Immune Evasion of SARS-CoV-2 Omicron Subvariants XBB.1.5, XBB.1.16 and EG.5.1 in a Cohort of Older Adults after ChAdOx1-S Vaccination and BA.4/5 Bivalent Booster.

The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report the neutralizing activities of 177 sera samples from 59 older adults, aged 62-97 years, 1 and 4 months after vaccination with a 4th dose of ChAdOx1-S (Oxford/AstraZeneca) and 3 months after a 5th dose of Comirnaty Bivalent Original/Omicron BA.4/BA.5 vaccine (Pfizer-BioNTech). The ChAdOx1-S vaccination-induced antibodies neutralized efficiently the ancestral D614G and BA.4/5 variants, but to a much lesser extent the XBB.1.5, XBB.1.16, and EG.5.1 variants. The results showed similar neutralization titers between XBB.1.16 and EG.5.1 and were lower compared to XBB.1.5. Sera from the same individuals boosted with the bivalent mRNA vaccine contained higher neutralizing antibody titers, providing a better cross-protection against Omicron XBB.1.5, XBB.1.16 and EG.5.1 variants. Previous history of infection during the epidemiological waves of BA.1/BA.2 and BA.4/BA.5, poorly enhanced neutralization activity of serum samples against XBBs and EG.5.1 variants. Our data highlight the continued immune evasion of recent Omicron subvariants and support the booster administration of BA.4/5 bivalent vaccine, as a continuous strategy of updating future vaccine booster doses to match newly emerged SARS-CoV-2 variants.

Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future.

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.

Seroprevalence of hepatitis E virus in patients with chronic liver disease.

INTRODUCTION: The seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to cirrhosis. OBJECTIVE: To estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic data and risk factors, as well as clinical-laboratory and ultrasound parameters. PATIENTS AND METHODS: Cross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and, in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out. RESULTS: Investigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17 with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age of 57 ± 13 years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative. Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema, lower platelet count, higher APRI and FIB-4 values, and splenomegaly. CONCLUSION: Although the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced chronic liver disease.

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D.

In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espírito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espírito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.

Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of São Paulo City, Brazil.

BACKGROUND: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. METHODS: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. RESULTS: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. CONCLUSION: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics.

COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS.

BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.

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.

Nucleocapsid single point-mutation associated with drop-out on RT-PCR assay for SARS-CoV-2 detection.

BACKGROUND: Since its beginning, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a challenge for clinical and molecular diagnostics, because it has been caused by a novel viral agent. Whole-genome sequencing assisted in the characterization and classification of SARS-CoV-2, and it is an essential tool to genomic surveillance aiming to identify potentials hot spots that could impact on vaccine immune response and on virus diagnosis. We describe two cases of failure at the N2 target of the RT-PCR test Xpert® Xpress SARS-CoV-2. METHODS: Total nucleic acid from the Nasopharyngeal (NP) and oropharyngeal (OP) swab samples and cell supernatant isolates were obtained. RNA samples were submitted to random amplification. Raw sequencing data were subjected to sequence quality controls, removal of human contaminants by aligning against the HG19 reference genome, taxonomic identification of other pathogens and genome recovery through assembly and manual curation. RT-PCR test Xpert® Xpress SARS-CoV-2 was used for molecular diagnosis of SARS-CoV-2 infection, samples were tested in duplicates. RESULTS: We identified 27 samples positive for SARS-CoV-2 with a nucleocapsid (N) gene drop out on Cepheid Xpert® Xpress SARS-CoV-2 assay. Sequencing of 2 of 27 samples revealed a single common mutation in the N gene C29197T, potentially involved in the failed detection of N target. CONCLUSIONS: This study highlights the importance of genomic data to update molecular tests and vaccines.

Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure.

A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.

Longer-term effectiveness of a heterologous coronavirus disease 2019 (COVID-19) vaccine booster in healthcare workers in Brazil.

Objective: To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Results: Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Conclusions: Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster.

Clinical characteristics and outcomes of patients with COVID-19 admitted to the intensive care unit during the first and second waves of the pandemic in Brazil: a single-center retrospective cohort study.

