Healthcare-associated infections on the ICU in 21 Brazilian hospitals during the early months of the COVID-19 pandemic: an ecological study.

OBJECTIVE: The COVID-19 pandemic has caused a global health crisis and may have affected healthcare-associated infections (HAI) prevention strategies. This study aims to evaluate the impact of the COVID-19 pandemic on HAI incidence in Brazilian ICUs. METHODS: This ecological study compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (pre-pandemic period) in 21 Brazilian hospitals. The difference in microbiologically confirmed central line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 patient days), the proportion of organisms that caused HAI, and antibiotic consumption (DDD) between the pandemic and the pre pandemic periods were compared in a pairwise analysis using the Wilcoxon signed rank sum test. RESULTS: We observed a significant increase in median CLABSI incidence during the pandemic (1.60 [0.44-4.20] vs. 2.81 [1.35-6.89], p = 0.002). There was no difference in VAP incidence between the two periods. In addition, there was a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida species during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. There was no significant change in ceftriaxone, piperacillin/tazobactam, meropenem, or vancomycin consumption between the studied periods. CONCLUSIONS: There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we observed an increase in the proportion of CLABSI caused by E. faecalis and Candida species in this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Shedding and Predictors of Viral Culture Positivity on Vaccinated Healthcare Workers With Mild Coronavirus Disease 2019.

In this prospective cohort of 30 vaccinated healthcare workers with mild Omicron variant infection, we evaluated viral culture, rapid antigen test (RAT), and real-time reverse-transcription polymerase chain reaction (RT-PCR) of respiratory samples at days 5, 7, 10, and 14. Viral culture was positive in 46% (11/24) and 20% (6/30) of samples at days 5 and 7, respectively. RAT and RT-PCR (Ct ≤35) showed 100% negative predictive value (NPV), with positive predictive values (PPVs) of 32% and 17%, respectively, for predicting viral culture positivity. A lower RT-PCR threshold (Ct ≤24) improved culture prediction (PPV = 39%; NPV = 100%). Vaccinated persons with mild Omicron infection are potentially transmissible up to day 7. RAT and RT-PCR might be useful tools for shortening the isolation period.

PREDITORES DE PROTEÇÃO CONTRA INFECÇÃO POR SARS-COV-2 APÓS DUAS DOSES DE CORONAVAC EM UMA COORTE DE PROFISSIONAIS DE SAÚDE

Introdução A elucidação dos preditores de proteção contra infecção pelo SARS-CoV-2 após a vacinação contra o mesmo pode auxiliar no controle da pandemia. Objetivo Identificar fatores de proteção contra infecção por SARS-CoV-2 após recebimento de duas doses de CoronaVac. Método Trata-se de uma coorte prospectiva de profissionais de saúde (PS) do HC-FMUSP vacinados com 2 doses da CoronaVac. O desfecho avaliado foi infecção pelo SARS-CoV-2 (confirmada por RT-PCR) desde 10 semanas após a segunda dose da vacina até pararem de trabalhar no HC-FMUSP ou até a data 08/03/2022. A infecção pelo SARS-CoV-2 foi verificada através dos registros do Centro de Atendimento ao Colaborador (CEAC) e do Núcleo de Vigilância Epidemiológica (NUVE) do HCFMUSP e através de entrevistas aos participantes do estudo. Os PS foram submetidos a sorologia para o SARS-CoV-2 para detecção de IgG anti-S (Liaison®/DiaSorin). Fatores de proteção contra infecção pelo SARS-CoV-2 foram avaliados com modelos de regressão de Cox. Os participantes assinaram um TCLE antes de ingressarem no estudo e o projeto foi aprovado no CEP do HC-FMUSP. Resultados Entre a 2ª e a 3ª dose da vacina, 3.979 PS foram avaliados. A idade mediana foi 44 anos e 79% era do sexo feminino. Casos de COVID-19 antes da 1ª dose da vacina foram detectados em 18% dos participantes. Sorologia reagente (título ≥ 33,8) foi detectada em 90% dos participantes em um teste realizado 10 semanas após a 2ª dose da vacina e houve 247 (6%) casos de COVID-19 entre a coleta desta sorologia e o recebimento da 3ª dose da vacina. Fatores de proteção contra infecção pelo SARS-CoV-2 neste período foram: diagnóstico de COVID-19 antes da 1ª dose da vacina (adjHR = 0,35), sorologia reagente coletada 10 semanas após 2ª dose da vacina (adjHR = 0,50) e idade entre 50-70 anos (adjHR = 0,52). Após a 3ª dose da vacina, 1305 PS foram avaliados. Sorologia reagente foi detectada em 99,8% dos participantes em um teste realizado 8 semanas após a 3ª dose da vacina e houve 159 (12%) casos de COVID-19 entre a coleta desta sorologia e o término do seguimento. Fatores de proteção contra infecção pelo SARS-CoV-2 no período foram: diagnóstico de COVID-19 antes da 3ª dose da vacina (adjHR = 0,57) e altos títulos da sorologia coletada 8 semanas após a terceira dose da vacina (adjHR = 0,99). Conclusão Diagnóstico prévio de COVID-19 e altos títulos de IgG contra o SARS-CoV-2 8-10 semanas após a vacinação são fatores protetores de infecção pelo SARS-CoV-2 em PS vacinados com CoronaVac. Ag. Financiadora: Instituto todos pela saúde. Nr. Processo: C1864.

Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.

Genetic risk factors and COVID-19 severity in Brazil: results from BRACOVID study.

