This paper is in the following e-collection/theme issue:

Theme Issue: Novel Coronavirus (COVID-19) Outbreak Rapid Reports (1484) JMIR Theme Issue: COVID-19 Special Issue (2394) Outbreak and Pandemic Preparedness and Management (1679) Infectious Diseases (non-STD/STI) (1490) JMH Theme Issue: COVID-19 and Mental Health: Impact and Interventions (374) Electronic Health Records (971) Personal Health Records, Patient-Accessible Electronic Health Records, Patient Portals (543) Anxiety and Stress Disorders (1013) Depression and Mood Disorders; Suicide Prevention (1290)

Published on in Vol 9 (2023)

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/43003, first published .
The Association of Acute Signs and Symptoms of COVID-19 and Exacerbation of Depression and Anxiety in Patients With Clinically Mild COVID-19: Retrospective Observational Study

The Association of Acute Signs and Symptoms of COVID-19 and Exacerbation of Depression and Anxiety in Patients With Clinically Mild COVID-19: Retrospective Observational Study

The Association of Acute Signs and Symptoms of COVID-19 and Exacerbation of Depression and Anxiety in Patients With Clinically Mild COVID-19: Retrospective Observational Study

Authors of this article:

Sumi Sung1, 2 Author Orcid Image ;   Su Hwan Kim2 Author Orcid Image ;   Changwoo Lee1 Author Orcid Image ;   Youlim Kim1 Author Orcid Image ;   Ye Seul Bae1, 3 Author Orcid Image ;   Eui Kyu Chie1, 4, 5 Author Orcid Image
Article Authors Cited by (3) Tweetations (6) Metrics

    Original Paper

    1Office of Hospital Information, Seoul National University Hospital, Seoul, Republic of Korea

    2Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

    3Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    4Department of Radiation Oncology, College of Medicine, Seoul National University, Seoul, Republic of Korea

    5Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea

    *these authors contributed equally

    Corresponding Author:

    Eui Kyu Chie, MD, PhD

    Office of Hospital Information

    Seoul National University Hospital

    101 Daehak-ro

    Jongno-gu

    Seoul, 03080

    Republic of Korea

    Phone: 82 2 2072 7600

    Fax:82 2 2072 0318

    Email: ekchie93@snu.ac.kr


    Background: To date, the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 has not been evaluated.

    Objective: This study was designed to assess the correlation between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 at a residential treatment center in South Korea.

    Methods: This retrospective study assessed 2671 patients with COVID-19 admitted to 4 residential treatment centers operated by Seoul National University Hospital, South Korea, from March 2020 to April 2022. Depression and anxiety were assessed using the 2-item Patient Health Questionnaire (PHQ-2) and 2-item Generalized Anxiety Disorder (GAD-2) scale, respectively. The exacerbation of depression and anxiety symptoms was identified from the differences in PHQ-2 and GAD-2 scores between admission and discharge, respectively. The patients’ clinical characteristics, including acute signs and symptoms of COVID-19, GAD-2 and PHQ-2 scores, were obtained from electronic health records. Demographic characteristics, a summary of vital signs, and COVID-19 symptoms were analyzed and compared between the patient groups with and those without exacerbated PHQ-2 and GAD-2 scores using the chi-square test. We applied logistic regression to identify the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety.

    Results: Sleep disorders were associated with exacerbated depression (odds ratio [OR] 1.09, 95% CI 1.05-1.13) and anxiety (OR 1.1, 95% CI 1.06-1.14), and the sore throat symptom was associated with exacerbated anxiety symptoms (OR 1.03, 95% CI 1.00-1.07). Patients with abnormal oxygen saturation during quarantine were more likely to have exacerbated depression (OR 1.27, 95% CI 1.00-1.62), and those with an abnormal body temperature during quarantine were more likely to experience anxiety (OR 1.08, 95% CI 1.01-1.16). As anticipated, patients who experienced psychological symptoms at admission were more likely to experience depression (OR 1.91, 95% CI 1.52-2.41) and anxiety (OR 1.98, 95% CI 1.54-2.53). Meanwhile, the PHQ-2 and GAD-2 scores measured at admission revealed that lower the score, higher the possibility of exacerbation of both depression (OR 0.15, 95% CI 0.11-0.22) and anxiety (OR 0.13, 95% CI 0.10-0.19).

    Conclusions: Results from this study suggest the importance of further interventions for patients with abnormal oxygen saturation, abnormal body temperatures, sore throat, and sleep disorder symptoms or initial psychological symptoms to mitigate the exacerbation of depression and anxiety. In addition, this study highlights the usability of short and efficient scales such as the PHQ-2 and GAD-2 in the assessment of the mental health of patients with clinically mild COVID-19 symptoms who were quarantined at home during the pandemic era.

    JMIR Public Health Surveill 2023;9:e43003

    doi:10.2196/43003

    Keywords

    COVID-19; depression; anxiety; vital signs; symptoms; electronic health records 


    The ongoing COVID-19 pandemic has not only affected physical health but also induced mental health issues such as depression, anxiety, stress, or insomnia [1-3]. A systematic review on the prevalence of psychological symptoms in the general population during the COVID-19 pandemic reported that the prevalence of depressive symptoms ranged from 14.6% to 48.3% and that of anxiety ranged from 6.33% to 50.9%, which is more than double the prevalence in the nonpandemic era [4]. South Korea is no exception because of its increased prevalence of psychological symptoms associated with depression and stress [5-7]. These remarkable increases in psychological symptoms are known to contribute to mental health problems such as anxiety, depression, insomnia, somatization, posttraumatic stress disorder, self-harm, and suicidal thoughts and behaviors. Thus, the importance of early detection and management of mental health disorders cannot be overemphasized [6,8].

