|Year : 2022 | Volume
| Issue : 2 | Page : 169-175
Incidence of psychiatric illness among COVID-19-positive individuals with and without loss of smell or taste symptoms in a Tertiary Care Hospital in South India – A prospective cohort study
S Shankar, M Mohamed Ilyas Rahamathulla
Department of Psychiatry, Government Mohan Kumaramangalam Medical College Hospital, Salem, Tamil Nadu, India
|Date of Submission||05-Mar-2022|
|Date of Decision||29-Apr-2022|
|Date of Acceptance||10-May-2022|
|Date of Web Publication||19-Aug-2022|
Dr. M Mohamed Ilyas Rahamathulla
Door No. 371, Flat 8, 3rd Floor, Srisairam Illam, Cherry Roa, Hasthampatti, Salem - 636 007, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: COVID infection is known to cause acute and long-term neuropsychiatric presentations. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. Materials and Methods: The study was conducted in a tertiary care hospital, and COVID-19-positive individuals were grouped based on the presence or absence of loss of smell (anosmia) or taste symptoms (ageusia). Group 1 without smell or taste disturbance, and Group 2 with smell or taste disturbance. Both groups were followed up for 6 months to assess the new onset of psychiatric illness. Results: The onset of new psychiatric illness was present in 8 out of 30 (26.66%) cases in group 2 when compared with 2 out of 30 (6.66%) cases in Group 1, with a relative risk of 4 (95% confidence interval 0.9247–17.3023). In 10 cases, the pattern of psychiatric illness was depression (16.66%), anxiety (6.6%), posttraumatic stress disorder (3.33%), acute psychosis (3.33%), and acute stress disorder (3.33%). Both groups were compared in terms of socio-demographic profile, inflammatory markers, and computed tomography severity score, and no significant difference was noted between the two. A relative risk of 4 indicates that COVID-19-infected individuals who lose their sense of smell or taste are more likely to develop new-onset psychiatric illness. Conclusion: Impact of COVID-19 on the central nervous system is very evident, and loss of smell or taste symptoms could be an early marker. Early recognition and prompt treatment with immunotherapy or newer therapies will prevent the emergence of psychiatric disturbance and its disability.
Keywords: Anosmia, ageusia, COVID-19 infection, new-onset psychiatric illness
|How to cite this article:|
Shankar S, Ilyas Rahamathulla M M. Incidence of psychiatric illness among COVID-19-positive individuals with and without loss of smell or taste symptoms in a Tertiary Care Hospital in South India – A prospective cohort study. Ann Indian Psychiatry 2022;6:169-75
|How to cite this URL:|
Shankar S, Ilyas Rahamathulla M M. Incidence of psychiatric illness among COVID-19-positive individuals with and without loss of smell or taste symptoms in a Tertiary Care Hospital in South India – A prospective cohort study. Ann Indian Psychiatry [serial online] 2022 [cited 2022 Sep 30];6:169-75. Available from: https://www.anip.co.in/text.asp?2022/6/2/169/354119
| Introduction|| |
The COVID-19 pandemic started in the year 2019. The timeline of this pandemic is largely unknown. Many have lost their lives and many have lost their loved ones, and the reminiscence of the infection is still prevalent in the form of chronic medical illness. One of them is a psychiatric illness. Psychiatric illness may occur during the acute as well as the chronic phase of illness. Fear, health anxiety, apprehension, uncertainty, and loneliness are some of the psychological causes for developing illness during the early phases of illness. Even though psychosocial factors play a major role in the genesis of psychiatric symptoms in COVID-19 infection, the direct effect of the virus is one of the main reasons for long-term consequences. Neuroinvasive properties were also present in previous viral outbreaks such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome, and H1N1; similarly, COVID-19 has an increased risk of the same. Viral infection of the brain may have multiple neurological and psychiatric consequences.
