Psychological distress related to the COVID-19 epidemic in an Italian population of People Living with HIV: an online survey

Purpose: Our aim was to explore the psychological impact of the 2019 Coronavirus Disease (COVID-19) on People Living with HIV (PLWH), a population at increased risk of psychological distress. Methods: PLWH participated to an online survey exploring demographic and clinical data, physical symptoms, contact history, knowledge and concerns, precautionary measures and additional information about COVID-19 during the rst phase of the pandemic in Italy. 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 comprised. Results: Out of 98 participants, 45% revealed from mild to severe psychological impact from COVID-19 according to IES-R. A lower percentage, instead, complained signicant levels of depression (14%), anxiety (11%) or stress (6%) according to DASS-21. Aging, education, being unemployed, number of possible COVID-19 physical symptoms, concerns about risk of contracting COVID-19 and pandemic situation in Italy, and needing additional information to prevent COVID-19 infection were positively associated to a higher risk of negative psychological impact. Moreover, female gender, fewer years from HIV diagnosis and not being aware of own viremia were associated to a higher risk of negative psychological outcomes. Conclusion: Almost half of our PLWH sample experienced signicant levels of distress related to COVID-19 pandemic. Women and those with recent HIV diagnosis seem the more psychological fragile subgroup. Our ndings could help to identify patients most in need of psychological interventions to improve wellbeing of PLWH.


Background
Outbreak of the Coronavirus Disease 2019 (COVID-19) is now affecting more than 200 countries and territories around the world, becoming a pandemic.
Italy has been the rst-hit European country to face the outbreak of COVID-19 and one of the most affected areas. On March 9 th 2020, the Italian Government settled several emergency containment measures that began to be loosened only from May 4 th onwards, to deal with the spread of the pandemic.
Evidence accumulated during the initial phase of the COVID-19 outbreak con rms that the pandemic is having a great psychological impact on individuals especially in worst-hit countries (Fiorillo and Gorwood 2020;Kang et al. 2020;Talevi et al. 2020). 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 (Ayittey et al. 2020;Brooks et al. 2020;Duan and Zhu 2020;Rubin 2020).
A review ) about the mental health outcomes of COVID-19 pandemic identi ed a wide list of negative psychological responses in Chinese general population: 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 (Cao et al. 2020;Li et al. 2020;Liu et al. 2020;Qiu et al. 2020;Wang C et al. 2020). Consistent predictors of psychological outcome were identi ed: female gender, aging, speci c physical symptoms, poor self-rated health status, speci c health information and certain precautionary measures, having relatives or acquaintances infected with COVID-19, and medical history of chronic illness (Qiu et al. 2020;Wang C et al. 2020;Zhang et al. 2020).
In Italy, a relevant percentage of the population (38%) have experienced from mild to to-severe psychological distress symptoms during the early phase of the COVID-19 outbreak (Moccia et al. 2020), and evidence suggests a higher proportion compared to other European countries (Jacobi et al. 2014;Mazza et al. 2020;Wittchen et al. 2010). Furthermore, high rates of negative mental health outcomes, including post-traumatic stress symptoms and anxiety, were found (Rossi et al. 2020).
Among predictors of psychological distress, a history of medical issues seems to be central to identify groups at greater risk of distress and needing tailored psychological interventions ).
Indeed, the Centers for Disease Control and Prevention highlighted people living with HIV (PLWH) as a population at increased risk for severe illness from COVID-19 compared to the general population (Coronavirus Disease 2019  in People with HIV 2020). COVID-19 is assumed to function in tandem with a myriad of health challenges faced by PLWH including HIV itself, chronic noncommunicable diseases, mental health burden, substance abuse, and other infections (Halkitis et al. 2020;Shiau et al. 2020). This situation is de ned a "syndemic", that is two or more epidemics interacting synergistically to produce an increased burden of disease in a population (Singer 2010). Therefore, due to the syndemic framework, the exposition to mental health issues (Brandt et al. 2016;Lynn et al. 2018) and to a chronic illness (Gebo 2008;Nachega et al. 2012), PLWH seem to be a group at greater risk of suffering from psychological distress during COVID-19 pandemic.
Currently, there are only few data about mental health of PLWH during COVID-19 epidemic reporting elevated levels of anxiety (Kuman TunÇel et al. 2020), and showing that COVID-19 and associated restrictive measures seem detrimental to the well-being and follow-up of PLWH (Siewe Fodjo et al. 2020).
Our aim was to better explore the psychological impact of the COVID-19 outbreak on an Italian cohort of PLWH and to assess the possible risk and protective factors, in order to help to tailor speci c psychological interventions.