    Patients confirmed with a COVID-19 diagnosis most commonly experience physical symptoms such as fever, cough, and fatigue [9,10]. In particular, nonhospitalized patients with a clinically mild COVID-19 infection have fatigue, headache, and sneezing as the most common acute symptoms, and fatigue and reduced smell and taste as the most severe symptoms [11]. While transitioning to focusing on the post–COVID-19 condition, symptoms such as fatigue may persist as long as 12 weeks in the long-term phase, and these symptoms are known to affect patients’ mental health and the quality of life [11,12].

    Despite attempts to explore acute and persistent symptoms of COVID-19 and patients’ mental health affected by persistent symptoms, little is known about the association between physical and psychological symptoms of acute COVID-19. Ismael et al [13] found that an increased number of COVID-19 symptoms may be associated with depression, anxiety, and posttraumatic symptoms. Perlis et al [14] reported that patients with COVID-19 who reported headaches during acute infection appeared to have an elevated risk of depression. During the transition to post–COVID-19 condition [15], it is necessary to examine the occurrence of acute signs and symptoms, changes in mental health, and their association while community-dwelling confirmed patients were quarantined.

    The Korean government has operated a residential treatment center (RTC) in response to the COVID-19 pandemic [16]. In the early stages of the COVID-19 outbreak, patients with COVID-19 could not be admitted to the hospital because of a lack of negative-pressure isolation beds. Accordingly, the government admitted all confirmed patients with clinically mild conditions to RTCs and transferred them to the hospital if their medical condition deteriorated to require admission-based care. Since then, with the rapid increase in the number of patients with COVID-19, high-risk patient groups with mild conditions have been selectively isolated to RTCs because it was difficult to isolate all confirmed patients at RTCs.

    As patients with confirmed COVID-19 without symptoms and those with mild symptoms were being monitored in quarantine at home, it was not easy to explore the status of their acute signs and symptoms and psychological diseases such as depression and anxiety. Therefore, it is important to ascertain the association between COVID-19–related acute signs and symptoms, and depression and anxiety, based on the accumulated retrospective data. With this background, we analyzed the association between acute signs and symptoms of COVID-19 and exacerbation of depression and anxiety in nonhospitalized patients with clinically mild COVID-19 symptoms who were admitted to RTCs.


    Study Design

    This retrospective study was performed at Seoul National University Hospital (SNUH).

    Study Setting

    The study setting was 4 RTCs operated by the SNUH in accordance with government guidelines [17]. The government RTC operating guidelines were periodically updated in consideration of the number of newly confirmed cases at the time the RTC operation and distribution of confirmed cases at the national level. The confirmed patients were assigned to each RTC by the government in accordance with this guideline. During the early phase of the pandemic, from December 2020 to November 2021, following the relevant Korean guidelines, all clinically mild cases among the confirmed cases in South Korea were quarantined at the RTC. With a rapid increase in the number of confirmed cases, all quarantine policies were modified to prioritize those who are more vulnerable to deterioration of their COVID-19 infection. Selection criteria for RTC admission include unvaccinated older individuals and patients in residential environments vulnerable to the spread of infection. All patients were quarantined independently in a separate room. All costs related to quarantine at an RTC were fully covered by the government. Quarantined patients requiring oxygen supply due to a persistent saturation of percutaneous oxygen (SpO2) of <94%, or those with a clinical condition requiring medical intervention, were transferred to the hospital. Table 1 shows the location, size in terms of the number of beds, operation period, and accumulated confirmed COVID-19 cases at the national level for operated RTCs in detail.

    Table 1. Details of residential treatment centers operated by the Seoul National University Hospital.
    NameLocationBeds, nOperation period (accumulated confirmed COVID-19 cases at the national level during the operational period, n) [17]
    ANear Daegu city in North Gyeongsang province99
    • March 2020 to April 2020 (7834)
      • ‎
    BNowon-gu, Seoul124
    • August 2020 to October 2020 (12,206)
      • ‎
    CSeongnam city in Gyeonggi province225
    • August 2020 to September 2020 (9506)
      • ‎
    DSeongnam city in Gyeonggi province334
    • December 2020 to January 2021 (43,998)
      • ‎
    • July 2021 to April 2022 (17,079,907)
      • ‎

    Study Participants

    Adult patients with a confirmed COVID-19 diagnosis admitted to 4 RTCs operated by the SNUH from March 2020 to April 2022 were included in this study. Patients who tested positive for COVID-19 on the reverse transcriptase–polymerase chain reaction test but had clinically mild conditions were subjected to RTC admission. A total of 5199 patients were admitted during the study period. Patients with missing data were excluded from the analysis.

    Data Sources

    Using the SNUH information and communication technology–based remote patient monitoring (RPM) system [18], it was mandatory for every patient admitted to the RTC operated by the SNUH to use the mobile app and to self-report their past medical history, vital signs, subjective acute COVID-19 symptoms, and psychological symptoms. Reporting was done once on admission, twice a day during the quarantine period, and once on discharge. These data were automatically stored in the hospital information system at the SNUH. The records were monitored in real time by health care providers. For any missing data in the records, health care providers directly checked the patient and filled in the missing data. We finally extracted these electronic health records using the SNUH Patient Research Environment (also known as “SUPREME”)—a clinical data warehouse at the SNUH. The data sources in the final analysis included RTC admission notes, daily progress notes, and discharge notes in the electronic health record.

