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1.
BMJ Glob Health ; 8(7)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37423621

RESUMO

High-level isolation units (HLIUs) are specially designed facilities for care and management of patients with suspected or confirmed high-consequence infectious diseases (HCIDs), equipped with unique infrastructure and operational features. While individual HLIUs have published on their experiences caring for patients with HCIDs and two previous HLIU consensus efforts have outlined key components of HLIUs, we aimed to summarise the existing literature that describes best practices, challenges and core features of these specialised facilities. A narrative review of the literature was conducted using keywords associated with HLIUs and HCIDs. A total of 100 articles were used throughout the manuscript from the literature search or from alternate methods like reference checks or snowballing. Articles were sorted into categories (eg, physical infrastructure, laboratory, internal transport); for each category, a synthesis of the relevant literature was conducted to describe best practices, experiences and operational features. The review and summary of HLIU experiences, best practices, challenges and components can serve as a resource for units continuing to improve readiness, or for hospitals in early stages of developing their HLIU teams and planning or constructing their units. The COVID-19 pandemic, a global outbreak of mpox, sporadic cases of viral haemorrhagic fevers in Europe and the USA, and recent outbreaks of Lassa fever, Sudan Ebolavirus, and Marburg emphasise the need for an extensive summary of HLIU practices to inform readiness and response.


Assuntos
COVID-19 , Doenças Transmissíveis , Febres Hemorrágicas Virais , Humanos , Pandemias , COVID-19/epidemiologia , Doenças Transmissíveis/epidemiologia , Febres Hemorrágicas Virais/epidemiologia , Surtos de Doenças/prevenção & controle
2.
Antimicrob Agents Chemother ; 67(8): e0054323, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37428075

RESUMO

Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. Analyses of serial clinical isolates of any Candida species are uncommon and often analyze a limited number of samples collected over months of antifungal therapy with multiple drug classes, limiting the ability to understand relationships between drug classes and specific mutations. Here, we performed comparative genomic and phenotypic analysis of 20 serial C. lusitaniae bloodstream isolates collected daily from an individual patient treated with micafungin monotherapy during a single 11-day hospital admission. We identified isolates with decreased micafungin susceptibility 4 days after initiation of antifungal therapy and a single isolate with increased cross-resistance to micafungin and fluconazole, despite no history of azole therapy in this patient. Only 14 unique single nucleotide polymorphisms (SNPs) were identified between all 20 samples, including three different FKS1 alleles among isolates with decreased micafungin susceptibility and an ERG3 missense mutation found only in the isolate with increased cross-resistance to both micafungin and fluconazole. This is the first clinical evidence of an ERG3 mutation in C. lusitaniae that occurred during echinocandin monotherapy and is associated with cross-resistance to multiple drug classes. Overall, the evolution of multidrug resistance in C. lusitaniae is rapid and can emerge during treatment with only first-line antifungal therapy.


Assuntos
Antifúngicos , Candidíase , Humanos , Micafungina/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candida , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Farmacorresistência Fúngica/genética , Resistência a Múltiplos Medicamentos , Testes de Sensibilidade Microbiana
3.
Ther Adv Infect Dis ; 10: 20499361231179668, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37332294

RESUMO

Background: Select circumstances require outpatient parenteral antimicrobial therapy (OPAT). The potency of OPAT agents presents an increased risk of adverse events and unscheduled medical care. We analyzed these outcomes among OPAT recipients as part of the implementation of a collaborative OPAT program. Methods: Adult patients discharged home from an academic hospital with OPAT between January 2019 and June 2021 were included in this retrospective cohort; participants discharged between June 2020 and June 2021 were part of the collaborative OPAT program. Patients with cystic fibrosis were excluded. Data on patient characteristics and outcomes were collected from electronic medical records by two reviewers. Multivariable analysis was conducted to identify predictors of vascular access device (VAD) complications, adverse drug events (ADEs), and OPAT-related emergency department (ED) visits and rehospitalizations. Results: Among 265 patients included in the cohort, 57 (21.5%) patients experienced a VAD complication; obesity [odds ratio (OR): 3.32; 95% confidence interval (CI): 1.38-8.73; p = 0.01) and multi-drug therapy (OR: 2.56; 95% CI: 1.21-5.39; p = 0.01) were associated with an increased odds of VAD complication. Eighty-two (30.9%) participants experienced an ADE; 30 (11.3%) experienced a severe/serious ADE. Lipo/glycopeptide receipt, (OR: 5.28; 95% CI: 1.89-15.43; p < 0.01) and Black/African American race (OR: 4.85; 95% (CI): 1.56-15.45; p < 0.01) were associated with an increased odds of severe/serious ADE. Inclusion in the OPAT collaborative was associated with a decreased odds of severe/serious ADE (OR: 0.26; 95% CI: 0.08-0.77; p = 0.01). Fifty-eight (21.9%) patients experienced an OPAT-related ED visit and 53 (20.0%) experienced an OPAT-related rehospitalization. VAD complication (OR: 2.37; 95% (CI): 1.15-4.86, p = 0.02) and ADEs (OR: 2.19; CI: 1.13-4.22; p = 0.02) were associated with OPAT-related ED visits. ADE was associated with 90-day OPAT-related rehospitalization (OR: 3.21; (CI): 1.59-6.58; p < 0.01). Conclusion: Adverse safety events and OPAT-related unscheduled care occurred often in our cohort. A structured OPAT program that includes ID pharmacist antibiotic reconciliation may reduce rates of ADEs.

