Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Molecular evolution of dengue virus: a Bayesian approach using 1581 whole-genome sequences from January 1944 to July 2022.

Dengue is a viral disease transmitted by mosquitoes that has spread rapidly across all continents in recent years. There are four distinct but closely related serotypes of the virus that causes dengue (DENV-1, DENV-2, DENV-3, and DENV-4). In the present study, we evaluated temporal spreading and molecular evolution of dengue virus (DENV) serotypes. Bayesian coalescent analysis was performed to study viral evolution, and it was estimated that the most recent common ancestor of DENV-1 was present in 1884 in Southeast Asia, that of DENV-2 was present in 1723 in Europe, that of DENV-3 was present in 1921 in Southeast Asia, and that of DENV-4 was present in 1876 in Southeast Asia. DENV appears to have originated in Spain in approximately 1682, and it was disseminated in Asia and Oceania in approximately 1847. After this period, the virus was introduced into North America in approximately 1890. In South America, it was first disseminated to Ecuador in approximately 1897 and then to Brazil in approximately 1910. Dengue has had a significant impact on global health worldwide, and the present study provides an overview of the molecular evolution of DENV serotypes.

Improving door-to-reperfusion time in acute ischemic stroke during the COVID-19 pandemic: experience from a public comprehensive stroke center in Brazil.

Background: The global COVID-19 pandemic has had a devastating effect on global health, resulting in a strain on healthcare services worldwide. The faster a patient with acute ischemic stroke (AIS) receives reperfusion treatment, the greater the odds of a good functional outcome. To maintain the time-dependent processes in acute stroke care, strategies to reorganize infrastructure and optimize human and medical resources were needed. Methods: Data from AIS patients who received thrombolytic therapy were prospectively assessed in the emergency department (ED) of Hospital de Clínicas de Porto Alegre from 2019 to 2021. Treatment times for each stage were measured, and the reasons for a delay in receiving thrombolytic therapy were evaluated. Results: A total of 256 patients received thrombolytic therapy during this period. Patients who arrived by the emergency medical service (EMS) had a lower median door-to-needle time (DNT). In the multivariable analysis, the independent predictors of DNT >60 min were previous atrial fibrillation (OR 7) and receiving thrombolysis in the ED (OR 9). The majority of patients had more than one reason for treatment delay. The main reasons were as follows: delay in starting the CT scan, delay in the decision-making process after the CT scan, and delay in reducing blood pressure. Several actions were implemented during the study period. The most important factor that contributed to a decrease in DNT was starting the bolus and continuous infusion of tPA on the CT scan table (decreased the median DNT from 74 to 52, DNT ≤ 60 min in 67% of patients treated at radiology service vs. 24% of patients treated in the ED). The DNT decreased from 78 min to 66 min in 2020 and 57 min in 2021 (p = 0.01). Conclusion: Acute stroke care continued to be a priority despite the COVID-19 pandemic. The implementation of a thrombolytic bolus and the start of continuous infusion on the CT scan table was the main factor that contributed to the reduction of DNT. Continuous monitoring of service times is essential for improving the quality of the stroke center and achieving better functional outcomes for patients.

COVID-19 outcomes in people living with HIV: Peering through the waves.

OBJECTIVE: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. METHODS: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. RESULTS: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). CONCLUSIONS: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Myocardial Injury and Prognosis in Hospitalized COVID-19 Patients in Brazil: Results From The Brazilian COVID-19 Registry. / Lesão Miocárdica e Prognóstico em Pacientes Hospitalizados com COVID-19 no Brasil: Resultados do Registro Nacional de COVID-19.

BACKGROUND: Cardiovascular complications of COVID-19 are important aspects of the disease's pathogenesis and prognosis. Evidence on the prognostic role of troponin and myocardial injury in Latin American hospitalized COVID-19 patients is still scarce. OBJECTIVES: To evaluate myocardial injury as independent predictor of in-hospital mortality and invasive mechanical ventilation support in hospitalized patients, from the Brazilian COVID-19 Registry. METHODS: This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals of 17 cities, March-September 2020. Primary outcomes included in-hospital mortality and invasive mechanical ventilation support. Models for the primary outcomes were estimated by Poisson regression with robust variance, with statistical significance of p<0.05. RESULTS: Of 2,925 patients (median age of 60 years [48-71], 57.1% men), 27.3% presented myocardial injury. The proportion of patients with comorbidities was higher among patients with cardiac injury (median 2 [1-2] vs. 1 [0-2]). Patients with myocardial injury had higher median levels of brain natriuretic peptide, lactate dehydrogenase, creatine phosphokinase, N-terminal pro-brain natriuretic peptide, and C-reactive protein than patients without myocardial injury. As independent predictors, C-reactive protein and platelet counts were related to the risk of death, and neutrophils and platelet counts were related to the risk of invasive mechanical ventilation support. Patients with high troponin levels presented a higher risk of death (RR 2.03, 95% CI 1.60-2.58) and invasive mechanical ventilation support (RR 1.87, 95% CI 1.57-2.23), when compared to those with normal troponin levels. CONCLUSION: Cardiac injury was an independent predictor of in-hospital mortality and the need for invasive mechanical ventilation support in hospitalized COVID-19 patients.