The clinical presentation of COVID-19 is dominated by respiratory signs with less frequent occurrence of gastrointestinal symptoms. The viral invasion is not only limited to these organs but also involves heart, kidney, brain, and endothelium. Loss of smell or taste symptoms are different from general constitutional symptoms and are more specific neuropsychiatric symptoms. The direct route of entry into the central nervous system (CNS) through the olfactory nerve is one of the reasons for the consistent early findings of loss of smell or taste symptoms in COVID-19. Smell dysfunction is a biomarker of COVID-19 infection. However, it is not clear whether all patients with olfactory symptoms would develop neuropsychiatric symptoms. Apart from the olfactory route, the virus enters the CNS through other routes such as infecting the endothelial lining of the brain vasculature, through the trigeminal nerve, and sensory fibers of the vagus that innervate the respiratory tract. Further evidence states that in neuro-inflammation, the downstream mechanisms of inflammation are multifactorial. Increases in peripheral and central inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6 (IL-6), and interferon, lead to oxidative stress and ultimately alter neurotransmission. These mechanisms have all been shown to play a role in psychiatric illness's development and progression. In the brain, cytokine production causes behavioral changes during illness or infection, manifesting in the form of depressive symptoms such as emotional hyper responsiveness, apathetic syndrome, anhedonia, Hyporexia, weight loss, hypersomnia, alternation of the circadian rhythm, and alteration in higher mental functions.,
Consequently, many important questions for psychiatrists arise. How common are psychiatric manifestations and who is at risk of developing a psychiatric illness?
Patients with COVID-19 showed higher manifestations of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms when compared with non-COVID controls with no history of psychiatric illness in the past. This could be due to an underlying neuropathological mechanism. Common psychiatric manifestations included anxiety and other related disorders (4.6%) and mood disorders (3.8%). Less than 1% of all psychiatric manifestations included emotional state, symptoms and signs (318, or 0.8%) and suicidal ideation (63, or 0.2%). Anxiety disorders, particularly phobias, and new-onset COVID infection are associated with obsessive–compulsive disorders and suicidal ideation. PTSD and acute stress disorder are two of the most common manifestations, next to depression and anxiety, which range from 20% to 30%. The emergence of psychiatric illness is more common in younger people, women, those who require intensive care unit (ICU) care, those who use steroids, and those who stay in the hospital for an extended period.
In recent times, many studies have begun to report neuropsychiatric manifestations in COVID infection. One such study reported that 31% or one-third of the patients had altered mental status, including delirium (13%), psychosis 8%, affective disorder 3%, and dementia 5%. Irrespective of the severity of viral illness, a mild or moderate state of the illness can also cause direct damage to the brain. A few researchers discussed the viral hypothesis in schizophrenia based on its previous influenza type of illness. We would like to assess the relationship between new loss of smell or taste and the emergence of psychiatric illness using the research findings presented above. Our aim is to assess the emergence of psychiatric illness in patients with COVID infection and to compare the emergence of psychiatric illness in COVID infection without new loss of smell or taste to that with new loss of smell or taste.
| Materials and Methods|| |
This research was conducted in a tertiary care center where COVID-19-positive individuals were admitted. This research has been approved by the ethics committee. Following informed consent, the patients were enrolled in the study. We selected 30 cases of COVID-19 positivity with no new loss of smell or taste (Group 1) and 30 cases of COVID-19 positivity with new loss of smell or taste (Group 2) with the following inclusion and exclusion criteria. The convenience sampling method followed. The following are the inclusion and exclusion criteria. The study was carried out with universal precautions by wearing Personal protective equipments (PPE) kit.
- 18 years of age or above
- Individuals infected with SARS-CoV-2 (i) who have developed a new loss of smell or taste and (ii) who have no new loss of smell or taste.
- A history of psychiatric illness and neurological illness prior to the onset of the SARS-CoV-2 infection and Patients Who were critically ill or on a ventilator
- Olfactory/gustatory disorders prior to SARS-CoV-2 infection.
