Psychological distress during the initial COVID-19 pandemic in an Italian cohort of people living with HIV: an online survey

Our aim was to explore the psychological impact of the initial 2019 Coronavirus (COVID-19) pandemic in a cohort of people living with HIV (PLWH), a population at increased risk of psychological distress. PLWH, treated at our unit, responded an online survey. Data on demographics, clinical and physical symptoms, contact history, as well as knowledge, concerns, precautionary measures and additional information required with respect to COVID-19 during the rst phase of the pandemic in Italy were collected. Additionally, the Impact of Event Scale-Revised (IES-R) (identifying COVID-19 pandemic as specic traumatic life event) and the Depression, Anxiety and Stress Scale (DASS-21) were also administered. Out of 98 participants, 44 (45%) revealed from mild to severe psychological impact distress from COVID-19 according to IES-R. According to DASS-21, a lower percentage of signicant levels of depression (14%), anxiety (11%) or stress (6%) were reported. Higher education, unemployment, number of perceived physical COVID-19 symptoms, concerns contracting COVID-19 and the situation regarding the pandemic in Italy, and the need of additional information to prevent COVID-19 infection were positively associated to psychological distress. Moreover, female gender, older age, recent HIV diagnosis and unawareness of own viremia were associated to a higher psychological distress. Almost half of our cohort experienced signicant levels of distress related to the COVID-19 pandemic. Women, elderly patients and those with recent HIV diagnosis resulted to be the more psychological fragile subgroup. Our ndings could help to identify patients in need of psychological interventions to improve wellbeing of PLWH. psychological of on Italian sample of in support and highlight to psychological interventions to psychological wellbeing.


Introduction
The 2019 Coronavirus Disease (COVID- 19), spreading from Wuhan (China) at the end of 2019, became soon a pandemic. The World Health Organization declared the COVID-19 outbreak on Jan 30th 2020 an international public health emergency affecting nowadays more than 200 countries and territories around the world. Italy has been hit rst in European and faced COVID-19 as one of the most affected areas. To deal with the spread of the pandemic, on March 9th 2020, the Italian Government settled several emergency containment measures, which began to be loosened only from May 4th onwards.
Evidence of the initial phase of the COVID-19 outbreak demonstrated a great negative psychological impact on individuals especially in worst hit countries [1][2][3]. Mental health outcomes seem to be related to many factors: widespread contagion, containment and prevention measures such as self-isolation, social distancing, lockdown, and socio-economic impact [4][5][6][7]. Given the unprecedented nature of the COVID-19 pandemic, an increase in anxiety has been prevalent worldwide [8].
A review [3] about mental health outcomes of the COVID-19 pandemic on the general Chinese population identi ed a wide list of negative psychological responses such as anxiety, depression, stress, insomnia, indignation, worries about their own and family health, sensitivity to social risks, life dissatisfaction, phobias, avoidance, social functioning impairment, compulsive behaviour and physical symptoms [9][10][11][12][13]. Consistent predictors of psychological distress were identi ed such as female gender, higher age, speci c physical symptoms, poor self-rated health status, the need of additional information with respect to COVID-19 (for example about precautionary measures), the experience of relatives or acquaintances infected with COVID-19, and medical history of chronic illness [11,[13][14][15].
In Italy, a relevant percentage of the general population (38%) have experienced from mild to to-severe psychological distress during the early phase of the COVID-19 outbreak [16], and evidence suggests a higher proportion compared to other European countries [17][18][19]. Furthermore, high rates of negative mental health outcomes, including post-traumatic stress symptoms and anxiety, were found [20].
A history of medical issues is among the predictors of psychological distress and could serve as an indicator to identify groups at higher risk of distress and in need for tailored psychological interventions [3].
Indeed, the Centre for Disease Control and Prevention highlighted that individuals with chronic health conditions, such as people living with HIV (PLWH), may develop a stronger stress response than the rest of the population [21].
Although there is no clear evidence that the risk of COVID-19 infection is higher among PLWH compared to the general population [22], to cope with COVID-19 outbreak might have significant effects on the biological, psychological and social aspects of their lives [8].
Firstly, outpatients' visits and treatment have been interrupted or postponed because of the lockdown [8] and the fear of contracting COVID-19 has led to decreased engagement with care among PLWH in several countries [23][24][25][26][27]. Additionally to complications related to HIV disease progression, an incorrect management of HIV could lead to an increased risk contracting COVID-19 and experiencing complications. [8].
Furthermore, the current pandemic is a significant stressor and could increase the risk of mental health concerns among PLWH [28].
Depression is the most common mental health disorder among PLWH [29], being two to four times more frequent than in HIV-negative people [30][31][32]. Symptoms of depression may be exacerbated by loneliness due to physical distancing necessary to contain COVID-19 and may have adverse effects on treatment adherence [33][34][35].
Additionally, COVID-19 is assumed to function in a syndemic framework "that is two or more epidemics interacting synergistically to produce an increased burden of disease in a population" [36] with several health challenges faced by PLWH including HIV itself, chronic non-communicable diseases, mental health burden, substance abuse, and other infections [37,38].
Therefore, due to the syndemic framework, the exposition to mental health issues [39,40] and to a chronic illness [8,41,42], PLWH seem to be a group at greater risk for psychological distress during COVID-19 pandemic.
Currently, only few data exists about mental health of PLWH during COVID-19 pandemic reporting elevated levels of anxiety [43], and showing that COVID-19 and associated restrictive measures seem detrimental to the well-being and follow-up of PLWH [44]. Our aim was to better explore the psychological impact of COVID-19 on an Italian cohort of PLWH and to assess the possible risk and protective factors, in order to tailor speci c psychological interventions.

