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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Neuropsychiatric manifestations in post-COVID patients in second wave of pandemic

1 Department of Psychiatry, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India
2 Department of Medicine, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India

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Date of Submission20-Feb-2022
Date of Acceptance22-Feb-2022
Date of Web Publication12-May-2022


Introduction: There is pooling and evolving literature on the neurological and psychological features of infection with severe acute respiratory syndrome (SARS)-CoV-2. Individuals treated for COVID may have persisting (long-haulers) and delayed onset of these symptoms. Focus has now shifted to the late sequelae of COVID infection, especially during the second wave of the pandemic. These post-COVID conditions vary in their presentation. Systematic approach is required to identify and quantify these late sequelae observed in COVID survivors.
Aim: This study is set to evaluate the neuropsychiatric manifestations of post-COVID status patients consulting psychiatric and medicine outpatient clinic.
Materials and Methods: The current study enrolled patients with post-COVID status visiting psychiatric/medicine outpatient clinics for neuropsychiatric symptoms which were persisting since their COVID infection or new-onset symptoms developing within 1 month of COVID infection. Psychiatric disorder is based on International Classification of Diseases 10 criteria while physician diagnosed the medical/neurological disorders.
Results: A total of 60 patients visiting psychiatry outpatient clinic and 46 patients consulting medicine outpatient department were enrolled in the study. Majority had onset of psychiatric symptoms 15 days after being tested positive for COVID infection. Anxiety disorders, depression, adjustment disorders were the major psychiatric diagnosis. Fatigue and myalgia were the predominant neurological symptoms. Neurological symptoms were more prevalent in patients aged above 50 years with preexisting medical conditions and those hospitalized for COVID infection.
Conclusion: Both psychiatric and neurological complications are evident as late manifestations of COVID infection. There is a need for longitudinal follow-up studies with control groups to assess post-COVID conditions. A better understanding of the post-COVID conditions and the factors that increase the proneness of an individual to these complications is essential. This knowledge will be beneficial in dealing with similar SARS infections in future.

Keywords: COVID 19 sequelae, long haulers, post-COVID conditions, severe acute respiratory syndrome-CoV-2 infection

How to cite this URL:
Pasupuleti S, Suresh R, Reddy S, Reddy Y J. Neuropsychiatric manifestations in post-COVID patients in second wave of pandemic. Arch Ment Health [Epub ahead of print] [cited 2023 Mar 22]. Available from: https://www.amhonline.org/preprintarticle.asp?id=345140

  Introduction Top

COVID 19 pandemic since its first emergence in Wuhan, China, as a novel and severe respiratory virus, had an unprecedented impact globally on individuals of all age groups with serious social, economical, emotional, physical, and psychological adverse consequences.[1] The rapid spread of the virus with mutations and mortality, especially during the second wave of the pandemic, has further disrupted the core of the health-care delivery system.[2] The psychiatric implications of COVID infection may not be limited to acute period of the outbreak but extend beyond it. It involves COVID infected patients, healthy individual's secondary to disruption caused by the pandemic, health-care workers who are intensely engaged in treating infected patients and individuals with prior mental disorders.[3] Neurological and Psychiatric presentations associated with COVID 19 have been increasingly reported. Viral infections are known to infect the central nervous system (CNS), causing neuropsychiatric syndromes affecting cognitive, affective, behavioral, and perceptual domains.[4] Much focus has been on behavioral manifestations of acute COVID infection with seroconversion in majority of cases within 2 weeks of onset of symptoms. There is also accumulating evidence pointing to persistent and lingering symptoms beyond the acute COVID infection. A population-based framework proposed a postacute hyperinflammatory illness 14–30 days after symptom onset and late sequelae as symptoms observed more than 30 days of illness onset.[5]

Research in this context has provided some evidence of ongoing neuropsychiatric symptoms beyond the acute phase of infection. The office for National Statistics, the UK based survey, reported that among the 20,000 participants who were tested positive for COVID, 13.7% continued to experience symptoms for at least 12 weeks.[6] A study conducted in outpatient setting in Geneva on the persistence of symptoms concluded that 32% had symptoms on 30–45 days of COVID diagnosis.[7] COVID-19 has been an multisystem disorder with documented involvement of systems including cardiovascular, pulmonary, renal, dermatologic, and neurologic. Multisystem inflammatory syndrome and autoimmune conditions have also been reported after COVID-19. Neurological manifestations included cerebrovascular events such as ischemic stroke and intracranial hemorrhage, encephalitis, encephalopathy, and CNS vasculitis.

