October highlights from Covidlandia
With a Halloween and presidential election finale
Welcome back to some monthly highlights from a place I call Covidlandia, a forgotten land between black and orange, 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. I curate and comment, and realize that one human being cannot possibly keep up with everything. But I try to highlight useful, actionable stuff. January, February, March, April, May, June, July, August, September and now October.
Where we are right now
Not too bad.
About 1 in every 125-150 people in the U.S. are estimated to have Covid presently.
So if you look around at a room full of people, or a full day’s worth of social contacts, here are the estimated chances that anyone in your daily life is infectious with Covid right now:
Let’s focus on the forecast for November. Predictably it will start bending upwards as we head indoors even more. By Thanksgiving some think we will be back to a million infections in the U.S. per day. This would be like 1 out of every 50 people having active Covid. So this might be a good time to get that updated Covid shot if you have not done so already this fall:
And don’t forget that WasteWaterSCAN is still a good resource for checking the local prevalence of SARS CoV-2 and many other nasty bugs in your area of the U.S.
Another study in support of using Paxlovid
If you’ve been keeping up with my posts here, you know that I’m frustrated with physician thought leaders who discount and undermine using antivirals like Paxlovid. They usually obsess upon the minority of studies showing little benefit, while discarding the many studies showing that treating patients with Paxlovid and other antivirals can reduce severe disease, hospitalization, death, and long Covid.
A Dubai-based retrospective cohort study published in Nature Scientific Reports analyzed electronic health records from 7,290 Covid patients (672 receiving Paxlovid, 6,618 without antivirals) between May 2022 and April 2023 to assess Paxlovid's impact on hospitalization and long Covid rates, with long Covid defined as symptoms persisting or emerging 28+ days post-infection.
After adjusting for factors, Paxlovid was associated with a 61% lower risk of hospitalization (adjusted hazard ratio [aHR], 0.39; 95% confidence interval [CI], 0.18 to 0.85).
During a 90-day follow up, 208 patients (2.8%) experienced long-Covid symptoms that prompted them to see a physician. Paxlovid was associated with a 58% reduced risk of developing such symptoms during that period (aHR. 0.42; 95% CI, 0.19 to 0.95).
I’m adding this one to my post called In Defense of Paxlovid, even though it is not a randomized controlled trial and has wide confidence intervals. It adds to the consistent evidence of benefit.
Masks help if and when you want to deploy one, and that should be OK even in 2024
I just wrote an editorial entitled “Why mask bans are the latest attack on American freedom.” It was published this weekend on a popular medical site read by clinicians and patients called KevinMD. I’ve been reading articles from this website for over 20 years now (gulp), and I contribute every so often.
Plus, a new comprehensive review of over 400 studies across multiple disciplines confirms that masks and respirators effectively reduce respiratory infection transmission, with effectiveness increasing with proper and consistent usage.
Future boosters with the new, updated Covid vaccines for 65 and up, and for immunocompromised
The CDC now recommends people 65 years and older and those who are moderately or severely immunocompromised receive a second dose of 2024-2025 COVID-19 vaccine six months after their first dose.
These updated recommendations also allow for flexibility for additional doses (i.e., three or more) for those who are moderately or severely immunocompromised.
Most of my highly motivated patients already received the updated shot in September. I got mine then, too. Most folks over age 65 would be recommended to get a booster around February. But there are plenty of individual considerations, timings, and scenarios to hash out with individual people.
Another confirmation of which public situations are higher risk for Covid transmission
Based on this systematic review and meta-analysis of 34 studies published in Journal of Infectious Diseases that examined SARS-CoV-2 transmission in indoor settings, singing events had the highest secondary attack rate at 44.9%, followed by indoor meetings/entertainment venues (31.9%), fitness centers (28.9%), and indoor dining settings (25.5%). Workplaces had the lowest rate at 6.2%, though workplaces are quite a heterogeneous mix of people, ventilation, and square footage . The researchers found that singing and exercise particularly increase virus-containing aerosols when compared to resting states.
