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Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals. [ABSTRACT FROM AUTHOR]

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020–2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37–0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72–84 IQR) vs. 67 years (55–78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02–1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events. [ABSTRACT FROM AUTHOR]

From the initial COVID-19 outbreak, Italy was the first Western country to be seriously affected by the pandemic. Understanding vaccine hesitancy can help efforts to achieve broad vaccination coverage. The objectives of this research were to determine the extent of vaccine hesitancy in Italy and to understand the characteristics of those segments of the population with some hesitancy. Between January and February 2021, 41,473 subjects answered the second questionnaire delivered in phase II of the web-based EPICOVID19 survey. Among the included adult volunteers living in Italy, 4653 (11.2%) reported having previously received at least one dose of the COVID-19 vaccine. In the sample of 36,820 respondents, all not vaccinated (age 51.1 ± 13.5; 59.7% female; 63.6% high level of education), the comparison between hesitant and inclined participants was accompanied by percentages and odds ratios. A total of 2449 individuals were hesitant (6.7% of the unvaccinated ones). Hesitancy was higher among women (OR = 1.48; 95%CI: 1.36–1.62); it was highest in the 50–59 and 40–49 age groups and among those with a lower educational level. A higher level of education was associated with a lower proportion of hesitancy (5.54%) compared with 9.44% among respondents with a low level of education (OR = 0.56; 95%CI: 0.46–0.68). Hesitancy was most common in subjects who did not report fear of infection (12.4%, OR = 4.0; 95%CI: 3.46–4.61). The results can guide the design of tailored information and communication campaigns through considering objective and subjective characteristics. [ABSTRACT FROM AUTHOR]

Critically ill COVID-19 patients are at an increased risk of bloodstream infections (BSIs). We performed a retrospective observational single-center study on COVID-19 patients admitted to intensive care unit (ICU) to assess the incidence of BSIs in four consecutive periods: 21 February–31 July 2020 (W1), 1 August 2020–31 January 2021 (W2), 1 February–30 September 2021 (W3) and 1 October 2021 and 30 April 2022 (W4). BSIs that occurred 48 h after ICU admission were included. The crude incidence of BSIs was estimated by means of Poisson distribution normalized to 1000 patient-days. A total of 404 critically ill COVID-19 patients were admitted to ICU, of whom 284 (61%) developed at least one episode of BSI with an overall crude incidence of 87 events every 1000 patient-days (95% CI 77–98) without a significant difference in consecutive epidemic periods (p = 0.357). Gram-positive bacteria were the most frequent etiological agents of BSIs, contributing to 74.6% episodes. A progressive decrease in BSIs due to Enterococcus spp. was observed (W1 57.4%, W2 43.7%, W3 35.7% and W4 32.7%; p = 0.004). The incidence of BSIs remained stable during different epidemic periods. Enterococcus spp. prevalence was significantly reduced, although still accounted for one third of BSIs in more recent epidemic periods. [ABSTRACT FROM AUTHOR]

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59–72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium. [ABSTRACT FROM AUTHOR]

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%. [ABSTRACT FROM AUTHOR]

To assess influenza vaccine uptake during the 2020/2021 flu season and compare it with that of the 2019/2020 flu season among respondents to the second phase of the web-based EPICOVID-19 survey, we performed an observational web-based nationwide online survey (January–February 2021) in which respondents to the first survey (April–June 2020) were contacted and asked to complete a second questionnaire. Factors associated with vaccine uptake in the 2020/2021 flu season were assessed by applying a multivariable multinomial logistic regression model. Out of the 198,822 respondents to the first survey, 41,473 (20.9%) agreed to fill out the follow-up questionnaire; of these, 8339 (20.1%) were vaccinated only during the 2020/2021 season, 8828 (21.3%) were vaccinated during both seasons and 22,710 (54.8%) were vaccinated in neither season. Educational level (medium (aOR 1.33 95%CI 1.13–1.56) and high (aOR 1.69 95%CI 1.44–1.97) vs. low) and socio-economic deprivation according to SES scoring (1 point aOR 0.83 (95%CI 0.78–0.89), 2 aOR 0.68 (95%CI 0.60–0.77) points or ≥3 points aOR 0.42 (95%CI 0.28–0.45) vs. 0 points) were found to be associated with flu vaccine uptake. Our study shows that social determinants seemed to affect flu vaccination uptake and identifies specific categories of the population to target during future influenza vaccination campaigns. [ABSTRACT FROM AUTHOR]

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction. [ABSTRACT FROM AUTHOR]

