Associations of SARS-CoV-2 cycle threshold values with age, gender, sample collection setting, and pandemic period

Cycle threshold (Ct) values in COVID-19 reverse-transcription polymerase chain reaction (RT-PCR) tests estimate the viral load in biological samples. Studies have investigated variables associated with SARS-CoV-2 viral load, aiming to identify factors associated with higher transmissibility. Using the results from tests performed between May/2020-July/2022 obtained from the database of a referent hospital in Sao Paulo, Brazil, we investigated associations between Ct values and patient’s age, gender, sample collection setting and pandemic period according to the predominant SARS-CoV-2 variant locally. We also examined variations in Ct values, COVID-19 incidence, mortality, and vaccination coverage over time. The study sample included 42,741 tests. Gender was not significantly associated with Ct values. Age, sample collection setting and the pandemic period were significantly associated with Ct values even after adjustment to the multivariable model. Results showed lower Ct values in older groups, during the Gamma and Delta periods, and in samples collected in emergency units; and higher Ct values in children under 10 years old, home-based tests, during the Omicron period. We found evidence of a linear trend in the association between age and Ct values, with Ct values decreasing as age increases. We found no clear temporal associations between Ct values and local indicators of COVID-19 incidence, mortality, or vaccination between February/2020-November/2022. Our findings suggest that SARS-CoV-2 Ct values, a proxy for viral load and transmissibility, can be influenced by demographic and epidemiological variables

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections

Prediction of intensive care admission and hospital mortality in COVID-19 patients using demographics and baseline laboratory data

Introduction: Optimized allocation of medical resources to patients with COVID-19 has been a critical concern since the onset of the pandemic. Methods: In this retrospective cohort study, the authors used data from a Brazilian tertiary university hospital to explore predictors of Intensive Care Unit (ICU) admission and hospital mortality in patients admitted for COVID-19. Our primary aim was to create and validate prediction scores for use in hospitals and emergency departments to aid clinical decisions and resource allocation. Results: The study cohort included 3,022 participants, of whom 2,485 were admitted to the ICU; 1968 survived, and 1054 died in the hospital. From the complete cohort, 1,496 patients were randomly assigned to the derivation sample and 1,526 to the validation sample. The final scores included age, comorbidities, and baseline laboratory data. The areas under the receiver operating characteristic curves were very similar for the derivation and validation samples. Scores for ICU admission had a 75% accuracy in the validation sample, whereas scores for death had a 77% accuracy in the validation sample. The authors found that including baseline flu-like symptoms in the scores added no significant benefit to their accuracy. Furthermore, our scores were more accurate than the previously published NEWS-2 and 4C Mortality Scores. Discussion and conclusions: The authors developed and validated prognostic scores that use readily available clinical and laboratory information to predict ICU admission and mortality in COVID-19. These scores can become valuable tools to support clinical decisions and improve the allocation of limited health resources

Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW).

We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35-1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24-5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09-4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09-1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities

The pervasive association between political ideology and COVID-19 vaccine uptake in Brazil: an ecologic study

Abstract Background Despite the unequivocal benefits of vaccination, vaccine coverage has been falling in several countries in the past few years. Studies suggest that vaccine hesitancy is an increasingly significant phenomenon affecting adherence to vaccines. More recently, during the COVID-19 pandemic, political views have emerged as an additional influencing factor for vaccine hesitancy. Methods In this ecologic study, we used information from publicly available databases to investigate the association between political ideology, depicted by the percentage of votes for the right-wing candidate Jair Bolsonaro in the presidential elections of 2018 and 2022, and COVID-19 vaccination in Brazilian municipalities. The primary endpoint was the COVID-19 vaccination index, calculated as the number of COVID-19 vaccine doses administered up to September 2022 divided by the number of inhabitants in each municipality. The analysis was conducted using Pearson correlation coefficients and linear regression models adjusted for HDI, the percentage of male voters, the percentage of voters who were older than 50 years old, and the percentage of voters with a middle school education or less. In addition, we explored whether the effect of the percentage of Bolsonaro voters on the COVID-19 vaccination index was modified in different quartiles of HDI using an interaction term. Results Five thousand five hundred sixty-three Brazilian municipalities were included in the analysis. For both the 2018 and 2022 elections, the percentage of votes for Jair Bolsonaro was significantly and inversely associated with COVID-19 vaccine uptake after adjustment for the sociodemographic characteristics of the voters (change in mean vaccination index in 2018 for each 1% increase in Bolsonaro voters -0.11, 95% confidence interval [CI] -0.13 to -0.08, p < 0.001; change in mean vaccination index in 2022 for each 1% increase in Bolsonaro voters -0.09, 95% CI -0.11 to -0.07, p < 0.001). We also found a statistically significant interaction between the primary predictor of interest and HDI scores, with a more significantly detrimental effect of the right-wing political stance in municipalities in the lower HDI quartiles (interaction p < 0.001 for the first HDI quartile; p = 0.001 for the second HDI quartile). Conclusion Our findings suggest that political ideologies have influenced COVID-19 vaccine hesitancy in Brazilian municipalities, affecting communities inequitably. The politicization of vaccines is a new challenge for vaccine programs. Strategies to face these challenges should include joint efforts from governments and civil society for a common public health goal