The 2022 mpox virus outbreak was sustained by efficient human-to-human transmission and spread predominantly through sexual networks of men who have sex with men (MSM). It is currently unclear what combination of factors resulted in the enhanced transmission. To investigate this, we established the peridomestic African rodent Mastomys natalensis as a new rodent model susceptible to infection after intraperitoneal, rectal, vaginal, and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Route-dependent shedding and tissue replication occurred in the presence of self-resolving localized skin, reproductive tract, or rectal lesions. Mucosal inoculation via both the rectal and vaginal route led to increased shedding compared to skin inoculation, and increased replication and a proinflammatory T-cell profile. Contact transmission was higher in rectally inoculated animals. This suggests that the spread in MSM communities may have been enhanced by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.

/pdf/rectal-and-vaginal-challenge-with-mpox-virus-increases-virus-2x9h7tmw.pdf

Rectal and vaginal challenge with mpox virus increases virus dissemination and contact transmission compared to skin challenge in the multimammate rat (Mastomys natalensis)

To investigate seasonality, epidemiologic characteristics, and clinical severity variations of respiratory syncytial virus (RSV)-associated hospitalizations following the easing of COVID-19 restrictions in Tuscany, Italy, up to the 2022-2023 season. 

Seasonality and severity of respiratory syncytial virus during the COVID-19 pandemic: a dynamic cohort study

The monkeypox virus (MPXV) has caused an unusual epidemiological scenario—an epidemic within a pandemic (COVID-19). Despite the inherent evolutionary and adaptive capacity of poxviruses, one of the potential triggers for the emergence of this epidemic was the change in the status of orthopoxvirus vaccination and eradication programs. This epidemic outbreak of HMPX spread worldwide, with a notable frequency in Europe, North America, and South America. Due to these particularities, the objective of the present study was to assess and compare cases of HMPX in these geographical regions through logistic and Gompertz mathematical modeling over one year since its inception. We estimated the highest contagion rates (people per day) of 690, 230, 278, and 206 for the world, Europe, North America, and South America, respectively, in the logistic model. The equivalent values for the Gompertz model were 696, 268, 308, and 202 for the highest contagion rates. The Kruskal–Wallis Test indicated different means among the geographical regions affected by HMPX regarding case velocity, and the Wilcoxon pairwise test indicated the absence of significant differences between the case velocity means between Europe and South America. The coefficient of determination (R2) values in the logistic model varied from 0.8720 to 0.9023, and in the Gompertz model, they ranged from 0.9881 to 0.9988, indicating a better fit to the actual data when using the Gompertz model. The estimated basic reproduction numbers (R0) were more consistent in the logistic model, varying from 1.71 to 1.94 in the graphical method and from 1.75 to 1.95 in the analytical method. The comparative assessment of these mathematical modeling approaches permitted the establishment of the Gompertz model as the better-fitting model for the data and the logistic model for the R0. However, both models successfully represented the actual HMPX case data. The present study estimated relevant epidemiological data to understand better the geographic similarities and differences in the dynamics of HMPX.

Comparative Epidemiological Assessment of Monkeypox Infections on a Global and Continental Scale Using Logistic and Gompertz Mathematical Models

Multiple sclerosis (MS) is a debilitating neurological disease that has been classified as an immune-mediated attack on myelin, the protective sheath of nerves. Some aspects of its pathogenesis are still unclear; nevertheless, it is generally established that viral infections influence the course of the disease. Cytomegalovirus (CMV) is a major pathogen involved in alterations of the immune system, including the expansion of highly differentiated cytotoxic CD8+ T cells and the accumulation of adaptive natural killer (NK) cells expressing high levels of the NKG2C receptor. In this study, we evaluated the impact of latent CMV infection on MS patients through the characterization of peripheral NK cells, CD8+ T cells, and NKT-like cells using flow cytometry. We evaluated the associations between immune cell profiles and clinical features such as MS duration and MS progression, evaluated using the Expanded Disability Status Scale (EDSS). We showed that NK cells, CD8+ T cells, and NKT-like cells had an altered phenotype in CMV-infected MS patients and displayed high levels of the NKG2C receptor. Moreover, in MS patients, increased NKG2C expression levels were found to be associated with higher EDSS scores. Overall, these results support the hypothesis that CMV infection imprints the immune system by modifying the phenotype and receptor repertoire of NK and CD8+ T cells, suggesting a detrimental role of CMV on MS progression. 