OBJECTIVE: To describe and compare the clinical characteristics and outcomes of patients admitted to intensive care units during the first and second waves of the COVID-19 pandemic. METHODS: In this retrospective single-center cohort study, data were retrieved from the Epimed Monitor System; all adult patients admitted to the intensive care unit between March 4, 2020, and October 1, 2021, were included in the study. We compared the clinical characteristics and outcomes of patients admitted to the intensive care unit of a quaternary private hospital in São Paulo, Brazil, during the first (May 1, 2020, to August 31, 2020) and second (March 1, 2021, to June 30, 2021) waves of the COVID-19 pandemic. RESULTS: In total, 1,427 patients with COVID-19 were admitted to the intensive care unit during the first (421 patients) and second (1,006 patients) waves. Compared with the first wave group [median (IQR)], the second wave group was younger [57 (46-70) versus 67 (52-80) years; p<0.001], had a lower SAPS 3 Score [45 (42-52) versus 49 (43-57); p<0.001], lower SOFA Score on intensive care unit admission [3 (1-6) versus 4 (2-6); p=0.018], lower Charlson Comorbidity Index [0 (0-1) versus 1 (0-2); p<0.001], and were less frequently frail (10.4% versus 18.1%; p<0.001). The second wave group used more noninvasive ventilation (81.3% versus 53.4%; p<0.001) and high-flow nasal cannula (63.2% versus 23.0%; p<0.001) during their intensive care unit stay. The intensive care unit (11.3% versus 10.5%; p=0.696) and in-hospital mortality (12.3% versus 12.1%; p=0.998) rates did not differ between both waves. CONCLUSION: In the first and second waves, patients with severe COVID-19 exhibited similar mortality rates and need for invasive organ support, despite the second wave group being younger and less severely ill at the time of intensive care unit admission.

Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022.

OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP). METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID. CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

Antimicrobial oral lavage reduces the SARS-CoV-2 load in intubated patients: randomized clinical trial.

Background: The oral cavity can be a reservoir for SARS-CoV-2 and may play a crucial role in the viral transmission in the hospital environment. Objective: To investigate whether an oral hygiene protocol with chlorhexidine (CHX) used alone and in combination with hydrogen peroxide (HP) in the intensive care unit was effective in reducing the SARS-CoV-2 viral load in the oral cavity. Methods: SARS-CoV-2 viral load was measured on oral fluid samples collected from patients undergoing orotracheal intubation. The study sample was randomly in: CHX group (n = 19) - oral rinse using only 0.12% CHX solution; HP+CHX group (n = 24) - oral rinse with 1.5% HP and 0.12% CHX. The samples were collected before the interventions (T0), immediately (T1), 30 minutes (T2) and 60 minutes (T3) after the procedure. Results: A significant viral load reduction was observed at T1 (mean ± SD:-0.57 ± 0.19 log10;-73.2%;p = 0.022) in the HP+CHX group. No statistically significant differences between any time points were observed in the CHX group. Conclusion: The HP+CHX oral rinses significantly reduced the SARS-CoV-2 viral load in the oral fluid immediately after the procedure. The CHX oral rinse alone did not result in any significant viral load reductions.

PNPLA3 GENE POLYMORPHISM AND RED MEAT CONSUMPTION INCREASED FIBROSIS RISK IN NASH BIOPSY-PROVEN PATIENTS UNDER MEDICAL FOLLOW-UP IN A TERTIARY CENTER IN SOUTHWEST BRAZIL.

BACKGROUND: Recent studies show an increase in nonalcoholic fatty liver disease (NAFLD) in populations with higher consumption of red meat, processed and cooked at high temperatures. On the other hand, the single nucleotide polymorphism rs738409 in the Patatin-like phospholipase domain containing 3 (PNPLA3) gene has been implicated in susceptibility to NAFLD and liver fibrosis. However, the synergistic effect between red meat consumption and the PNPLA3 gene polymorphism in NAFLD has not yet been evaluated. OBJECTIVE: To evaluate the association between the presence of the polymorphism in the PNPLA3 gene and the consumption of macronutrients, including meat consumption and its cooking method among NAFLD patients. METHODS: This was a cross-sectional study with 91 patients diagnosed with NAFLD by liver biopsy with genotyping for the polymorphism in the PNPLA3 gene were included. The consumption of calories and macronutrients was verified using the semi-quantitative food frequency questionnaire and the specific questionnaire on meat consumption. PNPLA3 gene polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR) and anthropometric evaluation was realized. RESULTS: The mean BMI was 32.38±4.58 kg/m² and the waist circumference was 107±10 cm. On liver biopsy, 42% of patients had significant fibrosis (F≥2). The odds ratio of F≥2 was 2.12 for the GG group and 1.54 for the CG group, compared to the CC group. The mean caloric intake was 1170±463.20 kcal/d. The odds ratio in the CC group concerning high red meat consumption in comparison to low consumption was 1.33. For white meat, the odds ratio was 0.8 when comparing high and low intake, also in the CC group. CONCLUSION: High red meat intake and PNPLA3 gene polymorphism seem to synergistically affect NAFLD and liver fibrosis, requiring confirmation in a larger number of patients and in different populations.

High prevalence of hepatitis B virus and low vaccine response in children and adolescents in Northeastern Brazil.

