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Background– COVID 19 illness is associated with psychological impairments. Whether this impairment is due to illness itself or inpatient stay also contributes to it needs to be ascertained. Present study was done to assess the change in severity of stress, depression and anxiety in COVID-19 patients on the day of hospital admission and on the day of discharge and its association with clinical variables.Methods– A cross sectional study design with sample of 104 patients admitted in the COVID wards. Socio-demographic and COVID related clinical variables and laboratory parameters were recorded. The severity of stress (PSS scale), anxiety (HAM-A scale) and depression (HAM-D scale) was assessed on the day of hospital admission & on the day of discharge. Association between change in severity of these and other variables was assessed.ResultsSignificant increase in severity of stress, anxiety and depression was found during indoor stay of Covid-19 patients. Severity increased despite improvement in physical status of subjects. There was no significant association of increased severity of stress, anxiety, depression with demographic variables and laboratory parameters.Conclusion– There was a significant increase in level of stress, anxiety and depression during the inpatient stay despite improvement in clinical symptoms, with minimal association with demographic and clinical variables.INTRODUCTIONSince the beginning of COVID 19 pandemic, issues related to mental health has been highlighted repeatedly. Apparently fear of the consequences of this deadly disease has led to increase in stress, anxiety and depression in COVID hospitalized patients.[1]The psychosocial stressors are not only limited to those who were infected but are also exacerbated in the un-infected individuals.[2] Various factors that may be responsible for this include the direct effect of virus in central nervous system, the neuropsychiatric effects of inflammatory markers, the psychological impact of contact isolation and the stigma of getting infected, and disrupted social functions associated with serious illness.[4] Few studies from other countries have shown that most of the hospitalized COVID 19 patients report increased symptoms of anxiety and depression during their inpatient stay. This was significantly associated with occupation status, level of education and severity of Covid-19 illness. [2, 3] However, most of published research available on psychological impact of COVID 19 had focussed more on healthcare workers [11,12,25] and general public or outpatient setting. [13]To our knowledge, there is no literature from India that had assessed change in severity of stress, anxiety and depression in COVID 19 and its associated variables during their hospital stay as indoor patients in Covid-19 Ward.The primary objective of present study was to assess the change in severity of stress, anxiety and depression in COVID-19 patients on the day of admission and on the day of discharge. Secondary objective was to find any association between the change in severity of stress, anxiety and depression with socio-demographic and Covid 19 related clinical variables.METHODSStudy Setting–COVID inpatient ward in a tertiary care medical college.Study Design–A cross-sectional study design with assessment of subjects at two points- 1st on the day of admission and 2nd on the day of discharge.Sample size–All the subjects admitted to COVID wards over two months period between 25th May 2021 and 24th July 2021 were approached for their willingness to participate in the study. We could recruit total 104 subjects who met eligibility criteria and gave informed consent.Eligibility Criteria -Inclusion criteria –1. Patients above 18 years of age with positive COVID RT-PCR report.2. Patients admitted to Covid-19 ward in the tertiary care hospital.Exclusion criteria – the following patients were excluded:1. Only Rapid Antigen Test positive2. Only HRCT suggestive of atypical pneumonia3. Pre-existing psychiatric illness and substance abuse except nicotine4. Non-invasive ventilation support or medically unstable5. Persons with impaired capacityEthical aspects –As per institution’s policy for research on human subjects approval from the Scientific Advisory Committee (SAC) and then from Ethics Committee for Research on Human Subjects (ECRHS) of the institute was obtained. Written informed consent was obtained from all the participants and they were explained about their right to leave the study at any point of time without any impact on their ongoing treatment for Covid-19 illness. No additional financial burden was put on the subjects by participation in study.Assessments– Subject’s socio-demographic and clinical information was recorded anonymously in a pre-designed and pilot tested format. Information included sex, age, marital status, employment status, education, income of head of family and details of primary care giver. The socio-economic status was classified using Kuppuswamy scale. We also recorded clinical variables related to COVID-19 illness like Heart Rate, temperature, Blood pressure, respiratory rate, Oxygen saturation (SPO2) on the day of admission and on the day of discharge to assess clinical improvement in Covid-19 illness. Severity of stress, Depression and anxiety were also assessed at same two time points. Level of stress was assessed using perceived stress scale (PSS) which classifies stress level into Mild stress (0-13), Moderate stress (14-26), Severe stress (27-40). [4,5] The severity of anxiety was assessed using Hamilton Anxiety rating scale (HAM-A). Total score obtained can be classified into No anxiety (0-7), mild anxiety (8-14), moderate anxiety (15-23), severe anxiety (>24). [6] Severity of depression was assessed using Hamilton Depression rating scale (HAM-D). Total score obtained classifies severity of depression as no depression (0-7) mild depression (8-16), moderate depression (17-23), severe depression (>24). [7] Both these scales are already validated to estimate the change in severity of anxiety and depression over a period in time.