In this retrospective, monocenter study, 17.1% (653/3817) of PLWH tested positive for SARS-CoV-2 via nasopharyngeal swab during the study period, and 34.9% (178/510) developed PCCs. Data obtained from the survey administrated by telephone interviews showed that the most commonly declared symptom 3 months after SARS-CoV-2 infection was fatigue (60/178; 33.7%). According to the regression analysis model, no variables influenced the PCCs risk in our cohort, including vaccination status or the period dominated by a specific SARS-CoV-2 variant. However, male subjects were found to be less likely to develop PCCs (adjusted OR: 0.62 IC 95% 0.39–0.99). Conversely, patients who were hospitalized for COVID-19 at the onset of infection appeared to be more likely to develop the PCCs (adjusted OR 1.90, 95% CI 0.98–3.66; p = 0.054). No patients reported PCCs after a second SARS-CoV-2 infection. Immunological (CD4+ cells, CD8+ cells, and CD4+/CD8+), virological (plasmatic HIV viremia), serological parameters for several infections (presence of CMV IgG, HCV antibodies, HBsAg, HBcAb or Toxoplasma IgG), and the number of comorbidities did not appear to alter the risk of PCCs in our cohort.

This study comprises a large number of PLWH with SARS-CoV-2 infection, covering the pre- and post-Omicron period and encompassing both vaccinated and unvaccinated patients against SARS-CoV-2. When the study was conducted, the Lombardy Region was the first and most heavily affected regions in Europe by the SARS-CoV-2 pandemic, beginning in February 2020 [11]. In January 2022, the Lombardy region faced a significant surge in SARS-CoV-2 cases attributed to the Omicron variant [12]. Despite a vaccination rate of approximately 90% (with at least one dose), this wave resulted in a higher number of infections, but fortunately a lower rate of deaths from the beginning of the pandemic [13]. Of course, the different virulence among the Omicron variant and the previously isolated might have had an influence.

Early in the pandemic, patients with frailty were identified as having a higher risk of short-term mortality from COVID-19 compared to non-frail patients. PLWH were also included in the context of frailty raising major concern regarding SARS-COV-2 impact on this population [14].

Brescia has one of the highest estimated incidence of HIV infection in Italy with a pre-pandemic rate of 5.8/100,000 compared to 4.7/100,000 in the whole country [15]. In our province, all PLWH are in follow-up in a single healthcare center: the Spedali Civili General Hospital of Brescia. During the early phases of the pandemic, an appropriate emergency response was mandatory to maintain the delivery of HIV care and protect our PLWH from COVID-19 [16]. As previously published, HIV infection was not associated with a higher risk of severe manifestations of SARS-CoV-2 during the acute phase compared to the general population in our Province [15]. Nonetheless, there is conflicting data in the literature regarding the severity of SARS-CoV-2 in PLWH, primarily because PLWH constitute a remarkably heterogeneous population in terms of immune competence, antiretroviral therapy coverage, and response to both and the SARS-CoV-2 vaccine [17, 18].

Most patients who recovered from acute COVID-19 experienced long-term effects on multiple organs and systems. Currently, there are no standardized criteria for diagnosing and categorizing post-COVID conditions, and the percentage of individuals reporting PCCs varies widely in the literature.

This variability can be attributed to several factors such as the time period, SARS-CoV-2 variant, patients included in the studies, geographical region, vaccination status, and the use of early therapies for COVID treatment [19,20,21,22,23]. Moreover, symptoms attributed to PCCs are often non-specific and may be due to other causes or concomitant morbidities. A nationwide Scottish population cohort study suggests that patients who had SARS-CoV-2 infection may mistakenly attribute their symptoms to long-COVID [24]. A debated topic is that SARS-CoV-2 infection could worsen a pre-existing inflammatory status, as chronic HIV infection [17]. Since in our cohort all the patients considered having PCCs fall into the WHO definition where post-COVID-19 conditions (symptoms of new onset, or if previously reported with a significant worsening, that could not be attributed to alternative causes [2]), we have not considered these symptoms as related to chronic HIV immune inflammation condition.

