take both metformin and Paxlovid. I saw him for a check up this month. He reported no significant side effects from the treatment regimen, and did great getting over Covid. He had no symptoms that I could attribute to long Covid at his check up.

N=1, but still.

I was happy for him.

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Masks and tests help, especially in healthcare situations, despite many abandoning both

In a cohort study published in JAMA Open Network analyzing 641,483 hospital admissions across 10 hospitals in the Mass General Brigham system from 2020 to 2024, researchers examined how changes in Covid testing and masking policies affected hospital-acquired respiratory viral infections. When universal masking and testing requirements were ended in May 2023, there was a 25% increase in hospital-onset respiratory viral infections compared to the previous period. After reinstating masking for healthcare workers in January 2024 during a winter surge, hospital-onset infections decreased by 33%.

The study's findings suggest that both masking and testing were effective measures for protecting hospitalized patients from respiratory viral infections.

I have yet to take off a mask while seeing patients in 100 square foot rooms.

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There is still time to speak up and speak out

As a primary care doctor I have felt my job get harder and harder over the years. There are many reasons for this, but germane to this post is the massively increasing effort I have to put into counseling people about vaccines. Even if RFK Jr and some number of his associates are not actually confirmed to lead our most important national health agencies, damage has already been done by giving them the credibility of large platforms.

Remember those Covid vaccines, the ones that saved over 20 million lives globally? Prevented more than 18 million additional hospitalizations and more than 3 million additional deaths in the United States alone? RFK Jr. would have blocked them.

I’m going to drop this illustrative excerpt from a great post on Science-Based Medicine.

HILLYARD: During the pandemic, the height of the pandemic, you were questioning the FDA and calling them out for approving the emergency authorization of the COVID vaccines. If you had been in charge of the FDA at that time would you have blocked the authorization of the COVID vaccines like you were suggesting publicly?

RFK JR: What I was saying at that time is the vaccines are not going to prevent transmission, which they were telling the public that they would. They were saying you need to take this vaccine in order to protect Grandma. I knew in May of 2020 that the vaccines were not going to protect against transmission, because I was actually reading the monkey studies…

HILLYARD (interjecting): But you would not have told the FDA to block the authorization of the vaccine…

RFK JR: I would have been honest with the American people and…

HILLYARD (interjecting): So you wouldn’t, you wouldn’t have blocked it?

RFK JR: I wouldn’t have directly blocked it. I would have made sure that we had the best science and there was no effort to do that at that time.

~Translation: RFK Jr. most definitely would have blocked the mRNA Covid-19 vaccines if he had been in charge in 2020.

While healthcare providers like me were in the grueling pandemic trenches, RFK Junior’s nonprofit organization was busy filing over 30 lawsuits related to vaccine requirements, online censorship, adverse event data, and the authorization of Covid shots. He’s been making 500K a year, and recently got a pay raise such that he was pulling down 20K a week from the nonprofit. Recently he sued my alma mater Rutgers University over the school’s vaccination requirement for students. I recall being a Rutgers student in 1994 when we had a measles outbreak. The school required MMR boosters, and I received one, gladly.

From The Annenberg Public Policy Center here at the University of Pennsylvania in Philly:

In December 2021, Kennedy falsely called the Covid-19 vaccine “the deadliest vaccine ever made,” citing deaths reported to the Vaccine Adverse Event Reporting System, which is part of the nation’s vaccine safety monitoring systems. But as we have explained, the reports are unverified and, as the VAERS website warns, any report “to VAERS is not documentation that a vaccine caused the event.” Expanded reporting requirements and intense scrutiny of the widely given Covid-19 vaccines did increase reporting to VAERS, but this doesn’t mean the shots are unsafe.

But it’s not just Covid vaccines that will be under threat. The Science-Based Medicine article further speculates upon which vaccines may be first targeted by RFK, Jr. should he be confirmed with a supporting cast of outliers who learned the wrong lessons from the pandemic. Expect the mRNA Covid vaccines, Measles/Mumps/Rubella shots for kids, and the HPV shots that have slashed cervical and oral cancer rates to be on the chopping block first. The concept of “choice” is often invoked by groups working to repeal vaccination mandates. But recall that MMR shots only prevent outbreaks if 90-95% of kids get them:

Worldwide, there were an estimated 10.3 million cases of measles in 2023, a 20% increase from 2022, according to new estimates from the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC). Inadequate immunization coverage globally is driving the surge in cases… The new data show that an estimated 107,500 people, mostly children younger than 5 years of age, died due to measles in 2023… Even when people survive measles, serious health effects can occur, some of which are lifelong. Infants and young children are at greatest risk of serious complications from the disease, which include blindness, pneumonia, and encephalitis (an infection causing brain swelling and potentially brain damage).

If and when H5N1 bird flu takes off, with a much higher mortality rate in a second “once in a lifetime” pandemic, don’t count on a new vaccine to be approved by a decimated public health system led by someone who has made a career out of undermining world health. When millions die, that sometimes includes us.

And finally, don’t forget that “major landmark study published by The Lancet that showed global immunization efforts have saved an estimated 154 million lives – the equivalent of 6 lives every minute of every year – over the past 50 years. The vast majority of lives saved – 101 million – were those of infants.”