Participants
In this cross-sectional study, PLWH followed at Infectious Diseases Institute of the Fondazione Policlinico Universitario A. Gemelli IRCCS of Rome, responded an online survey between May 9th and 25th 2020. This timeframe was chosen to assess participants' responses at the end of the rst phase of the COVID-19 pandemic, following the Italian Government Decree of May 4th 2020, which began to loosen emergency containment measures. Exclusion criteria were age <18 years and di culties with the Italian language.
All participants volunteered and did not receive any nancial remuneration for participating. The institutional ethics committee approved the study protocol (ID number 3123). All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants included in the study.
Each participant completed a 105-item online survey adapted from Wang C et al. (2020) [11], in which data on demographic, clinical and COVID-related variables were collected.

Demographic and HIV-associated clinical variables
Data were collected on gender, age, education, employment status, sexual orientation, presence of a stable relationship (cohabitant or married), parenthood, time from HIV diagnosis, time from rst combined Antiretroviral Treatment (cART), HIV-1 plasma viral load and adherence to cART in the last month (using a Likert scale from 1 [very bad] to 10 [excellently]).

Physical health status variables
We gathered information regarding health service utilization, including medical consultation, hospital admission, COVID-19 testing and quarantine. Moreover, physical symptom variables included fever, chills, headache, myalgia, cough, breathing di culty, dizziness, coryza, sore throat, and the triad of fever, cough and di cult breathing. Moreover, a self-report judgment about own health-state choosing one of the following answers (poor, passable, good, very good or excellent) was asked.

Contact history variables
We asked if the respondents had contacts with individuals with suspected or con rmed COVID-19 infection or with infected materials (surfaces, objects, utensils).