As the pandemic spread through past 2 years, there has been a growing recognition of the psychiatric implications of the virus apart from the physical effects. Unpredictability and uncertainty of the disease involving various aspects including effective treatment modalities and the fear of consequences of being infected with the virus have made population vulnerable to psychiatric disorders. Taquet et al. concluded that a first psychiatric diagnosis was more common in the 14–90 days after COVID infection.[4] In another research by Taquet et al. observed that in the 6-month post-COVID infection, about a third of individuals had a neurological or psychiatric disorder incidence being 33·62% for any diagnosis and 12·84% for the first diagnosis.[8]

Several surveys have suggested that patients with COVID-19 have symptoms of anxiety including posttraumatic stress disorder, depression, and insomnia. A meta-analysis of pooled data from studies that estimated the incidence of psychiatric disorders after the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome outbreaks suggested that coronavirus infections can lead to delirium, anxiety, depression, manic symptoms, poor memory, and insomnia.[9] Patients with preexisting psychiatric disorders on psychotropic medications infected with COVID 19, pharmacological interventions of COVID infection predisposing to psychiatric/medical disorders further complicates the scenario. There seems be a bidirectional relationship between psychiatric disorders and COVID 19. Patients with psychiatric disorders are at a higher risk of getting infected and psychiatric patients infected with COVID are more susceptible for worsening of psychiatric symptoms. Short course high-dose corticosteroid treatment in COVID-19 may cause delirium and changes in mood. Research found increased severity of COVID 19 in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycemia.

In Poland, mental health impact during the first and second waves of COVID infection in the country showed rising trend in the psychological consequences from 25% in the first wave to 40% in the second wave with significant increase depression, anxiety, and suicidal thoughts.[10] India has witnessed massive surge of cases and deaths, especially in young adults in the second wave of COVID 19 since March 2021. The altered viral replication, mutation, evolution, and pathogenicity have been implicated for the devastating aftermath. The emergence of Mucormycosis in COVID-infected patients further aggravated the fear and panic.[11] In this context, the current study embarked to evaluate the Neuropsychiatric manifestations in post-COVID patients.

  Materials and Methods Top

Patients with post-COVID status coming to psychiatric outpatient department (OPD) with the onset of neuropsychiatric manifestations within 30 days of COVID infection and persisting thereafter and those who consult in General medicine OPD for post-COVID follow-up with any neurological/medical symptoms will be contacted. The details of the study will be explained to them and written informed consent will be obtained from them. The interview will be conducted, and diagnosis will be made according to International Classification of Diseases (ICD) 10 for Psychiatric disorders. Medical/Neurological diagnosis is based on symptoms and clinical examination substantiated by necessary investigations by a physician. This was cross sectional observational study. Purposive sampling design was used to enroll all patients meeting the inclusion criteria. Study period was March to August 2021 during the second wave of COVID infection in India. All the details will be entered into a specially prepared pro forma individually for each subject. Details collected included sociodemographic data, details regarding COVID treatment, and psychiatric and neurological/medical diagnosis post-COVID.

The study was approved by the Institutional Ethics Review committee.

Inclusion criteria:

  1. More than 18 years
  2. Patients with positive diagnosis of COVID infection confirmed by reverse transcription-polymerase chain reaction (RTPCR) positive test result
  3. Patients visiting Psychiatry/Medicine OPD with the onset of neuropsychiatric symptoms within 30 days of COVID infection who were hospitalized and discharged for COVID infection or were in home isolation and received COVID treatment and tested RTPCR negative after treatment and visiting psychiatry/Medicine OPD for consultation for persisting symptoms within 3 months of being tested COVID positive
  4. Patients who have given informed consent to participate in study.

Exclusion criteria:

  1. Patients with known cognitive impairment and intellectual disability
  2. Sensory impairment in hearing and vision
  3. Acute physical illness requiring hospitalization.

  Results Top

Total of 72 post-COVID status patients consulted in psychiatry OPD during the study period. Out of which five patients were not willing to participate in the study and seven patients did not meet the inclusion criteria. Finally, 60 patients participated in study. Males constituted 32 (53.3%) and females 28 (46.8%). Majority of the patients were educated till primary school (N = 24, 40%), were employed (N = 45, 75%), belonged to the age group of 31to 50 years (N = 31, 51.67%) and earned an income of 25,000–75,000/month (N = 32, 53.33%) [Table 1].
Table 1: Sociodemographic profile of patients visiting psychiatry outpatient department