FUNDAMENTO: As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. OBJETIVOS: Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. MÉTODOS: Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. RESULTADOS: Dos 2925 pacientes [idade mediana de 60 anos (48-71), 57,1%], 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte (RR 2,03, IC95% 1,60-2,58) e suporte ventilatório mecânico (RR 1,87;IC95% 1,57-2,23), em comparação àqueles com níveis de troponina normais. CONCLUSÃO: Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19.

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians.

OBJECTIVES: To analyze the clinical characteristics and outcomes of admitted patients with the hospital- versus community-manifested COVID-19 and to evaluate the risk factors related to mortality in the first population. METHODS: This retrospective cohort included consecutive adult patients with COVID-19, hospitalized between March and September 2020. The demographic data, clinical characteristics, and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. RESULTS: Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while admitted for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs 10.8%) and alcoholism (8.8% vs 2.8%) than patients with community-manifested COVID-19 and also had a higher rate of intensive care unit requirement (45.1% vs 35.2%), sepsis (23.8% vs 14.5%), and death (35.8% vs 22.5%) (P <0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. CONCLUSION: Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested COVID-19 disease.

Molecular evolution of the human monkeypox virus.

Recently, in 2022, new cases of human monkeypox virus (hMPXV) occurred in Europe and North America. The first case was reported in Europe in May 2022, and subsequently, more than 50 000 new cases were confirmed in 100 countries. Currently, the classification of hMPXV according to the nextstrain occurs in five big clades (1A, A.1, A.2, A.1.1, and B.1). According to the resurgence of smallpox-like disease caused by hMPXV and the spread of the virus to the European and American continents, in the present study, we review and summarize the molecular evolution of the hMPXV, determining the molecular evolution of the main clades. A total of 442 hMPXV whole-genome sequences with available information from the country and sampling date (between October 2017 and 2022), were obtained and evaluated using the Bayesian method. The clade B.1 which is currently circulating was the most frequent (n = 415; 93.9%). The other clades presented the following frequencies: 1A (n = 13; 2.9%), A.1 (n = 10; 2.3%), A.2 (n = 3; 0.7%) and A.1.1 (n = 1; 0.2%) The overall nucleotide divergence of hMPXV was 5.590e-5. The 1A clade was detected between 2017 and 2020. A.1 was observed, and between 2019 and 2022 some A.2 sequences were detected. In 2022, the great predominance of B.1 was observed. The common ancestor of the hMPXV belongs to the clade 1A and the time to the Most Recent Common Ancestor (tMRCA) was 2017-04-04 (Highest Posterior Density 95% (HPD95%): 2017-03-09; 2017-08-04) on the West African continent. The tMRCA of A.1 was 2018-05-21 (HPD95%: 2018-05-20; 2018-07-04) with divergence of 6.885e-5 substitutions per site per year. This clade was of West African origin but was eventually detected in European countries. Also, A.2 was detected with sequences of North America and showed tMRCA of 2019-07-15 (HPD95%: 2018-11-18; 2020-02-24). A.1.1 showed tMRCA from 2021 to 06-05 (HPD95%: 2021-06-05; 2021-11-26) and this clade was detected in North America and was the precursor for the globally spreading B.1 which tMRCA was 2022-04-26 (HPD95%: 2022-02-27; 2022-04-26). hMPXV has been spread from West Africa to the United Kingdom, Israel, Singapore, the USA, Canada, Portugal, Spain, Ireland, France, Belgium, the Netherlands, Switzerland, Germany, Italy, Slovenia, Austria, the Republic Czech, Sweden, and Finland. hMPXV also reached countries such as Brazil, Mexico, Australia, and Taiwan. The common ancestor of the hMPXV belongs to the clade 1A with origin in the West African continent. Clade B.1 was responsible for the recent widespread worldwide. Immunization to prevent the spread of hMPXV is not yet available to the public, future studies should focus on the development of effective vaccines to contain the spread of this virus.