[8] Laboratory investigations like d-dimer, ferritin, Lactate Dehydrogenase, Erythrocyte Sedimentation Rate, C-Reactive Protein were recorded only once during the inpatient stay.Statistical analysis -The collected data was analysed using SPSS (Statistical Software for social Sciences) software version 25. Initially descriptive statistics was carried out for the variables using appropriate measures of central tendency. Association between the severity of stress, anxiety and depression with socio-demographic and clinical variables was done using the Wilcoxon Signed Ranks Test and spearman’s correlation. Significance was set with 95% confidence level and p value < 0.05 was taken as significant.RESULTSMajority of the patients were male (63.4%) with male to female ratio of 1.7. Maximum patients were in the age group of 31-40 years (35.5%) followed by 51 - 60 years (27.8%) and 41-50 years (24.2%). Most were from the rural area (79%), belonging to Hindu religion (95.2%) and had education up to middle school (34.6%). The participants were at clerk level (41.3%), married (85.6%), had full time job (79%). As per Kuppuswamy scale, the subjects could be classified as upper middle (10%), lower middle (67%), upper lower (23%) and none belonged to upper and lower class.Spouse (67%) were the most common caregivers. Average IPD stay in covid-19 ward was 8.23 (2.9).Table-1 shows change in severity of stress, anxiety, depression and clinical variables measured at two cross sections. It is evident that more number of patients experienced higher levels of stress, anxiety and depression at the time of discharge despite being sent to their homes to stay with their family members.Table 1Severity of Stress, anxiety and depression as measured on day of admission and day of discharge from COVID-19VariableSeverityOn day of Admission N (%)On day of discharge N (%)Significance (p value)Stress (PSS)Mild66 (63.46)46 (44.23)0.0054Moderate 33 (31.73)41 (39.42)0.2479Severe05 (4.80)17 (16.35)0.0069Anxiety (HAM-A)No Anxiety63 (60.57)53 (50.9)0.1614Mild16 (15.38)21 (20.19)0.3684Moderate14 (13.46)22 (21.15)0.1436Severe01 (0.96)08 (7.69)0.0173Depression(HAM-D)No Depression88 (84.61)77 (74.03)0.0602Mild12 (11.53)19 (18.26)0.1739Moderate02 (1.9)5 (4.8)0.2463Severe02 (1.9)3 (2.8)0.6691Change in stress level, anxiety and depression and the Covid -19 related clinical variables from day of admission to on day of discharge is stated in Table-2. Compared to the assessment on the day of admission, there was significant increase in the level of stress, anxiety and depression on the day of discharge, despite favourable improvement in physical condition as indicated by covid-19 related clinical variables (temperature, pulse rate, blood pressure and oxygen saturation) as listed in the table. This indicates that it’s not the clinical severity of Covid-19 illness itself that causes psychological distress, but inpatient stay and factors associated with it, may also lead to psychological distress in patients admitted to Covid-19 wards.Table 2Change in stress level, anxiety and depression and the Covid -19 related clinical variables from day of admission to on day of dischargeVariablesPSSHAM-AHAM-DTemperaturePulse RateRespiratory rateBP SystolicBP DiastolicOxygen Saturation Mean value (SD) on Admission10.30 (9.10)6.05 (6.54)3.78 (4.57)99.01 (1.54)90 (9.79)32 (32.8)123.96 (9.75)82.82 (6.14)94.28 (10.2)Mean value (SD) on Discharge15.08 (9.88)8.57 (8.65)4.91 (5.83)98.17 (0.60)84 (6.28)26 (9.73)120.55 (5.56)80.56 (5.56)96.98 (9.88)Difference-4.78-2.52-1.130.84663.412.26-2.7Z-4.93b-4.18b-3.20b-5.94a-5.72a-3.11a-3.38a-3.74a-7.49bP value0.0000.0000.0010.0000.0000.0020.0010.0000.000 Wilcoxon Signed Ranks Test. p<0.01 is highly significant, a=based on positive ranks, b=based on negative rank Table-3 demonstrates association between demographic variables, laboratory parameters with change in levels of stress, anxiety and depression during hospital stay. Among the demographic variables, there is a weak negative but significant association between perceived stress and level of education. There is no significant association with other demographic and pathological variables.When considering the increase in the level of anxiety during hospital stay, there is a weak negative but significant association with total stay and level of education. While, there is weak positive but significant association between increased level of anxiety and income, d-dimer levels. There is no significant association with other demographic and pathological variables. For change in level of depression there is a weak negative but significant association between total stay and SGOT levels. There is no significant association with other demographic and pathological variables.Table 3Association of the demographic and pathologicalvariables with the change the level of stress, Anxiety and Depression during the hospital stayVariables PSSHAMA HAMDTotal Stay in Covid