Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV.

BACKGROUND: Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence. METHODS: We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models. RESULTS: In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7-39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99-3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99-3.66). Notably, no viro-immunological variable modified the PCCs risk onset. CONCLUSIONS: Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.

Case report: An occult hepatitis B virus infection reactivation in an HIV/HCV coinfected patient during an immune reconstitution inflammatory syndrome.

The natural history of occult hepatitis B virus infection (OBI) and the mechanism involved in HBV reactivation are only partially understood. As regards people living with HIV (PLWH), HBV reactivation is estimated to occur with an incidence ratio of 0.019 cases per 100 person-year. Here we report the case of OBI reactivation in a HIV/HCV co-infected patient followed for 25 years at our Infectious Diseases Unit, but, unfortunately, lost to follow-up about 19 months after Direct-acting antivirals (DAAs) treatment. At re-engagement, blood tests showed high replication of plasmatic HIV-RNA along with severe immunosuppression and normal levels of liver enzymes. However, 3 months after ART reintroduction, an immune reconstitution inflammatory syndrome (IRIS) was diagnosed with high detectable HBV-DNA load and transaminase elevation. Our case report shows how the balance between the virus and the host immune system is quite a dynamic process that might significantly impact the course of the disease. The aim of this case report is to bring to the attention of physicians that, although OBI reactivation is a rather rare occurrence, even amongst PLWH, its potential consequences compel to a high alertness on the matter. Therefore, especially in patients with an impaired immune system and on a tenofovir or lamivudine-sparing regimen, HBV serological and virological markers should always be strictly monitored, even in the absence of a hepatitis flare.

Timing and implications for immune response to vaccine in SARS-CoV-2 breakthrough infections.

COVID-19 vaccines elicit a strong anti-S antibodies response. We aim to describe antibody titers in peri-vaccination SARS-CoV-2 infections. This is a retrospective longitudinal single-cohort study. Serological tests were performed at the time of the first SARS-CoV-2 vaccine dose (T0) and 60 (T1), 120 (T2), and 240 (T3) days after. The study included 4,682 subjects. Group A had the infection without an anti-S Ig response. Group B and C seroconverted for anti-N Ig between T0 and T1 and between T1 and T2, respectively. Group D was persistently anti-N Ig negative. Group B showed an initial sub-optimal response, reaching the highest titer at T3. Those who received the second dose 120 days after the infection had higher titers compared to those who received it 21 days after the first dose. The immune response depends on the number and the timing of vaccine doses, highlighting the need for a more personalized approach to vaccination.

Does the rapid initiation of antiretroviral therapy at HIV diagnosis impact virological response in a real-life setting? A single-centre experience in Northern Italy.

Rapid initiation of antiretroviral therapy (ART) has been proven efficacious and safe, but more investigations are needed to define feasibility of rapid ART approach in real-life settings.We conducted a retrospective, observational study on newly HIVdiagnosed patients referred to our Infectious Diseases Department from September 1st, 2015, to July 31st, 2019. According to the timing of ART initiation, we distinguished 3 groups of patients (rapid, intermediate and late group) and represented the trend of virological response during a 400-days-period. The hazard ratios of each predictor on viral suppression were estimated through the Cox proportional hazard model.The median time from HIV diagnosis to the first medical referral was 15 days and the median time from the first care access to therapy start was 24 days. Among patients, 37.6% started ART within 7 days, 20.6% between 8 and 30 days, and 41.8% after 30 days. Longer time to ART start and higher baseline viral load were associated with a lower probability of viral suppression. After one year, all groups showed a high viral suppression rate (99%). In a high-income setting the rapid ART approach seems useful to accelerate viral suppression which is great over time regardless of ART initiation timing.

Syphilis Infections, Reinfections and Serological Response in a Large Italian Sexually Transmitted Disease Centre: A Monocentric Retrospective Study.

Background: Syphilis infection does not confer definitive and protective immunity against reinfection, and crucial aspects of repeated episodes of syphilis are far from being understood, especially among people living with HIV (PLWH). Methods: In order to explore the burden of syphilis in a large cohort of HIV-negative patients and PLWH, this retrospective study describes the demographics, clinical presentation and treatment outcome of patients with syphilis treated at our clinic from 2013 to 2021. Results: Within the study period, 1859 syphilis episodes (827, 44.5% first infections and 1032, 55.5% reinfections) were recorded. A total of 663 patients, of whom 347 (52%) had PLWH, were considered. Syphilis was mostly diagnosed in males (77%) and European (79%) patients. More than half of syphilis episodes were recorded during the late latent stage (64%) or during follow-up/screening visits for other diseases, while symptomatic stages led to a diagnosis in almost half of HIV-negative patients (p < 0.001). PLWH with syphilis infection were predominantly homo/bisexual (p < 0.001). A significantly higher rate of syphilis reinfection was observed in PLWH, who also demonstrated a higher range of subsequent episodes. The serofast state was found to be similar at the 6- and 12-month follow-up visits. The multivariate analysis carried out in the HIV-positive group showed that an RPR titre >1:16 was an independent predictor for serological non-response. Conclusions: Syphilis reinfections are predominantly diagnosed in HIV-positive MSM. The high rate of asymptomatic presentation among PLWH supports the role of periodical syphilis screening. In PLWH, the only baseline factor associated with an increased risk of non-response was an RPR titre >1:16, while assessment at 12 months after treatment increased the possibility of detecting a serological response, indicating that PLWH have a slower serological response to treatment.

