To the Editor:
We read with great interest the recent report by Ferrando et al.,1 which described 3 patients who presented to the emergency department with similar symptoms including agitation, disorganization, paranoid ideation, and auditory hallucinations. They were all tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), albeit the method of testing was not specified, and found to be positive for the Coronavirus Disease 2019 (COVID-19). We have some thoughts on the observed association and hope this would generate greater discourse on the subject.
First, possible infective origins of mental illness were probably first hypothesized in 1845 by the French neurologist Jean Esquirol, and the theory was later refined by Swiss psychiatrist Eugen Bleuler in the 19th century.2 Given the systemic effects of SARS-CoV-2, which are well-reviewed in literature, it is certainly plausible that the coronavirus could, directly or indirectly, affect the brain and the central nervous system. However, in this case, we are mindful that the observed association in this report could also be fortuitous as this is a small sample of 3 individual cases, and in terms of epidemiological evidence, the onset of first-episode psychosis in the 30s is not uncommon. In a study of 555 individuals with first-episode psychosis, the median age of onset was found to be 27.3 years (interquartile range: 21.2, 36.5).3
Second, the authors appropriately mentioned the possibility of a stress-related trigger from the COVID-19 pandemic in psychiatrically vulnerable individuals. We recognise that all 3 of the patients presented had a prior psychiatric diagnosis: patient 1 and patient 2 both had a prior diagnosis of panic disorder while patient 3 had opioid use disorder, on methadone maintenance. Anxiety is the mother of psychopathology in predisposing, precipitating, and perpetuating symptoms. All three patients also appeared to respond to clonazepam, lorazepam, and low doses of quetiapine, which all exert anxiolytic effects.
In terms of their physical symptoms (or the lack thereof) and stable hemodynamics, there was no evidence of excessive immunologic response. Interestingly, Esquirol himself was also of the view that some mental illnesses may be caused by emotional disturbances rather than by organic brain damage.2 If we accept the prevailing biopsychosocial model of mental illness, psychosis is likely to have multiple causes, including genetic, neurobiological, psychological, and environmental factors. Psychiatric manifestations may be the indirect (“reactive” stress) result of this pandemic rather than the direct pathophysiological effects of the virus.
Third, the classification of acute-onset psychotic disorders is rather inexact, and although the authors reported that the patients did not verbalise preoccupation with COVID-19, this may be difficult to elicit from the patients when they are in an acute agitated and psychotic state.
Fourth, clinically, the elevations in C-reactive protein (0.6–1.9 mg/dL) were relatively minor and could well be within normal variations. “Normal” C-reactive protein levels have not been rigorously studied or defined, and the levels are known to vary with population, age, and ethnicity.4 , 5 To play devil's advocate, we know that struggling against restraints, physical agitation, or other common events could all result in an elevated C-reactive protein. Owing to the highly variable causality, a single C-reactive protein value at admission lacks clinical utility and is difficult to interpret in isolation.
Last but not least, it would be of value to follow up these patients and their symptoms longitudinally. Outcomes of patients with first-episode psychosis are known to be heterogeneous, ranging from complete recovery to recurrent and resistant psychotic symptoms. This may give us new insights beyond that of a “snapshot” picture or cross-sectional mental state examination. The SARS-CoV-2 is undoubtedly a novel virus, and there is much to be learnt from it—and it does surprise us sometimes.
Footnotes
Conflicts of Interest: No conflict of interests to declare.
Acknowledgments: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors alone are responsible for the content and writing of the article.
Authors' statement: Q.X.N. conceived the original idea for the article while K.T.C. supervised the study. All authors contributed to the writing and proofreading of the final manuscript. The final manuscript was discussed and approved by all authors. All authors are responsible for the content and writing of the article.
References
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