COVID is becoming like a spurned lover who is now stalking you. You can’t forget about it, and while you hope that’s it gone, you know it’s still there, lurking in the shadows. COVID has now killed over 6.3 million people worldwide, and over one million people in the US alone. But it’s possible that the greater toll of the disease is the morbidity of long COVID. A new study adds to our understanding of this burden.

We now have more effective tools than we had at the beginning of the pandemic. Physicians understand how to treat COVID acutely much better. There are effective antivirals approved for use, such as Paxlovid. And of course there are many COVID vaccines with high efficacy. Hospitals are no longer being overwhelmed, and while there can still be waves of the virus, they seem to be waning. The pandemic is evolving into the slow burn of an endemic infection, like the flu.

This, however, is not the time to take our eye off the ball. COVID is still a serious illness, and the more we learn about so-called long COVID the worse it seems. COVID is likely to become a significant source of morbidity and health care burden, and we need to treat it that way. Primarily we need to keep up pressure to get as many people vaccinated as possible, keep up with boosters, and update the vaccines to track the new variants.

A recent study presented at the 8th European Academy of Neurology (EAN) Congress adds more data to our knowledge of the long term effects of COVID. This is a Danish population-based study, so it is observational, not experimental, which means it can establish correlation only. They found:

Out of 919,731 individuals that were tested for COVID-19 within the study, researchers found that the 43,375 people who tested positive had a 3.5 times increased risk of being diagnosed with Alzheimer’s disease, 2.6 times with Parkinson’s disease, 2.7 times with ischaemic stroke, and 4.8 times with intracerebral hemorrhage (bleeding in the brain).

The researchers tried to control for confounding factors, statistically matching for age and other risk factors. The results are statistically robust, but they need to be confirmed with further sets of data. Of note, other neurological diseases were not increased in COVID-positive people. The effects seem to be limited to neurodegenerative disorders and neurovascular disorders, but not autoimmune diseases or other neurological disorders.

This fits with prior evidence that infections resulting in brain inflammation can increase the risk of neurodegenerative diseases, like Alzheimer’s disease and Parkinson’s. This also fits the natural history of COVID, which can cause headaches and “brain fog”, suggesting that infection can affect the brain. Often these symptoms persist long after the acute respiratory infection.

In addition to confirming these associations, further research should explore the degree to which vaccination prevents this increased risk in those who get COVID despite being vaccinated. We know that the COVID vaccines reduce the risk of developing long COVID, with estimates in the literature varying from 15% to 50% reduction. It’s probable that vaccines would similarly reduce this increased risk in neurological disease, and since we are talking about serious illnesses, such as Alzheimer’s and stroke, even the lower end would represent a significant reduction in morbidity. But we need to study this directly.

We also have to put these findings in to the context of ongoing research into similar effects of contracting the flu. Recent research has also been moving in the direction of an association between getting the flu and later risk of neurodegenerative disorders. The current Danish study also found this association, at similar levels to COVID, except for ischemic stroke, which was higher in COVID.

This does not mean that diseases like Alzheimer’s and Parkinson’s are entirely caused by viral infections, but such infection may be one trigger of neurodegeneration, or exacerbate it so that it presents earlier. This association is further supported by a recent study showing that getting flu vaccines reduces the risk of developing Alzheimer’s disease:

From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4.

That’s a relative risk reduction of 40% with an absolute risk reduction from 8.5% to 5.1% (3.4%). Again, that is highly significant, which means at least two things. First this is more evidence to support a causal link between certain viruses and neurodegenerative disease, in this case the flu viruses with Alzheimer’s. But also it highlights the protective roll of vaccines in preventing this risk. There was also a dose-response effects, with a greater number of annual flu vaccines being more protective.

The evidence is now moving in the direction that COVID is similar to flu in that it also increases the risk of degenerative diseases, with the added burden of also increasing neurovascular disorders. And while we have to confirm this, it seems highly likely that COVID vaccines will have a similar protective effect as do flu vaccines.

What all of this means is that there is a huge benefit to getting an annual flu vaccine, and likely to getting vaccinated against COVID and keeping up to date on boosters. Don’t let the lull in COVID cause a false sense of safety. This remains a serious illness, we have the tools to fight it, and we need to use them.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.