    Data on patients’ depressive and anxiety symptoms were extracted from the RTC admission and discharge notes. Patients’ self-reported scores on the 2-item Patient Health Questionnaire (PHQ-2)—a subscale of the Patient Health Questionnaire 9 [19]—and 2-item Generalized Anxiety Disorder Scale (GAD-2)—a subscale of the Generalized Anxiety Disorder Scale (GAD-7) [20]—via a mobile app at admission and discharge. One of the PHQ-2 items was, “Over the last 2 weeks, how often have you been bothered by any of the following problems?” with response options of “Little interest or pleasure in doing things,” and “Feeling down, depressed, or hopeless” on a 4-point Likert scale. Scores ranging from 0 to 6, with a cutoff score of ≥3 indicating depressive symptoms. The PHQ-2 was reported to have a sensitivity of 0.79 and a specificity of 0.86 for any depressive disorders [21]. One of the GAD-2 items was, “Over the last 2 weeks, how often have you been bothered by any of the following problems?” with response options of “Feeling nervous, anxious, or on the edge” and “not being able to stop or control worrying” with a 4-point Likert scale. Scores range from 0 to 6, with a cutoff score of ≥3 indicating anxiety symptoms. The GAD-2 was reported to have a sensitivity of 0.65 and a specificity of 0.88 as a general screening tool for anxiety disorders [22].

    Patient demographic characteristics (eg, age, sex, and admitted RTC site), medical history (diabetes mellitus, hypertension, cardiovascular disease, respiratory disease, sleep disorder, and psychological treatment), and initial psychological symptoms such as depression and panic were extracted from the RTCs’ admission notes. Patients’ smoking statuses were extracted from the RTCs’ discharge notes.

    Patients’ self-measured vital signs and acute COVID-19 symptoms were extracted from the RTCs’ daily progress notes, which were collected via a mobile app at least twice a day. The vital signs included systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, body temperature (BT), and SpO2. Acute COVID-19 symptoms consisted of the presence or absence of respiratory and nonrespiratory symptoms. Respiratory symptoms included cough, sputum production, fever, rhinorrhea, sore throat, dyspnea, and chest pain. Nonrespiratory symptoms include nausea, vomiting, abdominal discomfort, pain, constipation, diarrhea, abdominal pain, and sleep disorders.

    The loss of taste and smell was extracted from the RTCs’ discharge notes. At discharge, participants reported the presence or loss of smell and taste.

    Statistical Analysis

    Data preparation was conducted before data analysis. The exacerbation of depressive symptoms’ and anxiety symptoms’ cases were identified from the differences between PHQ-2 scores and GAD-2 scores at admission and discharge, respectively. Criteria for abnormal vital signs, in consultation with an infection medicine specialist, are as follows: a systolic blood pressure above 140 mm Hg or below 60 mm Hg, a diastolic blood pressure above 90 mm Hg or below 30 mm Hg, a heart rate above 110 bpm or below 40 bpm, respiratory rate above 21/minute or below 8/minute, BT above 38.0 °C or below 35.0 °C, and an SpO2 below 94%. The number of days with each abnormal vital sign and acute COVID-19 symptom was calculated.

    Demographic characteristics, summary of vital signs, and COVID-19 symptoms were analyzed and compared between the patient groups with and those without exacerbated PHQ-2 and GAD-2 scores, using the chi-square test. We then applied logistic regression with exacerbation of depressive and anxiety symptoms as dependent variables, and sociodemographic features, past medical history, initial psychological symptoms, initial PHQ-2 or GAD-2 scores, average number of days with abnormal vital signs, and average number of days with acute COVID-19 symptoms as independent variables, using R statistical software (version 4.2; R Project for Statistical Computing). Statistical significance was tested at α=.01.

    Ethical Considerations

    This study was approved by the SNUH’s institutional review board (H-2105-158-1221) and was conducted in accordance with the relevant guidelines and regulations. Informed consent was waived by the institutional review board considering the study design and adherence to the relevant guidelines. In particular, study data were deidentified to protect privacy and preserve the confidentiality of the study participants.


    Patients’ Clinical Characteristics

    In total, 2671 individuals reported COVID-19 infection without any missing values. The clinical characteristics of the patients are presented in Table 2. The mean age was 41.1 (SD 14.1) years, and the mean quarantine period was 7.07 days. Overall, 1242 (46.5%) participants were female, and 44 (1.6%) were admitted at RTC A, 324 (11.8%) at RTC B, 819 (30.7%) at RTC C, and 1494 (55.9%) at RTC D. A total of 746 (27.9%) patients were infected by the alpha variant of SARS-CoV-2, 1563 (58.5%) by the delta variant, and 362 (13.6%) by the omicron variant. Overall, 141 (5.3%) participants had a past medical history of diabetes mellitus, 361 (13.5%) had a medical history of hypertension, 168 (6.3%) had a medical history of sleep disorders, 158 (5.9%) had a history of psychological treatment. Upon admission, 1273 (47.7%) participants had initial psychological symptoms. Detailed clinical characteristics upon exacerbation of PHQ-2 and GAD-2 scores are presented in Multimedia Appendix 1.

