Authored by: Venkat Rao
Iceberg comes as a good analogy to what we currently know about the neurological and psychiatric disease burden of COVID-19. Just as little as one-eighth of an iceberg is visible above the water and most of the mass lies below the surface of water, what we know at present are the partially visible aspects of the neurological and psychiatric sequalae with much of the disease burden laying below and remains unknown.
Public health tends to focus mostly on the biomedical and clinical aspects of infectious disease epidemics but rarely on attendant mental health issues. At the peak of COVID-19 pandemic in 2020, there were initial reports on potential adverse psychiatric impact with 4 in 10 adults in the US reporting symptoms of anxiety or depressive disorder, specific negative impact on mental health and well being such as difficulty sleeping (36%) or eating (32%), increased consumption of alcohol or substance use (12%) and worsening conditions (12%) due to worry and stress over coronavirus.
There is a historical precedence to this. It should not come as a surprise to those closely following the pattern of disease burden posed by SARS virus, which first appeared on the global stage in 2003 and spread rapidly to about 30 countries reporting more than 8,000 cases, resulting in 774 deaths globally. This was the first instance of a global epidemic involving a novel virus causing deadly infectious diseases where national boundaries were meaningless, and existing medical countermeasures were ineffective to protect or treat those infected with the novel virus. Subsequent reporting on the long-term impact of the 2003-04 SARS epidemic made a striking observation of post-traumatic stress disorder (PTSD) as the most prevalent long-term psychiatric diagnoses among survivors of SARS.
Describing 2003 SARS global epidemic as a bio-disaster, research investigators identified psychological impact as a likely long-term health security issue among the survivors. According to published studies at that time, nearly 48% of the patients met the criteria for PTSD, and 26% continued to meet the PTSD criteria at 30-months post-SARS.
PTSD was identified as a critical long-term health burden among SARS survivors. PTSD is generally defined as a mental health condition that is triggered by a terrifying event—either experiencing it or witnessing it. PTSD symptoms may include flashbacks, nightmares, and severe anxiety, as well as uncontrollable thoughts about the event.
Notice the relative scale of impact that the 2003-04 SARS global epidemic was only about 8,000 confirmed cases and 774 deaths. In comparison, the 2020 COVID-19 pandemic, which continues to rage globally has to-date 624 million confirmed cases of the disease reported from all 195 nations in the world, and over 6.5 million deaths attributed to the disease.
Consider for a moment how substantially large COVID-19 impact on mental health could be?
The staggering costs of COVID-19 pandemic’s long-term impact on global health security are beginning to reveal as nations have begun comprehensive multi-sectoral assessment of the pandemic and attendant costs at national and global levels.
Let us focus on just one aspect involving neurological and psychiatric disorders among COVID-19 patients. Psychiatric and neurological disorders are among the lesser-known adverse impacts caused by COVID-19, but with potentials for serious long-term consequences.
SARS-CoV-2 Infection was associated with reports of psychological distress, fatigue, and sleep disorders among patients in primary care settings. This study involved health care records of nearly 12 million patients, including 226,521 patients with SARS-CoV-2 infection, found increased risk of sleep problems and fatigue, However, the results were less conclusive as to the observed psychiatric disorders link to SARS-CoV-2 infection.
Subsequently, in a comprehensive study published this week, in Lancet, analysis of a 2-year retrospective cohort study involving 1.28 million patients report serious, long-term neurological and psychiatric risks among individuals diagnosed with COVID-19 with a higher preponderant risk of psychotic disorder, cognitive deficit, dementia, epilepsy, or persistent seizures. The risk was particularly significant for neurological disorders listed here, whereas psychiatric disorders such as increased incidence of mood and anxiety were transient and at levels comparable to other respiratory infections.
In simple terms, the study analyzed medical data extracted from an international network of healthcare records of nearly 89 million patients collected mostly from the United States, Australia, the UK, Spain, India, Malaysia, and Taiwan. Confirmed cases of COVID-19 patients diagnosed between January 2020 and April 2022 were included as the patient study population. Study population of patients were sorted by age group as children (age less than 18 years), adults (18-64 years) an older adult (65 years and above). A total of 14 neurological and psychiatric diagnosis after SARS-CoV-2 infection were selected for risk assessment and compared with a matched cohort population to compare study results. The patient and control groups were sorted for alpha, delta, and omicron variant phases of the pandemic to analyze for the differential impact due to virus genomic variants on neurological and psychiatric disorders.
A key observation from this study was the bifurcated nature of the psychiatric and neurological impact on COVID-19 patients, with significantly higher risks of neurological effects with defined pathologies such as cognitive deficit, dementia, and epilepsy. Children demonstrated a relatively benign overall profile of psychiatric risks compared to adults and older adults.
Another notable observation from this large-scale study was that the psychiatric and neurological adverse effects were similar during the delta and omicron phases of the epidemic. The implication is that the onset of neurological and psychiatric adverse effects is independent of the viral variants in circulation and the health security assessments both at the individual and population-levels for neurological and psychiatric disease burdens should disregard the genomic makeup of the SARS-CoV-2 virus. The study design took into account likely confounders implicated in the previous studies yielding inconclusive results, to ensure a better association of neurological disease outcomes with SARS-CoV-2 infection.
SARS-CoV-2 virus induces neuropathology that remains persistent for months after infection. Although published literature does not demonstrate a strong link between infectious diseases and mental illness symptoms, SARS-CoV-2 seems to cause lasting neurological illness and in particular among older adult patients. Neurological symptoms of COVID-19 are linked to widespread response of the immune system to the infection which results in damaging nerve tissue in the brain and nervous system
SARS-CoV-2 virus is not detected in the brain of COVID-19 patients. The virus does not cross the blood-brain barrier, and as such is not directly implicated in the adverse effects on brain and nervous system. A massive response from a highly reactive immune system to infection in some individuals elicits significant damage to multiple vital organs and systems, including brain.
Going back to the iceberg analogy, we do not yet know how the SARS-CoV-2 infection damages the brain resulting in long-term neurological disorder. Researchers are examining the role of autoimmune response as another possible route for SARS virus-induced neurological effects. We do not know yet, if SARS-CoV-2 variants differ in their neurological risk profiles and how different it affects children and adults. Sitting as an iceberg, the scale and scope of COVID-19 neurological and psychiatric disease burden remains unknown.