Introduction

As the coronavirus disease (COVID-19) pandemic continues to be a multidimensional threat to humanity, more evidence has emerged of the neurological involvement associated with it¹. The neuroinvasive properties of COVID-19 have allowed the hypothesis of several pathogenic mechanisms related to acute and chronic neurological sequelae². Neuroimmune interaction may be important not only in the pathogenesis of neurological manifestations, but also in the implications of systemic hyperinflammation and its consequences at the cognitive level³. While COVID-19 primarily affects the respiratory system, other organs, including the brain, may be involved². In Western clinical studies, relatively mild neurological dysfunction, such as anosmia and dysgeusia, is common, while severe neurological disorders such as stroke and meningoencephalitis are less common⁴. It is unclear how much COVID-19 infection contributes to the incidence of central nervous system damage due to comorbidities in the affected population. Clinically defined cases of acute disseminated encephalomyelitis have been rarely verified, cases of Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in patients with COVID-19⁵. Common neuropathological findings in patients include microglial activation with microglial nodules in a subset, lymphoid inflammation, acute hypoxic-ischemic changes, and astrogliosis; subacute cerebral infarcts, spontaneous hemorrhage and microthrombi, and occasional infarcts of the anterior pituitary have also been noted⁶. Complications of COVID-19 can include neurological, psychiatric, psychological, and psychosocial sequelae. Little is known about the consequences of COVID-19 on the cognitive functions of patients in the subacute phase of the disease⁷. Much remains to be learned about the effects of direct viral infection of brain cells and whether COVID-19 persists in the long term, contributing to chronic symptoms. More research is needed to understand the causal mechanisms of a probable cognitive deterioration associated with this pathology, so our study proposal focuses on investigating the cognitive profile of the hospitalized patient with COVID-19, which would be an important contribution in the understanding of disease and a better understanding of the interaction of COVID-19 with its human host.

Subjects and methods

This was a cross-sectional study, conducted between April 2021 and August 2021 at the Eugenio Espejo Hospital in Quito, Ecuador. This hospital has been one of those designated for the care of patients with COVID-19 by the Ministry of Public Health. The study has the approval of the competent entities and the informed consent of all the participants was obtained patients with mild to moderate COVID-19 infection. That is, patients with a relationship between arterial oxygen pressure and inspired oxygen fraction (PaO₂/FiO₂) between 201 and 299, in the remission phase of acute symptoms, that is, after 21 days from the beginning of the symptoms were invited to participate in the research; all subjects had a positive polymerase chain reaction test for COVID-19 performed at the institution designated by the Ministry of Public Health of Ecuador. After signing the informed consent, the participants were evaluated using the Montreal Cognitive Assessment (MoCA) test⁸. The test was applied by a neuropsychologist and two resident physicians in psychiatry duly trained for its application. It was considered as a cutoff point < 26 cognitive impairment and ≥ 26 normal. In addition, this test is validated in Spanish in different Latin American countries⁹. Participants with a history of mental, neurological and oncological diseases were excluded in the study; in addition to those who are experiencing reactive mental illness. The age range of the subjects was between 18 and 65 years. The captured data were entered into an electronic database and descriptive statistics, the statistical analysis contemplated a 95% confidence interval, using Chi-square, for which the SPSS version 23 program was used. In all cases, a p < 0.05 is significant.

Results

A total of 50 subjects were recruited, mostly men 58% (n = 29), of which 86.21% (n = 25) had cognitive impairment and only four participants had a normal test. As for the female sex, 90.48% (n = 19) showed cognitive deterioration and only 9.52% (n = 2) had a normal performance. The participants who were between 51 and 65 years old are 34% (n = 17), whereas the subjects between 36 and 50 years old were 46% (n = 23) and the remaining 20% (n = 10) between 18 and 35 years old. Of the participants between 51 and 65 years old, 82.35% (n = 14) presented cognitive deterioration in relation to their counterpart without deterioration 17.64% (n = 3), on the other hand, of the group between 36 and 50 years old 95% (n = 22) present cognitive deterioration and only one subject presented the normal test, finally, of the participants between 18 and 35 years old, 80% (n = 8) were impaired and 20% (n = 2) it is not.

The patients with university education were 50% (n = 25), of these 88% (n = 23) presented cognitive deterioration. Those with secondary education were 36% (n = 18), of which 83.33% (n = 15) had some degree of deterioration and only 14% (n = 7) had primary education, all showing deterioration cognitive.

Of the sample collected, 88% (n = 44) presented cognitive deterioration and only 12% (n = 6) showed a normal score. Of the 44 subjects with cognitive impairment, 58.81% n = (25) had a score between 20 and 25 in the MoCA test, 34.09% n = (15) had a score between 10 and 19 in the test and in 9.09% n = (4) a score lower than 9 was found.

There was no statistically significant relationship after applying the Chi-square test between cognitive impairment and sex (p = 0.647), nor was there evidence of a relationship between age and cognitive impairment (p = 0.302), in the same way there was no relationship between education and cognitive impairment (p = 0.515).

Discussion

In this study, it has been possible to verify a prevalence of 88% of cognitive impairment in patients treated at the Eugenio Espejo Hospital in Quito, Ecuador, similar incidences can be verified in studies where the same test has been applied in the population under similar conditions¹⁰. In this sense, it is important to mention that most of these patients did not report cognitive alterations and therefore these types of problems go unnoticed.

The sequelae of cognitive disorders are increasingly seen as a major challenge in the COVID-19 pandemic. However, most of the evidence of cognitive alterations after COVID-19 infection and invasion of the virus by the central nervous system comes from severely affected individuals in the acute phase of the disease¹¹ in this study is verified the presence of cognitive impairment in patients with mild and moderate symptoms.

It is believed that direct viral entry and systemic mechanisms such as cytokine storm contribute to neuroinflammation in patients with COVID-19, the etiology of cognitive impairment would be multifactorial, among these factors would be age¹². Age seems to be a risk factor¹³. However, in this study, there seems to be no statistically significant relationship associated with age, which is clinically significant since there is the same incidence in young and old patients.

The clinical presentation of COVID-19 and its long-term effects are still a matter of study, the implications on mental health in the short and long term require clarification¹⁴, it is not clear if the cognitive deterioration persists over time or if there is remission of symptoms. COVID-19 infection can cause long-term effects on immune processes within the CNS by causing microglial dysfunction¹⁵. Our study shows that there is cognitive impairment in the remission phase of symptoms. Therefore, it is necessary to continue investigating relatively recent onset pathology.

Apparently, there are no significant differences in the incidence of cognitive impairment in people with COVID-19 related to sex¹⁶, however studies on the subject are scarce, in any case our data show that there is no difference.

As has been noted, there is a similar prevalence of cognitive impairment in patients with different levels of education, so it does not seem to be a protective factor. No scientific literature could be found in this regard, so data must be taken with caution.

Although it is true that the use of the psychometric instrument could have increased the number of diagnosed patients, we believe that the criteria used allowed us to select the most clinically significant cases. We consider as a serious limitation that it was not possible to increase the sample due to the considerable decrease in diagnosed cases due to vaccination against COVID-19 in Ecuador and there was no control group either. In any case, our data support the fact that there is a high incidence of cognitive impairment in patients with COVID-19 with mild to moderate symptoms in the remission phase.

Conclusions

In our cohort study, patients with COVID-19 with mild to moderate symptoms have a high risk of presenting cognitive impairment, a better understanding of the causal processes and evolution over time is required to develop preventive and therapeutic interventions.