    Table 2. Patients’ clinical characteristics (N=2671).
    Clinical characteristicsParticipants, n (%)
    Demographic data

    		Females1242 (46.5)

    		Aged under 30 years748 (28.0)

    		Aged 30 to 39 years500 (18.7)

    		Ages 40 to 49 years545 (20.4)

    		Aged 50 to 59 years556 (20.8)

    		Aged 60 years or older322 (12.1)

    		Admitted to residential treatment center A44 (1.6)

    		Admitted to residential treatment center B314 (11.8)

    		Admitted to residential treatment center C819 (30.7)

    		Admitted to residential treatment center D1494 (55.9)

    		Infected with the SARS-CoV-2 alpha variant746 (27.9)

    		Infected with the SARS-CoV-2 delta variant1563 (58.5)

    		Infected with the SARS-CoV-2 omicron variant362 (13.6)
    Medical history

    		Diabetes mellitus141 (5.3)

    		Hypertension361 (13.5)

    		Cardiovascular disease81 (3.0)

    		Respiratory disease44 (1.6)

    		Sleep disorder168 (6.3)

    		Psychological treatment158 (5.9)
    Initial psychological symptoms1273 (47.7)
    Initial score on the 2-item Patient Health Questionnaire

    		01641 (61.4)

    		1367 (13.7)

    		2 or above663 (24.8)
    Initial score on the 2-item Generalized Anxiety Disorder Scale

    		01461 (54.7)

    		1354 (13.3)

    		2 or above856 (32.0)
    Smoking status

    		Never smoked1600 (59.9)

    		Ex-smoker565 (21.2)

    		Smoker506 (18.9)
    BMI category

    		Underweight or normal1182 (44.3)

    		Overweight580 (21.7)

    		Obese909 (34.0)
    Abnormal vital signs

    		Systolic blood pressure564 (21.1)

    		Diastolic blood pressure1073 (40.2)

    		Heart rate86 (3.2)

    		Respiratory rate730 (27.3)

    		Body temperature375 (14.0)

    		Saturation of percutaneous oxygen72 (2.7)
    Acute respiratory COVID-19–related symptoms

    		Cough1759 (65.9)

    		Sputum1543 (57.8)

    		Fever544 (20.4)

    		Rhinorrhea1276 (47.8)

    		Sore throat1153 (43.2)

    		Dyspnea250 (9.4)

    		Chest pain421 (15.8)
    Acute nonrespiratory COVID-19–related symptoms

    		Nausea207 (7.7)

    		Vomit83 (3.1)

    		Abdominal discomfort453 (17.0)

    		Pain1047 (39.2)

    		Constipation426 (15.9)

    		Diarrhea490 (18.3)

    		Abdominal pain186 (7.0)

    		Sleep disorder624 (23.4)

    		Loss of smell1264 (47.3)

    		Loss of taste1243 (46.5)

    PHQ-2 and GAD-2 Scores Measured at Admission and Discharge

    The PHQ-2 and GAD-2 scores measured at admission and discharge are presented in Figure 1. At admission, the mean PHQ-2 score was 0.76 (SD 1.17). Of a total of 2671 patients, 663 (24.8%) had a PHQ-2 score of 2 or higher. The mean GAD-2 score was 0.93 (SD 1.27), and 856 (32.0%) had a score of 2 or higher. At discharge, the mean PHQ-2 score was 0.77 (SD 1.18), and 675 (25.3%) had a score of 2 or higher. The mean GAD-2 score was 0.84 (SD 1.21), and 744 (27.9%) had a score of 2 or higher.

    A total of 535 patients showed exacerbation of depression. In fully adjusted models, an abnormal SpO2 was associated with increased odds of exacerbation of depression (odds ratio [OR] 1.27, 95% CI 1.00-1.62). Among acute COVID-19 symptoms, presence of sleep disorder was associated with exacerbation of depression (OR 1.09, 95% CI 1.05-1.13). Women demonstrated higher odds of exacerbation of depression than men (OR 2.33, 95% CI 1.78-3.05) and higher odds of exacerbation of depression with increasing age (>60 years; OR 4.01, 95% CI 2.71-5.93). Patients admitted at RTC A demonstrated higher odds of exacerbation of depression than those who were admitted at RTCs B, C, and D (OR 2.93, 95% CI 1.24-6.93), and those diagnosed with COVID-19 due to the alpha variant of SARS-CoV-2 showed lower odds of symptom exacerbation than those with the delta variant (OR 0.57, 95% CI 0.36-0.90). Past medical history of sleep disorders demonstrated lower odds to associate with exacerbation (OR 0.60, 95% CI 0.36-0.98), whereas presence of initial psychological symptoms was associated with exacerbation (OR 1.91, 95% CI 1.52-2.41). The higher patients’ PHQ-2 scores at admission demonstrated lower odds of exacerbation of depression (OR 0.15, 95% CI 0.11-0.22). Figure 2 illustrates the ORs from the regression models adjusted for the patients’ clinical characteristics.

