Covid. It’s about as good as it gets right now. Wastewater surveillance, weekly deaths, and hospitalizations are at or near pandemic lows. Yet Covid is still a thing to watch, and many of us still adjust our behaviors based on the weather forecast. 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. And now April.
Covidlandia is a unique place. Here we try to see the gradient between black and white, carefree and cautious, pandemic beginning and end. We will start with some happy news.
Another vote of confidence in metformin to prevent long Covid
This is really big news, again.
A 42% reduction in long Covid rates for those average risk patients treated with oral metformin. That’s huge for a disease that is a slowly moving, mass disabling event for millions of people.
Here’s exactly what the study showed in addition to reducing long Covid rates:
In the COVID-OUT randomized trial for outpatient COVID-19, metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%.
Despite headlines this week trumpeting the news, and respected doctors like Paul Sax, MD writing mainstream commentaries, this data is not new. In fact, I’ve been writing about this good quality, randomized, placebo-controlled clinical trial called COVID-OUT for over a year now. For example:
my article entitled “How to prevent long Covid” from March, 2023
my article entitled “My self-treatment plan for Covid” from January, 2024
I shared this stuff on some doctor sites and mostly I got skeptical or even cynical feedback. Doctors (and people in general) can be really resistant to change and new ideas that are not obvious and accepted by the herd. I’ve had very few patients take me up on the offer to try metformin, as many have heard Covid is just a cold now.
So why is metformin finally poised to become a more mainstream treatment for Covid? I suppose it’s because this further data from the COVID-OUT trial published this week in Clinical Infectious Diseases really focused on a mechanism of action. Metformin reduced viral loads in the body by 3.6-fold.
Paxlovid also reduces viral loads by up to 90%, by the way, and I’ve written about how it has been discarded prematurely by many thought leaders as well. But I digress. Back to metformin.
Beyond the viral load reduction as a mechanism, metformin has other effects that were not measured in this trial. I’ll quote my previous article:
Metformin has some plausible mechanisms for why it might help reduce long Covid, including immunomodulatory effects, complement system protective effects, blunting damage of dopaminergic neurons, and mitochondrial protective effects.
So bottom line here is that long Covid is what I fear the most for myself and my patients… not so much hospitalization and death anymore. I also fear cumulative damage that goes undetected and shows up later, unofficially counted by ever-increasing excess mortality in the world; Covid has probably claimed 30 million precious lives. When people ask me for advice I’ll err on the side of aggressive treatment.
I’ve already shown you my cards.
Covid prevalence is low right now
I’m not telling anyone what to do. But my personal caution varies directly with prevalence rates. This is a lovely graph of coronaviruses detected in wastewater:
I’m not seeing a lot of Covid or flu in the office over the past month. But the best way to tell how much Covid and other stuff is going around continues to be this wastewater surveillance. You can search by your zip code here:
https://data.wastewaterscan.org/
Zoom out until you find a wastewater processing plant near you on the map, then click on the dot and you can see what kind of stuff is trending in the sewage near you. Lovely.
I previously linked to these other wastewater reporting systems:
As of May 1st, 2024, hospitals are no longer required to report Covid hospitalizations, so we are losing yet another data point. If you read about hospitalizations being low in the future, it’s not really helpful. So savor this last meaningful graph from the CDC below, and how nice and “low” Covid hospitalizations are right now:
Optimal initiation of Paxlovid in hospitalized COVID patients may be 3 to 5 days
Taking Paxlovid 3 to 5 days after COVID-19 symptom onset, not earlier or later, may result in the greatest reduction in viral loads, viral transmission, and viral rebound in hospitalized patients, according to a University of Hong Kong-led study.
The study, based on data from 208 hospitalized patients in Hong Kong, found that initiating Paxlovid 3 days after symptom onset had a low risk of viral rebound (17%) and a 12% lower risk of transmission among non-rebound patients.
However, starting Paxlovid before 3 days significantly increased the risk of viral rebound, while starting after 5 days lowered its ability to stem peak viral shedding.
This is interesting to me. One could speculate that with over-the-counter rapid antigen tests not turning positive until day 3 for some people, maybe that delay is not as bad as we would intuitively think. These hospitalized patients did better even when the antiviral was not started as soon as possible. Counterintuitive, but not a game changer. Still best to start antivirals ASAP until smarter people than me say otherwise. But maybe don’t sweat it if starting a day or two later when your repeat Covid test finally turns +.
Rapid antigen tests miss a lot of Covid infections
So there’s rapid antigen tests you can buy over-the-counter, and then there’s RT-PCR tests that can be collected at clinics or commercial labs and sent out, with results coming back in about a day.
A report released in April by the CDC showed that during November 2022–May 2023, among persons infected with SARS-CoV-2, sensitivity of rapid antigen tests was only 47% compared with PCR.
Antigen tests continue to detect potentially transmissible infection but miss many infections identified by positive PCR test results.
What are the implications for public health practice?
Rapid antigen tests can aid in identifying infectiousness of persons with Covid. They are good for self-diagnosis of Covid when people have symptoms.
