Implementing a provisional overarching intervention for COVID-19 monitoring and control in the Brazil-Colombia-Peru frontier.

Introduction: he challenge was to provide comprehensive health resources to a remote and underserved population living in the Brazil-Colombia-Peru border, amid the most disruptive global crisis of the century. Methods: In August 2021, Fundação Oswaldo Cruz Amazonia (FIOCRUZ Amazônia) and partner collaborators implemented an overarching provisional program for SARS-CoV-2 detection and lineages characterization, training of laboratory personnel and healthcare providers, donation of diagnostic supplies and personal protective equipment, and COVID-19 vaccination. The expedition was conducted at the Port of Tabatinga, a busy terminal with an intense flux of people arriving and departing in boats of all sizes, located in the Amazon River basin. Local government, non-profit organizations, private companies, and other stakeholders supported the intervention. Results: The expedition was accomplished in a convergence point, where migrant workers, traders, army personnel, people living in urban areas, and people from small villages living in riversides and indigenous territories are in close and frequent contact, with widespread cross-border movement. Using a boat as a provisional lab and storage facility, the intervention provided clinical and laboratory monitoring for 891 participants; vaccination for 536 individuals; personal protective equipment for 200 healthcare providers; diagnostic supplies for 1,000 COVID-19 rapid tests; training for 42 community health agents on personal protection, rapid test execution, and pulse oximeter management; and hands-on training for four lab technicians on molecular diagnosis. Discussion: Our experience demonstrates that multilateral initiatives can counterweigh the scarcity of health resources in underserved regions. Moreover, provisional programs can have a long-lasting effect if investments are also provided for local capacity building.

Emergence and Spread of the SARS-CoV-2 Variant of Concern Delta across Different Brazilian Regions.

The SARS-CoV-2 variant of concern (VOC) Delta was first detected in India in October 2020. The first imported cases of the Delta variant in Brazil were identified in April 2021 in the southern region, followed by more cases in different regions during the following months. By early September 2021, Delta was already the dominant variant in the southeastern (87%), southern (73%), and northeastern (52%) Brazilian regions. This study aimed to understand the spatiotemporal dissemination dynamics of Delta in Brazil. To this end, we employed a combination of maximum likelihood (ML) and Bayesian methods to reconstruct the evolutionary relationship of 2,264 VOC Delta complete genomes (482 from this study) recovered across 21 of the 27 Brazilian federal units. Our phylogeographic analyses identified three major transmission clusters of Delta in Brazil. The clade BR-I (n = 1,560) arose in Rio de Janeiro in late April 2021 and was the major cluster behind the dissemination of the VOC Delta in the southeastern, northeastern, northern, and central-western regions. The AY.101 lineage (n = 207) that arose in the Paraná state in late April 2021 and aggregated the largest fraction of sampled genomes from the southern region. Lastly, the AY.46.3 lineage emerged in Brazil in the São Paulo state in early June 2021 and remained mostly restricted to this state. In the rapid turnover of viral variants characteristic of the SARS-CoV-2 pandemic, Brazilian regions seem to occupy different stages of an increasing prevalence of the VOC Delta in their epidemic profiles. This process demands continuous genomic and epidemiological surveillance toward identifying and mitigating new introductions, limiting their dissemination, and preventing the establishment of more significant outbreaks in a population already heavily affected by the COVID-19 pandemic. IMPORTANCE Amid the SARS-CoV-2 continuously changing epidemic profile, this study details the space-time dynamics of the emergence of the Delta lineage across Brazilian territories, pointing out its multiple introductions in the country and its most prevalent sublineages. Some of these sublineages have their emergence, alongside their genomic composition and geographic distribution, detailed here for the first time. A special focus is given to the emergence process of Delta outside the country's south and southeast regions, the most populated and subjects of most published SARS-CoV-2 studies in Brazil. In summary, the study allows a better comprehension of the evolution process of a SARS-CoV-2 lineage that would be associated with a significant recrudescence of the pandemic in Brazil.

Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial.

