Covid. It’s still decent out there right now, but I am seeing a few more cases in the office, and wastewater surveillance has been trending up a bit. So welcome back to some monthly highlights from a place I call Covidlandia. 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. And now May.
![](https://substackcdn.com/image/fetch/w_1456,c_limit,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F1ede50f6-b16d-44e1-a9db-7c521f3e7645_2430x2938.jpeg)
Covidlandia is a unique place. Here we try to see the gradient between black and white, carefree and cautious, pandemic beginning and end. I’m going to start with a reality check on present Covid levels, then highlight a study on children, wind our way through 10 more important developments you might have overlooked, and conclude with an eye towards the future. It’s about a 10 minute read.
Covid levels are generally low in the U.S. but rising… unless you are in Hawaii, where it’s a mess
First I apologize to international readers as I’m just zooming in on the U.S. If Dr. Zhong is reading this one, please let me know if I’m correct about Australia below :)
This first graph shows where we are historically in terms of SARS CoV-2 levels in wastewater. The blue box all the way to the right represents the past 3 months. Pretty good, but certainly not zero SARS CoV-2 in American sewers.
The next graph below shows the different regions of the U.S., as well as a black line representing overall/national levels. Once again, pretty good, but the west is bending up sharply.
Turns out that it is not the entire western U.S. that is surging, but rather the state of Hawaii is breaking the curve with their current Covid levels (blowing past what was detected in the continental U.S. around the holidays this year). The theory is that because Hawaii is in closer proximity to Australia and New Zealand, which are entering winter and have high Covid rates, perhaps regional Pacific travel is to blame.
I’ve been seeing some Covid in my practice trickling in this month, and especially the past week. The wastewater near Philly is supposedly “LOW.” If you are traveling to Hawaii, I’m jealous, but I would be careful on the plane and while visiting right now.
Kids with long Covid can’t run and play as well. Objectively.
There has been a lot of gaslighting, trivialization, and dismissal of the potential harms of Covid in kids. Most seem to be doing pretty well after Covid, but many are not. Estimates for the incidence and prevalence of long Covid in kids range from about 1% if you check with the CDC… to 10 - 20% if you check with this recent study published in Pediatrics. That would be up to 6 million kids with some combination of:
…(lingering) cough, headaches, fatigue, and loss of taste and smell, new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome.
A recent study in The Pediatric Infectious Disease Journal confirms that 90% of kids with suspected long Covid who underwent exercise testing had objectively impaired functional capacity (expressed by a low VO2 peak), signs of deconditioning, and cardiogenic inefficiency. This compared to just 10% of kids without the diagnosis of long Covid.
To me this shows that we should still be keeping kids up to date with recommended vaccines, not sending them immediately back to school when sick, and asking them to wear a mask when they return to school while still contagious with Covid to protect their teachers and friends somewhat. Maybe 7 days from the start of symptoms would be a decent thing to do.
And here are the guidelines for treating or not treating your child when they have Covid. As usual, the focus is narrowly on preventing hospitalization and death, but we can assume some children develop lingering and permanent issues as a result of infections.
Antivirals can help reduce risks of long Covid in adults.
Ensitrelvir, an antiviral made in Japan and available elsewhere, didn't help reduce symptoms that much.
Japanese pharmaceutical company Shionogi said its Covid-19 pill treatment ensitrelvir (commercially known as Xocova) did not meet the primary endpoint of significantly reducing common Covid symptoms in a global late-stage trial.
However, the drug did demonstrate a potent antiviral effect compared to placebo. It is expected be another crucial option with Paxlovid for Covid treatment. Despite failing to meet the trial's primary endpoint, Shionogi said it will continue working with regulators to explore making ensitrelvir available.
As many of you know by now, I am still optimistic that reducing the burden of coronaviruses creating mayhem in our bodies when sick will have medium and long term benefits. Here is my defense of Paxlovid and why I plan to take it when sick.
I don’t consider the failure to reduce symptoms to be a non-starter for a Covid medication. Instead, making our bodies as inhospitable as possible for SARS CoV-2 viruses is my North Star, including staying up to date on vaccines and boosters.
Why is everyone obsessed with symptom reduction? I think it’s because guidance issued by the FDA in 2020 discussed pivoting to measurements of common symptoms of Covid-19 in drug clinical trials, which includes the use of patient-reported outcomes instead of focusing on death and hospitalization. These more severe outcomes now require much larger trials since death and hospitalization are less common with Covid. I still think this is myopic.
But the FDA has the power to approve meds, not me.
More evidence that Paxlovid can help reduce long Covid rates
I am not to Paxlovid/antivirals what Joe Rogan was to ivermectin. I’m basing my stuff on the science, which is heavily drawn from studies of the patients most ill with Covid. I admit I sometimes extrapolate a bit from there to where I live in primary care.
So here’s another vote of confidence in using Paxlovid.
