Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

Brain Behav Immun. 2020 Jul:87:34-39. doi: 10.1016/j.bbi.2020.04.027. Epub 2020 Apr 13.


The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

Keywords: COVID-19; Coronavirus pandemic; Post-viral neuropsychiatric sequelae; Public mental health.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Disease
  • Anxiety / etiology
  • Anxiety / immunology
  • Anxiety / psychology
  • Bacterial Translocation
  • Betacoronavirus
  • COVID-19
  • Chronic Disease
  • Coronavirus Infections / complications
  • Coronavirus Infections / immunology
  • Coronavirus Infections / psychology*
  • Coronavirus Infections / therapy
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / psychology*
  • Cytokine Release Syndrome / therapy
  • Demyelinating Diseases / etiology
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / physiopathology
  • Demyelinating Diseases / psychology
  • Depression / etiology
  • Depression / immunology
  • Depression / psychology
  • Humans
  • Immunologic Factors / adverse effects
  • Mental Disorders / etiology
  • Mental Disorders / immunology
  • Mental Disorders / psychology*
  • Mental Health
  • Nervous System Diseases / etiology
  • Nervous System Diseases / immunology
  • Nervous System Diseases / physiopathology
  • Nervous System Diseases / psychology*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / physiopathology
  • Neurodegenerative Diseases / psychology
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / psychology*
  • Pneumonia, Viral / therapy
  • Psychoneuroimmunology
  • Psychotic Disorders / etiology
  • Psychotic Disorders / immunology
  • Psychotic Disorders / psychology
  • Public Health
  • SARS-CoV-2
  • Stress Disorders, Post-Traumatic / etiology
  • Stress Disorders, Post-Traumatic / immunology
  • Stress Disorders, Post-Traumatic / psychology


  • Immunologic Factors