- Semi-structured pro forma for assessing socio-demographic and clinical data. Treatment details such as use of steroids, remdesivir, and enoxaparin were included. Inflammatory markers and the computed tomography (CT) severity index are used to assess the severity of illness
- Reverse transcriptase-polymerase chain reaction (RT-PCR)-based diagnostic tests (which detect viral nucleic acids) are considered the gold standard for detecting current SARS-CoV-2 infection. The test is a real-time RT-PCR test intended for the qualitative detection of nucleic acids from the SARS-CoV-2 in upper respiratory specimens (e.g., nasopharyngeal swabs, oropharyngeal swabs, sputum, BAL, and tracheal aspirates). The assay is composed of two principal steps: (1) extraction of RNA from patient specimens; and (2) one-step reverse transcription and PCR amplification with SARS-CoV-2-specific primers and real-time detection with 2019-nCoV-specific probes
- Examination of Smell and Taste: The tests were carried out using coffee powder, lemon, and peppermint. The patient must compress each nostril in turn and, by sniffing through the other, show that the airway is clear. The test odor is placed under one nostril while the other is compressed, and the patient is told to take two good, but not overexuberant, sniffs. He is then asked (i) if he can smell anything, and (ii) if he can identify the odor. The test is then repeated in the other nostril. After an interval to allow that odor to disperse, the test is then repeated with two more odors and, in addition to the above, he is asked (iv) If he can distinguish the different odors. Examination of taste – The test is carried out with sugar, salt, vinegar, and quinine in that order. The patient must protrude the tongue to one side, keep it out throughout the test, and not talk. The four possible tastes are written on a card. The tip of the tongue is held gently with a piece of gauze and the side of the tongue is moistened from the tip with a little of the test substance. The patient should indicate the taste by pointing to the card. In between each test, he must swill out his mouth with water. Based on the above tests, patients with COVID-19 infections are categorized as with loss of smell/taste symptoms or without loss of smell/taste symptoms
- Inflammatory markers: Inflammation is the body's innate response to injury or insult, including infection, trauma, surgery, burns, and cancer. Certain proteins are released into the bloodstream during inflammation; if their concentrations increase or decrease by at least 25%, they can be used as systemic inflammatory markers. The following are the inflammatory markers taken for this study,,,
- A D-dimer is a protein fragment (a small piece) that is made when a blood clot dissolves in the body. Blood clotting is an important process that prevents the body from losing too much blood that is injured. Normally, the body will dissolve the clot once the injury has healed (normal range: 500 ng/mL). Several studies suggest that the levels of D-dimer may rise sharply in the case of COVID-19 and that this is associated with the severity of the disease
- C-reactive protein (CRP) is a substance produced by the liver in response to inflammation. A high level of CRP in the blood can be a marker of inflammation. A wide variety of conditions can cause it, from infections to cancer (normal range: 8.0 mg/L). CRP levels were found in patients with COVID-19, with levels ranging from 20 to 50 mg/L on average. Elevated levels of CRP were observed in up to 86% of severe COVID-19 patients
- Lactate dehydrogenase (LDH) plays an important role in making the body's energy. It is found in almost the body tissues, including those in the blood, heart, kidneys, brain, and lungs. When these tissues are damaged, they release LDH into the bloodstream or other body fluids. Elevated LDH levels were linked to a 6-fold increased risk of severe COVID-19 disease
- Ferritin is an intracellular blood protein that contains iron. The ferritin level in the blood mostly depends on the severity of the COVID-19 disease (normal range: females, 10–200 mcg/L; males, 30–300 mcg/L)
- IL-6 is one of the key mediators of inflammation and viral cytokine storm in COVID-19 patients. Normal range (5–15 pg/ml). Elevated levels of the above markers were considered abnormal values.