Monkeypox, a Literature Review: What Is New and Where Does This concerning Virus Come From?

Among the Poxviridae family, orthopoxvirus is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus (VACV). These orthopoxviruses still remain a public health concern as VACV or CPXV still cause emerging endemic threads, especially in developing countries. MPXV is able to cause sporadic human outbreaks of a smallpox-like zoonotic disease and, in May 2022, hundreds of cases related to MPXV have been reported from more than 30 countries around the globe. At the end of July, monkeypox (MPX) outbreak was even declared a global health emergency by the World Health Organization (WHO). Many aspects remain unclear regarding this outbreak and a deep understanding of orthopoxvirus might have crucial and evident implications. During the era in which people under 45 years old are not protected against VACV, the potential use of orthopoxviruses as a biological weapon raises global concern considering the rapid spreading of the current MPX outbreak in vulnerable populations. Hence, we review the most recent evidence about phylogenesis, pathogenesis, prevention, and treatment for this concerning disease.

Omicron BA.2 Lineage, the "Stealth" Variant: Is It Truly a Silent Epidemic? A Literature Review.

The epidemic curve of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is silently rising again. Worldwide, the dominant SARS-CoV-2 variant of concern (VOC) is Omicron, and its virological characteristics, such as transmissibility, pathogenicity, and resistance to both vaccine- and infection-induced immunity as well as antiviral drugs, are an urgent public health concern. The Omicron variant has five major sub-lineages; as of February 2022, the BA.2 lineage has been detected in several European and Asian countries, becoming the predominant variant and the real antagonist of the ongoing surge. Hence, although global attention is currently focused on dramatic, historically significant events and the multi-country monkeypox outbreak, this new epidemic is unlikely to fade away in silence. Many aspects of this lineage are still unclear and controversial, but its apparent replication advantage and higher transmissibility, as well as its ability to escape neutralizing antibodies induced by vaccination and previous infection, are rising global concerns. Herein, we review the latest publications and the most recent available literature on the BA.2 lineage of the Omicron variant.

Explorative study regarding influenza vaccine hesitancy among HIV-infected patients.

There are scarce data regarding influenza vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the COVID-19 pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects' adherence to influenza vaccine over the last three seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to become vaccinated. The population was divided into two groups: fully adherent to influenza vaccine (all three campaigns, 117 patients) and non-fully adherent (one or two campaigns, 102 patients). Adherence increased in the non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbeliefs emerged: the influenza vaccine was considered protective against SARS-CoV-2 (22.8% of the total population); almost half of all patients thought the influenza vaccine could improve their CD4 T cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p < .05). In 2020-2021 campaign, three quarters of the non-fully adherent group would not have been vaccinated in a location other than our clinic (75.5% vs. 88.9% in the fully adherent group, p < .05). Conclusively, offering a secure and private space for vaccination against influenza seems to encourage vaccination; healthcare professionals should improve counseling to increase adherence and correct misbeliefs.

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review.

The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.

Gram-Negative Endogenous Endophthalmitis: A Systematic Review.

Background: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk factors, and early ocular lesions in cases of Gram-negative EBE. Methods: All peer-reviewed articles between January 2002 and August 2022 regarding Gram-negative EBE were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. Results: A total of 115 studies and 591 patients were included, prevalently Asian (98; 81.7%) and male (302; 62.9%). The most common comorbidity was diabetes (231; 55%). The main aetiologies were Klebsiella pneumoniae (510; 66.1%), Pseudomonas aeruginosa (111; 14.4%), and Escherichia coli (60; 7.8%). Liver abscesses (266; 54.5%) were the predominant source of infection. The most frequent ocular lesions were vitreal opacity (134; 49.6%) and hypopyon (95; 35.2%). Ceftriaxone (76; 30.9%), fluoroquinolones (14; 14.4%), and ceftazidime (213; 78.0%) were the most widely used as systemic, topical, and intravitreal anti-Gram-negative agents, respectively. The most reported surgical approaches were vitrectomy (130; 24.1%) and evisceration/exenteration (60; 11.1%). Frequently, visual acuity at discharge was no light perception (301; 55.2%). Conclusions: Gram-negative EBEs are associated with poor outcomes. Our systematic review is mainly based on case reports and case series with significant heterogeneity. The main strength is the large sample spanning over 20 years. Our findings underscore the importance of considering ocular involvement in Gram-negative infections.