The coronavirus disease 2019 (COVID-19) pandemic has changed the paradigms for disease surveillance and rapid deployment of scientific-based evidence for understanding disease biology, susceptibility and treatment. We have organized a large-scale genome-wide association study (GWAS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals in Sao Paulo, Brazil, one of the most affected areas of the pandemic in the country, itself one of the most affected in the world. Here, we present the results of the initial analysis in the first 5233 participants of the BRACOVID study. We have conducted a GWAS for COVID-19 hospitalization enrolling 3533 cases (hospitalized COVID-19 participants) and 1700 controls (non-hospitalized COVID-19 participants). Models were adjusted by age, sex and the 4 first principal components. A meta-analysis was also conducted merging BRACOVID hospitalization data with the Human Genetic Initiative (HGI) Consortia results. BRACOVID results validated most loci previously identified in the HGI meta-analysis. In addition, no significant heterogeneity according to ancestral group within the Brazilian population was observed for the two most important COVID-19 severity associated loci: 3p21.31 and Chr21 near IFNAR2. Using only data provided by BRACOVID, a new genome-wide significant locus was identified on Chr1 near the genes DSTYK and RBBP5. The associated haplotype has also been previously associated with a number of blood cell related traits and might play a role in modulating the immune response in COVID-19 cases.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Impact of the COVID-19 pandemic on the incidence of multidrug-resistant bacterial infections in an acute care hospital in Brazil.

BACKGROUND: The impact of COVID-19 on healthcare- associated infections (HCAI) caused by multidrug-resistant (MDR) bacteria that contribute to higher mortality is a growing area of study METHODS: This retrospective observational study compares the incidence density (ID) of HCAI caused by MDR bacteria (CRE, CRAB, CRP, MRSA and VRE) pre-COVID (2017-2019) and during the COVID-19 pandemic (2020) in overall hospitalized patients and in intensive care (ICU) units. RESULTS: We identified 8,869 HCAI, of which 2,641 (29.7%) were caused by bacterial MDR, and 1,257 (14.1%) were from ICUs. The overall ID of MDR infections increased 23% (P < .005) during COVID-19. The overall per-pathogen analysis shows significant increases in infections by CRAB and MRSA (+108.1%, p<0.005; +94.7%, p<0.005, respectively), but not in CRE, CRP, or VRE. In the ICU, the overall ID of MDR infections decreased during COVID, but that decline was not significant (-6.5%, P = .26). The ICU per-pathogen analysis of ID of infection showed significant increases in CRAB and MRSA (+42.0%, P = .001; +46.2%, P = .04), significant decreases in CRE and CRP (-26.4%, P = .002; -44.2%, P = 0.003, respectively) and no change in VRE. CONCLUSIONS: The COVID-19 pandemic correlates to an increase in ID of CRAB and MRSA both in ICU and non-ICU setting, and a decrease in ID of CRE and CRP in the ICU setting. Infection control teams should be aware of possible outbreaks of CRAB and MRSA and promote rigorous adherence to infection control measures as practices change to accommodate changes in healthcare needs during and after the pandemic.

Torquetenovirus in saliva: A potential biomarker for SARS-CoV-2 infection?

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.

Prolonged presence of replication-competent SARS-CoV-2 in mildly symptomatic individuals: A report of two cases.

It has been estimated that individuals with COVID-19 can shed replication-competent virus up to a maximum of 20 days after initiation of symptoms. The majority of studies that addressed this situation involved hospitalized individuals and those with severe disease. Studies to address the possible presence of SARS-CoV-2 during the different phases of COVID-19 disease in mildly infected individuals, and utilization of viral culture techniques to identify replication-competent viruses, have been limited. This report describes two patients with mild forms of the disease who shed replication-competent virus for 24 and 37 days, respectively, after symptom onset.

Clinical features and natural history of the first 2073 suspected COVID-19 cases in the Corona São Caetano primary care programme: a prospective cohort study.

BACKGROUND: Despite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19. METHODS: The Corona São Caetano programme is a primary care initiative providing care to all residents with COVID-19 in São Caetano do Sul, Brazil. It was designed to capture standardised clinical data on community COVID-19 cases. After triage of potentially severe cases, consecutive patients presenting to a multimedia screening platform between 13 April and 13 May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days with phone calls every 2 days. RT-PCR-negative patients were offered additional SARS-CoV-2 serology testing to establish their infection status. We describe the clinical, virological and natural history features of this prospective population-based cohort. FINDINGS: Of 2073 suspected COVID-19 cases, 1583 (76.4%) were tested by RT-PCR, of whom 444 (28.0%, 95% CI 25.9 to 30.3) were positive; 604/1136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8.6%) tested SARS-CoV-2 seropositive. The most common symptoms of confirmed COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever (OR 3.0, 95% CI 2.4 to 3.9), anosmia (OR 3.3, 95% CI 2.6 to 4.4) and ageusia (OR 2.9, 95% CI 2.3 to 3.8) were most strongly associated with a positive COVID-19 diagnosis by RT-PCR or serology. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia and closer to symptom onset. The rates of hospitalisation and death among 444 RT-PCR-positive cases were 6.7% and 0.7%, respectively, with older age and obesity more frequent in the hospitalised group. CONCLUSION: COVID-19 presents in a similar way to other mild community-acquired respiratory diseases, but the presence of fever, anosmia and ageusia can assist the specific diagnosis. Most patients recovered without requiring hospitalisation with a low fatality rate compared with other hospital-based studies.