P.S. - A secondary attack rate (SAR) is the percentage of contacts of an initial infected person (called the index case) who end up testing positive for the infection. In this study specifically, they defined it as the percentage of people who shared an indoor space with an infected person and later tested positive for SARS-CoV-2 through PCR or antigen testing. For example, in singing events where the SAR was 45%, this means that on average, about 45% of the people who were in close contact with an infected person during a singing event ended up contracting COVID-19 themselves.
Covid doesn’t care if you are a Marine
The few, the proud, the Marines. I have massive respect for those who serve in our military. I do not know how many young Marines are staying up to date with Covid vaccinations, but these shots are no longer mandatory (like immunization for other diseases). Perhaps they should be. Here’s a troubling study published in The Lancet:
In this study from Spring 2020 to April 2022, researchers followed 899 young U.S. Marines (median age 18) to assess long-term effects of COVID-19, with vaccination rates increasing from 31.8% during first visits to 82.9% by second visits. Among the 798 Marines who had COVID-19 (88.8% of participants), about a quarter (24.7%) developed Post-Acute Sequelae of COVID-19 (PASC/Long Covid) lasting at least 4 weeks, with the most common symptoms in that quarter being loss of taste/smell (41.6%), shortness of breath (37.6%), and cough (22.8%). Those with PASC showed decreased physical performance, running 25 seconds slower on average in their three-mile fitness tests compared to pre-pandemic reference groups, and also reported higher rates of depression, anxiety, and somatic symptoms.
These rates seem a little higher than other studies to me. Perhaps this reflects that Marines are presumably not given much time to recover, and we know that too much physical exertion right after Covid can actually damage muscle.
Covid survey in China
The broad strokes here are that many people complain of lingering symptoms after Covid. Repeat infections lead to more prevalent complaints. And “Vaccination, particularly multiple boosters, significantly reduced long-term symptoms by 30%–70%.” In my opinion this study has lots of problems, but to dismiss what people are reporting also has lots of problems.
In this large-scale online survey conducted in China from November 2023 to January 2024 and published in The Lancet, 68,200 participants were analyzed, finding that 10-30% experienced long COVID symptoms, with fatigue, memory decline, decreased exercise ability, and brain fog being most common. Most participants had their first infection around late 2022/early 2023 when China adjusted its zero-COVID policy. The study identified key risk factors (being female, underlying diseases, smoking, drinking, and severe acute COVID) and protective factors (vaccination, especially boosters). Reinfections, though milder in acute symptoms, led to more complaints of long Covid. The study had several limitations, including potential exclusion of elderly and children, self-selection bias, reliance on self-reported symptoms rather than clinical assessments, demographic distribution issues, memory-based timing, inability to isolate effects of co-infections, limited vaccine variety among participants, lack of SARS-CoV-2 negative control data, and inability to determine specific viral variants.
And yet we have to listen to people. Recall that’s how the very concept of long Covid arose. Patients were the first to tell us about novel syndromes after this novel illness.
Low dose naltrexone for long Covid treatment
I have three patients, all of whom are in their 30’s, who are trying low dose naltrexone for their debilitating long Covid syndromes. One has noticed definite improvement, while the other two with mild/moderate improvement so far. One way this medicine works is that it binds to and blocks opiate receptors, which seems like the wrong thing to do in people with chronic pain. But at low doses one of the theories is that the body then upregulates (increases the number) of natural opiate receptors in the body. Plus other mechanisms.
This is a great article about it. Low-dose naltrexone (LDN), originally developed for opioid and alcohol addiction in the 1960s, is being investigated in multiple clinical trials as a potential treatment for long Covid, building on decades of off-label use for conditions like chronic pain and ME/CFS. A major Australian trial is studying LDN's effects on long Covid symptoms by tracking multiple indicators including cognitive function, pain, sleep, and fatigue in 100 participants, with researchers discovering that the drug may help "unlock" faulty calcium ion channels in immune cells. Early observational data from Stanford's long Covid clinic suggests that about one-third of patients experienced significant improvements in fatigue, post-exertional symptom exacerbation, and sleep quality when taking LDN, though researchers emphasize the need for more rigorous clinical trials to confirm these benefits.