All initial chest HRCT scans were performed on the day of the patient's presentation. The severity of lung involvement was visually scored according to the method described in previous studies. A 5-point scale was used to quantitatively evaluate the extent of inflammatory pulmonary lesions for each of the five lung lobes: 0: no lesion; 1: 1%–5% involvement; 2:25% involvement; 3:26%–50% involvement; 4: 51%–75% involvement; 5:76%–100% involvement. The total CT score of the bilateral lungs was equal to the sum of the scores of the five lobes, with a maximum total score of 25 points. 7 or less mild, 8–15-moderate, 16 or more severe,,The ICD-10 Diagnostic Criteria for Research based on the Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders were used to assign diagnoses of mental illness.
Group 1: 30 cases of COVID-19 without new loss of smell or taste as Group 1 and 30 cases of SARS-CoV-2 infection with new loss of smell or taste as Group 2. From December 2020 to May 2021, 60 patients were enrolled in the study and were subjected to psychiatric assessment using ICD RDC during admission as well as 1st, 3rd, and 6th month follow-ups. The follow-up visits are made either in person or through Tele-consultation. For all patients, a chest CT scan and laboratory tests including inflammatory markers, LDH, D dimer, IL-6, ferritin, and CRP were taken. Then, we documented the data, including demographics, drug history, laboratory markers, CT chest severity score, and psychiatric history.
The statistical design was formulated using the data collected. As above, for each of the scales and socio-demographic variables, the central values and dispersion were calculated. A Chi-square test was used in the comparison of data for categorical variables. The SPSS 20.0 version (SPSS 20, IBM, and Armonk, NY, United States of America) was used for the statistical analysis.
| Results|| |
[Table 1] shows socio-demographic data of the two groups: Majority of the study population were between 31 and 45 years of age, 50% in Group 1 and 43.35% in Group 2. Male preponderance was observed with 66.7% in group 1 and 70% in group 2 being male. In both groups, 80% of the study population were married and employed in at least one job. Similarly, the majority had studied up to 12th grade, with 70% in group 1 and 86.7% in group 2. People with loss of smell or taste symptoms were more common among less-educated people, but statistically not significant. In terms of place of residence, rural outnumbers urban by 66.7% in Group 1 and 73.3% in Group 2, although the difference is not statistically significant. Most of them belong to the upper middle class in both groups, with 50% in group 1 when compared with 43.3% in Group 2.
Three major parenteral drugs (1) steroids (methylprednisolone), (2) remdesivir, and (3) enoxaparin, were used for COVID-19 infection. The these drugs were given based on a CT severity score of more than 10 or in any case with breathing difficulty, irrespective of CT score. In this study, 90% of Group 2 people received steroids during admission. Similarly, 46.7% received remdesivir and enoxaparin. When compared to Group 1, 76.7% received steroids during admission and 26.7% received Remdesivir and Enoxaparin. This shows that Group 2 cases were severe in presentation, so loss of smell or taste symptoms at the early phase of the illness may be considered for close monitoring as they may go to a severe state during illness. The difference between the groups is statistically not significant.
LDH, D-Dimer, and CRP were elevated in 33.3% of cases in group 1 when compared with 40–50% in Group 2. Ferritin and IL-6 were elevated in 33.3% and 26.7%, respectively, in Group 1 when compared to 40% and 30% in Group 2. Most of the cases show elevated levels of inflammatory markers, but those with loss of smell or taste symptoms have a slightly higher risk of having elevated levels of these markers, but this is not statistically significant.
In Group 1, the majority (70%) had a score of <7, 16.7% scored between 8 and 15, and only 4 people had a CT score of more than 16. In Group 2, the majority of 56.7% scored under 7, 16.7% scored between 8 and 15, and 26.7%, i.e., 8 cases had scores of more than 16. There is a difference between both groups, but it is statistically not significant. The majority of them had severe illness based on this score.