If you are concerned, call your senator, especially if your Republican senator happens to be on the Senate Finance Committee, which is the first step for HHS confirmation. Forward this email. Vaccination stuff is particularly relevant to Covidlandia citizens, but there are plenty more concerns about this guy.

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Persistent mistrust in Covid vaccines stands at about 35%

Glass half full or half empty?

A new study analyzed data from surveys conducted between 2021-2023 to examine how trust in Covid-19 vaccine science influenced vaccine acceptance in the United States, finding that trust levels remained relatively stable at around 65% throughout the period. The research revealed that males, those with higher income and education levels, and people who had lost family members to Covid illness were more likely to trust vaccine science, with trust in science in general being a crucial predictor of both initial vaccine acceptance and willingness to receive boosters. Additionally, trust in the CDC as a source of information was significantly correlated with vaccine acceptance, though trust levels in the US were consistently lower than global averages, highlighting the need for improved science literacy and public health communication.

And yet vaccination rates this fall are much lower than the ~64% trust level. As of 12/2/2024 the percent of the population reporting receipt of the updated 2024-25 Covid-19 vaccine is only 9.4% for children and 19.7% for adults age 18+, including 41.6% among adults age 65+.

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Another study shows benefits of vaccinating kids

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe post-Covid condition that occurs 2-8 weeks after infection, causing fever, inflammation, and multi-organ involvement in children under 21.

A California-based study published in the journal Vaccine compared MIS-C rates between vaccinated and unvaccinated children, finding that unvaccinated children aged 12-17 were 23 times more likely to develop MIS-C than vaccinated children, while unvaccinated children aged 5-11 were 3.3 times more likely to develop it than their vaccinated peers. All four deaths from MIS-C in the study occurred in unvaccinated children, and unvaccinated children were more likely to have severe cases involving six or more organ systems. About 2,000 American kids have died of Covid. Despite some limitations like potential underreporting and small sample size, the study provides strong evidence that the Pfizer-BioNTech vaccine significantly reduces the risk of developing MIS-C in both age groups.

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Long-term neurological effects of Covid: younger/middle aged populations disproportionately affected

A new study for review from Annals of Neurology. The neurological impact of Covid is significant and widespread, with approximately 45% of Covid survivors experiencing persistent symptoms at least one month after infection, based on a systematic review and meta-analysis of about 200 worldwide studies comprising over 700,000 patients. This drops to 15% after twelve months.

According to recent survey data from September 2024, among US adults nearly 30% reported experiencing long Covid at some point, with 8.7% still experiencing symptoms. The most common neurological symptoms in those experiencing some were brain fog (affecting over 80% of these patients), headache (56-71%), and dizziness (54%). Notably, these neurological symptoms disproportionately affected younger and middle-aged adults, who made up the majority of cases despite older adults having more pre-existing conditions and abnormal neurological exam findings.

Do I see these symptoms in primary care? Yes. Can I confidently blame Covid in the moment? It’s a tricky discussion and work up.

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Conclusion

You made it. We made it!

Let me summarize each main section of this month’s edition:

• I’m hanging around Bluesky - join me if you are, too. And if you want to support my writing, give Examined a sincere boost. We can’t have all the angry contrarians at the top.

• The data continues to support early intervention with antivirals like Paxlovid and molnupiravir, with more studies showing significant reductions in hospitalization and death rates even in our current “endemic phase.” I keep offering treatment, and encourage testing when people are sick. Even when they think it’s sudden allergies.

• Long Covid remains a significant concern, potentially affecting more people (23%) than previously estimated (7%) according to AI analysis of medical records. We now have several promising treatment approaches, though much more research is needed.

• Vaccination timing matters, as does staying up to date - studies show that getting vaccinated within 5 months before infection significantly reduces long Covid risk. The updated XBB.1.5 booster was pretty effective against the JN.1 variant. The current updated vaccine will likely show similar results.

• Basic preventive measures still work - the hospital studies remind us that masks and testing continue to play important roles in reducing transmission, particularly in healthcare settings.

• Children's vaccination still has benefits, as illustrated by a study showing that unvaccinated youth had significantly higher risks of serious complications like MIS-C. I’ve written about other benefits, too.

• The neurological impact of Covid-19 is substantial and somewhat unexpected, disproportionately affecting younger and middle-aged adults with symptoms persisting in 45% of survivors after one month. It’s partly why I’m aggressive with offering treatment.

• Despite strong evidence supporting vaccine efficacy (with trust levels around 65%), actual vaccination rates remain concerningly low at under 20% for the newly updated shot.

• As we mark five years since Covid-19's emergence, we face both medical and political challenges. While we have effective tools to fight this virus, maintaining public trust and evidence-based policies remains crucial for public health. We will miss it when it’s gone on both sides of the aisle, but our state enemies and circulating viruses will be satisfied.

Looking ahead, our focus must remain on following the data, protecting vulnerable populations, and maintaining vigilance against both the virus and misinformation. The pandemic may be "over," but Covid-19→24 continues to evolve as both a medical and public health challenge.

Take good care!