Neuropsychiatric Risks in COVID-19 Survivors: Key Study Findings

Researchers employed a large, binational cohort (total n = 4,731,778) in a recent study that was published in the journal Nature Human Behaviour to examine the short- and long-term relationships between SARS-CoV-2 infections and ensuing negative neuropsychiatric outcomes. They compared the results of their samples to those of the general population and people who had a respiratory infection other than SARS-CoV-2 using exposure-driven propensity score matching.

The results of the study showed that survivors of COVID-19 had a markedly increased risk of encephalitis, sleeplessness, cognitive impairments, and at least four other neuropsychiatric aftereffects. Guillain-Barré syndrome (aHR, 4.63), cognitive deficit (aHR, 2.67), anxiety disorder (aHR, 2.23), encephalitis (aHR, 2.15), ischemic stroke (aHR, 2.00), mood disorder (aHR, 1.93), nerve/nerve root/plexus disorder (aHR, 1.47) were among the specific disorders mentioned. Positively, vaccination was found to lessen the infection’s neuropsychiatric consequences. Clinicians and healthcare policymakers will find these results particularly intriguing because they suggest that early COVID-19 management may benefit patients’ short- and long-term mental health.

Context

The coronavirus disease 2019 (COVID-19) pandemic, which was sparked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains one of the worst medical disasters in human history, with over 700 million cases and over 7 million fatalities in the three years since its discovery. Regretfully, for those who survive it, the illness has been known to cause chronic physical and mental health problems that last long after the initial infection.

A multisystemic sickness with enduring or recently established COVID-19 symptoms or comorbidities that lasts for three months or longer after recovery from the initial SARS-CoV-2 infection is known as “long COVID.” It is anticipated that between 18% and 70% of COVID-19 survivors are long-term COVID patients, which is alarming. The published numbers of confirmed cases, which exceed 65 million, are likely to represent only a small portion of the unreported global prevalence of the virus. Thus, one of the most burdensome healthcare issues of the current era is long-COVID.

Since long-COVID was only recently discovered, it is a condition with limited understanding. An increasing amount of studies show that long-term COVID, which frequently lasts more than six months, is linked to neuropsychiatric disorders like anxiety, depression, sleeplessness, and cognitive impairment. Sadly, prior research comparing the psychiatric risks of COVID-19 survivors to the general population has been hampered by small sample sizes, short follow-up periods, and—most importantly—strongly biased hospital-derived cohorts. Such research’ contradictory findings undermine Long-COVID mitigation and management initiatives.

Concerning the study

The goal of the current binational (South Korea and Japan) study is to compare the whole population to COVID-19 survivors in terms of the relative risk of unfavorable neuropsychiatric outcomes. Additionally, it contrasts this risk for survivors of an additional respiratory infection (ARI) with that of the previous cohort. In this study, diagnosing one of 13 categories of neuropsychiatric diseases was the primary outcome, and the primary exposure was the development of laboratory-confirmed COVID-19 (or ARI).

There were two sections to the study dataset: “validation” and “discovery.” The K-COV-N cohort, a population-based, nationally representative summary of the South Korean National Health Information Database (n = 10,027,506), provided the discovery dataset. A validation dataset (n = 12,218,680) was obtained from the Japanese claims-based cohort (JMDC). Patient-level information such as age (>20 years), sex, income, medical history, dwelling area, and insurance claim data were included in both databases. The World Health Organization’s (WHO) International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes were used to record all participant outcomes.

To construct baseline-corrected comparisons between COVID-19 survivors and the general population or ARI, the study technique used exposure-driven propensity score matching. This accomplished the dual goals of assessing the reliability of observations and extrapolating research results over the sizable binational sample population.

To determine the short-, long-, and overall neuropsychiatric risk between the included sample subgroups (SARS-CoV-2 infection and ARI), statistical studies included the development of Cox proportional hazards regression models (also known as “adjusted hazards ratios [aHR]”). This process created reverse causation. The Charlson comorbidity indices, smoking status, physical activity levels, alcohol intake, and body mass indices (BMIs) of the included subjects were taken into consideration as covariates.

Study results

10,027,506 people were initially in the validation cohort and 12,218,680 in the discovery cohort. A final sample size of 4,731,778 participants was obtained by excluding people with inadequate medical records, a history of neuropsychiatric illnesses, COVID-19 and ARI coinfections, and multiple confirmed COVID-19 reinfections. Participants in the study had a mean age of 48.4 years, and 50.1% of them were men.

According to the results of exposure-driven propensity score matching, the ratios for COVID-19 versus the general population (validation/Japanese sample) and the general population (discovery/South Korean sample) were 1:4, 1:2, and 1:1 for COVID-19 versus ARI (both validation and discovery) respectively.

In comparison to the general population, COVID-19 survivors had a significantly higher risk of neuropsychiatric events (aHR = 2.35) in the short term (less than 30 days after infection recovery). Certain conditions, such as encephalitis (aHR = 12.34), Guillain-Barré syndrome (aHR = 11.89), and insomnia (aHR = 5.36), showed an alarmingly elevated risk. These results were in line (although somewhat diminished) with those seen in comparisons between SARS-CoV-2 infection and ARI, where the former showed an aHR of 1.36 in contrast to the latter.

88 Similar findings were found in long-term risk assessments: compared to the general population and ARI, COVID-19 survivors had a considerably higher likelihood of maintaining neuropsychiatric problems for longer than 30 days (aHR = 1.71 and 1.60, respectively).

Time attenuation assessments showed that, although South Koreans recovered to nearly general population risk levels within a year after the initial infection, the Japanese group did not have the same outcome. Positively, the degree of the infection and immunization status had a significant impact on the patient’s risk of neuropsychiatric episodes; risks were reduced for milder cases of SARS-CoV-2 infection and for those who had gotten multiple vaccines. 

In conclusion

This study demonstrates that in South Korean and Japanese individuals, COVID-19 infections are associated with an increased risk of developing neuropsychiatric consequences. It is also the first to compare this risk with that of other respiratory illnesses, the general population, and COVID-19 survivors. Even though time attenuation results show that Japanese people are still at risk even a year after recovering from COVID-19, doctors and healthcare policymakers can better manage their patients and this silent global pandemic by understanding the relationships between infection severity, vaccination status, and risk.

For more information: Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan, Nature Human Behaviour, https://doi.org/10.1038/s41562-024-01895-8