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Letter to the Editor
DOI: 10.1016/j.rpsm.2020.07.002
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Disponible online el 9 de Septiembre de 2020
COVID-19 natural herd immunity and risk of neuropsychiatric disorders
Inmunidad natural de grupo y riesgo de trastornos neuropsiquiátricos de la COVID-19
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Beatriz Losilla-Rodrígueza,1, Natalia Maldonadob,c,d,1, Elisa Moreno-Melladob,c,d, Álvaro López-Díaza,d,e,
Autor para correspondencia
a UGC Salud Mental, Hospital Universitario Virgen Macarena, Seville, Spain
b UGC Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain
c Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), Seville, Spain
d Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
e Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Seville, Spain
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Dear Editor:

The current global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has affected over 200 countries with more than seven million confirmed cases and about 415,000 deaths worldwide as of June 12, 2020.1 Its rapid expansion has collapsed the healthcare systems in most countries and quarantine measures taken by governments to flatten the curve of the disease are causing a socio-economic impact without precedent. These circumstances have led to many negative psychological consequences for the population, causing an increase in the incidence of psychiatric disorders.2,3 After several months struggling, many countries are finally coming out of the so-called “first wave” of the COVID-19 pandemic, and population-level seroepidemiological studies are beginning to be published showing a low prevalence of community infection.4 The lack of a vaccine until at least the first half of 2021, the socio-economic costs of lockdown and strengthening preparation of healthcare systems for facing the pandemic have made the concept of natural herd immunity reemerge as a possible strategy for coping with a more than probable “second wave” as social distancing measures are relaxed.5

Herd immunity is an epidemiological phenomenon observed when a large enough number of individuals in a population, by having acquired immunity to an infection, provide indirect protection to the rest of the population that is not immune.6 The protection becomes effective when a certain immunity threshold is reached. This threshold varies depending on the basic reproduction number (R0) of the pathogen, the rate at which the pathogen can spread among the population.6 Since the R0 of SARS-CoV-2 is from 2 to 6, the herd immunity threshold of the disease would be approximately 67%.6 Assuming that this threshold was uniform, and in the absence of a vaccine for COVID-19, up to two thirds of the world's population would have to recover from the infection for natural herd immunity to be reached. This would imply that expected deaths from COVID-19 throughout the world would exceed 30 million and lead to saturation of the healthcare systems, which would cause, not only high mortality from COVID-19, but also a higher mortality from all causes.6 Such figures would be inadmissible, especially when the immune response to COVID-19 is still not completely understood, and it is unknown whether recovery from the disease confers effective permanent post-infection immunity.7

Another major concern is the potential neuroinvasiveness of SARS-CoV-2 and the relatively little information on possible neuropsychiatric effects the infection could cause. Direct viral infection, through the neuronal pathway by retrograde axonal transport from peripheral nerves or by a hematogenous pathway via the blood-brain barrier, is thought to be the main neuropathogenic mechanism of the virus.8 Indirect mechanisms may include angiotensin-converting enzyme 2 down-regulation, myeloid cell trafficking, hypoxia-induced apoptosis, cytokine release syndrome, and gut microbial translocation.8 Among the acute neuropsychiatric complications of COVID-19 are mild, such as headache, dizziness, anosmia and dysgeusia or severe manifestations such as delirium, seizures, encephalitis, encephalopathy and cerebrovascular accident.9 These acute neuropsychiatric symptoms in COVID-19 cases are similar to those commonly observed in patients with severe infection requiring intensive care management.10 However, little is known regarding post-infectious neuropsychiatric complications of COVID-19, and it will take years before they can be properly appreciated. In this vein, delayed or chronic neuropsychiatric sequelae have been reported in past coronavirus outbreaks such as the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).9 Neuromuscular complications and demyelinating diseases such as myopathy, peripheral neuropathy, Guillain–Barre syndrome or Bickerstaff brainstem encephalitis, and neurodegenerative processes have been observed.9 In addition, psychotic disorders, major affective disorders, anxiety and trauma-related disorders, obsessive compulsive disorders and neurocognitive disorders have been associated with coronavirus infections.9,11 Notwithstanding, the magnitude of the current pandemic is much greater than that of the SARS-CoV or the MERS-CoV, and this could lead, apart from a greater mental health burden on society, to seeing in the coming years a dramatic increase in neuropsychiatric sequelae of COVID-19 infection similar to that observed after the 1918 influenza pandemic.2,9,11 In the decades following that pandemic, there was an overall increase in the incidence of severe mental disorders such as schizophrenia, especially in the offspring of pregnant women infected by the virus, suggesting a complex interrelationship between infection, immunity, inflammation and the risk of development of neuropsychiatric disorders.9,12

