By Davide Perego
From "The CoESPU MAGAZINE" nr. 2 - 2020
Selection: "In Depth" , pag.68
DOI Code: 10.32048/Coespumagazine2.20.9
CORONAVIRUSES AND OTHER SIMILAR INFECTIONS IN OUR BRAIN: THEY CAN PRODUCE PSYCHIATRIC SINDROMES?
By Davide Perego
Coronaviruses are single-stranded RNA viruses. They belong to a large family of respiratory viruses that can cause mild to moderate illnesses from the common cold disease to respiratory syndromes. In the past we known the effects of this type of viruses with severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012.
On Dec 31, 2019, WHO was made aware of several cases of atypical pneumonia in Wuhan, China, which were subsequently identified as being caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
There is the common idea that the first target of these viruses is the respiratory tract, although COVID-19 showed pleiotropic effects, example dermatologic and vascular damages. It is interesting take into consideration also, eventually psychiatric and neuropsychiatric effects of SARS, MERS, and COVID-19.
Coronaviruses have also been detected in both the brain and the cerebrospinal fluid of individuals with seizures, encephalitis, and encephalomyelitis. In general viral infections are known to infect CNS, causing neuropsychiatric syndromes affecting cognitive, affective, behavioural, and perceptual domains.
As the pandemic of the disease has spread, there has been a growing recognition of the psychiatric implications of the disease. In the meantime the wider social impact of the pandemic and the governmental response, including physical distancing measures and quarantine, has interested all the people independent of the age and the status.
Both the infected and non-infected population might be susceptible as a result of pandemic period, such as widespread anxiety, social isolation, stress in health-care workers and other essential workers, and unemployment and financial difficulties.
But over general effects, experiences might be specific to individuals who are infected with the virus, such as concern about the outcome of their illness, stigma, and amnesia or traumatic memories of severe illness.
Neuropsychiatric consequences as mental disorders that are the sequelae of brain damage or disease, can arise either thorough direct effects of infection of the CNS or indirectly via an immune response or medical therapy. A case series from Wuhan found that among patients admitted to hospital for infection with SARS-CoV-2, 36% had neurological features, mostly consisting of mild symptoms such as dizziness and headache, although these symptoms might be manifestations more of systemic illness than a specific neurological syndrome (Mao L Jin H Wang M et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020; (published online April 10.). A study by University of Cincinnati researchers and University of Brescia (Brescia), University of Eastern Piedmont (Novara), and University of Sassari, Sassari, have took consideration images from 725 hospitalized patients with confirmed COVID-19 infection between February 29 and April 4. Of these, 108 (15%) had serious neurological symptoms and underwent brain or spine imaging. Most patients had brain CT scans, while others had head and neck CT imaging and brain MRI. Investigators found that 59% of patients reported an altered mental state and 31% experienced stroke, which were the most common neurological symptoms. Patients also experienced headache (12%), seizure (9%) and dizziness (4%), among other symptoms.
SARS-CoV-2 invades human host cells by the angiotensin-converting enzyme 2 receptor (ACE2r), which has little expression in the brain.
There has been hypotesis that other routes of CNS infiltration might account for the respiratory failure caused by infection with SARS-CoV-2, although there isn't, actually, evidence.There is preliminary in-vitro evidence that SARS-CoV-2 can replicate in neuronal cells, but the translation of this finding to in-vivo settings remains unclear.
Previous influenza pandemics have been associated with long-lasting neuropsychiatric consequences, so it is possible that other viral infections on a large scale could cause sustained mental morbidity.
From a systematic review and meta-analysis of the psychiatric consequences of coronavirus infection published by “The Lancet” in May 2020, were identified 72 independent studies that provided data on both the acute and post-illness psychiatric and neuropsychiatric features of coronavirus infection, including seven medRxiv preprints (Medrxiv is an Internet site distributing unpublished manuscripts about health sciences).
The scientific literature predominantly consists of data on patients with SARS and MERS treated in hospital, so there should be caution to extend any findings to COVID-19, particularly for patients who have mild symptoms. The main findings are that:
- signs suggestive of delirium are common in the acute stage of SARS, MERS, and COVID-19;
- there is evidence of depression, anxiety, fatigue, and post-traumatic stress disorder in the post-illness stage of previous coronavirus epidemics, but there are few data yet on COVID-19.
In SARS and MERS in the acute stage, using data from two studies, the most important finding was that confusion occurred in 27·9% of patients, suggesting that delirium was common. Other common psychiatric findings were depression, anxiety, and insomnia. Diagnoses of mania and psychosis did occur in a small minority (0·7%), but in a small sample this diagnosis appeared to be almost entirely related to use of exogenous corticosteroids, which are rarely prescribed to treat SARS-CoV-2 infection.
Notably, insomnia, emotional lability, irritability, pressured speech, and euphoria were relatively common, suggesting that although a full syndrome of mania was uncommon, not detectable symptoms might be present.