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Regarding the COVID symptoms, 45 patients (75.0%) had a symptomatic presentation and 15 (25.0%) had asymptomatic presentation. 36 patients were hospitalized for treatment of COVID infection and 24 (40.0%) received treatment in home isolation. Of the patients hospitalized for COVID treatment 17 of the cases (28.3%) had received intensive care unit (ICU) care [Table 2]. COVID appropriate behavior was followed fully in 14 (23.7%) and partially obliged in 27 (45.7%) and not followed in 18 (30.51%).
Table 2: COVID related clinical characteristics of patients visiting psychiatry outpatient department

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Onset of psychiatric symptoms from day of being tested COVID positive 44 patients (73.3%) had onset 15–30 days of being tested COVID positive and 16 (26.6%) developed psychiatric symptoms 1–15 days of being tested positive. Fourteen out of the 60 patients were diagnosed to have anxiety disorder followed by Depression (N = 9, 15.0%) and adjustment disorder, somatoform disorders (hypochondriasis, somatoform pain disorder, somatoform autonomic dysfunction), and Schizophrenia [Table 3]. Other psychiatric diagnosis includes acute psychotic disorder, acute stress disorder, mania, posttraumatic stress disorder, alcohol dependence, delusional disorder, psychosis not otherwise specified, and suicide attempt.
Table 3: Psychiatric diagnosis of patients visiting psychiatry outpatient department

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Out of the 60 cases, 20 had known family history of psychiatric history and 26 patients had past history of psychiatric disorders. Out of the 26 cases, 16 were compliant with psychiatric treatment till prior COVID infection, two patients had discontinued treatment as per psychiatrist advice, three patients had discontinued treatment during treatment for COVID infection and five patients were noncompliant to psychiatric treatment.

Fear of being re-infected with COVID infection was expressed by 9 out 60 patients and fear of the health consequences of being infected with COVID was observed in 6 cases. Others expressed fear of infecting other family members, fear of dying due COVID infection, fear of oxygen saturation levels falling and no help available, grief of loss of other family members to COVID infection, fear of being infected with Mucormycosis, guilt of surviving when other family members succumbed to COVID infection, negative experiences of COVID related hospital admission and treatment, loneliness, isolation, frustration, anger, helplessness, financial constraints, work-related stress during and after COVID treatment, feeling claustrophobic while admitted for COVID treatment, worried about avoidance and discrimination from relatives and neighbors due to their COVID infection, excessive time spent on social media during and after COVID infection aggravating their anxiety, dissatisfaction with COVID impact disrupting their lives.

Patients consulting for neurological and medical symptoms were 46 out of which 29 were male and 17 were female. 54.34% of the cases belonged to more than 50 years and 65.2% were employed. Thirty-two of the cases were hospitalized for treatment of COVID infection with 22 cases requiring ICU care and 14 patients were in home isolation for COVID treatment. Majority of the cases (67%) had preexisting medical conditions prominent being cardiovascular, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, cerebrovascular disease, thyroid dysfunction, and chronic kidney disease. Out of the 46 patients 6 cases developed a new-onset diabetes mellitus, 4 had new-onset hypertension, 8 developed uncontrolled diabetes, and 2 cases developed stroke post-COVID treatment. Majority of the cases consulting medicine OPD had symptoms of fatigue and myalgia followed by palpitations, gastrointestinal symptoms, persistent cough, chest pain, and memory disturbances [Table 4].
Table 4: Neurological symptoms of patients consulting medicine outpatient clinic

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  Discussion Top

This study set to evaluate the psychiatric and medical/neurological implications of patients with post-COVID status consulting for their persisting symptoms within 3 months of being tested COVID positive. The term long COVID has frequently been used for symptoms that persist or new-onset symptoms that develop after the acute phase of the infection (first 4 weeks of COVID infection).[12] A understanding of the pathophysiology of COVID infection is relevant to comprehend effects in acute phase and ongoing symptoms. Several explanations have been postulated from inflammatory reaction, autoantibody response, endotheliitis, vasculitis to hypoxemic changes, and the resultant multiorgan involvement.[13] The recovery from the organ damage requires a longer time and is implicated in the presentation of long COVID.

Studies across United States, Europe, and China have consistently reported of residual or continuation of symptoms after COVID infection. Fatigue, dyspnoea, myalgia were most reported symptoms which is in line with the current study.[14],[15],[16] Research indicates hypertension, diabetes mellitus and cardiovascular disorders are common comorbid conditions which was the finding in the current study.[17] In follow-up studies of COVID 19 survivors 1 month to 6 months of acute infection reported psychiatric sequelae of depression, anxiety, and sleep difficulties in one quarter to one-half of the patients with a similar trend noted in our study with most patients reporting depression and anxiety disorders.[16],[18] In postacute COVID study women reported more symptoms of fatigue and depression/anxiety which contrasts with our study where more males consulted outpatient services.[19] This could be because of males having more concerns about their well-being as there are the bread winners and their symptoms interfering with their job.