A retrospective study published in The Lancet examined the effect of the Covid-19 antiviral drug nirmatrelvir-ritonavir on post-Covid conditions in hospitalized patients in Hong Kong between March 11, 2022, and Oct 10, 2023. Among over 50,000 hospitalized Covid patients, those treated with nirmatrelvir-ritonavir had significantly lower risk of:
post-acute inpatient death ↓38%
heart failure ↓30%
atrial fibrillation ↓37%
coronary artery disease ↓29%
chronic lung disease ↓32%
acute respiratory distress ↓29%
interstitial lung disease ↓83%
end-stage renal disease ↓63%
The study ran for the 19 months noted above, and the outcomes were only measured starting a minimum of 3 weeks after infection and running through the end of the study period.
These extended benefits of treatment were studied in inpatients. But intuitively and along a continuum we would expect the same underlying beneficial mechanisms to work over time for others with Covid, repeatedly, cumulatively. Ultimately it’s your own call though.
More evidence that masks work when you want to deploy them
The dangers of not thinking intuitively until proven otherwise are manifest in the topic of masking. After a crappy Cochrane meta-analysis purported to show that masking did not work, many with anti-mask agendas took this study and ran with it.
But common sense and decades of infectious disease experience with masking should never have been discarded with just the latest news. You would never go into an ICU full of Covid patients without wearing a mask yourself, yet some of the same doctors who might admit this still rallied their angry readers and categorically decried masks as worthless.
A really great narrative review and new meta-analysis was published last month. It summarizes a broad evidence base on the benefits—and also the practicalities, harms, personal, sociocultural and environmental impacts—of masks and masking. They looked at over 100 studies and re-analyzed contested meta-analyses of key clinical trials, and found the following 7 key points:
There is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens.
Masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect.
Respirators (think N95s) are significantly more effective than medical or cloth masks.
Mask mandates are, overall, effective in reducing community transmission of respiratory pathogens.
Masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation.
While there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably deaf people) are disadvantaged when others are masked.
There are risks to the environment from single-use masks and respirators.
The authors call for sensible, evidence-based improvements based upon their findings.
As this might apply to the primary care world, keep wearing a mask when you want to. It’s your tool, and you’re not crazy for doing what you will to protect yourself. You have the freedom to decide, until North Carolina, Texas, and other government leaders take that away from you.
25% of Covid-infected people have SARS-CoV-2 antigens in their blood for up to 14 months after infection
The study published in The Lancet Infectious Diseases discusses the possibility of SARS-CoV-2 virus persistence as a potential cause of long Covid symptoms. Evidence of viral antigens and RNA in some patients months after infection suggests the virus may not be fully cleared.
However, the presence of viral remnants does not necessarily mean actively replicating virus. Ongoing trials are testing antivirals and antibodies to target potential viral reservoirs and alleviate long Covid symptoms, recognizing that long Covid likely has multiple underlying causes across different subgroups of patients.
More evidence that Covid sucks
Higher rates of dementia.
Higher rate of Parkinson’s.
Stay up to date with vaccines. Prioritize ventilation. Up your game when waves are occurring. Make infections worth the risk of the activity.
Covid is still worse than the flu
There are a lot of ways to support this statement. But one of the more recent ones is that in those people hospitalized with influenza or Covid, we are seeing persistently higher rates of death with Covid.
35% higher rates actually, with the absolute numbers being 5.7% rate with Covid versus 4.2% with influenza for people admitted for those diagnoses in the fall-winter 2023-2024.
This is better than last year 2022-2023, when hospital mortality rates for Covid were 60% higher than for the flu.
Poorly ventilated spaces are a boon for coronaviruses
One way of conceptualizing how coronaviruses and other infectious particles hang in the air is to picture another person smoking. You are going to smell those particles, delivered like viruses into your nose.
Turns out it’s not just the buildup of viruses that happens in poorly ventilated spaces, but the carbon dioxide gas itself alters the acid base chemistry of the air, making it more acidic. This lower pH is favorable for SARS CoV-2 viruses, and actually drives more infections, too.
As a college student I taught chemistry over two summers, so I just thought this one was fascinating (even as I did not have time to really pour over the details or relearn stoichiometry).
Increasing the concentration of carbon dioxide (CO2) in the air limits the increase in pH of respiratory aerosols, thereby improving the aerostability (ability to remain infectious in aerosol form) of SARS-CoV-2.
Even moderate increases in CO2 concentration (e.g., from 500 ppm to 800 ppm) significantly improve the aerostability of SARS-CoV-2 variants, including the Delta and Omicron variants.
The improved aerostability of SARS-CoV-2 at higher CO2 concentrations is predicted to increase the overall risk of COVID-19 transmission, especially in poorly ventilated indoor environments.
Primary care relevance? Ventilation. Go for it.
Long Covid is way under-reported
According to a study by researchers published in The Lancet eClinicalMedicine, the true prevalence of long Covid in England is likely an order of magnitude (10 times) higher than indicated by the diagnostic or referral codes in electronic health records (EHRs).