Methods
Participants This is a cross-sectional survey enrolling PLWH, followed at Infectious Diseases Institute of "Policlinico Gemelli Foundation" of Rome, between 9 th -25 th May 2020. This timeframe was chosen to assess participants' responses at the end of the rst phase of COVID-19 outbreak, following the Italian Government Decree-Law of May 4 th 2020 that began to loosen emergency containment measures. All subjects were volunteers. They did not receive any nancial remuneration for participating.
Exclusion criteria were age <18 years and di culties with the Italian language.

Procedure
Each participant completed a 105-item online survey adapted from Wang C et al. (2020), in which data on demographic, clinical and COVID-related variables were collected "since the Decree-law of March 9 th 2020 to today" (see below).

Demographic and HIV-associated clinical variables
Data were collected on gender, age range, education, employment status, sexual orientation, 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 consultation with a doctor, admission to the hospital, being tested for COVID-19 infection and being quarantined by a health authority. Moreover, physical symptoms 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, it was collected a self-report judgment about own health-state choosing one of the following answer options: poor, passable, good, very good or excellent.

Contact history variables
It was asked if the respondents had contacts with individuals with suspected or con rmed COVID-19 infection or with infected materials.
Knowledge and concerns about COVID-19 variables Regarding knowledge of COVID-19, we collected data about respondents' habit of keeping informed about pandemic trend (number of infections, hospitalizations and deaths), the main source of health information, the level of satisfaction on health information [using a Likert scale from 1 (not satis ed) to 10 (extremely satis ed)], the knowledge about routes of transmission and likelihood of surviving if infected with COVID-19, choosing one of the following answer options: no chance, unlikely, likely, very likely and highly likely. The COVID-19 epidemic 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 of COVID-19 situation in Italy, to contract COVID-19 and about other family members getting COVID-19 infection [using a Likert scale from 1 (no concern) to 10 (extremely concern)], and feeling too much unnecessary worried about the epidemic, choosing one of the following answer options: always, most of times, sometimes, occasionally and never.

Precautionary measures variables
We investigated precautionary measures against COVID-19 put in place among: washing hands with soap and water, washing hands immediately after coughing, rubbing nose or sneezing, washing hands after touching contaminated objects, avoiding sharing of utensils during meals, covering mouth when coughing and sneezing, wearing mask regardless of the presence or absence of symptoms (choosing one of the following answer options: always, most of times, sometimes, occasionally and never), and average number of hours staying at home per day to avoid COVID-19 infection.

Additional health information variables
Further data were collected about the global trend of pandemic, 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 outbreak and Mental health status measures
To measure Psychological Impact of the COVID-19 outbreak, the Impact of Event Scale-Revised (IES-R) was administered (Christianson and Marren 2012). The IES-R is a 22-items self-report measure designed to assess current subjective distress for a speci c traumatic life event. Respondents are asked to identify a speci c stressful life event and then indicate how much they were distressed or bothered during the past seven days by it. In our survey the stressful event to refer 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 -(Gayle Beck et al. 2008). The IES-R total score provides an indication of the level of distress experienced and a higher score indicates a greater psychological impact (Creamer et al. 2003;Reynolds et al. 2008).
To measure Mental Health Status the "Depression, Anxiety and Stress Scale" (DASS-21) was administered (Henry and Crawford 2005;Norton 2007). 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 self-esteem/incentives and depressed mood. The second subscale (DASS-Anxiety) measures fear and anticipation of negative events. The third subscale (DASS-Stress) measures persistent state of overarousal and low frustration tolerance. The higher the score, the more severe the emotional distress was (Oei et al. 2013).

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 the 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 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
Overall, 45% (n=44) of PLWH revealed from mild to severe psychological impact of COVID-19 outbreak according to the IES-R. As regards 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 patients obtained a score in the "extremely severe" range.
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 levels of distress measured by IES-R, and of depression, anxiety and stress measured by DASS-21 (detailed in Online Resource 1).

Contact history variables and physical health status
A detailed description of contact history and physical health status is reported in Table 3.
Seventy-six (77.5%) participants reported good or very good health status and only 2 (2%) had been under quarantine by a health authority. The most frequent physical symptom was headache (33.7%).
A complete analysis of associations between Contact History variables or physical health status and psychological impact as well as mental health status scales is reported in Online Resource 2. Table 4. 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.

