Neuropsychiatric Manifestations of COVID-19: A Review

A pandemic, as defined by the World Health Organization [1], is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people. Presently, the COVID-19 pandemic is raging through the USA, and as time is progressing, the larger undercurrent of neuropsychiatric ailments and disorders is making its presence felt. At the time of writing this paper, in the last week of November 2020, 1 year after the detection of the first case of COVID-19 in Wuhan, China, there have been over 57.8 million cases and 1.3 million deaths worldwide [2]. Most patients with COVID-19 present initially with fever (83%–99%), cough (59%–82%), fatigue (44%–70%), anorexia (40%–84%), and shortness of breath (31%–40%) [3]. However, the signs and symptoms present at the illness onset may vary widely and involve various organ systems. Recent literature is beginning to shed light on the impact of COVID-19 on the nervous system and its neuropsychiatric sequelae. Studies describing the association between COVID-19 and neuropsychiatric symptoms are limited. Large-scale cohort studies are currently not available in the extant literature. A recent study assessing the potential relationship between COVID-19 and psychiatric disorders found a reciprocal relationship between the two [4]. This study included 62,354 patients diagnosed with COVID-19 with the primary outcomes being the incidence and hazard ratios for psychiatric disorders, dementia, and insomnia during the first 14 to 90 days after a diagnosis of COVID-19 was established. The authors observed that the patients recovering from COVID-19 had a significantly higher rate of psychiatric disorders. There was a 5.8% probability of being newly diagnosed with a psychiatric illness within 90 days post COVID-19 diagnosis. The most frequently acquired psychiatric diagnosis was anxiety disorder, with a probability of outcome within 90 days of 4.7%. Among anxiety disorders, adjustment disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and panic disorder were the most frequent. The probability of a new diagnosis of mood disorder within 14 to 90 days after COVID-19 diagnosis was 2%. Interestingly, previous psychiatric illness was found to be independently associated with an increased risk of being diagnosed with COVID-19. A diagnosis of a psychiatric disorder 1 year prior to the onset of the COVID-19 pandemic was associated with a 65% increased risk of COVID-19 compared with a cohort matched for established physical risk factors for COVID-19, but without a psychiatric diagnosis. This finding held ground in sensitivity analyses. In this article, we will review and discuss the existing evidence regarding various neuropsychiatric manifestations of COVID-19, including delirium, cognitive impairment, psychosis, depression, suicide, mania, and anxiety in patients with COVID-19 and COVID-19 survivors. We will also discuss the neurobiological mechanisms that are hypothesized to be involved in developing neuropsychiatric symptoms. Furthermore, we will discuss the potential role of medications used for treatment of COVID-19 in causing/worsening neuropsychiatric symptoms. Lastly, we will review the psychosocial factors contributing to the psychiatric presentations of infected individuals considering how important psychosocial factors are in the occurrence of primary psychiatric disorders.