The analysis of National Health Service clinical data from over 19 million adults found that only 55,465 patients were flagged for long Covid, while a separate community infection survey suggested around 2.1 million people self-reported having long Covid in January 2023. The researchers conclude that using EHR codes has major limitations in identifying and ascertaining true cases of long Covid, and alternative approaches may be preferable to accurately capture the extent of the condition.
This is why I try harder than most to avoid repeated Covid infections, stay up to date with vaccines, plan on antiviral treatment, and pay attention to wastewater estimates of Covid prevalence. The studies out there on long Covid are hamstrung by severe difficulties in data collection, and diagnostic challenges and courage.
The updated XBB vaccines were effective, although less so against JN.1. Bring on KP-2 for this fall?
A study published in the NEJM showed that the updated Covid vaccine (against XBB.1.5) that many of us received last fall, and that many over age 65 received a booster with this spring, worked fairly well… but with the following qualifications:
Protection against infection waned faster than we would like.
Overall benefit has been a bit less against the currently dominant coronavirus variant called JN.1.
Specifically, the updated shots from Moderna, Pfizer-BioNTech, and Novavax over a 5-month period from September 2023 to February 2024:
Reduced infections by:
52% after 4 weeks (but dropping to 44% when JN.1 became dominant)
33% after 10 weeks
20% after 20 weeks
Reduced hospitalizations by
67% (but dropping to 60% when JN.1 became dominant) after 4 weeks
57% after 10 weeks
Reduced deaths:
So bottom line on this one is that overall the updated XBB vaccines were effective, although less so against JN.1. The effectiveness was greater against hospitalization and death than against infection, and this waned moderately from its peak over time. This pattern is similar to previous years.
This study found lower rates of protection than a previous one I highlighted in the February edition of Covidlandia. I’ll quote myself, quoting the experts:
The updated XBB Covid vaccine, which only 22% of American adults received this fall/winter, provided approximately 54% protection against symptomatic SARS-CoV-2 infection when compared with not getting the updated vaccine.
This updated vaccine was specifically found to provide good protection against the JN.1 variant which has dominated for months, and has also worked well against other circulating lineages.
What’s more, the new updated vaccine continued to provide 49% protection out to 119 days studied after the shot (about 4 months and counting).
What’s next? The updated vaccines for fall 2024 will likely target JN.1, or maybe the related FLiRT variants KP.2 and KP.3, or whatever whack-a-mole trends upwards as the FDA advisory committee meets on June 5th this week!
But with KP.2 trending upwards quickly, I think this would be the best call right now. Anyone taking bets?
Take home points
We shouldn’t gaslight kids with long Covid, and the reality is that a much larger number of kids are probably affected. Protect them as we would protect ourselves.
Don’t hate on new antivirals just because they don’t reduce symptoms like the FDA wants.
Paxlovid reduces long Covid risks.
Masks work when you want to wear one, and respirators are better. To say otherwise is stubborn, counterintuitive, and popular. I don’t care about popularity, and never did.
Up to 25% of people are having trouble clearing coronavirus antigens, RNA, and sometimes replication-competent virus. This is a major target for future therapies, some presently being studied.
Covid still potentially sucks, and is still worse than the flu, though that gap might be closing in the next 5-10 years, who knows.
The build up of CO2 in rooms indicates poor ventilation, and affects the acid-base chemistry of the air to the delight of coronaviruses.
Long Covid is out there, and it won’t be captured by looking at diagnosis codes in charts like the ones I use every day seeing patients in the real world.
The XBB booster worked pretty well this fall/winter, the spring booster was a good idea for >65 yo’s, and watch for the FDA guidance to the vaccines makers regarding the updated vaccine to be cooked up for this fall/winter. I’m betting JN.1 at least but a large side bet on KP-2. If you know a bookie who can take my $1 bet, please advise.
Take good care :)
Masking is a great idea & a small annoyance. Why is it that most medical offices suggests masks BUT most of the staff do not wear them? Very confusing
Your monthly Covidlandia reports are terrific, and the take-home points incredibly helpful. Very sad to learn how many children are suffering long covid. We have really failed our kids on this one. The ventilation/acid-based air was intriguing—there are so many benefits to good ventilation, and here is another!
Re the Hawaii stats, yet more confirmation of your point sometime back that it’s good to check what’s going on locally, as well as regionally and nationally. On that score, “interesting” to see that in New York, New York City has far worse stats than the rest of the state.
In “local” news: unfortunately, there is still no NYC data showing on the CDC site—I will be writing a follow-up to the city health department, as I thought that should have been happening by now. It’s important for many reasons, one of which is the CDC site is much better, eg, at showing trends. Also, a la what you note about Hawaii, an “outlier” state can affect the stats for a whole region, so it’s important to be able to tease that out. For NYC—and I think this would remain true if NYC were reporting data to the CDC?—I do not rely on regional reporting, as it appears that NYC is typically an outlier there, and not in a good way.
There is so much to take into account, it’s not surprising so many just give up. But this is why your reports are so invaluable. You are definitely in the Jetelina mold of clear, well-informed, reporting. Thank you so much!