KATELYN JETELINA
JAN 18, 2024
We continue to learn a lot about long Covid, which is great given that this is where most concerns lie at this point of the pandemic. Here is the latest scientific story.

Note: This post builds on previous YLE posts about long Covid. If you missed those, search for “long Covid” in the YLE archive.

How many people have long Covid?
What we knew: The prevalence (# people in our community) and incidence (# new people who get it) of long Covid remain difficult to estimate.

New info: England has one of the best ongoing surveillance systems where they randomly survey the public for long Covid. Prevalence started declining in 2022 despite ongoing infection waves (see graph below). We see this in U.S. data, too (7.5% in June 2022 → 5.3% in October 2023.)

Figure Source: Altmann et al., Nature Reviews Immunology.
The risk of long Covid after subsequent infections has not been rigorously tested. A small number of studies found that getting infected again is worse than not getting infected again. This seems obvious, but it means the risk isn’t zero for subsequent infections. Similarly, the UK survey (above) found the risk of long Covid dropped after the second infection compared to the first infection (4% → 2.4%).

Why may prevalence be decreasing? Some scientists (including me) believe this is due to a decline in severe disease—one of the strongest predictors of long Covid— and due to the virus changing over time. But the ongoing risk is not zero, and millions still suffer today.

Vaccines help protect against long Covid, even among kids
What we know: Vaccines have many benefits, including preventing long Covid. We didn’t know the incremental benefit of additional doses, especially for kids.

New info:

Among children, the vaccine provides a 35% effectiveness against probable long Covid (symptom-based) and 42% protection against diagnosed long Covid within a year of receiving the vaccine. Protection was more robust for adolescents and waned over time (61% → 11% at 18 months after vaccination).

Among adults, the more vaccines you get, the less likely you will get long Covid. This is called a dose-response relationship: one dose of vaccine reduces risk by 21%, 2 doses reduces risk by 59%, and 3+ doses reduces risk by 73% in a study that followed patients through fall 2022.

Why does it matter? Beyond avoiding infection, keeping up with vaccines helps. Vaccines prevent infection in the short term, and even if one becomes infected, vaccines reduce viral load. (And we know that viral load predicts long Covid.)

Long Covid is an umbrella term
What we knew: We had a suspicion that long Covid isn’t just one disease but rather a compilation of many different causes.

Figure Source: Peluso and Deeks, Trends in Immunology.
New Info: We see evidence of all of these root causes.

Growing evidence of viral persistence or viral reservoirs hiding in our tissues.

The immune response doesn’t stop in long Covid patients after initial infection. This means it’s continually responding to something.

Some long Covid among females may be explained by autoimmunity due to lower testosterone.

The makeup of the gut microbiome may be linked to a person’s risk.

Covid may damage the vagus nerve—an important part of the nervous system that helps regulate fundamental processes like blood pressure and heart rate.

Covid can reactivate other viruses lingering in the body, such as the Epstein-Barr virus.

Why does this matter? Root causes likely vary. Pooling all patients together in studies may hurt our understanding of treatment options.

Long Covid is different from long flu
What we knew: An array of viral infections can lead to long-term symptoms, including flu. Early studies suggested long Covid was more common than long flu, though.

New info: The first 90 days of severe infection is the defining moment for the long Covid trajectory, with much higher risk than for “long flu.” After that, though, the rate is similar to flu, at least for people who are hospitalized for Covid-19.

Figure Source: Xie et al., Lancet Infectious Diseases. Annotations by YLE.
In addition, long Covid and long flu are very different diseases: Long flu is purely pulmonary, while long Covid is multisystemic. (Note: There have been concerns raised about the framing of this paper, and my conclusions don’t necessarily match those of the authors.)

Treatment options are… on the horizon?
What we know: We are desperate for long Covid treatments. Long Covid physicians are still treating the symptoms rather than underlying causes.

New info: Treatment options seem to be on the horizon:

Pre-Probiotics reduced long Covid symptoms (Randomized control trial; Hong Kong). This complements anecdotal evidence from the patient community (Remission Biome Project).

Low cortisol predicts long Covid. This may suggest potential therapy options, but clinical trials are needed.

Metformin showed promising results as prevention in the pre-vaccine and pre-Paxlovid era. Importantly, the benefit in vaccinated people was not apparent, suggesting that it is very hard to show additional benefits against long COVID after the risk reduction from vaccination. It’s not clear if the results hold up today.

Though some doctors may suggest exercise as a treatment, research has shown it can be harmful to people with a certain long Covid symptom (post-exertional malaise). Why? It ignites cell death in the muscles, which may explain pain, fatigue, and weakness.

What about Paxlovid? Evidence is mixed.
What we knew: Antivirals, like Paxlovid, prevent SARS-CoV-2 from replicating. Biologically speaking, this should help against long Covid.

What’s new: Unfortunately, there is mixed evidence on the effectiveness:

Risk reduced by 25% in older adults with risk factors for severe disease. This is a VA population, though, so it may not be generalizable.

A general population study recently found it didn’t work for younger people (who are at higher risk for long Covid). It helped older adults.

A second general population study similarly found it didn’t help prevent long Covid.

A clinical trial testing Paxlovid as a treatment ended early because it wasn’t working.

Why the different results? Two hypotheses: 1. The 5-day course isn’t enough, and we must test longer courses. 2. We have too broad of a definition of long Covid. (For example, it could help with viral persistence but not autoimmunity mechanisms.)

Other 2023 advancements
Machine learning showed that long Covid could be efficiently predicted from immunological data alone.

Patients and scientists are collaborating, which is paying off. Studies from the Patient-Led Research Collaborative, for example, are beginning to lead to novel results.

Health and Human Services announced a new Long Covid office. The office’s director starts work this month.

Congress has called for a HELP Committee hearing to address long Covid, which is happening today.

Bottom line
Our understanding of long Covid is slowly but surely growing. The good news is that vaccines help, but we are still trying to find answers for treatment. While the prevalence of long Covid is declining, it’s clear this is a life-changing disease I don’t want to get.

Love, YLE

Note: For those interested in real-time updates on long Covid developments, please subscribe to The Sick Times— a nonprofit publication covering long Covid from journalists Betsy Ladyzhets and Miles Griffis. Betsy and Miles contributed research and recommendations for this post.

“Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, M.P.H. Ph.D.—an epidemiologist, wife, and mom of two little girls. During the day, she is a senior scientific consultant to several organizations, including CDC. At night, she writes this newsletter. Her main goal is to “translate” the ever-evolving public health world so that people will be well-equipped to make evidence-based decisions. This newsletter is free, thanks to the generous support of fellow YLE community members.