I read with great interest the excellent prospective cohort study by Augustin et al. [1]. In this study of non-hospitalized patients with mild COVID-19, the authors described symptoms and predictors for post-COVID syndrome (PCS). Most common symptoms at disease onset were cough (64.4%), ageusia (59.1%), anosmia (54.3%), body aches (53.2%), headache (53.1%), and fever (44.6%). Most common symptoms after a median follow-up of four months were anosmia (12.4%), ageusia (11.1%), fatigue (9.7%), and shortness of breath (8.6%). A lower baseline level of SARS-CoV-2 IgG, anosmia, and diarrhea during acute COVID-19 were predictors for a PCS after seven months. As discussed below, I believe these findings could shed light on a possible mechanism underlying post-COVID-19 fatigue syndrome.
Anosmia usually shows spontaneous improvement over a 2–3 week period [2]. However, some COVID-19 patients remain anosmic for longer time periods [2]. The most likely explanation is that in those cases, a larger area of the olfactory epithelium is affected, possibly with a more profound destruction of the epithelium that included death of a larger number of olfactory receptor neurons [3]. I recently proposed that post-COVID-19 fatigue syndrome may result from damage to olfactory sensory neurons, causing an increased resistance to cerebrospinal fluid outflow through the cribriform plate, and further leading to congestion of the glymphatic system with subsequent toxic build-up within the brain [4]. From this point of view, it can be anticipated that the COVID-19 patients with persistent anosmia and persistent fatigue at month four (or month seven) are largely the same, and I wonder if the authors have such data for review.
Funding
No funding to declare.
Author contributions statement
PW wrote the original draft.
Declaration of Competing Interest
The author declares no conflicts of interest.
References
- 1.Augustin M, Schommers P, Stecher M. Post-COVID syndrome in non-hospitalized patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur. 2021 doi: 10.1016/j.lanepe.2021.100122. published online May 18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Altundag A, Saatci O, Sanli DET. The temporal course of COVID-19 anosmia and relation to other clinical symptoms. Eur Arch Otorhinolaryngol. 2021;278:1891–1897. doi: 10.1007/s00405-020-06496-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Butowt R, von Bartheld CS. Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist. 2020 doi: 10.1177/1073858420956905. published online Sep 11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Wostyn P. COVID-19 and chronic fatigue syndrome: is the worst yet to come? Med Hypotheses. 2021;146 doi: 10.1016/j.mehy.2020.110469. [DOI] [PMC free article] [PubMed] [Google Scholar]