In SARS and MERS, after recovery from the infection, sleep disorder, frequent recall of traumatic memories, emotional lability, impaired concentration, fatigue, and impaired memory were reported in more than 15% of patients at a follow-up period ranging between 6 weeks and 39 months. Emotional lability, pressured speech, and euphoria were only reported by patients and relatives after a short follow-up in one studying which corticosteroids had frequently been prescribed at high doses and symptoms; therefore, it might be of limited relevance to the COVID-19 pandemic. The point prevalences of anxiety disorders, depression, and post-traumatic stress disorder were high, although the lack of adequate comparison groups or assessment of previous psychiatric disorder means that it is hard to separate the effects of the infection from the impact of an epidemic on the population.
In terms of severity, mean scores for depression and anxiety on standard scales were below clinical cutoffs. Measures of health-related quality of life were considerably lower in patients with SARS than in control groups. However, the impairment in social functioning was greater than the effects on mental health, suggesting that the effect of coronaviruses is broad and not specific to mental health.
In terms of applicability to COVID-19, conclusions must be cautious because data on the acute effects of the illness are limited and no data exist on the post-illness phase, and the higher mortality of SARS and MERS might be correlated with poorer psychiatric outcomes.
The information available suggests that in the acute stage (as in SARS and MERS) confusion is a common feature, so delirium is probably a significant clinical problem. In the longer term, the data from SARS and MERS suggest that the prevalence of depression, anxiety, post-traumatic stress disorder, and fatigue might be high, but as yet data on these diagnoses in patients with COVID-19 are preliminary or unpublished.
In patients with severe illness requiring ICU admission, neurocognitive impairment might be a feature. The researchers found only three cases of SARS-CoV-2-related psychiatric symptoms that were explicitly linked to hypoxic or encephalitic brain injury; this finding is consistent with the rarity of case reports that have associated detection of coronaviruses in the CNS with acute encephalitis or encephalomyelitis (mainly in immunocompromised or immunodeficient children).
The aetiology of the psychiatric consequences of infection with coronavirus is likely to be multifactorial and might include the direct effects of viral infection, including brain infection, cerebrovascular disease (including in the context of a procoagulant state), the degree of physiological compromise (eg, hypoxia), the immunological response, medical interventions, social isolation, the psychological impact of a novel severe and potentially fatal illness, concerns about infecting others, and stigma. The immune response in SARS-CoV-2 infection is of interest and there might be a hyper inflammatory state similar to that seen in haemophagocytic lymphohisticytosis in which there are increased concentrations of C-reactive protein, ferritin, and interleukin-6, although this state is likely to be short lived.
The link between inflammation and depression is well described in the literature, and might explain some of the psychiatric morbidity.
Survivors of critical illness are at risk of persistent psychiatric impairment after discharge from hospital. At 1 year, the pooled prevalences of clinically relevant depressive was 29%, anxiety 34%, and post-traumatic symptoms 34%.
The majority of patients with severe acute respiratory distress syndrome, a key feature of severe COVID-19 illness, show impairments of memory, attention, concentration, or mental processing speed.
None of the studies included in the review completed systematic neuropsychological assessments apart from one report of severe SARS-CoV-2 cases, which described a dysexecutive syndrome in a third of survivors.
Acute respiratory distress syndrome and prolonged mechanical ventilation are also associated with greater reductions in quality of life than ICU admissions for other reasons.
However, although the frequencies of ICU admission and ventilation were similar for patients admitted to hospital with SARS-CoV infection (13% ICU admission and 7% ventilation) and SARS-CoV-2 (18% and 6%), they were considerably higher in patients with MERS (60% and 51%).
Given that a very large number of individuals will be infected with SARS-CoV-2, the immediate impact on mental health could be considerable. An acute rise in cases of delirium will probably prolong hospital stay; there is also some preliminary evidence that delirium was associated with raised mortality in MERS.
There is a risk of common mental illnesses in patients with disease that require hospital admission, which might be compounded by the effects of social isolation.
Given this psychiatric morbidity and high frequency of persistent fatigue, some patients might have difficulty in returning to their previous employment, at least in the short term, although physical (as well as mental) recovery is intrinsic to such a broad functional outcome.
In conclusion, although there are many ways in which mental health might be adversely affected by a pandemic, my opinions are, that most people do not suffer from a psychiatric disorder following coronavirus infection, and second, that so far there is little to suggest that common neuropsychiatric complications beyond short-term delirium are a feature. It is clear that a long hospitalization and to stay in ICU could be arise psychological and neuropsychological consequences, and that is very important to assist the patients also in this domains.
Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms - Abdul Mannan Baig, Areeba Khaleeq Usman Ali, Hira Syeda. Published online 2020 Mar 13. doi: 10.1021/acschemneuro.0c00122
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic - Jonathan P Rogers, MRCPsych, Edward Chesney, MRCPsych, Dominic Oliver, Msc, Thomas A Pollak, PhD, Prof Philip McGuire, FmedSci, Paolo Fusar-Poli, PhD et al. Published:May 18, 2020 DOI:https://doi.org/10.1016/S2215-0366(20)30203-0.