Brain Mechanisms Involved in Post COVID Syndrome: A Narrative Review 2024

Abstract

Potentially, patients with COVID-19 can experience long-term disturbances after the acute infection period, even people with no symptoms or mild illness. Our current understanding of brain-associated post COVID-19 condition and why some people are more affected is limited. Post COVID syndrome or long COVID, with continuing symptoms of impaired brain functioning, in particular, ‘brain fog’, chronic fatigue, cognitive decline, mood disturbances, anxiety, and depression, is due to multiple molecular mechanisms. This narrative review updates most important cellular and molecular brain mechanisms as well as system mechanisms underlying post COVID syndrome.


INTRODUCTION
COVID-19 was initially considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, it became clear that the disease affects various organs/systems, including the central and peripheral nervous systems [1]. COVID-19 is a multi-systemic disease which can target the lungs, the cardiovascular system, other organs of the body, and can also affect regions of the brain for expanded periods of time. Post COVID-19 condition, also known as post COVID syndrome (PCS) or long COVID, refers to long-term symptoms that some people experience after they have had COVID-19. Though most people fully convalesce from COVID-19, current evidence suggests that up to 20% of people experience a variety of mid and long-term effects after they recover from their initial illness [2]. According to other sources, international evidence on COVID-19 estimates the incidence of PCS about 10–30% of non-hospitalized cases, 50–70% of hospitalized cases and 10–12% of vaccinated cases [3].

Most long COVID symptoms disappear within 6‑12 months, but in some cases, it can take longer. During the PCS, the SARS-CoV-2 nucleocapsid antigen is present in cerebrospinal fluid in the absence of viral RNA [4]. The symptoms of PCS might persist from the initial illness or develop after recovery; they can come and go or relapse over time. Indeed, the term “post COVID condition” or PCS may be regarded as an umbrella name for the wide variety of ongoing, novel or recurring symptoms of physical and mental health consequences occurring in a number of patients a month or later after SARS-CoV-2 infection, including the patients with initially mild or even asymptomatic acute infection. A prospective cohort study showed that factors that were found to be associated with a higher risk of developing PCS were female gender, older age and active smoking, but not severity of the acute disease [5].

The impacts of COVID-19 infection on mental health are mediated by increased stress load and result in affective and neurological symptoms including anxiety, depression, difficulty thinking and/or concentrating, headache, sleep problems, dizziness, pins-and-needles feeling, changes in smell or taste [6]. People with COVID-19 who had severe illness might have organ damage affecting the lungs, heart, kidneys, and brain. This damage may be associated with inflammation and problems with the immune system. COVID-19 illness can induce the development of new conditions, such as diabetes or a heart or nervous system condition. People with severe symptoms of COVID-19 often needed to be treated in a hospital intensive care unit. This could result in extreme weakness and posttraumatic stress disorder (PTSD) triggered by regarding severe COVID-19 illness as a terrifying event.

Understanding of post COVID conditions remains incomplete. This narrative review aims to update most important cellular and molecular brain mechanisms underlying PCS or long COVID.

Brain Mechanisms Involved in Post COVID Syndrome: A Narrative Review | Neurochemical Journal