Knowledge and concerns about COVID-19 variables
Regarding knowledge of COVID-19, we collected data about respondents' habits staying informed about the pandemic such as infection numbers, hospitalizations, deaths, main source of health information, satisfaction level of health information (using a Likert scale from 1 [not satis ed] to 10 [extremely satis ed]), knowledge about transmission roots and likelihood of surviving if infected with COVID-19 (using the following options: no chance, unlikely, likely, very likely and highly likely). COVID-19 concerns were investigated as follows: level of con dence in the own doctor's ability to diagnose COVID-19 (using a Likert scale from 1 [no trust] to 10 [full con dence]), concern regarding COVID-19 situation in Italy, concerns getting infected yourself or family members getting infected with COVID-19 (using a Likert scale from 1 [no concern] to 10 [extremely concern]), and feeling excessively worried about the pandemic (using the following options: always, mostly, sometimes, occasionally and never).
We investigated precautionary COVID-19 measures such as hand hygiene immediately after coughing, rubbing nose, sneezing, touching contaminated objects, avoiding to share utensils during meals, covering mouth when coughing and sneezing, wearing masks regardless of the presence or absence of symptoms (choosing one of the following answers: always, mostly, sometimes, occasionally and never), and average number of hours staying at home per day to avoid COVID-19 infection.

Additional information required with respect to COVID-19
Further data were collected about the pandemic trend, more details on symptoms, additional advices on prevention, routes of transmission, treatment and the availability of medicines/vaccines, further regular updates on the state of pandemic and the number of people infected in their location and on the management of the outbreak in foreign countries, and more tips for moving from home safely during the outbreak.
Psychological impact of the COVID-19 pandemic and mental health status measures To measure the psychological impact of the COVID-19 pandemic, the Impact of Event Scale-Revised (IES-R) was administered [45]. The IES-R is a 22-items self-report measure designed to assess current subjective distress for a speci c traumatic life event, according to the DSM-IV symptoms of Post Traumatic Stress Disorder. Respondents were asked regarding a speci c stressful life event and to indicate how much distressed they experienced during the past seven days. In our survey, the stressful event was the COVID-19 pandemic. The IES-R was constructed with three subscales: intrusions e.g., repeated thoughts about the trauma, avoidance e.g., effortful avoidance of situations that serve as reminders of the trauma, and physiological hyperarousal e.g., irritability, hypervigilance and di culty concentrating [46]. Items were rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) with a higher score indicating a greater psychological impact [47][48]. Mean scores can also be calculated for each subscale (range 0-4) and lower score means smaller psychological impact [49].
To measure mental health status the Depression, Anxiety and Stress Scale-21 (DASS-21) was administered [50,51]. The DASS-21 is a set of three self-report scales designed to measure the emotional states of depression, anxiety, and stress. The rst subscale (DASS-Depression) measures loss of selfesteem/incentives and depressed mood. The second subscale (DASS-Anxiety) measures fear and anticipation of negative events. The third subscale (DASS-Stress) measures the persistent state of over arousal and low frustration tolerance. The higher the score, the more severe the emotional distress [52].
The principal difference between IES-R and DASS-21 (stress subscale) is that the former assesses the psychological impact of a speci c traumatic event, while the latter does not identify any speci c event. To clarify, we indicated the construct measured by IES-R (i.e. concerning a speci c event) as "distress", and that one measured by DASS-Stress subscale (i.e. do not related to any speci c event) as "stress".

Statistical analysis
Descriptive statistics were calculated for qualitative and quantitative variables. We performed binary logistic regression analyses to explore factors signi cantly associated with mild-to-severe psychological distress measured by IES-R as well as with mild-to-extremely severe levels of depression, anxiety, and stress measured by DASS-21. A two-tailed p value of less than 0.05 was considered statistically signi cant.
Due to high inter-correlations between the collected COVID-19 related variables, only univariate analyses were run for these factors.
All analyses were performed using SPSS version 21.0 software package (SPSS Inc., Chicago, IL).
Sixty-four (65.3%) and fty-nine (60%) of respondents showed a time >10 years from HIV diagnosis and from rst cART, respectively. Overall, 74.5% (n=73) of patients reported HIV-RNA<50 copies/mL and the mean adherence to cART was 9.48 (standard deviation, SD 1.10) on a 0-10 scale. Full demographic and clinical characteristics are summarized in Table 1.

Psychological impact and mental health evaluation
According to the IES-R, 45% (n=44) of PLWH revealed mild to severe psychological impact of COVID-19 on their life. We considered the mean scores of the IES-R subscales within the group of patients with mild to severe effect and the highest mean score was observed in the physiological hyperarousal subscale (1.84, SD 0.74) followed by the avoidance subscale (1.78, SD 0.46) and the intrusion subscale (1.64, SD 0.62), all indicating few symptoms of post-traumatic stress.
Regarding the DASS-21, 14.3% (n=14), 11.2% (n=11) and 6.1% (n=6) of PLWH obtained a score suggesting the presence of mild to severe levels of depression, anxiety and stress, respectively; no patient obtained a extremely severe score.
Complete descriptive statistics of IES-R and DASS-21 item scales are shown in Table 2.
Demographic and clinical factor associated to psychological impact and mental health evaluation We explored factors associated to signi cant mild-to-severe levels of distress measured by IES-R, and to mild-to-severe levels of depression, anxiety and stress measured by DASS-21. For simplicity, only signi cant associations at multivariate analyses where reported. A full description of these logistic regression analyses is shown in Table 3a  Others factors related to the severity of HIV infection (time from rst cART, HIV-1 plasma viral load and adherence to cART in the last month) were not found to be associated with psychological impact and mental health evaluation.

Contact history variables and physical health status
A detailed description of contact history and physical health status is reported in Table 4. For conciseness, only signi cant associations at logistic univariate analyses where reported. Contact history variables were not signi cantly associated to IES-R and DASS-21 scores. Instead, the number of possible COVID-19 symptoms was positively associated to mild-to-severe psychological distress measured by IES-R (OR 1.42; 95% CI 1.07/1.88; p= 0.014), and of mild-to-severe depression (OR 1.40; 95% CI 1.03/1.90; p= 0.032), anxiety (OR 1.50; 95% CI 1.08/2.09; p= 0.016) and stress (OR 1.56; 95%CI 1.03/2.34; p= 0.032) measured by DASS-21. A complete description of associations between psychological impact and mental health measures and each physical symptoms complained is shown in Table 5.
Knowledge and concerns about COVID-19 variables A detailed description of knowledge and concerns about COVID-19 is reported in Table 6. About 94% (n=92) of the respondents usually kept themselves informed about COVID-19 outbreak. The most common source of health information was from television (59.2%, n=58) and the mean satisfaction with the amount of available health information was 6.48 (SD 2.08) on a 0-10 scale.
The majority of participants knew routes of transmission of COVID-19: 87% (n=85) agreed with route of transmission through droplets and 85% (n=83) through contaminated objects. About 61% (n= 60) of respondents considered very likely surviving if infected with COVID-19.
Regarding COVID-19 pandemic concerns, mean concerns of situation in Italy was 6.39 (SD 2.47), and 37% (n=36) of respondents sometimes felt too much unnecessary worry about the pandemic.
Precautionary variables were not signi cantly correlated to psychological distress levels measure by IES-R and depression, anxiety and stress levels measured by DASS-21.
Additional information required with respect to COVID-19

Discussion
We found that, during the rst 2 months after the beginning of COVID-19 pandemic in Italy, almost half of our PLWH cohort experienced mild to severe psychological distress according to the IES-R scale, which measures emotional states referring to a speci c event. This percentage is higher compared to that observed in previous studies reporting 37% and 38% of distress in the general population [16,20], which con rms that PLWH might be a more fragile population in need of particular care.
Similarly to a previous Chinese survey [11], a lower percentage of our sample complained elevated levels of depression, anxiety and stress, which was assessed with DASS-21. This result might be explainable with the fact that this scale investigates emotional states not referring to a speci c event and, consequently, it could be less sensitive in case of pandemic-related psychological impact.
In accordance with previous evidence [3,11,14,16,18,19,8,53], we con rm that several factors are associated with a higher risk of negative psychological impact during the COVID-19 pandemic. To be more speci c, we found that female gender was associated with a good trend towards a statistical signi cance with increased distress [54]. In addition, higher age con rmed its negative association with mental health, probably because the physical distancing due to lockdown has exacerbated isolation and loneliness [55][56] especially among elderly people [38]. In our study, higher education was correlated with distress.
However, in literature, inconsistent results can be found [3]. Indeed both high [13][14] and low [11] education levels have been found as possible risk factors for adverse psychological outcomes. Additionally, we found unemployment a risk factor for distress, suggesting that the pandemic's disproportionate impact on economically disadvantaged persons may have ampli ed pre-existing health disparities within the HIV epidemic [8]. Furthermore, a greater need of additional health information about COVID-19 prevention measures was associated to negative mental health outcomes, suggesting the usefulness of providing accurate health information during the pandemic to reduce the impact of rumours by government and health authorities [5]. On the other hand, PLWH staying informed about COVID-19 outbreak showed a lower depression levels.
To experience higher number of possible COVID-19 physical symptoms, higher concerns contracting COVID-19 or regarding pandemic evolution in Italy were correlated to adverse psychological impact.
Among HIV factors, fewer years from HIV diagnosis were associated with a higher risk of depression, maybe due to an increased mental health burden during the rst years after HIV diagnosis [40], and unawareness of own viremia caused higher levels of anxiety. In other words, "those who perceive their own health as poor might feel more vulnerable when facing a new disease" [57]. In our sample, other factors related to the severity of HIV infection associated with mental health evaluation were not identi ed, maybe due to the high prevalence of patients with full adherence to cART and virally suppressed.
Our study has some limitations, as the cross-sectional study design and future longitudinal studies are needed to con rm and check the progress of our ndings. Secondly, further investigations including a HIV-negative control group would be useful to check for any differences in psychological impact or mental health status between PLWH and the general population. Moreover, reliability of self-administered questionnaires may be partially biased because of socially desirable responses. Furthermore, we used an online survey leaving a population not using network devices unexplored, and due to requirements on anonymity and confidentiality, some demographics and clinical data we were not available. Since all of our patients were over 30 years old, further investigations including younger PLWH are needed; however, an older cohort is more representative for the current Italian population with HIV infection.
In conclusion, this study shows that almost half of an Italian cohort of PLWH experienced from mild to severe adverse psychological impact related to the rst stage of the COVID-19 pandemic. Taken together, our ndings suggest that among PLWH, women and elderly, and those with recent HIV diagnosis might be at greater risk of distress from COVID-19 might require particular care. Regular health check-ups and accurate information about COVID-19 in the media appear important to prevent stress and anxiety. Our results describe a rst picture of the psychological impact of COVID-19 on an Italian cohort of PLWH. This overview could help to identify patients requiring support and highlights the importance to tailor speci c psychological interventions to improve psychological wellbeing of PLWH, especially during the COVID-19 crisis. To be more speci c, during the COVID-19 pandemic, it could be necessary to implement a more modern model of care integrating special interventions like telepsychology, that is the provision of psychological services using telecommunication technologies [56]. To this purpose, health providers have to develop the knowledge, skills, and attitudes needed to utilize telehealth technologies by speci c training according with the American Psychological Association's (APA) guidelines. [58].
Funding: No funds, grants, or other support was received. No institution or funding has been used as the nancial resource of this study.

Conclusions
This study shows that almost half of an Italian cohort of PLWH experienced from mild to severe adverse psychological impact related to COVID-19 pandemic. Especially, women and those with more recent HIV diagnosis seem to be at greater risk of negative psychological outcomes. In conclusion, our results describe a rst picture of the psychological impact of COVID-19 on an Italian sample of PLWH, and could help to identify patients most in need of support and highlight the importance to tailor speci c psychological interventions to improve their psychological wellbeing. Ethics Approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Study was approved by the Ethics Committee of the Catholic University of Sacred Heart, Rome, Italy. Informed consent was obtained from all individual participants included in the study.

Consent for publication
Not applicable.

Availability of data and materials
The datasets generated for this study are available on request to the corresponding author.
Code availability Not applicable.