Children have an increased likelihood of becoming carriers of the chronic hepatitis B virus. A total of 1,381 children and adolescents were assessed in five municipalities of Maranhao State, Brazil, for detection of anti-HBc, HBsAg and anti-HBs serologic markers and sociodemographic and behavioral features. Among those who were HBsAg negative and anti-HBc negative, the proportion of anti-HBs positives was calculated after the individuals had completed the vaccination schedule. The robust variance of the Poisson's regression model was used in order to have adjusted tables and calculate the prevalence ratio. Multivariate analysis was performed to identify the factors associated with the prevalence of anti-HBc with or without HBsAg and the vaccine response. It was observed that 163 children were anti-HBc positive and nine individuals were HBsAg positive. The factors associated with the infection were: municipality of residence (residing in Morros municipality or Humberto de Campos municipality), residence in a rural area, aged between 13 and 15 years old, and illicit drug use. The percentage of individuals who were anti-HBc negative and received all three doses of the vaccine was 48.5%. Among these, only 276 (38.9%) had antibodies at protective concentrations. In an adjusted analysis, Morros municipality presented an increased positivity of vaccine response (p < 0.001), and the age ranging between 6 and 10 years old presented a reduced frequency of response. This study reveals a high prevalence of current and past HBV infection within the targeted age group which, in addition to the low vaccination coverage and serological responses, raises concerns about the management of prevention measures, especially the quality of vaccination in these locations.

Hepatitis A virus infection in Brazilian correctional facilities.

Hepatitis A virus (HAV) infection is transmitted by the fecal-oral route, through interpersonal contact and ingestion of contaminated food or water. Prisoners are at higher risk of acquiring HAV infection mainly due to the environment of closed penal institutions and socioeconomic conditions. This study aims to determine the seroprevalence of anti-HAV and its associated risk factors among inmates from twelve prisons in Central Brazil. A cross-sectional study was conducted between March 2013 and March 2014. A total of 580 prisoners participated in the study. The participant's samples were tested for Total and IgM anti-HAV antibodies by electrochemiluminescence immunoassay (ECLIA). Risk factors associated with anti-HAV seropositivity were also analyzed. The prevalence rate of HAV exposure was 88.1% (95% CI: 85.5-90.7). No sample had a positive reaction to IgM anti-HAV. Increasing age, low level of education, and being imprisoned in Corumbá city were independently associated with HAV exposure among prisoners. To prevent the burden of the disease, vaccination strategies should be considered for susceptible prisoners in Central Brazil.

Cellular and Humoral Immune Responses to Vaccination for COVID-19 Are Negatively Impacted by Senescent T Cells: A Case Report.

BACKGROUND: Herein, we aimed to follow up on the cellular and humoral immune responses of a group of individuals who initially received the CoronaVac vaccine, followed by a booster with the Pfizer vaccine. METHODS: Blood samples were collected: before and 30 days after the first CoronaVac dose; 30, 90, and 180 days after the second CoronaVac dose, and also 20 days after the booster with the Pfizer vaccine. RESULTS: Whilst the positivity to gamma interferon-type cellular response increased after the first CoronaVac dose, neutralizing and IgG antibody levels only raised 30 days after the second dose, followed by a drop in these responses after 90 and 180 days. The booster with the Pfizer vaccine elicited a robust cellular and humoral response. A higher number of double-negative and senescent T cells, as well as increased pro-inflammatory cytokines levels were found in the participants with lower humoral immune responses. CONCLUSION: CoronaVac elicited an early cellular response, followed by a humoral response, which dropped 90 days after the second dose. The booster with the Pfizer vaccine significantly enhanced these responses. Furthermore, a pro-inflammatory systemic status was found in volunteers who presented senescent T cells, which could putatively impair the immune response to vaccination.

Polimorfismo no gene PNPLA3 e o consumo de carne vermelha aumentam o risco de fibrose em pacientes com DHGNA comprovado por biópsia em acompanhamento médico em um centro terciário no Sudoeste do Brasil / Pnpla3 gene polymorphism and red meat consumption increased fibrosis risk in nash biopsy-proven patients under medical follow-up in a tertiary center in southwest brazil

ABSTRACT Background: Recent studies show an increase in nonalcoholic fatty liver disease (NAFLD) in populations with higher consumption of red meat, processed and cooked at high temperatures. On the other hand, the single nucleotide polymorphism rs738409 in the Patatin-like phospholipase domain containing 3 (PNPLA3) gene has been implicated in susceptibility to NAFLD and liver fibrosis. However, the synergistic effect between red meat consumption and the PNPLA3 gene polymorphism in NAFLD has not yet been evaluated. Objective: To evaluate the association between the presence of the polymorphism in the PNPLA3 gene and the consumption of macronutrients, including meat consumption and its cooking method among NAFLD patients. Methods: This was a cross-sectional study with 91 patients diagnosed with NAFLD by liver biopsy with genotyping for the polymorphism in the PNPLA3 gene were included. The consumption of calories and macronutrients was verified using the semi-quantitative food frequency questionnaire and the specific questionnaire on meat consumption. PNPLA3 gene polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR) and anthropometric evaluation was realized. Results: The mean BMI was 32.38±4.58 kg/m² and the waist circumference was 107±10 cm. On liver biopsy, 42% of patients had significant fibrosis (F≥2). The odds ratio of F≥2 was 2.12 for the GG group and 1.54 for the CG group, compared to the CC group. The mean caloric intake was 1170±463.20 kcal/d. The odds ratio in the CC group concerning high red meat consumption in comparison to low consumption was 1.33. For white meat, the odds ratio was 0.8 when comparing high and low intake, also in the CC group. Conclusion: High red meat intake and PNPLA3 gene polymorphism seem to synergistically affect NAFLD and liver fibrosis, requiring confirmation in a larger number of patients and in different populations.