Much less data is available regarding PCCs in PLWH, with a variable prevalence ranging between 3%-78% [25]. Some studies investigated whether PLWH are at increased risk of PCCs compared to PLWH without SARS-COV-2 infection or with HIV-seronegative people with different results [8, 25,26,27,28,29,30,31]. In our cohort, the PCCs prevalence in PLWH was 35%, but the fact that HIV/AIDS might contribute to the PCCs symptomatology could not be ruled out, since we have not compared it to the PCCs prevalence among the general population in our setting. However, as highlighted in Table 3, an absence of statistical difference in viro-immunological characteristics of the two groups of PLWH (with and without PCCs) is reported. Given this, it is possible to infer that HIV/AIDS has not primarily affected the symptomatology of PCCs.

Comparing PLWH with and without SARS-CoV-2 infection, an elevated risk of multi-system dysfunction (i.e., respiratory, cardiovascular, and metabolic) was described among PLWH at 12 months post COVID-19 compared to PLWH without SARS-COV-2 infection [32]. Contrasting findings described how exercise capacity measured by a cardiopulmonary exercise testing was reduced among PLWH, but no differences are reported between SARS-CoV-2 infected and uninfected or among PLWH with or without PCC at 16 months after SARS-CoV-2 infection [33].

Yendewa et al. reported that PLWH had higher odds of PASCs, defined as persistence or occurrence of a new-onset health condition at least 28 days following COVID-19, compared to HIV-seronegative people and SARS-CoV-2 vaccination was protective [34]. Similar results were reported by Antar et al. who assessed the presence and severity of 49 long COVID-associated symptoms at 2 months following SARS-CoV-2 infection, although these findings were not consistent at 4–6 months post-infection [35].

The effectiveness of COVID-19 vaccines in preventing post-COVID conditions among vaccinated individuals remains uncertain, and it might vary depending on the number of vaccine doses received. A recent meta-analysis suggested that receiving a complete COVID-19 vaccination before contracting SARS-CoV-2 infection significantly reduces the risk of PCCs, even during the Omicron era. However, it did not protect against PCCs for those who received COVID-19 vaccination after COVID-19 infection (23). Since at the time of our study 46% of PLWH resulted unvaccinated, and 25% not completely vaccinated for COVID 19, the COVID vaccine may have played only a small role in reducing PCCs in our cohort. Furthermore, no statistical difference was seen between the PLWH with PCCs and without PCCs according to vaccine status. Therefore, we could infer that vaccination only had a marginal influence in our study.

Taken together, our results suggest that key variables related to HIV infection may not necessary increase the risk of PCCs, but they confirm some of the risk factors described in general population, such as gender, and severity of acute infection measured by hospitalization. One possible explanation could be that in our cohort of PLWH who completed the questionnaire, the majority had well-controlled HIV infection with plasma HIV RNA < 20 copies/ml (92%; 473/510), and a mean of CD4+ of 753 cells/mm3. Additionally, 65% (334/510) did not have any comorbidities, and 53% (274/510) had received at least 2 doses of COVID-19 vaccine at the time of SARS-CoV-2 infection. Moreover, 60% of them (309/510) acquired SARS-COV-2 infection during Omicron wave. Further studies are needed in different cohorts and settings to confirm our findings.

The main limitations of our study include the absence of a control group comprising individuals without HIV infection, or PLWH without SARS-CoV-2 infection, the collection of symptoms was performed via telephone interview and the lack of evaluation regarding the use of COVID therapies, including antiviral drugs. Additionally, people with mild symptoms may have been less likely to undergo SARS-CoV-2 testing. Moreover, Omicron wave surge coincides with the inoculation of the 3rd dose of SARS-CoV-2 vaccine during the Italian vaccination campaign, hence eventual adverse effects of the vaccine considered as PCCS in fully vaccinated PLWH could not be ruled out. However, we did not observe any statistical difference among PLWH with PCCs and without PCCs according to the vaccination status (unvaccinated, incomplete or complete vaccination). Strengths of this study include the large sample size and the linkage with the local health service, which provided all notifications of SARS-CoV-2 test results performed in the Brescia Local Health Agency.