Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19

Abstract

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

Neuropsychiatric and Cognitive Sequelae of COVID-19

“…For a detailed discussion of these mechanisms, please see Wu et al (2020). The neuronal pathway via the olfactory nerve and role of ACE2 has been observed to be the primary pathophysiological mechanisms contributing to neuropsychiatric and cognitive complications in COVID-19 (Mirfazeli et al, 2020;Pantelis et al, 2020). This is mainly because coronaviruses affect the respiratory tract and can reach the ACE2-enzymes in the respiratory epithelial cells, and the olfactory nerve, providing a pathway for the coronavirus to enter the CNS.…”

A Review on SARS-CoV-2-Induced Neuroinflammation, Neurodevelopmental Complications, and Recent Updates on the Vaccine Development

“…The neural tissues of animal models are beneficial to examine the SARS-CoV-2-induced modulation in ACE-2 [33,177,178]. Dysregulation of RAS systems in COVID-19 infection contributes to ischemic brain injury through small-vessel hypoperfusion and arterial atherothrombosis [179]. Molecular mechanisms regulating these processes can be deciphered using mice models of SARS-CoV-2 infection.…”

“…The global COVID-19 pandemic raised concern for pregnant women regarding the outcomes of SARS-CoV-2 infections, as this viral infection may invoke potential fetal defects viz., long-term neurodevelopmental impacts [215].There are three primary considerations for a developing fetus: Vertical transmission of the disease from the mother The prenatal effects of maternal systemic infection on the fetus The possible effects on placental functioning and consequent pregnancy outcomes [179] The presence of ACE-2 receptors in the placenta suggests the potential risk of getting SARS-CoV-2 transmission. In addition to vertical transmission, the maternal infection may invoke neurodevelopmental alterations during fetal development.…”

Walter Patrick Memorial Lecture: COVID Pandemic Public Health Consequences and Prospects and How It Will Change Public Health Education

“…The latter is due to stress over COVID and the disruption it has caused and more and more neurological consequences of COVID-19 infection are being reported. 17-19 This will require a global response, best coordinated through the WHO.…”