The Impact of Cytomegalovirus Infection on Natural Killer and CD8+ T Cell Phenotype in Multiple Sclerosis

Background: We aimed to identify the risk factors for impaired cellular and humoral immunity after three doses of the SARS-CoV-2 vaccine. Methods: Six months after the third vaccine dose, T-cell immunity was evaluated using interferon-gamma release assays (IGRAs) in 60 healthy and 139 immunocompromised (IC) individuals, including patients with hematologic malignancy (HM), solid malignancy (SM), rheumatic disease (RD), and kidney transplantation (KT). Neutralizing antibody titers were measured using the plaque reduction neutralization test (PRNT) and surrogate virus neutralization test (sVNT). Results: T-cell immunity results showed that the percentages of IGRA-positive results using wild-type/alpha spike protein (SP) and beta/gamma SP were 85% (51/60) and 75% (45/60), respectively, in healthy individuals and 45.6% (62/136) and 40.4% (55/136), respectively, in IC individuals. IC with SM or KT showed a high percentage of IGRA-negative results. The underlying disease poses a risk for impaired cellular immune response to wild-type SP. The risk was low when all doses were administered as mRNA vaccines. The risk factors for an impaired cellular immune response to beta/gamma SP were underlying disease and monocyte%. In the sVNT using wild-type SP, 12 of 191 (6.3%) individuals tested negative. In the PRNT of 46 random samples, 6 (13%) individuals tested negative for the wild-type virus, and 19 (41.3%) tested negative with omicrons. KT poses a risk for an impaired humoral immune response. Conclusions: Underlying disease poses a risk for impaired cellular immune response after the third dose of the SARS-CoV-2 vaccine; KT poses a risk for impaired humoral immune response, emphasizing the requirement of precautions in patients. 

Risk Factors for Impaired Cellular or Humoral Immunity after Three Doses of SARS-CoV-2 Vaccine in Healthy and Immunocompromised Individuals

Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an increased risk of developing severe COVID-19 compared to the general population. We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled. Binding and neutralizing antibody (Ab) titers were evaluated using chemiluminescence immunoassay (CLIA) and Plaque Reduction Neutralization Test (PRNT) respectively. T-cell response was analyzed using multiparametric flow cytometry. CPs who were administered three vaccine doses showed lower Ab titers than CPs with four doses and HDs. Overall, a lower cell-mediated response was found in CPs, with a predominance of monofunctional T-cells producing TNFα. Lower Ab titers and a weaker T-cell response were observed in CPs without prior SARS-CoV-2 infection when compared to those with a previous infection. While no differences in the humoral response were found comparing immunotherapy and non-immunotherapy patients, a stronger T-cell response in CPs treated with immunotherapy was observed. Our results emphasize the need of booster doses in cancer patients to achieve a level of protection similar to that observed in healthy donors and underlines the importance of considering the treatment received to reach a proper immune response. 

COVID-19 vaccination in cancer patients: Immune responses one year after the third dose.

Abstract In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, the nasopharynx, and the rectum, underlying generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At this early stage, an increase of cytotoxic and activated T cells was observed, while a reduction in CD56dimCD57+ NK cells compared with recovery time point was observed.

/pdf/longitudinal-virological-and-immunological-profile-in-a-case-37f7gqgt.pdf

Longitudinal Virological and Immunological Profile in a Case of Human Monkeypox Infection

Archived HIV-1 Drug Resistance Mutations: Role of Proviral HIV-1 DNA Genotype for the Management of Virological Responder People Living with HIV

Following the pandemic restrictions, the epidemiology of respiratory syncytial virus (RSV) has changed, leading to intense hospitalization peaks. This study, conducted at multiple sites in Italy, aimed to describe the temporal dynamics of two post-COVID-19 RSV epidemics. Additionally, the circulating RSV-A and -B lineages were characterized and compared to those found in 2018 and 2019. Respiratory specimens and data were collected from RSV-positive patients, both inpatients, and outpatients, of all ages at three sites in north-central Italy. To analyze these samples, roughly one-sixth were sequenced in the attachment glycoprotein G gene and subjected to phylogenetic and mutational analyses, including pre-pandemic sequences from north-central Italy. The first post-pandemic surge of RSV cases was quite intense, occurring from October 2021 to early January 2022. The subsequent RSV epidemic (from November 2022 to early March 2023) also had a high impact, characterized by a rise in elderly patient cases. Post-pandemic cases of RSV-A were caused by various strains present in Italy prior to COVID-19. In contrast, a distinct RSV-B lineage, which was concurrently spreading in other countries, was identified as the main cause of the surge in 2022–2023 but remained undetected in Italy before the pandemic. This study describes the temporal dynamics of post-pandemic RSV subgroups and uncovers a lineage of RSV-B with high genetic divergence that may have increased the impact of decreased population immunity. 

Sequence analysis of respiratory syncytial virus cases reveals a novel subgroup -B strain circulating in north-central Italy after pandemic restrictions.

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COVID-19 vaccination in cancer patients: Immune responses one year after the third dose.

Longitudinal Virological and Immunological Profile in a Case of Human Monkeypox Infection

Archived HIV-1 Drug Resistance Mutations: Role of Proviral HIV-1 DNA Genotype for the Management of Virological Responder People Living with HIV

Sequence analysis of respiratory syncytial virus cases reveals a novel subgroup -B strain circulating in north-central Italy after pandemic restrictions.