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022.

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).

Hospital mortality rates between 2015 and 2022: a comparison between the pre-pandemic and pandemic period shows that COVID-19 is a critical health problem

Introduction: COVID-19 caused 6.2 million deaths in the world. The present study aims to evaluate hospital mortality rates from 2015 to 2022, to compare the pre and during the pandemic period.Methods: The study was carried out in a private hospital in southern Brazil. 174,013 hospital discharges between January 2015 and March 2022 were analyzed. Pearson's chi-squared test was performed to evaluate the mortality rate by year. Differences between mortality rates before and during the pandemic was tested with Student's t-test. P-values < 0.05 for all tests were considered significant.Results: Mortality rates were 2.29% in 2015; 2.37% in 2016; 2.25% in 2017; 2.31% in 2018; 2.46% in 2019; 3.45% in 2020; 3.58% in 2021 and 2.77% in 2022 (p< 0.01). The mortality for 2020 and 2021 was higher than in the other years (3.50% ± 0.14 vs 2.34% ± 0.05; p < 0.01).Conclusion: The mortality rates were significantly higher in the years 2020 and 2021, demonstrating that COVID-19 is a critical health problem.

COVID-19 outcomes in people living with HIV: Peering through the waves

Abstract Objective To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. Methods This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Results Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Conclusions Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Lesão Miocárdica e Prognóstico em Pacientes Hospitalizados com COVID-19 no Brasil: Resultados do Registro Nacional de COVID-19 / Myocardial Injury and Prognosis in Hospitalized COVID-19 Patients in Brazil: Results From The Brazilian COVID-19 Registry

Resumo Fundamento As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. Objetivos Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. Métodos Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. Resultados Dos 2925 pacientes [idade mediana de 60 anos (48-71), 57,1%], 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte (RR 2,03, IC95% 1,60-2,58) e suporte ventilatório mecânico (RR 1,87;IC95% 1,57-2,23), em comparação àqueles com níveis de troponina normais. Conclusão Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19.

Abstract Background Cardiovascular complications of COVID-19 are important aspects of the disease's pathogenesis and prognosis. Evidence on the prognostic role of troponin and myocardial injury in Latin American hospitalized COVID-19 patients is still scarce. Objectives To evaluate myocardial injury as independent predictor of in-hospital mortality and invasive mechanical ventilation support in hospitalized patients, from the Brazilian COVID-19 Registry. Methods This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals of 17 cities, March-September 2020. Primary outcomes included in-hospital mortality and invasive mechanical ventilation support. Models for the primary outcomes were estimated by Poisson regression with robust variance, with statistical significance of p<0.05. Results Of 2,925 patients (median age of 60 years [48-71], 57.1% men), 27.3% presented myocardial injury. The proportion of patients with comorbidities was higher among patients with cardiac injury (median 2 [1-2] vs. 1 [0-2]). Patients with myocardial injury had higher median levels of brain natriuretic peptide, lactate dehydrogenase, creatine phosphokinase, N-terminal pro-brain natriuretic peptide, and C-reactive protein than patients without myocardial injury. As independent predictors, C-reactive protein and platelet counts were related to the risk of death, and neutrophils and platelet counts were related to the risk of invasive mechanical ventilation support. Patients with high troponin levels presented a higher risk of death (RR 2.03, 95% CI 1.60-2.58) and invasive mechanical ventilation support (RR 1.87, 95% CI 1.57-2.23), when compared to those with normal troponin levels. Conclusion Cardiac injury was an independent predictor of in-hospital mortality and the need for invasive mechanical ventilation support in hospitalized COVID-19 patients.

Frequency and burden of neurological manifestations upon hospital presentation in COVID-19 patients: Findings from a large Brazilian cohort.