Only 2 cases (6.7%) out of 30 developed psychiatric illness in Group 1, whereas 26.66%, i. e., 8 out of 30 cases developed psychiatric illness in Group 2. On comparison of both groups, the statistical results showed a significant value (P = 0.037667). This shows that COVID-19-infected individuals with loss of smell or taste have a higher chance of developing psychiatric illness during their course of illness than those individuals without loss of smell or taste symptoms.
[Table 2] shows the timeline of new-onset psychiatric illness between two groups: In Group 1, one case occurred during the 1st month post-COVID, and another one occurred during the 3rd month of follow-up. In Group 2, one case occurred during admission, four cases occurred during the 1st month, two cases occurred during the 3rd month, and one case occurred during the 6th month of follow-up.
|Table 2: The timeline of new-onset psychiatric illness in the two groups|
Click here to view
[Table 3] shows the type of psychiatric illness in the two groups: Different types of psychiatric illness were present in both groups. Two of the patients in Group 1 developed depression, whereas in Group 2, 3 cases had depression, 2 had anxiety, and 1 person each had acute stress disorder, PTSD, and acute psychosis.
[Table 4] shows the relative risk assessment in the two groups: The relative risk between the two groups is 4 (95% CI 0.9247–17.3023). The RR >1 shows the association is positive.
| Discussion|| |
To the best of our knowledge, this study is one of the few attempts to explore the new-onset psychiatric illness in COVID-19-infected individuals with loss of smell or taste symptoms. This study's report of the prevalence or pattern of psychiatric illness is similar to other studies. One study retrospectively analyzed 214 patients with a molecular diagnosis of COVID-19 from three different hospitals found 36.4% had psychiatric symptoms when compared to our study's 33.33% (both groups).
Similarly, in a United Kingdom-wide surveillance study, 153 patients were reported to have neurological and neuropsychiatric complications following COVID-19 infection. Twenty-one of these cases developed a newly diagnosed psychiatric disorder.
In this study, majority of them developed psychiatric illness during 1st month. This shows that the illness predominantly occurs during the 1st month, after the acute phase of the illness gets over. However, any phases have a risk of developing psychiatric illness.
Similar to this, one study reported an increased risk during the 1st month. Following COVID-19 infection, patients are at increased risk for depression and anxiety. At approximately 1 month following infection, 31%–38% of patients report depressive symptoms, 22–42% report anxiety symptoms, and 20% report obsessive–compulsive symptoms., Another study reported an increased risk at the 3rd month following COVID-19 diagnosis, in which 18% of patients were diagnosed with a psychiatric disease, with nearly 6% representing a new diagnosis (e.g., dementia, anxiety, and insomnia).
Different types of psychiatric illness were present in both groups. This pattern is consistent with other studies. Increased incidence of depression, anxiety, adjustment disorders, acute stress reactions, somatization, and obsessive–compulsive disorders has also been reported. Recent studies among COVID-19 patients have found a greater occurrence of depressive and anxiety disorders in people who are in quarantine front-line workers, or among family members of affected patients. Less than 12.8% reported anxiety disorders, compared to 6.666% in this study.
Similarly, PTSD is widespread in severe COVID-19-positive individuals, as reported by a greater number of cases in many studies. However, just one case (3.33%) had PTSD in this study. However, in many studies, the prevalence of PTSD among COVID-19 patients appears to vary from 20% to 30%, while the prevalence of strictly defined posttraumatic stress symptoms varies widely. The reason for the low number of cases is due to the sampling method we used, as we excluded severe cases on the ventilator or ICU because they were more unstable for the interview than those admitted to the general ward.
In our study, a new onset of psychosis was seen in 1 case, 3.33%. Many people reported a higher prevalence of psychotic disorders in the post-COVID state. The CoroNerve surveillance study identified new-onset psychosis in 10 of the first 153 patients with acute COVID-19-related neuropsychiatric complications. There have been several cases from many countries detailing first-episode psychotic symptoms in COVID-19 patients. COVID-19 treatment may also precipitate psychosis. Specifically, chloroquine and hydroxychloroquine, which were previously the mainstays of COVID-19 care, can cause hallucinations and other psychotic symptoms. The administration of high-dose corticosteroids, which remains one of the few effective treatments for severe COVID-19 infection, can cause psychotic symptoms, which have also been specifically described in the setting of viral illness treatment.
Maternal viral (and other) infections during pregnancy can affect the offspring, with a greater incidence of neurodevelopmental disorders, such as autism, schizophrenia, and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. Irrespective of vertical transmission, maternal infection could lead to neurodevelopmental changes in the fetus. Schizophrenia incidence rates have risen following previous influenza epidemics.
Although there were no cases of neurodegenerative disorders in our study, many studies have reported neurocognitive impairment as one of the long-term consequences of COVID infection. One study of 279 patients hospitalized with COVID-19 found that 34% reported memory loss and 28% described impaired concentration approximately 3 months after discharge. In a large EHR study, new-onset dementia following hospitalization for COVID-19 was 2–3 times more common than what was observed after hospitalization for other medical events. In more severe cases of COVID-19, long-term cognitive deficits are likely the sequelae of delirium experienced during the acute phase of the illness. Olfactory deficits have been previously reported in several viral infections and are characteristic of neurodegenerative disorders. Notably, loss of smell or taste symptoms are linked to high levels of IL-6, an inflammatory mediator causally involved in brain disorders.,
Many studies reported psychiatric or neuropsychiatric illness secondary to COVID-19, but none of them studied the link between psychiatric illness and loss of smell or taste symptoms. The relative risk between the two groups is 4 (95% confidence interval 0.9247–17.3023). The RR > 1 shows the association is positive. Hence, this study showed that the presence of loss of smell or taste in COVID-19 infection has an increased the chance of developing new-onset psychiatric illness than COVID-19 infection cases without loss of smell or taste.
The demographic characteristics of the COVID-19 infection with new-onset psychiatric illness showed a majority (50%) above 45 years of age, a male preponderance (70%), 70% of them were married, all of them studied up to 12th grade, 70% of them belonged to a rural background, 90% of them were employed, and 60% belonged to the upper middle class. Among the inflammatory markers, LDH is the least elevated in patients with new-onset psychiatric illness, whereas IL-6 and D dimers are elevated in up to 60% of cases, and CRP and ferritin are elevated in 70% of the cases. In the CT severity score assessment for psychiatric illness, 5 cases had a score of > 16 and 3 cases had a score of between 8 and 15, and only 2 cases had a CT score less than 7. Many studies reported that the risk of psychiatric illness was associated with COVID illness severity. Patients with COVID-19-related psychosis may exhibit elevations in CRP, ferritin, LDH, and D-Dimer, with either elevated or depressed WBC or platelet levels. Severe COVID-19 disease was associated with higher rates of these diagnoses, but all patients with COVID-19 had higher rates of psychiatric diagnoses when compared to controls. Depressive and/or anxiety symptoms following COVID-19 are more likely in females and those with infected family members, post-infection physical discomfort, severe infection, and elevated inflammatory markers.,,,
In this study, the new-onset psychiatric illness with a relative risk of 4 in COVID-19-positive individuals with new loss of smell or taste (Group 2), when compared with individuals without new loss of smell or taste (Group 1) was linked to neuroinvasive etiology. The majority of cases with new-onset psychiatric illness are related to elevated inflammatory markers related to neuroinflammation etiology. The CT score was also increased in cases with new-onset psychiatric illness. The majority of patients were given steroids, remdesivir, and enoxaparin, indicating that those with severe illness are more likely to develop psychiatric illness during the post infectious state. Loss of smell or taste may be considered as a biomarker for psychiatric symptoms that occur during the later course of illness. Early identification of the same helps in giving standardized care and treatment of psychiatric illness, preventing disability. As the pandemic is not coming down, newer therapies including plasma therapy or novel drug treatments may help to prevent the emergence of psychiatric illness in COVID-19-infected patients in the long run. They can imply association at maximum, not causation, which needs more systematic research.
