Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.

Clinical features, etiologies, and outcomes of central nervous system infections in intensive care: A multicentric retrospective study in a large Brazilian metropolitan area.

PURPOSE: The goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates. MATERIALS AND METHODS: We conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality. RESULTS: In a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5-25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27-53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression. CONCLUSIONS: Patients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies.

Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case.

BACKGROUND: According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. OBJECTIVE: To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. METHODS: We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). FINDINGS: We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. MAIN CONCLUSIONS: Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.

Evaluation of Mpox Knowledge, Stigma, and Willingness to Vaccinate for Mpox: Cross-Sectional Web-Based Survey Among Sexual and Gender Minorities.

BACKGROUND: The 2022 multicountry mpox outbreak positioned the condition as a public health emergency of international concern. By May 2023, Brazil ranked second globally in the cumulative number of mpox cases and deaths. The higher incidence of mpox among gay and other men who have sex with men in the current mpox outbreak deepens the stigma and discrimination against sexual and gender minorities (SGM). This might worsen the structural barriers impacting access to health services, which ultimately leads to undertesting and underreporting of cases. There are no data available on mpox knowledge and stigma in Latin America. OBJECTIVE: We aimed to evaluate mpox knowledge, stigma, and willingness to vaccinate for mpox among SGM, and to describe sociodemographic and behavioral characteristics according to self-reported mpox diagnosis. METHODS: A cross-sectional, internet-based survey was conducted in a convenience sample of adults (aged >18 years) living in Brazil recruited through advertisements on dating apps, social media, referral institutions for infectious diseases websites, and mass media (October-November 2022). We compared participants' characteristics according to self-reported mpox diagnosis using chi-square test or Fisher exact test for qualitative variables and Kruskal-Wallis test for quantitative variables. RESULTS: We enrolled 6236 participants: 5685 (91.2%) were cisgender men; 6032 (96.7%) were gay, bisexual, or pansexual; 3877 (62.2%) were White; 4902 (78.7%) had tertiary education; and 4070 (65.2%) reported low or middle income. Most participants (n=5258, 84.4%) agreed or strongly agreed that "LGBTQIA+ individuals are being discriminated and stigmatized due to mpox." Mpox awareness was 96.9% (n=6044), and 5008 (95.1%) were willing to get vaccinated for mpox. Overall, 324 (5.2%) reported an mpox diagnosis. Among these, 318 (98.1%) reported lesions, 178 (56%) local pain, and 316 (99.4%) sought health care. Among participants not reporting a diagnosis, 288 (4.9%) had a suspicious lesion, but only 158 (54.9%) of these had sought health care. Compared to participants with no diagnosis, those reporting an mpox diagnosis were younger (P<.001), reported more sex partners (P<.001), and changes in sexual behavior after mpox onset (P=.002). Moreover, participants diagnosed with mpox reported more frequently being tested for HIV in the prior 3 months (P<.001), living with HIV (P<.001), currently using HIV pre-exposure prophylaxis (P<.001), and previous sexually transmitted infection diagnosis (P<.001). CONCLUSIONS: Our results point to high mpox knowledge and willingness to vaccinate among SGM in Brazil. Participants self-reporting mpox diagnosis more frequently reported to be living with HIV, STI diagnosis, and current pre-exposure prophylaxis use, highlighting the importance of an mpox assessment that includes comprehensive sexual health screenings. Efforts to decrease stigma related to mpox among SGM are necessary to avoid mpox underdiagnosis.

Clinical Presentation of Parvovirus B19 Infection in Adults Living with HIV/AIDS: A Case Series.

Parvovirus B19 (B19V) infection varies clinically depending on the host's immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults living with human immunodeficiency virus (HIV) with B19V infection. All cases presented severe anemia and required red blood cell transfusions. The first patient had low CD4+ counts and was treated with intravenous immunoglobulin (IVIG). As he remained poorly adherent to antiretroviral therapy (ART), B19V detection persisted. The second patient had sudden pancytopenia despite being on ART with an undetectable HIV viral load. He had historically low CD4+ counts, fully responded to IVIG, and had undiagnosed hereditary spherocytosis. The third individual was recently diagnosed with HIV and tuberculosis (TB). One month after ART initiation, he was hospitalized with anemia aggravation and cholestatic hepatitis. An analysis of his serum revealed B19V DNA and anti-B19V IgG, corroborating bone marrow findings and a persistent B19V infection. The symptoms resolved and B19V became undetectable. In all cases, real time PCR was essential for diagnosing B19V. Our findings showed that adherence to ART was crucial to B19V clearance in HIV-patients and highlighted the importance of the early recognition of B19V disease in unexplained cytopenias.

Ambulatory and hospitalized patients with suspected and confirmed mpox: an observational cohort study from Brazil.

Background: By October 30, 2022, 76,871 cases of mpox were reported worldwide, with 20,614 cases in Latin America. This study reports characteristics of a case series of suspected and confirmed mpox cases at a referral infectious diseases center in Rio de Janeiro, Brazil. Methods: This was a single-center, prospective, observational cohort study that enrolled all patients with suspected mpox between June 12 and August 19, 2022. Mpox was confirmed by a PCR test. We compared characteristics of confirmed and non-confirmed cases, and among confirmed cases according to HIV status using distribution tests. Kernel estimation was used for exploratory spatial analysis. Findings: Of 342 individuals with suspected mpox, 208 (60.8%) were confirmed cases. Compared to non-confirmed cases, confirmed cases were more frequent among individuals aged 30-39 years, cisgender men (96.2% vs. 66.4%; p < 0.0001), reporting recent sexual intercourse (95.0% vs. 69.4%; p < 0.0001) and using PrEP (31.6% vs. 10.1%; p < 0.0001). HIV (53.2% vs. 20.2%; p < 0.0001), HCV (9.8% vs. 1.1%; p = 0.0046), syphilis (21.2% vs. 16.3%; p = 0.43) and other STIs (33.0% vs. 21.6%; p = 0.042) were more frequent among confirmed mpox cases. Confirmed cases presented more genital (77.3% vs. 39.8%; p < 0.0001) and anal lesions (33.1% vs. 11.5%; p < 0.0001), proctitis (37.1% vs. 13.3%; p < 0.0001) and systemic signs and symptoms (83.2% vs. 64.5%; p = 0.0003) than non-confirmed cases. Compared to confirmed mpox HIV-negative, HIV-positive individuals were older, had more HCV coinfection (15.2% vs. 3.7%; p = 0.011), anal lesions (45.7% vs. 20.5%; p < 0.001) and clinical features of proctitis (45.2% vs. 29.3%; p = 0.058). Interpretation: Mpox transmission in Rio de Janeiro, Brazil, rapidly evolved into a local epidemic, with sexual contact playing a crucial role in its dynamics and high rates of coinfections with other STI. Preventive measures must address stigma and social vulnerabilities. Funding: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz).

The first case of acute HIV and monkeypox coinfection in Latin America.

Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenital lesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.

Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case

BACKGROUND According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. OBJECTIVE To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. METHODS We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). FINDINGS We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. MAIN CONCLUSIONS Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.

The first case of acute HIV and monkeypox coinfection in Latin America

ABSTRACT Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenitallesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.