    ‎
    Figure 1. Scores on the 2-item Patient Health Questionnaire (PHQ-2) and the 2-item Generalized Anxiety Disorder Scale (GAD-2) measured at admission and discharge.
    View this figure
    ‎
    Figure 2. Forest plot showing the association of acute signs and symptoms of COVID-19 and exacerbation of depression. BT: body temperature; DBP: diastolic blood pressure; HR: heart rate; PHQ-2: 2-item Patient Health Questionnaire; RR: respiratory rate; RTC: residential treatment center; SBP: systolic blood pressure; SpO2: saturation of percutaneous oxygen.
    View this figure

    Association of Acute Signs and Symptoms of COVID-19 and Exacerbation of Anxiety

    A total of 523 patients presented exacerbation of anxiety. Among abnormal vital signs, abnormal BT was associated with exacerbation of anxiety (OR 1.08, 95% CI 1.01-1.16). Among acute COVID-19 symptoms, the presence of sleep disorders and sore throat were associated with exacerbation of anxiety (sleep disorders: OR 1.1, 95% CI 1.06-1.14; sore throat: OR 1.03, 95% CI 1.00-1.07). Women showed higher odds of exacerbation of anxiety than men (OR 2.21, 95% CI 1.69-2.88) and higher odds of exacerbation of anxiety with increased age (>60 years; OR 3.07, 95% CI 2.05-4.60). Presence of initial psychological symptoms was associated with the exacerbation of anxiety (OR 1.98, 95% CI 1.54-2.53). The higher patients’ GAD-2 scores at admission indicated lower odds of exacerbation of anxiety (OR 0.13, 95% CI 0.10-0.19). Figure 3 illustrates the ORs from the regression models adjusted for patients’ clinical characteristics.

    ‎
    Figure 3. Association of acute signs and symptoms of COVID-19 and exacerbation of anxiety. BT: body temperature; DBP: diastolic blood pressure; HR: heart rate; PHQ-2: 2-item Patient Health Questionnaire; RR: respiratory rate; RTC: residential treatment center; SBP: systolic blood pressure; SpO2: saturation of percutaneous oxygen.
    View this figure

    Principal Findings

    To the best of our knowledge, this study is the first to explore the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 [13-15]. Among sociodemographic features, we found that female sex and older age affected the likelihood of exacerbation of depression and anxiety in patients with clinically mild COVID-19, which is consistent with previous studies [23-26]. In addition, RTC A, located in Daegu and Gyeongbuk province, where patients in the early phase of COVID-19 with social stigma were admitted, was found to be highly associated with exacerbation of anxiety.

    The most common acute COVID-19 symptoms are cough, sputum, rhinorrhea, sore throat, and loss of smell and taste. The proportion of these symptoms was ~40%-65%, which was relatively lower than that reported in previous studies on acute and persistent symptoms in nonhospitalized patients with COVID-19 [11]. This may reflect the results of triage, which incorporates multiple symptoms in accordance with the hospitalization policy of the Korea Disease Control and Prevention Agency. The types of acute COVID-19 symptoms most commonly complained of were consistent with those reported in previous studies in that fever, cough, myalgia, and fatigue were described as common symptoms of COVID-19 [9,10] and loss of smell and taste as prevalent and relatively discriminative symptoms of COVID-19 [27-29]. Sputum production has been regarded as a less common symptom of early COVID-19 [30,31] but was reported as one of the most common symptoms in this study. The reason for the high proportion of sputum production seems to be that study participants included patients infected with the omicron variant of SARS-CoV-2 whose complains of sputum symptoms were relatively high [32].

    Among acute COVID-19 symptoms, patients who experienced sleep disorder symptoms more frequently during quarantine showed higher odds of exacerbation of depression (P<.001) and anxiety (P<.001) than those who did not. Sleep disorders are a core symptom of depression and anxiety, and this study shows a strong association between them, which is consistent with those reported in previous studies [33-35]. We also found that those who had experienced sore throat more frequently during quarantine had an elevated risk of anxiety symptoms (P<.05). The more the patient experiences sore throat, which is one of the representative upper respiratory symptoms of COVID-19 infection with the omicron variant, the higher the risk of exacerbation of anxiety, which means that early active intervention for mental health may be necessary. We expected that other similarly frequently reported acute symptoms such as cough, sputum production, rhinorrhea, and loss of smell and taste would also be associated with exacerbation of depression and anxiety, but this correlation was not found. Although it is difficult to generalize the results of this study, the association between physical symptoms and depression and anxiety is well known, and it is also well known that depression and anxiety accompany somatic symptoms. Thus, in the acute phase within 1 week of COVID-19 infection, health care providers should examine both physical and mental health during the treatment course of patients with acute COVID-19.

    On the contrary, the vital signs of COVID-19 were stable, with a small proportion of patients presenting abnormal ranges during quarantine at the RTC. These results indicate that most patients admitted to the RTC had clinically mild conditions and did not require inpatient treatment. Patients who presented abnormal SpO2 during quarantine demonstrated higher odds of exacerbation of depression (P<.05) than those who did not. In addition, patients who had an abnormal BT during quarantine demonstrated higher odds of exacerbation of anxiety (P<.05). It is important to note that patients who often had unstable vital signs during quarantine showed the possibility of exacerbation to depression and anxiety due to exposure.

    As anticipated, patients who had experienced psychological symptoms at admission had higher odds of exacerbation of depression (P<.001) and anxiety (P<.001) than those who did not. Meanwhile, the PHQ-2 and GAD-2 scores measured at admission showed that lower the score, higher the association between exacerbation of both depression (P<.001) and anxiety (P<.001). In addition, patients who had received previous psychological treatment were less likely to experience exacerbation of depression (P<.001). The group that received psychological treatment might have had a higher PHQ-2 or GAD-2 score at admission. Thus, these results can be interpreted as follows: higher the PHQ-2 or GAD-2 score at admission, narrower the range of scores that can be exacerbated.