Knowledge and concerns about COVID-19 variables A detailed description of Knowledge and Concerns about COVID-19 is reported in
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 subjects considered very likely surviving if infected with COVID-19.
Regarding COVID-19 epidemic 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 epidemic.
A complete analysis of associations between psychological impact and mental health status scales with knowledge and concerns about COVID-19 variables is reported in Online Resource 3.

Precautionary measures variables
Table 5 details precautionary measures adopted by participants.
The two most frequently adopted precautionary measures were always washing hands with soap and water (84%, n=82), and always washing hands after touching contaminated objects (80%, n=79).

Precautionay measures variables seemed not signi cantly correlated to psychological distress levels measure by IES-R and depression, anxiety and stress levels measured by DASS-21.
A complete analysis of associations between Precautionary measures variables and psychological outcomes is reported in Online Resource 4. Table 6 describes Additional health information variables reported by participants. Requiring further information on prevention of COVID-19 infection was associated to a higher risk for mild-to-severe levels of anxiety (OR 5.06; 95% CI 1.25/20.51; p= 0.023) measured by DASS-21.

Additional health information variables
A complete analysis of associations between additional health information variables and psychological outcomes are reported in Online Resource 5.

Discussion
We found that, during the rst 2 months after the beginning of COVID-19 outbreak in Italy, almost half of our cohort of PLWH suffered from mild to severe psychological distress according to the IES-R scale, that measures emotional states referring to a speci c event. This proportion is higher compared to that one observed in the general population (Moccia et al. 2020;Rossi et al. 2020), con rming that PLWH might be a more fragile population needing a particular care.
Similarly to a previous Chinese survey (Wang C et al. 2020), a lower percentage of our sample complained elevated levels of depression, anxiety and stress as measured by the DASS-21, probably because this scale investigates emotional states that do not refer to a speci c event and, consequently, it could be less sensitive in case of pandemic-related distress.
According to previous evidence (Ho et al. 2019;Mazza et al. 2020;Moccia et al. 2020;Talevi et al. 2020;Kuman TunÇel et al. 2020;Wang C et al. 2020;Wittchen et al. 2010), we identi ed many factors associated with a higher risk of distress: female gender, higher number of possible COVID-19 physical symptoms, aging, higher education, being unemployed, higher concerns about risk of contracting COVID-19 or regarding epidemic evolution in Italy, and greater need of additional health information about COVID-19 prevention. These factors were associated to a higher risk of depression, anxiety and stress during the rst phase of epidemic. At the opposite, PLWH usually keeping themselves informed about COVID-19 outbreaks showed a lower risk of depression. Furthermore, 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 (Spizzichino 2008), and not being aware of own viremia emerged as a risk factor for higher levels of anxiety. In other words, those who perceive their own health as poor might feel more vulnerable when facing a new disease (Hatch et al, 2018). Taken together our ndings suggested that patients (especially women) with recent HIV diagnosis and worse physical and psychological health might be at greater risk of distress from COVID-19 compared to the general population.
We acknowledge that our study has some limitations. First of all, this is a cross-sectional observation and future longitudinal studies are needed to con rm and check the progress of our ndings. Secondly, further investigations including a healthy 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 probable socially desirable responses. Furthermore, we used an online survey leaving unexplored the population who does not use network devices, and due to requirements on anonymity and confidentiality, we were not allowed to collect some personal information from the respondents. Therefore, since all of our patients were over 30 years old, further investigations including younger subjects are needed; however, an older sample is more representative of the current Italian HIV-infected population.

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.

Declarations Funding
No funding was received for this study.

Con ict of Interest
AB fee for advisory board by ViiV Healthcare, personal fee by Janssen Cilag. MF received speakers' honoraria and support for travel to meetings from Bristol-Myers Squibb (BMS), Gilead, Janssen-Cilag, Merck Sharp & Dohme (MSD), ViiV Healtcare, and fees for attending advisory boards from BMS, Gilead and Janssen-Cilag. SDG received speakers' honoraria and support for travel to meetings from Gilead, Janssen-Cilag (JC), Merck Sharp & Dohme (MSD) and ViiV Healtcare. All other authors: none to declare.

Author contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Delle Donne Valentina, Massaroni Valentina and Ciccarelli Nicoletta. The rst draft of the manuscript was written by Delle Donne Valentina and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript.

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. Adherence*, on a 0-10 scale 10 (9-10)    Table 5 Precautionary measures adopted by participants. Abbreviations: N number Table 6 Additional health information variables reported by participants. Abbreviations: N number