This study was not without limitations. We should consider that some of these neuropsychiatric presentations might be due to reasons other than coronavirus, such as medication side effects, electrolyte disturbance, hypoxia, or comorbid diseases. Larger sample sizes with larger laboratory measures could show a better picture of the disease. Second, this study lacks randomization, and confounding factors could not be matched. However, we expect that this study will provide the groundwork for future research studies exploring the neuropsychiatric impact of COVID-19 in more detail with respect to loss of smell or taste symptoms.
| Conclusion|| |
The timeline of this pandemic is largely unknown, and the upcoming months are extremely important for using epidemiological and longitudinal studies, both to understand the viral effects on the brain system and to find out possible solutions. The neuropsychiatric sequelae of COVID-19 represent a serious clinical challenge that has to be considered for future complex therapies. Clinicians need to be aware of these manifestations in COVID-19 patients given the morbidity and mortality of neuropsychiatric involvement. The long-term effects of these neuropsychiatric manifestations remain unknown. Early recognition, prompt management, and long-term follow-up are warranted to provide better and more efficient patient care.
I am deeply indebted to Dr. M. Rajeswari M.D, D.P.M., and Dr. K.S. Ravishankar M.D, D.P.M., Professors of Psychiatry Department of Psychiatry, Government. Mohan Kumaramangalam Medical College Hospital, Salem, for the valuable guidance and encouragement rendered throughout this project.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Zorec R, Županc TA, Verkhratsky A. Astrogliopathology in the infectious insults of the brain. Neurosci Lett 2019;689:56-62.
Vetter P, Lan Vu D, L'Huillier AG, Schibler M, Kaiser L, Jacquerioz F, et al
. Clinical features of covid-19. BMJ 2020;369:m1470.
Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL. Smell dysfunction: A biomarker for COVID-19. Int Forum Allergy Rhinol 2020;10:944-50.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al.
Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur Arch Otorhinolaryngol 2020;277:2251-61.
Woo MS, Malsy J, Pöttgen J, Seddiq Zai S, Ufer F, Hadjilaou A, et al.
Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun 2020;2:fcaa205.
Klein RS, Garber C, Funk KE, Salimi H, Soung A, Kanmogne M, et al.
Neuroinflammation during RNA viral infections. Annu Rev Immunol 2019;37:73-95.
Manglani M, McGavern DB. New advances in CNS immunity against viral infection. Curr Opin Virol 2018;28:116-26.
Varatharaj A, Thomas N, Ellul MA, Davies NW, Pollak TA, Tenorio EL, et al.
Neurological and neuropsychiatric complications of COVID-19 in 153 patients: A UK-wide surveillance study. Lancet Psychiatry 2020;7:875-82.
Lu S, Wei N, Jiang J, Wu L, Sheng J, Zhou J, et al.
First report of manic-like symptoms in a COVID-19 patient with no previous history of a psychiatric disorder. J Affect Disord 2020;277:337-40.
Bo HX, Li W, Yang Y, Wang Y, Zhang Q, Cheung T, et al.
Posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with COVID-19 in China. Psychol Med 2021;51:1052-3.
Yang Y, Li W, Zhang Q, Zhang L, Cheung T, Xiang YT. Mental health services for older adults in China during the COVID-19 outbreak. Lancet Psychiatry 2020;7:e19.
Steardo L Jr., Steardo L, Verkhratsky A. Psychiatric face of COVID-19. Transl Psychiatry 2020;10:261.
Centers for Disease Control and Prevention. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19); 2020. Available from: https://www.cdc.gov/coronavirus/2019
. [Last retrieved on 2022 May 22].