    The novelty of this study is the use of both contactless RPM systems and screening scales. First, data were obtained through a contactless RPM system for patients with COVID-19. More than 80% of patients with COVID-19 had clinically mild conditions, and these patients were quarantined at home or RTCs, not medical institutions, and monitored with a contactless RPM system. The establishment of a contactless RPM system for patients with clinically mild conditions who do not require intensive care unit care has been gradually attempted in various studies [36-38], and the SNUH has also established a contactless RPM system [18]. The data analyzed in this study were also the results of establishing the system at 4 RTCs operated by the SNUH.

    Second, the results of this study provide supporting evidence that depression and anxiety can be assessed by the PHQ-2 and GAD-2, which are useful and efficient scales for patients with COVID-19 quarantined at home. As the prevalence of mood disorders has increased after the onset of the COVID-19 pandemic [4-7], concerns about individuals’ mental health are growing. Patients with COVID-19 who are self-isolated at home or at an RTC might be in a clinically mild condition and are not fully aware of the need for mental health assessment. Since they are not hospitalized and have limited access to medical personnel, it is necessary to assess the mental health of patients using a readily accessible simple convenient tool. In that sense, the PHQ-2 and GAD-2, which have already been validated as having high sensitivity and specificity as the PHQ-9 and GAD-7, may be regarded as useful screeners and efficient tools for monitoring treatment progress and outcomes in primary medical settings [21,39-43]. Furthermore, the results from this study suggest the importance of considering further interventions that might mitigate the exacerbation of depression and anxiety associated with acute signs and symptoms during the post–COVID-19 condition [15].

    Limitations

    This study is not without its limitations. First, this was a retrospective observational study; therefore, causal relationships cannot be inferred, and further analysis of additional data such as socioeconomic factors, not collected in the hospital information system at the SNUH, was not possible. Second, the data analyzed were retrieved from a single tertiary hospital operating 4 RTCs of different sizes in accordance with government regulations. The possibility of influence or correlation with various unmeasured variables such as, but not limited to, lack of social interactions, financial loss, and vaccination status may limit the generalizability of our findings. Third, sample bias was possible as patients with missing data were excluded. Fourth, there were no follow-up longitudinal data after discharge from the RTC. Thus, it was not possible to explore the associations between COVID-19–related acute signs and symptoms and the exacerbation of depression and anxiety, considering the acute and chronic periods in response to post–COVID-19 condition. Fifth, there may be a social desirability bias as patients self-reported their signs and symptoms and were not objectified by the caregivers. Lastly, while the mean quarantine period of participants was approximately 7 days, the PHQ-2 and GAD-2 measures depression and anxiety symptoms over the last 2 weeks. These timeline issues should be considered when interpreting the results. Further, other tools may be used in future studies.

    Conclusions

    This study explored the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 who were admitted at RTCs. Among the acute signs and symptoms of COVID-19, exacerbation of depressive symptoms was associated with an abnormal SpO2 (OR 1.27, 95% CI 1.00-1.62) and sleep disorder (OR 0.60, 95% CI 0.36-0.98). Exacerbation of anxiety symptoms was associated with an abnormal BT (OR 1.08, 95% CI 1.01-1.16), sleep disorder (OR 1.1, 95% CI 1.06-1.14), and sore throat (OR 1.03, 95% CI 1.00-1.07). As anticipated, patients who had experienced initial psychological symptoms at admission were more likely to experience depression (OR 1.91, 95% CI 1.52-2.41) and anxiety (OR 1.08, 95% CI 1.01-1.16) than those who did not. Meanwhile, the PHQ-2 and GAD-2 scores measured at admission showed that lower the score, higher the possibility of exacerbation of both depression (OR 0.15, 95% CI 0.11-0.22) and anxiety (OR 0.13, 95% CI 0.10-0.19). Our results suggest the importance of considering further interventions that might mitigate the exacerbation of depression and anxiety in patients with an abnormal SpO2, abnormal BT, sore throat, and sleep disorders or those with initial psychological symptoms. In addition, we propose the use of the PHQ-2 and GAD-2, which are short and efficient scales, in the assessment of mental health for patients with clinically mild COVID-19 who are quarantined at home.

    Acknowledgments

    This work was supported by an Institute of Information & Communications Technology Planning & Evaluation grant funded by the Korean government (2021-0-00312: Development of Non-Face-to-face Patient Infection Activity Prediction and Protection Management SW Technology at Home and Community Treatment Centers for Effective Response to Infectious Disease).

    Data Availability

    The data sets generated or analyzed during this study are not publicly available in accordance with the hospital’s regulations, adhering to the National Privacy Act and relevant guidelines. However, they may be available from the corresponding author on reasonable request after review and approval of the institutional review board and the institutional data steering committee.

    Authors' Contributions

    SS, YSB, and EKC conceptualized the study and reviewed and edited the manuscript. SS, SHK, and YSB developed the study methodology and drafted the manuscript. SS, SHK, CL, YK, and YSB carried out the formal analysis. EKC supervised the study and acquired funding for the study. All authors reviewed the results and approved the final version of the manuscript. YSB and EKC contributed equally to this work as the corresponding author.

    Conflicts of Interest

    None declared.

    ‎
    Multimedia Appendix 1

    Detailed clinical characteristics by exacerbation of PHQ-2 and GAD-2 scores.