Ward-0.147/NS-0.271(r)/0.005** -0.285/0.003**Urban / rural Locality0.021/NS-0.008/NS0.050/NSEducation-0.196/0.046*-0.246/0.012*-0.052/NSIncome of family0.131/NS0.279/0.004**0.004/NSOccupation0.165/NS0.126/NS0.020/NSEmployment status of subjects-0.111/NS0.025/NS0.037/NSInteraction with caregiver0.085/NS0.128/NS-0.054/NSSocio-economic Status0.085/NS0.128/NS-0.057/NSHaemoglobin-0.050/NS-0.079/NS0.128/NSLymphocyte percentage0.040/NS-0.065/NS-0.051/NSNeutrophil percentage0.046/NS0.105/NS0.116/NSSGOT-0.156/NS-0.126/NS-0.2370.017*Lactate Dehydrogenase (LDH)-0.026/NS0.070/NS0.014/NSD-DIMER0.110/NS0.214/0.035*0.174/NSSpearman’s correlation. *p<0.05 is statistically significant, **p<0.01 is statistically highly significant, NS = Not significantDISCUSSIONFindings of present study reveal that as compared to day of admission, many more subjects with covid-19 illness experienced significantly higher level of stress, anxiety and depression at the time of discharge. This is happening despite clinical improvement in these subjects. For demographic variables, in line with previously published studies, a higher proportion of patients in our study were in the age group of 31 – 60 years, more than half were male, belonged to rural region, had some education,and majority were doing clerical jobs or any part time jobs,and belonged to lower middle class.[1,2] A recent study conducted to assess the level of stress anxiety and depressions during hospitalization reported similar demographic profile with majority participants being male, married and had good level of education and were employed.[1]Few studies which were of cross sectional nature suggested high levels of anxiety as a form of psychological stress, especially following the isolation to seek treatment of COVID 19 infection. [2, 9] Our study had assessed these at two points and the level of stress, anxiety and depression was found to be more on the day of the discharge from hospital than on day of admission. In contrast to this, a study from Israel found that the level of anxiety and depression decreased one month following hospitalization. [15] Some studies included the past psychiatric illness and substance use as a variable, but we excluded the subjects with pre-existing or past psychiatric illness from our study to avoid confounding effect. [1,2] Authors in an Italian study evaluated COVID 19 patients in the emergency department and then screened for psychopathology approximately 1 month after initial emergency department evaluation. It was found that 56% of patients screened positive in at least one psychiatric domain. Approximately 31% screened positive for depression, 42% for anxiety, and 28% for obsessive-compulsive symptoms. [10] In our study there was no association between interaction with care giver and severity of stress, anxiety and depression, however few studies also found that isolation and lack of support from care givers and relatives was the key factor for anxiety and depression where less social supports led to more anxiety and depressive symptoms and more depression was found in caregivers. [3,15,21] A study conducted in Wuhan China, the prevalence rate of depression and anxiety was found to be 21% and 16.4% respectively. [14] Few other studies also reported psychological distress after hospital discharge. [17, 18, 23]In our study severity of stress, anxiety and depression is not strongly associated with demographic and social variables, may be due to strong social support and intact family bonding in Indian settings. Depression was also found in quarantined patients. The family support & social interaction was alleviating factor. [24] This differs from findings of studies from other countries which reported that lack of social support for patients with COVID-19 being associated with depression and socioeconomic status bearing major impact on severity of depression. [18,19,20]Present study was unique from our country to assess the change in the severity level of stress, anxiety and depression during hospital stay in indoor patients of Covid-19 illness. Findings of our study highlight need for inclusion of psychological screening and appropriate management of all patients admitted to Covid-19 ward. Similar recommendations had been made by other authors. Cognitive Behavioural Therapy was found to be effective in reducing psychological distress in patients. [22] Among our subjects, all those with significant levels of anxiety and depression were provided treatment at the time of discharge itself. They were informed to be on regular follow in psychiatry OPD after discharge from the ward. After completion of study and preliminary analysis of data, to reduce the stress of admitted patients, we conducted stress management sessions in COVID wards itself as an initiative of our department.STRENGTHS AND LIMITATIONSThe major strength is this is the first study in India which has assessed the change in levels of stress, anxiety and depression during the inpatient [IPD] stay of COVID 19 patients and initiated appropriate management for same. The results of the study should be interpreted with the limitations of it being a single centre study with assessment of only inpatients and cross-sectional design of the study.CONCLUSIONSThere was a significant increase in level of stress, anxiety and depression during the inpatient stay of COVID 19 patients despite improvement in fever and respiratory distress. This change was associated with level of their income and some lab parameters. 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