Take Covid seriously in kids
If we are only worried about hospitalization and death from Covid, kids are doing great. But I’m still concerned about the long game with kids. It’s why my daughter stays up to date with Covid vaccines. I received some hate mail calling me a murderer for doing this. So ridiculous.
Here’s what the hive mind has decided to do about staying up to date with Covid vaccines this year:
As we prepare for another winter of COVID-19, vaccines — now one of our only remaining collective health measures — are very underutilized. Only 12% of adults and 4% of children had received updated COVID-19 vaccines as of October 12, per the CDC.
Here is a great bit of reality from Dr. Ruth Crystal:
COVID is not benign for children. A new piece in Scientific American shows that 10-20% of children infected will get Long COVID, often with symptoms such as cognitive difficulties, memory issues, pain, and fatigue. On last estimate, 5.8 million American children have Long COVID, which can impact nearly every organ system and contribute to both learning and behavioral challenges. Repeat infections have been found to increase the risk of Long COVID in adults and probably does in children as well. It is important to protect kids with vaccination, improved air quality in schools, and better health policies such as staying home when sick.
I listed the evidence supporting our decision to keep our daughter up to date with CDC recommendations. I think it’s unfortunate that 95% of kids are missing the chance to prevent a Covid infection for a while, or to reduce the severity of their next one, or to reduce their cumulative Covid toll over such a long horizon. Of course repeated vaccines might be found to be problematic some day, but that kind of evidence is just not rolling in… for kids or adults. Why keep waiting for it? Hoping for it?
And one last thought about the most vulnerable. One recent study from the CDC found that infants under six months of age (too young to be vaccinated) were hospitalized for Covid at higher rates than any other age group except for the oldest (over age 75) from fall 2022 through spring 2024. Recall that vaccination during pregnancy significantly reduces the risk for babies to become severely ill from Covid.
Nasal sprays are underrated (and understudied)
I’ve written about how cheap, safe, easy-to-use nasal sprays might help reduce our risk of contracting Covid. They also seem to help with treatment, with the likes of boring nasal saline stubbornly showing benefit. The studies looking at these possibilities are few and far between, and so it is very easy to dismiss nasal sprays. But enterprising companies continue to work in relative obscurity on them, and they might just prove essential someday.
For example - a new multi-modal nasal spray called PCANS is being developed that combines pathogen capture and neutralization with extended nasal retention. It’s still being studied, but is this a tantalizing peak at a future addition to the armamentarium against Covid?
In a severe Influenza A mouse model, a single pre-exposure dose of PCANS leads to a >99.99% reduction in lung viral titer and ensures 100% survival, compared to 0% in the control group. PCANS suppresses pathological manifestations and offers protection for at least 4 hours.
Consider investing in some fancy Covid tests
Rapid antigen tests are about $10 each here in the U.S. These are the ones we are familiar with over-the-counter. Or the free ones the government sends out from time to time. But increasingly rapid antigen tests are not turning positive until several days into Covid illnesses. This delay can result in transmitting Covid to other people, missing a chance to take antivirals like Paxlovid, and missing a chance to document an infection as it pertains to future complications like long Covid.
In fact, another study published in The Lancet last month found that rapid antigen tests might only be around 34% sensitive for picking up Covid infections in the real world (where people test once and have better neutralizing defenses from previous infections and vaccinations).
PCR testing is much more accurate, but usually involves heading to an urgent care for a visit and a swab. Results can take 1-3 days. But a good article in Lifehacker details at least 4 options for home PCR testing that we can buy OTC. The cost is not great, starting at like $40 a test… but for those who are motivated, or have serious health problems and want to take antivirals ASAP with Covid, investing in these tests might be an option.