    DOCX File , 19 KB
    1. Brown E, Gray R, Lo Monaco S, O'Donoghue B, Nelson B, Thompson A, et al. The potential impact of COVID-19 on psychosis: a rapid review of contemporary epidemic and pandemic research. Schizophr Res 2020 Aug;222:79-87 [FREE Full text] [CrossRef] [Medline]
    2. Huang Y, Zhao N. Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 outbreak in China: a web-based cross-sectional survey. Psychiatry Res 2020 Jun;288:112954 [FREE Full text] [CrossRef] [Medline]
    3. Oh T, Park H, Song I. Risk of psychological sequelae among coronavirus disease‐2019 survivors: a nationwide cohort study in South Korea. Depress Anxiety 2020 Dec 07;38(2):247-254. [CrossRef]
    4. Xiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, et al. Impact of COVID-19 pandemic on mental health in the general population: a systematic review. J Affect Disord 2020 Dec 01;277:55-64 [FREE Full text] [CrossRef] [Medline]
    5. Min J, Kwon D, Lee W, Kang C, Park C, Heo S, et al. Individual and regional characteristics associated with changes in mental health before and during the COVID-19 pandemic in South Korea. Sci Rep 2022 Aug 19;12(1):14189 [FREE Full text] [CrossRef] [Medline]
    6. Jeong H, Park S, Kim J, Oh K, Yim H. Mental health of Korean adults before and during the COVID-19 pandemic: a special report of the 2020 Korea National Health and Nutrition Examination Survey. Epidemiol Health 2022;44:e2022042 [FREE Full text] [CrossRef] [Medline]
    7. Kim S, Park I, Kim M, Park A, Jhon M, Kim J, et al. Risk and protective factors of depression in the general population during the COVID-19 epidemic in Korea. BMC Psychiatry 2021 Sep 08;21(1):445 [FREE Full text] [CrossRef] [Medline]
    8. Cénat JM, Felix N, Blais-Rochette C, Rousseau C, Bukaka J, Derivois D, et al. Prevalence of mental health problems in populations affected by the Ebola virus disease: a systematic review and meta-analysis. Psychiatry Res 2020 Jul;289:113033. [CrossRef] [Medline]
    9. Grant M, Geoghegan L, Arbyn M, Mohammed Z, McGuinness L, Clarke EL, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One 2020;15(6):e0234765 [FREE Full text] [CrossRef] [Medline]
    10. Mizrahi B, Shilo S, Rossman H, Kalkstein N, Marcus K, Barer Y, et al. Longitudinal symptom dynamics of COVID-19 infection. Nat Commun 2020 Dec 04;11(1):6208 [FREE Full text] [CrossRef] [Medline]
    11. Bliddal S, Banasik K, Pedersen OB, Nissen J, Cantwell L, Schwinn M, et al. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients. Sci Rep 2021 Jun 23;11(1):13153 [FREE Full text] [CrossRef] [Medline]
    12. Jacobs LG, Gourna Paleoudis E, Lesky-Di Bari D, Nyirenda T, Friedman T, Gupta A, et al. Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One 2020 Dec 11;15(12):e0243882 [FREE Full text] [CrossRef] [Medline]
    13. Ismael F, Bizario J, Battagin T, Zaramella B, Leal FE, Torales J, et al. Post-infection depressive, anxiety and post-traumatic stress symptoms: a prospective cohort study in patients with mild COVID-19. Prog Neuropsychopharmacol Biol Psychiatry 2021 Dec 20;111:110341 [FREE Full text] [CrossRef] [Medline]
    14. Perlis RH, Ognyanova K, Santillana M, Baum MA, Lazer D, Druckman J, et al. Association of acute symptoms of COVID-19 and symptoms of depression in adults. JAMA Netw Open 2021 Mar 01;4(3):e213223 [FREE Full text] [CrossRef] [Medline]
    15. The Lancet. Facing up to long COVID. Lancet 2020 Dec;396(10266):1861. [CrossRef]
    16. Kang E, Lee SY, Jung H, Kim MS, Cho B, Kim YS. Operating protocols of a community treatment center for isolation of patients with coronavirus disease, South Korea. Emerg Infect Dis 2020 Oct;26(10):2329-2337 [FREE Full text] [CrossRef] [Medline]
    17. Coronavirus (COVID-19) Republic of Korea, 2022. Korea Disease Control and Prevention Agency.   URL: https://ncov.kdca.go.kr/ [accessed 2022-12-22]
    18. Bae Y, Kim K, Choi S, Ko T, Jeong CW, Cho B, et al. Information technology-based management of clinically healthy COVID-19 patients: lessons from a living and treatment support center operated by Seoul National University Hospital. J Med Internet Res 2020 Jun 12;22(6):e19938 [FREE Full text] [CrossRef] [Medline]
    19. Kroenke K, Spitzer R, Williams J. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001 Sep;16(9):606-613 [FREE Full text] [CrossRef] [Medline]
    20. Spitzer R, Kroenke K, Williams J, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006 May 22;166(10):1092-1097. [CrossRef] [Medline]
    21. Löwe B, Kroenke K, Gräfe K. Detecting and monitoring depression with a two-item questionnaire (PHQ-2). J Psychosom Res 2005 Feb;58(2):163-171. [CrossRef] [Medline]
    22. Kroenke K, Spitzer R, Williams J, Monahan P, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007 Mar 06;146(5):317-325. [CrossRef] [Medline]