RESUMO Contexto: Estudos recentes mostram um aumento da doença hepática gordurosa não alcoólica (DHGNA) em populações com maior consumo de carne vermelha, processada e cozida em altas temperaturas. Por outro lado, o polimorfismo rs738409 no gene Patatin-like fosfolipase contendo 3 (PNPLA3) tem sido implicado na suscetibilidade à DHGNA e fibrose hepática. No entanto, o efeito sinérgico entre o consumo de carne vermelha e o polimorfismo no gene PNPLA3 na DHGNA ainda não foi avaliado. Objetivo: Avaliar a associação entre a presença do polimorfismo no gene PNPLA3 e o consumo de macronutrientes, incluindo o consumo de carne e seu modo de cozimento em pacientes com DHGNA. Métodos: Realizamos um estudo transversal com 91 pacientes diagnosticados com DHGNA por biópsia hepática e genotipados para o polimorfismo no gene PNPLA3. O consumo de calorias e macronutrientes foi verificado por meio do questionário de frequência alimentar semi-quantitativo (QFA) e do questionário específico sobre consumo de carnes. O polimorfismo no gene PNPLA3 foi analisado por reação em cadeia da polimerase em tempo real (RT-PCR) e a avaliação antropométrica foi realizada. Resultados: O índice de massa corporal médio foi de 32,38±4,58 kg/m² e a circunferência da cintura foi de 107±10 cm. Na biópsia hepática, 42% dos pacientes apresentavam fibrose significativa (F≥2). O odds ratio de F≥2 foi de 2,12 para o grupo GG e 1,54 para o grupo GC, comparado ao grupo CC. A ingestão calórica média foi de 1.170±463,20 kcal/d. O odds ratio para alto consumo de carne vermelha no grupo CC em comparação ao baixo consumo foi de 1,33. Para a carne branca, este valor foi de 0,8 ao comparar o alto e o baixo consumo, também no grupo CC. Conclusão: A alta ingestão de carne vermelha e o polimorfismo no gene PNPLA3 parecem afetar sinergicamente a DHGNA e a fibrose hepática, necessitando de confirmação em maior número de pacientes e em diferentes populações.

Effectiveness of two coronavirus disease 2019 (COVID-19) vaccines (viral vector and inactivated viral vaccine) against severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in a cohort of healthcare workers.

OBJECTIVE: We investigated real-world vaccine effectiveness for Oxford-AstraZeneca (ChAdOx1) and CoronaVac against laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil between January 1, 2021 and August 3, 2021, to assess vaccine effectiveness. We calculated vaccine effectiveness as 1 - rate ratio (RR), with RR determined by adjusting Poisson models with the occurrence of SARS-CoV-2 infection as the outcome and the vaccination status as the main variable. We used the logarithmic link function and simple models adjusting for sex, age, and job types. RESULTS: In total, 13,813 HCWs met the inclusion criteria for this analysis. Among them, 6,385 (46.2%) received the CoronaVac vaccine, 5,916 (42.8%) received the ChAdOx1 vaccine, and 1,512 (11.0%) were not vaccinated. Overall, COVID-19 occurred in 6% of unvaccinated HCWs, 3% of HCWs who received 2 doses of CoronaVac vaccine, and 0.7% of HCWs who received 2 doses of ChAdOx1 vaccine (P < .001). In the adjusted analyses, the estimated vaccine effectiveness rates were 51.3% for CoronaVac, and 88.1% for ChAdOx1 vaccine. Both vaccines reduced the number of hospitalizations, the length of hospital stay, and the need for mechanical ventilation. In addition, 19 SARS-CoV-2 samples from 19 HCWs were screened for mutations of interest. Of 19 samples, 18 were the γ (gamma) variant. CONCLUSIONS: Although both COVID-19 vaccines (viral vector and inactivated virus) can significantly prevent COVID-19 among HCWs, CoronaVac was much less effective. The COVID-19 vaccines were also effective against the dominant γ variant.

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

ABSTRACT 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.