Mental and Neurologic problems after COVID-19 in children and adults

.Lancet Psychiatry published a study measuring the psychiatric and brain neurologic conditions after COVID-19 infection.

The authors are from Oxford and Cambridge University in the UK.

The findings are essential for clinicians and health policymakers but also laypeople.

The study collected 89 million patient records from several countries, including the USA, Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan.

Patients diagnosed with COVID-19 between Jan 20, 2020, and April 13, 2022, were identified. They were compared to a control group, a cohort of patients with other respiratory infections.

Both groups were matched (1:1) based on demographic factors, risk factors for COVID-19 and severe COVID-19 illness, and vaccination status.

They aim to assess the risk of 14 neurological and psychiatric diagnoses after SARS-CoV-2 infection between the two groups.

After identifying the diagnosis, the patient’s psychiatric and neurologic conditions were followed (using health records), and a 2-year risk trajectory was calculated. Risk trajectory is the risk of developing a disease with time.

Results

The study sample is huge. In 89 million patients, they gathered 1,284,437 people who had COVID-19. There were 185,748 children (<18 years), 856,588 adults 18-64 years, and 242,101 older adults (>65 years).

The overall mean age was 42.5 years, 57.8% were female, and 42.2% were male. They are all matched to the same number of control subjects with other respiratory infections.

Findings

The following is for all age groups.

The incidence of mood and anxiety disorders was increased but only temporarily.

Risks of the common psychiatric disorders returned to baseline after 1-2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group.

The risks of several psychiatric and neurologic conditions are presented below. The x-axis (horizontal line) is the duration of follow-up in days.

A green line represents the Risk Horizon on the right. If the green line is below the dotted line, the lower risk, and vice versa. Risk horizon is the chance of developing a particular condition within a period, which in this study is two years. Notice that the risk horizon decreases with time for mood and anxiety disorders.

Source: Taquet M et al. Lancet Psychiatry. 2022

Neurologic changes

The risks of cognitive deficits (aka brain fog), dementia, psychotic disorders, and epilepsy or seizures remained increased at the end of the 2-year follow-up period.

A sizable number of older adults who were diagnosed with dementia or epilepsy, or seizures died in both groups.

This suggests that the high mortality reflects general physical ill health rather than being related to SARS-CoV-2 infection.

This time the risk horizon for dementia, psychotic disorders, and epilepsy persisted until the end of the study, which is two years. It makes you wonder how long it really is.

Children After COVID-19

Children were not at an increased risk of mood or anxiety disorders In the six months after the SARS-CoV-2 infection.

Children have an increased risk of cognitive deficit, insomnia, intracranial hemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures.

The neurologic conditions with the highest risk (Hazard Ratio) after COVID-19 among children are in the red box below.

Fortunately, the risk of a cognitive deficit in children is temporary, about 75 days. In adults, the cognitive deficits last longer and manifest as dementia.

Children have a higher risk than adults of developing complications

The figure below compares the hazard ratios of several conditions among the three age groups. Notice that children are at risk for more COVID complications than adults and older adults.

According to the authors, this could be because more adults die during acute COVID-19, and that lowers the hazard risk.

Source: Taquet M et al. Lancet Psychiatry. 2022

Could a case be made to vaccinate the children to avoid complications? Not so fast; we must first identify the children at risk and weigh the benefits against the risk of developing myocarditis and other adverse effects.

Risk profiles among the Alpha, Delta, and Omicron Variants

The study compared the psychiatric and neurologic conditions following infection of the Alpha Delta and Omicron variants of the SARS-CoV-2. Again, the mortality rate among the variants affected the risk ratios.

For the Alpha variant, there was no increase in the risk of developing mood and neurologic conditions.

But, in the Delta, there is an increased risk of strokes, seizures, dementia, insomnia, anxiety, and a higher death rate.

During Omicron, the death rate was lower, but the risk of dementia, brain bleeding, mood disorder, and nervous system disorder remained the same.

Just after (vs. just before) the emergence of the delta variant (n=44,835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate.

With omicron (n=39,845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.

Why did the complications happen?

In their discussion, they cited the work of Ray et al., who suggested that acute disseminated encephalomyelitis (ADEM) could be the cause in children.

Another explanation is that endotheliopathy or damage to the blood vessels can also explain the increased risk of cognitive deficit and dementia, psychotic disorder, and epilepsy or seizures two years after SARS-CoV-2 infection.

Incidentally, the spike protein in the vaccines also causes blood vessel damage.

As for the children, the relatively short duration of mood disorders is explained by the authors as,

One possible explanation is that COVID-19 precipitates mood and anxiety disorders in individuals with an underlying predisposition, via a short-lived stress-related pathogenesis to which children are less susceptible.

Comment

It would have been better if they separated the age groups of the children instead of lumping them together as <18.

I would like to see if there was any risk difference between the vaccinated and unvaccinated in the control group who did not have COVID-19. That will give us an idea of the effects of the COVID shots. But that was not part of the study protocol. The data the authors have may provide the answer for another study.

Take away Message

The risks of intracranial hemorrhage, mood disorders, nervous system damage, and dementia can continue even with future SARS-CoV-2 variants that are less lethal.

Studies (Rashedi et al., Xie et al., Ghosh et al.) have shown that preexisting comorbidities like diabetes and cardiovascular diseases before contracting COVID-19 are risk factors for developing Long COVID. Control of medical problems can help reduce the risk of post-COVID complications.

With regards to dementia, the findings of this study from the UK give real-world evidence on another research that showed that there are strong parallels between brain changes after a COVID-19 infection and Alzheimer’s dementia.

I talked about that study in Similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals.

Brain changes after COVID-19 and Alzheimer’s dementia are due to inflammation. Intermittent fasting is an effective way to decrease the number of monocytes that produces pro-inflammatory cytokines. You can read about them at

Long COVID or Post Acute Sequelae of COVID-19 (PASC) may also present as brain fog and memory problems. The Front Lins COVID Critical Care Alliance has a protocol for that.

The I-RECOVER Management Protocol for Long Haul COVID-19 Syndrome

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Reference:

Taquet M, et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry. 2022 Oct;9(10):815-827. doi: 10.1016/S2215-0366(22)00260-7. Epub 2022 Aug 17. PMID: 35987197; PMCID: PMC9385200.

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