Covid infections increase cardiovascular risk
I’m going to preface this next one by stating that the data used here was from a time before vaccines, prior infections, antivirals, etc. I think 2024 cardiovascular risks are less than what this study found looking at the past… but in my mind it does support staying up to date with Covid vaccines, treating infections with antivirals, and some personal choice of caution in certain situations.
Using data from the UK Biobank, researchers found that COVID-19 patients, especially those requiring hospitalization, had a significantly increased risk of major adverse cardiac events (heart attack, stroke, or death) that persisted for up to 3 years after infection. The risk was so high in hospitalized COVID-19 patients without pre-existing cardiovascular disease that it was equivalent to (or even slightly higher than) the risk seen in people who already had cardiovascular disease, suggesting that severe COVID-19 should be considered a major cardiovascular risk factor requiring aggressive preventive treatment.
Additionally, the study discovered that people with non-O blood types (A, B, or AB) who were hospitalized with COVID-19 had about twice the risk of heart attack or stroke compared to those with type O blood, representing one of the first known examples of a gene-pathogen interaction affecting cardiovascular outcomes.
Vaccines helped prevent serious cardiac problems, but increased a few less serious cardiac issues
A study published in European Heart Journal of over 8 million Swedish adults between 2021 and 2022 found that Covid vaccination reduced overall cardiovascular disease risks by 20-30% compared to no vaccination, though there were temporary increased risks of minor issues like extra heartbeats after individual doses, particularly in older men. To minimize risks while maximizing benefits, the data suggests getting fully vaccinated is important since it significantly protects against severe cardiovascular outcomes like heart attack and stroke, while any increased risks from individual doses are temporary and mostly limited to less severe conditions.
Long Covid research continues
Covid is the kind of thing they will be teaching in medical schools for a long time. Back in the day it was said that to understand Syphilis was to understand Medicine (because the disease touches on so many aspects of biology, anatomy, and physiology). So it is with Covid now. Here is a comprehensive review, but I’m guessing the figure below will suffice for an overview of where we are in October 2024:
And another great summary article on long Covid from Ziyad Al-Aly, especially if you are trying to avoid reading about the election all day.
Your summary for October
• Current Covid Status: About 1 in 125-150 people in the US currently have Covid, with predictions of increased cases by Thanksgiving 2024 and beyond.
• Paxlovid Study: A Dubai study showed Paxlovid reduced hospitalization risk by 61% and long Covid risk by 58%.
• Mask Effectiveness: A comprehensive review of 400+ studies confirmed masks and respirators effectively reduce respiratory infection transmission. I wrote an editorial, too.
• Booster Recommendations: CDC now recommends a second dose of 2024-2025 Covid vaccine for those 65+ and immunocompromised, six months after first dose.
• High-Risk Settings: A meta-analysis revealed singing events (44.9%), entertainment venues (31.9%), and fitness centers (28.9%) have highest Covid transmission rates.
• Marine Study: Research showed 24.7% of infected young Marines developed long Covid including the earlier days of the pandemic, with decreased physical performance and increased mental health issues.
• China Survey: A large-scale survey found 10-30% of participants experienced long Covid symptoms, with vaccination reducing long-term symptoms.
• Low Dose Naltrexone: Early research suggests this drug might help treat long Covid symptoms, with positive results in some patients.
• Children and Covid: Only 4% of children are vaccinated, despite evidence that 10-20% of infected children may develop long Covid.
• Nasal Sprays: New developments in nasal spray treatments show promise, including one that showed significant protection in mouse studies.
• Covid Testing: Home PCR testing options are available but expensive ($40+), while rapid antigen tests are showing as low as 34% real world sensitivity in one study.
• Cardiovascular Risk: UK Biobank data showed increased risk of cardiac events up to 3 years after Covid infection, especially in hospitalized patients.
• Vaccine Cardiac Effects: Swedish study found Covid vaccination reduced overall cardiovascular disease risks by 20-30%, though some temporary minor cardiac issues occurred.
• Long Covid Research: an overview of ongoing research into long Covid's various manifestations and effects.
Great work again, Ryan.
Thank you for another thorough edition of Covidlandia, doc.