Faced with such an uncertain scenario and in absence of an effective vaccine in the short-to-mid term, it does not seem recommendable to promote natural herd immunity as a measure for preventing the spread of COVID-19. In addition, it would be important to carry out follow-up studies on everyone who has had COVID-19, including those who were assymptomatic, to examine in detail the appearance of neuropsychiatric disorders in this population. Likewise, post-mortem brain samples should be taken from COVID-19 patients to see the neuroinvasive and neuropathogenic extent of the virus, as well as in vitro studies to understand its neurotropic properties better.

Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

None.

References
[1]
World Health Organization. Coronavirus disease (COVID-2019) situation reports. Situation Report – 144; 2020.
[2]
M.J. Valdés-Florido, Á. López-Díaz, F.J. Palermo-Zeballos, I. Martínez-Molina, V.E. Martín-Gil, B. Crespo-Facorro, et al.
Reactive psychoses in the context of the COVID-19 pandemic: clinical perspectives from a case series.
Rev Psiquiatr Salud Ment, 13 (2020), pp. 90-94
[3]
E. Vieta, V. Pérez, C. Arango.
Psychiatry in the aftermath of COVID-19.
Rev Psiquiatr Salud Ment, 13 (2020), pp. 105-110
[4]
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Covid-19: surveys indicate low infection level in community.
BMJ, 369 (2020), pp. m1992
[5]
P. Amin, M. Abdelmalek, L. Bruggeman.
How herd immunity may protect us from COVID-19.
ABC News, (2020),
[6]
H.E. Randolph, L.B. Barreiro.
Herd immunity: understanding COVID-19.
Immunity, 52 (2020), pp. 737-741
[7]
R.D. Kirkcaldy, B.A. King, J.T. Brooks.
COVID-19 and postinfection immunity: limited evidence many remaining questions.
JAMA, 323 (2020), pp. 2245-2246
[8]
Y. Wu, X. Xu, Z. Chen, J. Duan, K. Hashimoto, L. Yang, et al.
Nervous system involvement after infection with COVID-19 and other coronaviruses.
Brain Behav Immun, 87 (2020), pp. 18-22
[9]
E.A. Troyer, J.N. Kohn, S. Hong.
Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms.
Brain Behav Immun, 87 (2020), pp. 34-39
[10]
A. Varatharaj, N. Thomas, M.A. Ellul, N.W.S. Davies, T.A. Pollak, E.L. Tenorio, et al.
Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study.
Lancet Psychiatry, 2 (2020), pp. 1-8
[11]
J.P. Rogers, E. Chesney, D. Oliver, T.A. Pollak, P. McGuire, P. Fusar-Poli, et al.
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
Lancet Psychiatry, 7 (2020), pp. 611-627
[12]
A.P. Kępińska, C.O. Iyegbe, A.C. Vernon, R. Yolken, R.M. Murray, T.A. Pollak.
Schizophrenia and influenza at the centenary of the 1918–1919 Spanish influenza pandemic: mechanisms of psychosis risk.
Front Psychiatry, 11 (2020), pp. 1-19

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