INTRODUCTION
A large and increasing body of scientific literature points towards significant effect of the post COVID-19 syndrome following a mild to severe COVID-19 infection on the cognitive function (A, B, C, D, E, F, G, H).
Three hypotheses for post COVID-19 syndrome have been considered:
– The persistence of the virus in the organism.
– The s.c. cytokine storm triggered by the virus in its acute phase.
– The existence of autoantibodies that may perturbate the immune function.
IS COVID INDUCED COGNITIVE IMPAIRMET ASSOCIATED WITH AGE?
Elena Herrera et al. in the Department of Psychology, University of Oviedo, Spain, assessed for individuals with post COVID-19 syndrome [but not COVID-19 sequelae with observed organ damage] the association of the level and probability of cognitive impairment with the age, level of education, cognitive reserve [correlates with age and education, see the original research paper] and time since COVID-19 diagnosis of the patient.
They conducted the study with 214 patients selected by the following eligibility criteria: (i) 18 years or older, (ii) confirmed diagnosis of COVID-19 or RT-PCR positive at least 4 months before the study, (iii) symptoms suggestive of post COVID-19 syndrome [WHO definition] with present neurological complaints that appeared during or after SARS-CoV-2 infection, (iv) no brain damage, neurodegenerative, autoimmune or psychiatric disease that could lead to cognitive problems, and (v) no history of alcohol or drug abuse.
The mean age of the participants was 47.5 years (SD=7.4), and they were divided into three age groups, 26-39 years, 40-49 years, and 50-64 years. In the total sample 182 (85%) were women. The participants had in average 16.3 years (SD=5.9) of education, the average time from diagnosis to cognitive tests was 508 days (SD=150), 24% had been hospitalised, 2.7% in ICU for COVID-19.
Each participant underwent 22 cognitive ability tests covering attention, working memory, verbal memory, visual memory, visuospatial function, speed processing, executive functions, and language [Spanish].
For each test the result of each participant was scaled into a Z-score [Z-score distributions for the applied tests are available for the Spanish population. An individual test result of 0.0 refers to the mean, -1.0 to one standard deviation below the mean, +1.0 to one standard deviation above the mean]. Separately in each test the participants were assigned into one of four groups, high (Z > 1.5), mean (-1.5 < Z < 1.5), mild impairment (Z < -1.5), and severe impairment (Z < -3.0, i.e., more than 3 standard deviations below the Spanish population mean).
CONTRARY TO EXPECTATION THE YOUNGER ARE IMPAIRED MORE THAN THE OLDER
Table 4 in the study report presents for each test the percentages of the participants in the four Z-score groups and then in the three age groups within each Z-score group. I amended the original Table 4 by writing in the group and test definitions from the actual text body instead of just the shorthand symbols seen in the column and line titles in Table 4 of the publication. The structure and numerical contents of Table 4 in the study report and in my Table are identical.
Table: The percentages of the participants in the four Z-score groups and then in the three age groups within each Z-score group for each of the 22 cognitive ability tests.
To help grasp a general impression of the cognitive ability test results I computed weighed averages of the 22 test results for the three age groups and compare just the highest (Z > 1.5) and the lowest (Z < -3.0) test score groups. In no way should this mini-table be seen to replace the much more informative full table.
In the youngest age group only 1/10 found themselves in the highest test scores group, but almost half in the lowest, i.e., with severe cognitive impairment. In contrast, in the oldest age group, 3/10 were in the highest test scores group, but only 1/10 in the lowest. The results obtained by the oldest age group were significantly higher in all neuropsychological tasks in which statistically significant differences were observed.
ASSOCIATION OF COGNITIVE IMPAIRMET WITH YOUNG AGE IS SIGNIFICANT AND CONSISTENT, AND THE IMPAIRMENT PERSISTS AT LEAST 1…2 YEARS AFRER COVID-19 INFECTION
Indeed, the most striking result of the study was that all the correlations found between the neuropsychological tests and age were positive (i.e., the older the age, the better the scores on the tests), except for the ROCF (complex figure copying) task, in which a negative correlation was found.
The facts that only 51 of the 214 study participants had been hospitalised, and that there was no correlation between the COVID-19 severity and the cognitive ability tests outcomes, indicates that most of the observed outcomes resulted from mild infections.
The youngest group showed the highest percentages in brief attention and severe verbal memory impairment, as well as deficits in semantic verbal fluency tasks and reasoning tasks.
The mean time from COVID-19 diagnosis to cognitive ability tests was 508 days, which suggests that cognitive difficulties are often maintained up to two years or more. On some tasks, however, such as the verbal learning phase and immediate recall of visual memory, patients with longer time since COVID-19 diagnosis showed better results, suggesting that some cognitive areas might improve over time.
FINDINGS SUPPORT THE AUTOIMMUNE HYPOTHESIS FOR LONG COVID
The facts that women appear to suffer much more frequently from the post COVID-19 syndrome than men, gives indirect support to the autoimmune hypothesis of the post COVID-19 syndrome since several studies (e.g., I) have found that this type of disease affects women more than men in a ratio of 80–20%. The outcome that the youngest, 26-39 yr, age group in the current study suffers significantly more frequently from both mild and severe cognitive impairment than the oldest, 50-64 yr, age group is contrary to a priori expectations, since younger age usually induces a better prognosis in virtually all disorders with cognitive deficits, such as dementia and acquired brain injury. The result, however, does agree with an earlier Italian study (J). It also supports the autoimmune hypothesis, since aging affects the immune system by weakening it, so that the autoimmune response will also be weaker.
THE IMPLICATIONS FOR FINLAND [and most other countries] ARE DIRE
A recent investigation of the global proportions of individuals with persistent fatigue, cognitive, and respiratory symptoms following COVID-19 (K) estimates that 6.2% (2.4 – 13.3%) of individuals who had symptomatic COVID-19 experienced Long COVID symptoms, including 2.2% (0.3 – 7.6%) for cognitive problems after adjusting for health before COVID-19.
National Institute for Health and Welfare in Finland (THL) estimated that by September 2022 70% of the total population had experienced COVID-19. The proportion must have increased significantly in the following autumn-winter COVID-wave, although many if not most of those cases have been reinfections. Assuming conservatively that 75%, or 4.1 million Finns have experienced COVID-19 at least once, 256 thousand would be suffering from Long COVID and 91 thousand from cognitive impairment. For the time being these percentages and numbers continue to grow.
The findings of Elena Herrera et al. suggest that in the order of ¾ of the impaired are women, and that most of theimpaired are not old and vulnerable – as the authorities and media like to see it – but, instead, adults in their prime age and working career. These are bad news even if you would ignore the human tragedy of the individuals, who find that their regular day to day tasks at home or at work have become too difficult to manage – not at the age of 86 but of 40 years. The news are seriously bad for the availability, capability and, thus, productivity of our skilled labour force, for the dependency ratio, and for the whole economy and society. Just try to imagine physicians, nurses, bus drivers, rescue troopers, airline pilots, police officers, etc. whose cognitive capacities have dropped via one or more COVID infections to three standard deviations below the national mean – in other words, to the lowest 0.5% category.