We aimed to assess the reported rate of flu vaccination in the 2019/2020 season for respondents to the Italian nationwide online EPICOVID 19 survey. A national convenience sample of volunteers aged 18 or older was assessed between 13 April and 2 June 2020. Flu vaccine rates were calculated for all classes of age. The association between the independent variables and the flu vaccine was assessed by applying a multivariable binary logistic regression model. Of the 198,822 respondents, 41,818 (21.0%) reported having received a flu vaccination shot during the last influenza season. In particular, 15,009 (53.4%) subjects aged 65 years or older received a flu vaccination shot. Being 65 years aged or older (Adjusted Odds Ratios (aOR) 3.06, 95% Confidence Interval (CI) 2.92–3.20) and having a high education level (aOR 1.34. 95%CI 1.28–1.41) were independently associated to flu vaccination. Heart and lung diseases were the morbidities associated with the higher odds of being vaccinated (aOR 1.97 (95%CI 1.86–2.09) and aOR 1.92 (95%CI 1.84–2.01), respectively). Nursing home residents aged ≥ 65 years showed lower odds of being vaccinated (aOR 0.39 (95%CI 0.28–0.54)). Our data indicate the need for an urgent public heath effort to fill the gap of missed vaccination opportunities reported in the past flu seasons. [ABSTRACT FROM AUTHOR]

Background: Although studies assessing cardiovascular comorbidities and myocardial injury in Coronavirus disease 2019 (COVID-19) patients have been published, no reports focused on clinical outcomes of myocardial injury in patients with and without chronic coronary syndromes (CCS) are currently available. Methods: In this study, consecutive COVID-19 patients admitted to four different institutions were screened for enrolment. Patients were divided into two groups (CCS vs. no-CCS). Association with in-hospital mortality and related predictors represented the main study outcome; myocardial injury and its predictors were deemed secondary outcomes. Results: A total of 674 COVID-19 patients were enrolled, 112 (16.6%) with an established history of CCS. Myocardial injury occurred in 43.8% patients with CCS vs. 14.4% patients without CCS, as confirmed by high-sensitivity cardiac troponin (hs-cTn) elevation on admission or during hospitalization. The mortality rate in the CCS cohort was nearly three-fold higher. After adjusting for disease severity, myocardial injury resulted significantly associated with in-hospital mortality in the no-CCS group but not in CCS patients. Conclusions: Patients with CCS and COVID-19 showed high mortality rate. Myocardial injury may be a bystander in CCS patients and COVID-19, while in patients without known history of CCS, myocardial injury has a significant role in predicting poor outcomes. [ABSTRACT FROM AUTHOR]

The present study aims to evaluate whether influenza and pneumococcal vaccinations are associated with positive nasopharyngeal swab (NPS) testing to detect SARS-CoV-2. Data from the Italian cross-sectional web-based survey (EPICOVID19), based on a self-selection sample of individuals aged ≥18, were considered. The probability of a positive SARS-CoV-2 NPS test result as a function of influenza or anti-pneumococcal vaccination was evaluated using multivariable logistic regression, stratifying analysis by age (<65 years, ≥65 years). From April 2020, 170,731 individuals aged <65 years and 28,097 ≥65 years filled out the EPICOVID19 questionnaire. Influenza and anti-pneumococcal vaccinations were received, respectively, by 16% and 2% of those <65 years, and by 53% and 13% of those ≥65 years. SARS-CoV-2 NPS testing was reported by 6680 participants. Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS positive test in the younger participants (OR = 0.61, 95% CI 0.41–0.91; OR = 0.85, 95%CI 0.74–0.98; respectively). A significantly lower probability of a positive test result was detected in the individuals ≥65 years who received anti-pneumococcal vaccination (OR = 0.56, 95%CI 0.33–0.95). These results need to be confirmed by further investigations, but they are relevant given the probable coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn–winter season. [ABSTRACT FROM AUTHOR]

Psychological distress imposed by the SARS-CoV-2 outbreak particularly affects patients with pre-existing medical conditions, and the progression of their diseases. Patients who fail to keep scheduled medical appointments experience a negative impact on care. The aim of this study is to investigate the psychosocial factors contributing to the cancellation of medical appointments during the pandemic by patients with pre-existing health conditions. Data were collected in eleven Italian hospitals during the last week of lockdown, and one month later. In order to assess the emotional impact of the SARS-CoV-2 outbreak and the subject's degree of psychological flexibility, we developed an ad hoc questionnaire (ImpACT), referring to the Acceptance and Commitment Therapy (ACT) model. The Impact of Event Scale-Revised (IES-R), the Depression, Anxiety and Stress Scale (DASS) and the Cognitive Fusion Questionnaire (CFQ) were also used. Pervasive dysfunctional use of experiential avoidance behaviours (used with the function to avoid thought, emotions, sensations), feelings of loneliness and high post-traumatic stress scores were found to correlate with the fear of COVID-19, increasing the likelihood of cancelling medical appointments. Responding promptly to the information and psychological needs of patients who cancel medical appointments can have positive effects in terms of psychological and physical health.