However, higher risk people might not want to rely upon rapid antigen tests alone. They and their clinicians should consider RT-PCR testing so a chance to start antiviral treatment is not missed.
For example, Quest Labs offers RT-PCR testing for $73, without your doctor even being involved.
SARS-CoV-2 can persist in the body for more than a year after infection.
This was from a new study in The Lancet. In the blood of 171 people who had Covid-19, researchers found proteins from the virus in 25% of the participants.
“The fact that every new SARS-CoV-2 infection has the potential to become chronic is perhaps the single most concerning aspect of this virus,” said Polybio president Amy Proal. The study’s authors said SARS-CoV-2 persistence could contribute to long Covid in adults and children.
This is also what I’m talking about with antiviral treatment, staying up to date with vaccines, and never feeling ashamed by choosing your own level of caution.
It’s not just me. In a recent interview NIH Director Monica Bertagnolli, MD confirmed that data shows live SARS-CoV-2 virus can persist in tissues for months or even years. Not just old particles and viral junk, but actual live replicating virus. She also discussed the need for better antiviral medications to stop viral reservoirs in the body to possibly prevent Long Covid. It was noted by Dr. Ruth Crystal that “this was the first time that someone from the government said that there are definitely viral reservoirs of SARS-CoV-2 in the body.”
Time to pick up the pace. The remaining studies will be highlighted in 2 sentences each. You’re doing great… and just picture me typing this as I want to go to bed now. Let’s finish this together!
Myocarditis and vaccines? Minimal worries at this point.
Also from the CDC: Oregon health officials investigated potential sudden cardiac deaths among young people after COVID-19 vaccination but found no clear association. They examined death certificates and vaccination records for individuals aged 16-30 who died from cardiac or undetermined causes between June 2021 and December 2022 and did not find evidence linking the vaccines to sudden cardiac deaths in this age group.
A Norwegian study finds vaccination reduced long Covid by 40%, among other benefits
This study in The Lancet found that COVID-19 vaccines consistently prevent long COVID symptoms and post-COVID thromboembolic and cardiovascular complications across different age groups and underlying health conditions in the Norwegian population. It confirms the reproducibility and generalizability of previous findings from other countries.
How many people have long Covid in the U.S.?
According to the CDC/Census Bureau Pulse Survey: rates of long Covid remain steady, with around 7% of adults (roughly 17 million people) reporting currently having long Covid as of March 2024, suggesting long COVID may persist indefinitely unless new prevention or treatment methods are discovered.
~
Earlier in the pandemic the true number might have been more like 21%, based on the novel idea of testing blood donors for anti-nucleocapsid antibodies (markers of true infection) and asking them about symptoms. Of 238,828 blood donors, 43.3% of those with antibody-proven Covid infection reported new long-term symptoms, compared to only 22.1% of those without a proven prior infection —> suggesting by subtraction that around 21.2% experienced long COVID symptoms attributable to their infection.
Vaccines benefit kids, so keep them up to date, too.
A study from the CDC: During December, 2021–October, 2023, receipt of ≥2 doses of an original mRNA COVID-19 vaccine was 52% effective against pediatric hospitalization and 57% effective against critical illness related to COVID-19, when the last dose was received within the 4 months preceding hospitalization, but protection decreased over time.
These findings support existing recommendations that children and adolescents aged 5–18 years remain up to date with COVID-19 vaccination.
POTS syndrome affects 2-14% of people after Covid
A good article in The Washington Post this month focused on the condition known as POTS - Postural Orthostatic Tachycardia Syndrome. It can happen as a consequence of Covid infections. Young, athletic, flexible women seem to be at higher risk. Symptoms include:
lightheadedness, fainting, nausea, tremors, fatigue, headache, brain fog, blurry vision, palpitations and chest tightness, and shortness of breath. The impact can be measured by elevations in heart rate when people change position.
We can help manage symptoms with diet, exercise, hydration, compression stockings, and medications, but there is no cure. I see this in my practice.
If you feel like people are getting sick more than they used to before Covid, you’re right
A new study shows that SARS-CoV-2 caused a 21% excess of acute respiratory infections during the winter of 2022-23, suggesting that COVID-19 will add a significant burden during cold and flu seasons.
The study, published in the International Journal of Infectious Diseases, was based on an online survey of 70,000 participants, and it found that adults aged 30 to 39 years had the highest cumulative incidence of respiratory infections.
Another new virus to catch, and one that knocks our immune systems down.
Lactoferrin doesn’t seem to help long Covid
Remember that recent study showing that low iron levels might be implicated in the pathogenesis of long Covid? Well at least one prospective trial now shows that treatment with lactoferrin (related to iron) doesn’t seem to help treat long Covid. Nothing in medicine is ever easy.
Finish line
But you know what is kind of easy-ish?
Springtime in Covidlandia.
I hope you can enjoy the lower risk season we seem to be having right now. It will never be zero risk, so use your own judgment, and I’ll be hoping that I’ve served you well with these curated highlights from April, 2024.
Goodnight, and take good care.
Thanks for the April tour through Covidlandia. It is always appreciated. ( And the artist is clearly talented!)
Thank you! And what a great watercolor! Enjoying the season.