New onset psychiatric disorders post-COVID infection in our study is 56.6%. Various reasons have been stated for the acute psychiatric manifestations of SARS infection like increased antibody titre, proliferation of virus in limbic structures, drug compliance, inadequate follow-up, and stress diathesis.[20],[21] Psychosocial impacts of pandemic like COVID 19 are well documented. It affects both noninfected and infected population.[22] Patients in our study have enumerated various psychological effects of being infected with COVID. Whether the psychological causes or the direct effects of SARS infection or a combination of both have contributed to the psychiatric sequelae cannot be established in our study. However, psychiatric morbidity was reported to be higher in COVID 19 patients when compared to health-care workers and general population.[23] Uncertainty of treatment outcomes, perception of threat, mortality, stigma, traumatic memories of illness, social isolation, and discrimination could attribute to rise in psychiatric conditions in COVID patients. Preexisting psychiatric disorders could be another contributing factor. Psychiatric patients scored higher on depression and anxiety scores during the peak of the pandemic with strict lockdown measures irrespective of COVID infection.[24] In a study investigating psychopathology after 1-month follow-up after hospital discharge revealed that prior psychiatric ailments increased impact as measured by various psychiatric scores.

This study also reported that younger age and those patients who were in home quarantined for COVID treatment demonstrated higher psychiatric symptoms with similar findings in our study majority of the OPD consultations were from those who were treated at home for COVID and in the age group of 18–50 years[18],[25] Further medications given during COVID treatment like corticosteroids and antivirals have neuropsychiatric effects and poses a challenge to psychiatrists to confirm whether symptoms of post-COVID onset are due to the primary psychiatric disorder or secondary to COVID 19 infection and its pharmacological treatment.[26] In a study assessing psychiatric sequelae, 3-month post-COVID reported of 12.2% of posttraumatic stress disorder (PTSD) symptoms.[27] In contrast, though our study reported of 3 cases (5%) of PTSD, these patients had contracted COVID during the first wave of infection in the country. No PTSD was documented during the second wave post-COVID. This could be due to duration criteria of a PTSD disorder according to ICD 10 not satisfied and no specific rating scales being used that could detect PTSD symptoms. Similarly, cognitive impairment including memory loss, lack of concentration, and “brain fog” were not severe enough to satisfy any diagnostic criteria according to ICD 10 though these disturbances have been reported 3-month post-COVID.[28]

Neuropsychiatric implications in acute phase of the infection differ from its long-haul presentation. Initial phase of the infection reported of delirium, encephalopathy, encephalomyelitis, Guillain–Barre syndrome, seizures, musculoskeletal involvement, ischemic and hemorrhagic events.[29] While the persisting neurological symptoms were nonspecific and may point toward a systemic illness rather a primary neurological syndrome.[12] It is evident that neuropsychiatric manifestations may vary during the infection and over few months following the infection. Although the recovery time differs among the individuals, most of ongoing and new-onset symptoms tend to recover within 3 months of the COVID infection signifying the relevance of the current study.[30]

Limitation of the study is no matched control group was used, though the neuropsychiatric manifestations were elaborated no causal relationship can be established to COVID-19 infection or the aftermath of infection. No psychiatric rating scales were used for the diagnosis or assessing the severity of psychiatric presentation. Since the current study focused only on outpatient consultations for ongoing symptoms, it does not represent all cases in the general population with existing symptomology. Since we did not have data of the total COVID hospitalizations or of patients treated for COVID in home isolation prevalence rates of the neuropsychiatric effects post-COVID could not be extrapolated. Our study was limited to the first 3 months following COVID infection which may not be reflective of long-term implications of the infection.

  Conclusion Top

It has been reported that those with persistent symptoms after COVID infection more often visited outpatient clinics and were treated without the requirement of hospital admission. It also imperative to note that not all cases with ongoing symptoms had an hospital encounter. However, the burden and the impairment of the quality-of-life cannot be underestimated. Large population-based controlled studies are required to enhance the current understanding of neuropsychiatric persisting symptoms of COVID infection. Both psychiatrist and physician need to liaise to identify and treat post-COVID presentations. Increased awareness of post-COVID sequelae should propel the treating clinicians to focus on regular review consultations and develop appropriate treatment plans. A holistic approach which is inclusive of the psychological and physical complications of the individual following a COVID-19 diagnosis will go a long way in addressing this novel issue.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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Correspondence Address:
Sreelatha Pasupuleti,
Department of Psychiatry, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amh.amh_36_22


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