To the best of the authors’ knowledge, this is the first analysis of the trajectory curve of recovery of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors. The mosaic plots revealed that most patients developed “de novo” post-COVID cognitive symptoms. In fact, although the prevalence of post-COVID cognitive symptoms was considerable, a higher number of patients tended to recover than those that developed them “de novo”, explaining the decreasing prevalence trend. Nevertheless, the trajectory curves were not as pronounced as expected, suggesting that cognitive symptoms will be long-lasting post-COVID symptoms. In fact, the trajectory curve of memory loss was slower than that of brain fog and concentration loss, suggesting that memory loss may be present for longer than three years after the infection thus requiring further attention and treatment.
An interesting result revealed by mosaic plots was that a proportion of COVID-19 survivors not experiencing cognitive symptoms at the first follow-up period presented them at a second and longer follow-up, supporting the hypothesis of a potential delayed-onset post-COVID cognitive symptom development . This finding would support the hypothesis that COVID-19 might trigger a latent neurodegenerative process in this group of patients. We aimed to identify if these individuals developing delayed new-onset post-COVID cognitive symptoms presented difference acute-phase clinical findings than those developing new-onset post-COVID cognitive symptoms at an earlier follow-up, but not significant differences were identified. It is possible that other factors, e.g., differences in neurodegenerative or neuroinflammation biomarkers, could be related to a delayed-onset of post-COVID cognitive symptoms.
Prevalence rates of post-COVID cognitive symptoms observed in our study were lower than those previously reported [5, 6]; however, considering the longer-term follow-up period of the current study, this could be expected according to potential recovery . Several theories including viral encephalitis, neuroinflammation, damage to blood–brain barrier integrity or altered excitability and neurotransmission in the primary motor cortex, could explain the development of post-COVID cognitive symptoms [14, 15]. Considering the long regeneration time of the nervous system neurons, the recovery of post-COVID cognitive symptoms could be longer than one could expect. Hence, identification of risk factors associated with the development of post-COVID cognitive symptoms may help to better understand the evolution and treatment of these symptoms. In fact, there is evidence suggesting that female gender, older age, and ICU admission are factors associated with post-COVID cognitive symptoms . Additionally, this study focused on memory post-COVID cognitive symptoms, however, there is also evidence suggesting that executive function could be also affected in long haulers. We could hypothesize that subgroups of patients with different post-COVID cognitive impairments, i.e., memory vs. executive, could exist. Longitudinal studies investigating the evolution of executive impairments in people with long COVID are needed.
We acknowledge some potential weaknesses in this study. First, only hospitalized patients aged around 60-years old from the first wave were included. Second, we collected self-reported cognitive symptoms. Identification of specific cognitive deficits (memory, sensorineural, spatial) using quantitative neurological tests should be conducted in future studies. In fact, we cannot rule out that some deficits were present before the infection, although participants were particularly asked for those symptoms starting after hospital discharge. Similarly, we just focused on post-COVID cognitive symptoms. An interaction between cognitive symptoms with other neurological symptoms, e.g., headache, or emotional disorders, e.g., anxiety or depression, might be present. Therefore, studies investigating the interactions between different post-COVID symptoms during the following years are needed.