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Mental Health and COVID-19

Nothing - poem by Rossana Cama...

The pandemic we are facing now and over the following years

Post-COVID-19 syndrome is the persistence of clinical signs and symptoms that appear during or after suffering COVID-19 and that remain for more than 12 weeks and have no association with concomitant conditions. Symptoms are consistent and present as flare-ups or fluctuations. These symptoms are independent of the infection’s severity and are estimated to occur in approximately 10 to 36% of COVID-19 survivors. The most frequent symptoms are fatigue, dyspnea, attention, concentration, and memory problems, as well as sleep disturbances, anxiety, and depression.

More studies worldwide show that at least 1 in 5 patients may develop neuropsychiatric problems within 90 days after infection. One of the first studies on these sequelae was conducted in Wuhan and published in the journal JAMA. The trial described that 36% of patients developed different neurological disorders post-infection. Following the same line, Brain published a study by the University of Oxford in which the trial described neurological disorders during hospitalization and after hospital discharge. A retrospective study published in the journal Lancet, evaluating 62,354 patients with COVID-19 in the United States, confirmed the conditions; the study proved the relationship between neuropsychiatric sequelae and infection.

Although it seems paradoxical at first glance, a brain infection is unnecessary to develop these neuropsychiatric disorders. The chronic inflammatory response can cause these conditions. It could also, among others, modify the functional permeability of the blood-brain barrier (a semipermeable cellular barrier that envelops the brain and spinal cord and regulates the passage of molecules to the brain), which is very sensitive to peripheral inflammatory changes.

On the other hand, inflammatory molecules such as IFN-γ, IL-1, IL-6, and TNF-α induce metabolic changes in the brain and the periphery, such as the inhibition of tetrahydrobiopterin, a critical cofactor for the synthesis of dopamine. When inhibited, dopamine concentration decreases; dopamine is an essential neurotransmitter for motor behavior, emotionality and affectivity, and neuroendocrine communication.

Another metabolic change is the activation of indolamine 2 3-dioxygenase in leukocytes and microglia; this results in decreased serotonin levels critical for regulating mood, emotions, appetite, and digestion; therefore, there is an increase in the synthesis of kinunerins, which has neurotoxic effects at increased concentrations. Altogether, these changes in neurotransmitter levels trigger behavioral changes, anxiety, emotional flattening, and mood swings, among other psychiatric symptoms in the susceptible population.

Biological mechanisms triggering neuropsychiatric conditions have not yet been elucidated. As previously mentioned, these conditions could result from inflammatory alterations, autoimmune responses, and a sustained increase in the production of reactive oxygen species secondary to SARS-CoV-2 infection.

Because it might be responsible for the post-COVID psychiatric effects, one of the phenomena currently under investigation is residual inflammation in COVID-19 survivors. This inflammation is possibly caused by the persistence of the virus or by hematopoietic changes induced by infection. Such as those changes in emergency hemopoiesis secondary to viral infection, characterized by an increase in highly reactive exhausted T lymphocytes. Similarly, another source of inflammation is histological damage to organs like the heart, endothelium, kidney, and lung.

Recently it has been pointed out that hypocortisolism secondary to damage to the pituitary gland or the pituitary gland may be involved in the development of complications since cortisol regulates the inflammatory response, and low levels of this hormone increase the inflammatory response. Additionally, we must consider that the inflammatory response occurs when acute and chronic stressful events present. This inflammation is relevant because healthcare professionals are susceptible to developing psychiatric conditions due to the constant stress due to the care of patients and the fear of infecting themselves or their relatives; in the same way, individuals in isolation are subject to continuous stress due to confinement.

Another damage mechanism possibly involved in neuropsychiatric changes is autoantibodies induced by SARS-CoV-2 infection. Antibodies are circulating proteins that generate after disease to provide immunity. In some cases, antibodies directed against virus proteins can crossrecognize proteins expressed in their neurons and thus cause psychiatric conditions. There are some reports of similar neuropsychiatric problems induced by autoantibodies in the medical literature and are called “PANDAS” or autoimmune encephalitis.

A critical precedent is a SARS-CoV outbreak that affected China in 2002, where patients had high psychiatric morbidity with the presence of chronic fatigue that persisted until at least four years after the outbreak despite presenting a physical improvement after the infection. Noteworthy, frontline healthcare workers who attended this outbreak showed even higher levels of stress, depression, anxiety, and post-traumatic stress symptoms than the infection survivors. According to a report by the World Health Organization, mental health has been significantly affected in several countries, not only by psychiatric problems but also by an increase in the consumption of alcoholic beverages and substance abuse, as a result of the social changes derived from the pandemic.

For all of the above, it is vital to generate innovative strategies in the field of public health to mitigate this problem. One of the ravages that COVID-19 has left is the mental health pandemic that has been worsening over the past months; it is necessary to continue researching and understanding the etiopathogenesis of post-COVID complications and to develop efficient strategies for prevention and treatment.

It is important to note that vaccines do not make us immune to infection and much less will prevent the onset of the aftermath of COVID-19. It has been reported that 10% of infected and vaccinated individuals have neuropsychiatric complications. Thus, prevention measures must be reinforced since the number of infected patients is constantly growing.

We thank Dr. Lissette García Mena for her contribution to the development of this paper.