    23. Mazza C, Ricci E, Biondi S, Colasanti M, Ferracuti S, Napoli C, et al. A nationwide survey of psychological distress among Italian people during the COVID-19 pandemic: immediate psychological responses and associated factors. Int J Environ Res Public Health 2020 May 02;17(9):3165 [FREE Full text] [CrossRef] [Medline]
    24. Moccia L, Janiri D, Pepe M, Dattoli L, Molinaro M, De Martin V, et al. Affective temperament, attachment style, and the psychological impact of the COVID-19 outbreak: an early report on the Italian general population. Brain Behav Immun 2020 Jul;87:75-79 [FREE Full text] [CrossRef] [Medline]
    25. Moghanibashi-Mansourieh A. Assessing the anxiety level of Iranian general population during COVID-19 outbreak. Asian J Psychiatr 2020 Jun;51:102076 [FREE Full text] [CrossRef] [Medline]
    26. Nemani K, Li C, Olfson M, Blessing EM, Razavian N, Chen J, et al. Association of psychiatric disorders with mortality among patients with COVID-19. JAMA Psychiatry 2021 Apr 01;78(4):380-386 [FREE Full text] [CrossRef] [Medline]
    27. Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol 2020 Jul;10(7):806-813 [FREE Full text] [CrossRef] [Medline]
    28. Peyrony O, Marbeuf-Gueye C, Truong V, Giroud M, Rivière C, Khenissi K, et al. Accuracy of emergency department clinical findings for diagnosis of coronavirus disease 2019. Ann Emerg Med 2020 Oct;76(4):405-412 [FREE Full text] [CrossRef] [Medline]
    29. Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020 Jul 11;26(7):1037-1040 [FREE Full text] [CrossRef] [Medline]
    30. 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 Mar;395(10229):1054-1062. [CrossRef]
    31. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020 Mar 17;323(11):1061-1069 [FREE Full text] [CrossRef] [Medline]
    32. Kim M, Lee B, Choi YY, Um J, Lee K, Sung HK, et al. Clinical characteristics of 40 patients infected with the SARS-CoV-2 omicron variant in Korea. J Korean Med Sci 2022 Jan 17;37(3):e31 [FREE Full text] [CrossRef] [Medline]
    33. Nutt D, Wilson S, Paterson L. Sleep disorders as core symptoms of depression. Dialogues Clin. Neurosci 2022 Apr 01;10(3):329-336. [CrossRef]
    34. Krystal AD. Psychiatric disorders and sleep. Neurol Clin 2012 Nov;30(4):1389-1413 [FREE Full text] [CrossRef] [Medline]
    35. Freeman D, Sheaves B, Waite F, Harvey AG, Harrison PJ. Sleep disturbance and psychiatric disorders. Lancet Psychiat 2020 Jul;7(7):628-637. [CrossRef]
    36. Coffey JD, Christopherson LA, Glasgow AE, Pearson KK, Brown JK, Gathje SR, et al. Implementation of a multisite, interdisciplinary remote patient monitoring program for ambulatory management of patients with COVID-19. NPJ Digit Med 2021 Aug 13;4(1):123 [FREE Full text] [CrossRef] [Medline]
    37. Annis T, Pleasants S, Hultman G, Lindemann E, Thompson JA, Billecke S, et al. Rapid implementation of a COVID-19 remote patient monitoring program. J Am Med Inform Assoc 2020 Aug 01;27(8):1326-1330 [FREE Full text] [CrossRef] [Medline]
    38. Gordon WJ, Henderson D, DeSharone A, Fisher HN, Judge J, Levine DM, et al. Remote patient monitoring program for hospital discharged COVID-19 patients. Appl Clin Inform 2020 Oct 25;11(5):792-801 [FREE Full text] [CrossRef] [Medline]
    39. Arroll B, Goodyear-Smith F, Crengle S, Gunn J, Kerse N, Fishman T, et al. Validation of PHQ-2 and PHQ-9 to screen for major depression in the primary care population. Ann Fam Med 2010 Jul 19;8(4):348-353 [FREE Full text] [CrossRef] [Medline]
    40. Manea L, Gilbody S, Hewitt C, North A, Plummer F, Richardson R, et al. Identifying depression with the PHQ-2: a diagnostic meta-analysis. J Affect Disord 2016 Oct;203:382-395. [CrossRef] [Medline]
    41. Plummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: a systematic review and diagnostic metaanalysis. Gen Hosp Psychiatry 2016;39:24-31. [CrossRef] [Medline]
    42. Sapra A, Bhandari P, Sharma S, Chanpura T, Lopp L. Using Generalized Anxiety Disorder-2 (GAD-2) and GAD-7 in a primary care setting. Cureus 2020 May 21;12(5):e8224 [FREE Full text] [CrossRef] [Medline]
    43. Staples L, Dear B, Gandy M, Fogliati V, Fogliati R, Karin E, et al. Psychometric properties and clinical utility of brief measures of depression, anxiety, and general distress: the PHQ-2, GAD-2, and K-6. Gen Hosp Psychiatry 2019;56:13-18 [FREE Full text] [CrossRef] [Medline]

    ‎
    BT: body temperature
    GAD-2: 2-item Generalized Anxiety Disorder
    OR: odds ratio
    PHQ-2: 2-item Patient Health Questionnaire
    RPM: remote patient monitoring
    RTC: residential treatment center
    SNUH: Seoul National University Hospital
    SpO2: saturation of percutaneous oxygen

    Edited by T Sanchez, A Mavragani; submitted 28.09.22; peer-reviewed by N Guo, CY Lin; comments to author 12.12.22; revised version received 30.12.22; accepted 12.01.23; published 30.01.23

    Copyright

    ©Sumi Sung, Su Hwan Kim, Changwoo Lee, Youlim Kim, Ye Seul Bae, Eui Kyu Chie. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 30.01.2023.

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.