Monoclonal Antibodies against SARS-CoV-2: Current Scenario and Future Perspectives.

Monoclonal antibodies (mAbs) have been known since the 1970s. However, their therapeutic potential in the medical field has recently emerged, with the advancement of manufacturing techniques. Initially exploited mainly in the oncology field, mAbs have become increasingly relevant in Infectious Diseases. Numerous mAbs have been developed against SARS-CoV 2 and have proven their effectiveness, especially in the management of the mild-to-moderate disease. In this review, we describe the monoclonal antibodies currently authorized for the treatment of the coronavirus disease 19 (COVID-19) and offer an insight into the clinical trials that led to their approval. We discuss the mechanisms of action and methods of administration as well as the prophylactic and therapeutic labelled indications (both in outpatient and hospital settings). Furthermore, we address the critical issues regarding mAbs, focusing on their effectiveness against the variants of concern (VoC) and their role now that a large part of the population has been vaccinated. The purpose is to offer the clinician an up-to-date overview of a therapeutic tool that could prove decisive in treating patients at high risk of progression to severe disease.

A 2021 Update on Syphilis: Taking Stock from Pathogenesis to Vaccines.

In 2021 the scientific community's efforts have been focused on solving the back-breaking challenge of the COVID-19 pandemic, but sexually transmitted infections (STI) are still one of the most common global health problems. Syphilis is a systemic disease caused by the spirochaete Treponema pallidum (TP) and is one of the oldest known diseases. Its incidence has increased in the last few years and syphilis still remains a contemporary plague that continues to afflict millions of people worldwide. Despite research improvements, syphilis pathogenesis is not completely clear; clinical presentation is very heterogeneous and the diagnosis can sometimes be difficult. Furthermore, few therapeutic options are available, and a vaccine has not been found yet. In this review, we describe the most recent evidence concerning the clinical manifestation, diagnosis, treatment and vaccine prospectives for this disease.

Decrease in new diagnosis of HIV/AIDS in the two years period 2019-2020: impact of COVID-19 pandemic.

The emergence SARS-CoV-2 in late 2019 and early 2020 has caused a pandemic of unprecedented proportions. Management of COVID-19 became emergent public health priorities, and the impact on other public health initiatives, such as expanded HIV screening and linkage to care, remain largely unknown. In this Single-Center retrospective observational study, we describe the characteristics and circumstance of the new HIV cases during 2020 compared to 2019. We observed a decrease of HIV diagnosis during this period. Interestingly, median age at HIV diagnosis decreased of one decade and percentage of female patients was higher. In addition, more patients received diagnosis during hospitalization and more AIDS-defining conditions, such as Pneumocystis pneumonia, were detected. We express our concern that HIV new diagnoses will increase as a result of people's inability to get tested or treated in this period. More efforts are needed to improve local screening programs both during and after COVID-19 pandemic.

Pneumocystis jirovecii pneumonia in breast cancer mimicking SARS-CoV-2 pneumonia during pandemic.

Pneumocystis jirovecii pneumonia (PJP) is one of the most common HIV-related opportunistic infection. Apart from HIV patients, subjects treated with an associated therapy of high doses glucocorticoids and immunosuppressive drugs should be considered at risk. SARS-CoV-2 has become worldly known as the responsible of the pandemic that hit the world in late 2019 and that is still ongoing. Italy, and especially Brescia, was one of the area most struck by the pandemic, with a significant number of cases being reported (more than 112,648 as of October 2021). The diagnosis of SARS-CoV-2 is mainly based on RT-PCR assays performed on nasopharyngeal swab, X-ray of the chest and clinical manifestations. We describe two cases of PJP in two immunocompromised patients with breast cancer who were admitted at Spedali Civili of Brescia hospital, Italy, with an initial diagnosis of SARS-CoV-2 pneumonia, despite testing negative to RT-PCR on nasopharyngeal swabs. We also retrospectively reassessed all cases of pneumonia deemed as SARS-CoV-2-related upon admission and then converted to PJP as the final diagnosis. We describe the two following cases to emphasize that clinicians should always be alert about PJP, even during the SARS-CoV-2 pandemic, and avoid focusing on COVID-19 exclusively. PJP should always be considered as a differential diagnosis in patients, particularly if immunosuppressed, with an X-ray or TC of the chest suggestive of interstitial pneumonia and a negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs.