Covid passes, the headache stays

“The coronavirus pandemic is over!” As these words were pronounced a good two years after the outbreak of a hitherto unknown viral infection, which had the whole world paralysed for a long time, there was great relief. After years of uncertainty, restrictions, and loss, we had actually made it, and it was now time to reflect and pick up the threads of our former lives.

But not for everyone. Because the virus has – and this is one of its characteristics which is particularly hard to understand – a more long-term effect on a portion of infected people, beyond the acute infection and illness. “Long COVID” is the term intended to describe this difficult-to-grasp complex of varying symptoms which continues to burden affected people even after they are technically recovered.

What is long COVID?

The World Health Organisation (WHO) defines long COVID as symptoms which:

• generally begin around three months after becoming sick with COVID
• last for at least two months and
• cannot be explained by another diagnosis.

As imprecise as this definition may be, this is how varied the symptoms of the illness are. For this reason, it also presents a particular challenge for the usual medical differential diagnosis. Affected people generally do not present with all the symptoms which are considered ‘typical’ for long COVID. Moreover, the signs of illness are not permanent, vary in their intensity, and can also reoccur after an apparently symptom-free period. Most affected people are significantly impacted both in everyday life and in their overall wellbeing.

An unclear set of symptoms

Headaches, tiredness, shortness of breath, sleeping problems, joint and muscle pain, as well as anxiety and depression are among the frequently mentioned symptoms. In addition, there can be reductions in the ability to concentrate (also known as “brain fog”). There are also descriptions of changes to the senses of taste and smell – a phenomenon which is familiar from acute COVID-19.

In terms of the frequency of the illness, the data from the available studies varies significantly. Incidences of between 7 and around 40 percent have been found among patients who initially became infected with COVID-19, including both mild and severe courses, as well as hospitalisation.

An evaluation of more than 30 studies showed, for example, that two months after the acute stage of the illness, the proportion of patients with long COVID was around 17 percent, after six months this became 8 percent. According to an American study from 2023, 7 percent of convalescent patients showed symptoms of long COVID. One in four of those affected complained of limitations in everyday life.

Headache as a companion to viral illnesses – and also afterwards for COVID-19

The fact that headaches are one of the most common symptoms both in the context of an acute COVID-19 illness and for long COVID has been proven by numerous studies. This is unsurprising, as other viral infections can also often be accompanied by headaches. However, with long COVID there is also a significant risk that this pain could become chronic and impact affected people for a long time, even after the viral infection has worn off.

Studies on the connection between long COVID and headaches show several variations. For example, people with migraine may find that their existing illness worsens: attacks occur more frequently after the infection with coronavirus or last longer than they did before. For people who did not suffer from headaches prior to becoming ill with COVID-19, headaches can develop for the first time after the actual infection has worn off. Chronic issues seem to be more likely to occur in people with pre-existing symptoms than in those with no prior history with headaches.

A long COVID headache can manifest in affected people either as symptoms similar to migraine or as symptoms which are more consistent with tension headache.

How does a long COVID headache develop?

The mechanisms behind the development of the long COVID headache have been the subject of intensive research since the phenomenon was discovered. For a long time, the reason for the symptoms was unclear. It was speculated that the virus led to overall organ damage, that the immune system was affected, that viruses were persisting in the body, or that the prescribed medications had caused unwanted side effects.

A recently published paper from the USA (October 2023) could signal a breakthrough in the search for a cause. In an analysis of several studies, the team led by Maayan Levy at the Perelman School of Medicine in Philadelphia discovered that, during the acute illness with COVID-19, patients experienced a drop in serotonin, a messenger substance circulating in the blood. For convalescent patients, serotonin levels returned to normal after they had overcome the viral infection. However, if the affected people developed long COVID, serotonin levels remained low. A similar lack of serotonin was also found in patients who had become infected with other viruses. Potentially, these findings have uncovered a general response to viral infections in the human body.

Immune response, serotonin levels and headaches – a sensitive connection

When we come into contact with a virus, our innate immune system releases an increased number of so-called type I interferons. These immune messenger substances affect the intestinal mucosa, in which serotonin is formed from the amino acid tryptophan. The interferons hinder the absorption of tryptophan in the cells of the intestinal mucosa. This means that the raw material needed to make serotonin is not there, and serotonin levels in the blood will fall. Low levels of serotonin impact the coagulation activity of certain blood cells, the thrombocytes. This leads increasingly to the formation of small clots in the blood vessels, known as microthrombosis, which are frequently found in patients with long COVID, and which can impact the blood supply.

The lack of the neuroactive messenger substance serotonin also affects the function of the brain. While it cannot overcome the so-called blood-brain barrier, researchers suspect that there is another mode of influence: if there is not enough serotonin available, the function of the vagus nerve is affected. Among other things, this nerve is actively involved in controlling processes affecting memory, information storage, and also headache occurrences. This would explain the symptoms of long COVID which lead to the typical neuronal dysfunctions – ‘brain fog’ – i.e., difficulty concentrating and fatigue, as well as headaches.

Vaccines are the key – for long COVID as well

The good news: it is now well-substantiated that the COVID-19 vaccine can not only protect you from severe cases of the actual illness, but also significantly lowers the risk of long COVID. This means: the vaccine can also help you to avoid secondary symptoms. A so-called booster vaccine, i.e., refreshing the protection given by the vaccination, is particularly effective here. A study published in 2022 on healthcare workers was able to show an inverse relationship between the number of COVID-19 vaccinations and the risk of becoming sick with long COVID. The study found that the likelihood of long COVID was reduced by two thirds after three vaccinations. We can therefore assume that the most effective preventative measure, not only against becoming ill through an infection with the virus, but also against long COVID, is the consistent use of the vaccine.