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population. METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital of admission, and whether or not patients had underlying neurological disease. RESULTS: From 6,635 hospitalized patients with COVID-19, 30.8% presented reported neurological manifestations, 10.3% were diagnosed with a neurological syndrome and 60.1% did not show any neurological manifestations. In patients with reported symptoms, the most common ones were headache (20.7%), ageusia (11.1%) and anosmia (8.0%). In patients with neurological syndromes, acute encephalopathy was the most common diagnosis (9.7%). In the matched analysis, patients with neurological syndromes presented more cases of septic shock (17.0 vs. 13.0%, p = 0.045), intensive care unit admission (45.3 vs. 38.9%, p = 0.023), and mortality (38.7 vs. 32.6%, p = 0.026; and 39.2 vs. 30.3%, p < 0.001) when compared to controls. CONCLUSION: COVID-19 in-hospital patients with clinically defined neurological syndromes presented a higher incidence of septic shock, ICU admission and death when compared to controls.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

COVID-19 pandemic in Southern Brazil: Hospitalizations, intensive care unit admissions, lethality rates, and length of stay between March 2020 and April 2022.

Coronavirus disease 2019 (COVID-19) pandemic spread rapidly with more than 515 million cases and 6.2 million deaths. Epidemiological factors are important for understanding the state of the pandemic. This study aims to evaluate the hospitalizations, intensive care unit (ICU) admissions, and lethality from March 2020 to April 2022. Data were collected from a hospital in Porto Alegre city, southern Brazil. The Mann-Whitney, analysis of variance, and Kruskal-Wallis tests were used to compare quantitative variables. Categorical variables were compared by Pearson's χ2 test. p values <0.05 for all tests were considered significant. Were observed 3784 hospitalizations. Males were 51.4% and the age was 60.4± 20.3. Intensive care unit (ICU) patients were 31.2%, the median length of stay (LOS) was 9.0 and lethality was 13.3%. ICU lethality was 34.5% versus 4.6% in other inpatients (p < 0.01). The LOS of ICU patients was 22.0 versus 7.0 in other inpatients (p < 0.01). The first peak (July-Novemebr 2020) showed ICU occupancy of 79.1%. The second peak (December 2020-June 2021) with 91.6% occupancy. The third peak January-March 2022 with 81.0% occupancy (p < 0.01). Lethality rates were 10.3% in 2020, 14.9% in 2021 and 15.4% in 2022 (p < 0.01). In conclusion, the ICU occupancy rate was higher in 2021 and the lethality rates of ICU patients were high during pandemic years (10.3% in 2020, 14.9% in 2021, and 15.2% in 2022). The lethality of these patients ranged from 25.0% in March to 21.8% in December 2020, from 20.9% in January 22.2% in Decemebr 2021, and 35.7% in January 2022 to 21.4% in April 2022. These data demonstrate that COVID-19 is a critical illness, even in a private hospital setting.

Success and failure after surgery of degenerative disease of the lumbar spine: an operational definition based on satisfaction, pain, and disability from a prospective cohort.

BACKGROUND: To describe success and failure (S&F) after lumbar spine surgery in terms equally understandable across the entire health ecosystem. METHODS: Back and leg pain and disability were prospectively recorded before and up to 12 months after the procedure. Satisfaction was recorded using a Likert scale. Initially, patients were classified as satisfied or unsatisfied. Optimal satisfaction/unsatisfaction cutoff values for disability and pain were estimated with ROC curves. Satisfied and unsatisfied groups underwent a second subdivision into four subcategories: success (satisfied AND pain and disability concordant with cutoff values), incomplete success (satisfied AND pain and disability nonconformant with cutoff values), incomplete failure (unsatisfied AND pain and disability nonconformant with cutoff values), and failure (unsatisfied AND pain and disability concordant with cutoff values). RESULTS: A total of 486 consecutive patients were recruited from 2019-2021. The mean values of preoperative PROMs were ODI 42.2 (+ 16.4), NPRS back 6.6 (+ 2.6) and NPRS leg 6.2 points (+ 2.9). Of the total, 80.7% were classified as satisfied, and 19.3% were classified as unsatisfactory. The optimal disability and pain cutoff values for satisfaction/unsatisfaction (NPRS = 6, AND ODI = 27) defined a subdivision: 59.6% were classified as success, 20.4% as incomplete success, 7.1% as incomplete failure and 12.4% as failure. The descriptions of each group were translated to the following: success-all patients were satisfied and presented no or only mild to tolerable pain and no or borderline disability; incomplete success - all patients were satisfied despite levels of pain and/or disability worse than ideal for success; incomplete failure - all patients were not satisfied despite levels of pain and/or disability better than expected for failure; failure - all patients were unsatisfied and presented moderate to severe pain and disability. CONCLUSION: It is possible to report S&F after surgery for DDL with precise and meaningful operational definitions focused on the experience of the patient.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil. Methods: PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units. Results: When compared with the private setting (n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability. Conclusion: Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.