Prasad K, Yadav R. Bickerstaff's Neurological Examination in Clinical Practice, Seventh Adapted Edition. Wiley India Pvt Ltd; 2013. p. 44, 93.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.
Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al.
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846-8.
Francone M, Iafrate F, Masci GM, Coco S, Cilia F, Manganaro L, et al.
Chest CT score in COVID-19 patients: Correlation with disease severity and short-term prognosis. Eur Radiol 2020;30:6808-17.
Zhou S, Chen C, Hu Y, Lv W, Ai T, Xia L. Chest CT imaging features and severity scores as biomarkers for prognostic prediction in patients with COVID-19. Ann Transl Med 2020;8:1449.
World Health Organization. (1993). The ICD-10 classification of mental and behavioural disorders : diagnostic criteria for research. World Health Organization. Geneva, Switzerland: World Health Organization; 1993.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al.
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.
Deng J, Zhou F, Hou W, Silver Z, Wong CY, Chang O, et al.
The prevalence of depression, anxiety, and sleep disturbances in COVID-19 patients: A meta-analysis. Ann N Y Acad Sci 2021;1486:90-111.
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al.
Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun 2020;89:594-600.
Czeisler MÉ, Lane RI, Petrosky E, Wiley JF, Christensen A, Njai R, et al.
Mental health, substance use, and suicidal ideation during the COVID-19 pandemic – United States, June 24-30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1049-57.
Rajkumar RP. COVID-19 and mental health: A review of the existing literature. Asian J Psychiatr 2020;52:102066.
Qiu J, Shen B, Zhao M, Wang Z, Xie B, Xu Y. A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen Psychiatr 2020;33:e100213.
Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: Retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry 2021;8:130-40.
Mascolo A, Berrino PM, Gareri P, Castagna A, Capuano A, Manzo C, et al.
Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: A review article. Inflammopharmacology 2018;26:1141-9.
Wada K, Yamada N, Sato T, Suzuki H, Miki M, Lee Y, et al.
Corticosteroid-induced psychotic and mood disorders: Diagnosis defined by DSM-IV and clinical pictures. Psychosomatics 2001;42:461-6.
Meyer U. Neurodevelopmental resilience and susceptibility to maternal immune activation. Trends Neurosci 2019;42:793-806.
Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, et al
. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and metaanalysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020;7:611-27.
Han AY, Mukdad L, Long JL, Lopez IA. Anosmia in COVID-19: Mechanisms and Significance. Chem. Senses. 2020;45:423–8.
Gialluisi A, de Gaetano G, Iacoviello L. New challenges from Covid-19 pandemic: An unexpected opportunity to enlighten the link between viral infections and brain disorders? Neurol Sci 2020;41:1349-50.
Parker C, Shalev D, Hsu I, Shenoy A, Cheung S, Nash S, et al.
Depression, anxiety, and acute stress disorder among patients hospitalized with covid-19: A prospective cohort study. J Acad Consult Liaison Psychiatry 2021;62:211-9.
Ma YF, Li W, Deng HB, Wang L, Wang Y, Wang PH, et al.
Prevalence of depression and its association with quality of life in clinically stable patients with COVID-19. J Affect Disord 2020;275:145-8.
Nie XD, Wang Q, Wang MN, Zhao S, Liu L, Zhu YL, et al.
Anxiety and depression and its correlates in patients with coronavirus disease 2019 in Wuhan. Int J Psychiatry Clin Pract 2021;25:109-14.
Xie Q, Fan F, Fan XP, Wang XJ, Chen MJ, Zhong BL, et al.
COVID-19 patients managed in psychiatric inpatient settings due to first-episode mental disorders in Wuhan, China: Clinical characteristics, treatments, outcomes, and our experiences. Transl Psychiatry 2020;10:337.
[Table 1], [Table 2], [Table 3], [Table 4]