How Can Chronic COVID (Long-COVID Syndrome) Be Diagnosed and Treated?

Dear Editor:

We read with interest the guideline paper by Seo et al. on the clinical practice suggestions for the diagnosis and treatment of long-term coronavirus disease (COVID) [1]. The guidelines contain recommendations for diagnosis and treatment that can be applied in clinical practice and are based on 32 key questions related to patients with long-term COVID [1]. The guideline is impressive, but several points need to be discussed.

The first point refers to the recommendation that people should get vaccinated to prevent long-term COVID [1]. This suggestion is understandable, but does not take into account that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination can have similar long-term side effects to SARS-CoV-2 infection [2]. This post-vaccination syndrome is referred to as post-acute coronavirus vaccination syndrome (PACVS) and manifests itself in a variety of systemic, neurological, psychiatric, endocrine, cardiac, gastrointestinal, renal, and immunological impairments [3]. This comment should not be interpreted as opposition to vaccination, but as an appeal to develop better and more sophisticated vaccines against SARS-CoV-2 or other viruses in the future. Vaccination has probably saved millions of lives, but may also have harmed thousands of PACVS patients and worsened their quality of life. Before recommending vaccination against SARS-CoV-2, it should be assessed whether there is a group of people who are at increased risk of developing PAVCS, most likely patients with multimorbidity, those with pre-existing immunological conditions and those who regularly take immunosuppressants.

The second point relates to the diagnostic criteria for long-term COVID [1]. As COVID-19 is a global disease, the development of diagnostic criteria for long-term COVID should be based on a multinational approach involving experts from all fields of medicine, health management and medical science. Such international bodies should discuss whether the diagnosis of long-term COVID should include symptoms and signs that did not appear during the acute phase but developed weeks or even months after the acute infection. It should also be discussed whether the diagnostic criteria for long-term COVID should include serologic or cerebrospinal fluid biomarkers that can be detected in some or even all patients with long-term COVID.

The third point refers to the recommendation for patients who have been complaining of fatigue due to COVID for a long time [1]. As several cases of new-onset post-COVID myasthenia and exacerbation of already known myasthenia have been reported [4], recommendations should also include the exclusion of myasthenia or myasthenic syndrome.

The fourth point refers to recommendations for patients who have been treated with COVID for a long time and complain of cognitive impairment or brain fog [1]. These patients also need psychiatric and neuropsychological evaluation to rule out depression or anxiety disorder as a cause of brain fog. In addition, cerebral MRI should be performed in patients with long-term COVID in whom cerebral imaging was not performed during the acute phase of the infection.

The fifth point relates to the selection of the literature used to produce the guidelines [1]. Surprisingly, only the literature published until June 2023 was included in the article. As the manuscript was submitted in February 2024, we should know why at least eight months of publication activity in this area was not included in the review. The guidelines may have overlooked a number of important papers that have been published on this topic since then [5].

In summary, the proposed guidelines have some limitations that put the recommendations given into perspective. Addressing these limitations could strengthen the conclusions and underpin the value of the guidelines.