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days. Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical-radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit. Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission. Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis. Trial Registration: ClinicalTrials.gov, Identifier: NCT04343729.

Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the United Kingdom. Here we study the ability of monoclonal antibodies and convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2, complement this with structural analyses of Fab/receptor binding domain (RBD) complexes, and map the antigenic space of current variants. Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2, suggesting that individuals infected previously by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insights for immunization policy with future variant vaccines in non-immune populations.

High Prevalence and Onward Transmission of Non-Pandemic HIV-1 Subtype B Clades in Northern and Northeastern Brazilian Regions.

The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (BPANDEMIC), while Caribbean non-pandemic subtype B clades (BCAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 BPANDEMIC and BCAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian BCAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the BCAR strains reached 16 out 21 Brazilian states here analyzed. The BCAR clades comprise a low fraction (<10%) of subtype B infections in most Brazilian states analyzed, with exception of Roraima (41%), Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that BCAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of BCAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region.

Etiology of genital ulcer disease in a sexually transmitted infection reference center in Manaus, Brazilian Amazon.

OBJECTIVES: To determine the etiology and factors associated with genital ulcer disease (GUD) among patients presenting to a sexually transmitted infections clinic in Manaus, Brazil; and to compare a multiplex polymerase chain reaction (M-PCR) assay for the diagnosis of GUD with standard methods. METHODS: Ulcer swabs were collected and used for Tzanck test and processed in an M-PCR to detect herpes simplex virus (HSV-1/2), Treponema pallidum (T. pallidum), and Haemophilus ducreyi (H. ducreyi). Sera were tested for HIV and syphilis antibodies. Multivariable analysis was used to measure the association between clinical aspects and GUD. M-PCR results were compared with syphilis serology and Tzanck tests. RESULTS: Overall, 434 GUD samples were evaluated, 84.8% from men. DNA from HSV-2 was detected in 55.3% of GUD samples, T. pallidum in 8.3%, HSV-1 in 3.2%, and 32.5% of GUD specimens were negative for the DNA of all three pathogens. No cases of H. ducreyi were identified. HIV serology among GUD patients was 3.2%. Treponemal antibodies and Tzanck test positivity for genital herpes was detected in 25 (5.8%) and in 125 (30.3%) of GUD patients, respectively. In multivariable analysis genital herpes etiology by M-PCR was associated with the vesicular, multiple and recurrent lesions whereas T. pallidum with non-vesicular, non-recurrent lesions. Compared to M-PCR, syphilis serology was 27.8% sensitive and 96.2% specific whereas Tzanck test was 43.8% sensitive and 88.9% specific. CONCLUSIONS: The predominance of genital herpes etiology suggests a revision of existing national syndromic treatment guidelines in Brazil to include antiherpetic treatment for all GUD patients. The use of M-PCR can significantly improve the diagnosis of GUD and provide a greater sensitivity than standard diagnostics.

Decreased RNA expression of interleukin 17A in skin of leprosy.

Interleukin-17A (IL-17A) is a proinflamatory cytokine that plays an important role in fighting pathogens at mucosal interfaces, by summoning neutrophils and upregulating cytoplasmatic antimicrobial peptides. So far, the presence of IL-17A in leprosy has not been demonstrated. The expression of IL-17A and related cytokines (IL-6 and IL-23p19) was addressed through RNA extraction and cDNA quantitative amplification in macerated biopsies of active lesions of 48 leprosy patients and 20 fragments of normal skin of individuals. Blood levels of IL-17A, IL-23p19 and IL-6 were determined by ELISA. We found an abrogated mRNA IL-17A response in all biopsies of leprosy patients, as compared with controls. Circulating IL-17A and IL-23p19 were undetectable in both patients and controls, but IL-6 was higher in lepromatous patients. Although at low levels, IL-17A mRNA in lepromatous patients had an inverse linear correlation with bacillary burden. Low expression of IL-17A in patients may be a constitutive genetic feature of leprosy patients or a circumstantial event induced by the local presence of the pathogen, as an escape mechanism.