5.
Ann Intern Med ; 175(12): 1716-1727, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36442063

RESUMO

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Adulto , Humanos , Antivirais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Dexametasona , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Lancet Respir Med ; 10(9): 888-899, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35617986

RESUMO

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.


Assuntos
Tratamento Farmacológico da COVID-19 , Adolescente , Adulto , Azetidinas , Dexametasona , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas , Resultado do Tratamento
8.
Health Secur ; 20(S1): S4-S12, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483049

RESUMO

The National Emerging Special Pathogens Training and Education Center (NETEC) was established in 2015 to improve the capabilities of healthcare facilities to provide safe and effective care to patients with Ebola and other special pathogens in the United States. Through NETEC, a collaborative network of 10 Regional Emerging Special Pathogen Treatment Centers (RESPTCs) undertook readiness activities that included potential respiratory pathogens. These preparations, which took place before the COVID-19 pandemic, established a foundation of readiness that enabled RESPTCs to play a pivotal role in the US COVID-19 pandemic response. As initial COVID-19 cases were detected in the United States, RESPTCs provided essential isolation capacity, supplies, and subject matter expertise that allowed for additional time for healthcare systems to prepare. Through the Special Pathogen Research Network, RESPTCs rapidly enrolled patients into early clinical trials. During periods of high community transmission, RESPTCs provided educational, clinical, and logistical support to a wide range of healthcare and nonhealthcare settings. In this article, we describe how NETEC and the RESPTC network leveraged this foundation of special pathogen readiness to strengthen the national healthcare system's response to the COVID-19 pandemic. NETEC and the RESPTC network have proven to be an effective model that can support the national response to future emerging special pathogens.


Assuntos
COVID-19 , Doença pelo Vírus Ebola , Humanos , Controle de Infecções , Pandemias/prevenção & controle , Isolamento de Pacientes , Estados Unidos/epidemiologia
9.
PLoS One ; 17(4): e0266410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35468153

RESUMO

BACKGROUND: Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection. METHODS: We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20-02/21/21 and in round 2 from 12/18/20-02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity. RESULTS: In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician's Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68]. CONCLUSIONS: SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting-particularly working in the ICU-is associated with higher risk for SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Vacinas contra COVID-19 , Criança , Pessoal de Saúde , Humanos , Estudos Soroepidemiológicos
10.
Mayo Clin Proc ; 97(4): 754-760, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379422

RESUMO

Most SARS-CoV-2 antibody assays cannot distinguish between antibodies that developed after natural infection and those that developed after vaccination. We assessed the accuracy of a nucleocapsid-containing assay in identifying natural infection among vaccinated individuals. A longitudinal cohort composed of health care workers in the Minneapolis/St. Paul area was enrolled. Two rounds of seroprevalence studies separated by 1 month were conducted from November 2020 to January 2021 among 81 participants. Capillary blood from rounds 1 and 2 was tested for IgG antibodies against spike proteins by enzyme-linked immunosorbent assay (spike-only assay). During round 2, IgGs reactive to SARS-CoV-2 nucleocapsid protein (nucleocapsid-containing assay) were assessed. Vaccination status at round 2 was determined by self-report. Area under the curve was computed to determine the discriminatory ability of the nucleocapsid-containing assay for identification of recent infection. Participants had a mean age of 40 years (range, 23 to 66 years); 83% were female. Round 1 seroprevalence was 9.5%. Before round 2 testing, 46% reported vaccination. Among those not recently infected, in comparing vaccinated vs unvaccinated individuals, elevated levels of spike 1 (P<.001) and spike 2 (P=.01) were observed, whereas nucleocapsid levels were not statistically significantly different (P=.90). Among all participants, nucleocapsid response predicted recent infection with an area under the curve of 0.93 (95% CI, 0.88 to 0.99). Among individuals vaccinated more than 10 days before antibody testing, the specificity of the nucleocapsid-containing assay was 92%, whereas the specificity of the spike-only assay was 0%. An IgG assay identifying reactivity to nucleocapsid protein is an accurate predictor of natural infection among a partially vaccinated population, whereas a spike-only assay performed poorly.


Assuntos
COVID-19 , Adulto , Idoso , Anticorpos Antivirais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto Jovem
11.
Access Microbiol ; 4(1): 000316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252754

RESUMO

Staphylococcus aureus (SA) colonization has significant implications in healthcare-associated infections. Here we describe a prospective study conducted in pre-surgical outpatients, done with the aim of identifying demographic and clinical risk factors for SA colonization. We found younger age to be a potential predictor of SA colonization.

12.
Infect Control Hosp Epidemiol ; 43(5): 657-660, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33706827

RESUMO

Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Atenção à Saúde , Pessoal de Saúde , Humanos , Programas de Rastreamento
13.
Lancet Respir Med ; 9(12): 1365-1376, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34672949

RESUMO

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Interferon beta-1a/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , México , Pessoa de Meia-Idade , Oxigênio , Saturação de Oxigênio , República da Coreia , SARS-CoV-2 , Singapura , Resultado do Tratamento , Estados Unidos
14.
medRxiv ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33907763

RESUMO

IMPORTANCE: Identification of SARS-CoV-2 infection via antibody assays is important for monitoring natural infection rates. Most antibody assays cannot distinguish natural infection from vaccination. OBJECTIVE: To assess the accuracy of a nucleocapsid-containing assay in identifying natural infection among vaccinated individuals. DESIGN: A longitudinal cohort comprised of healthcare workers (HCW) in the Minneapolis/St. Paul metropolitan area was enrolled. Two rounds of seroprevalence studies separated by one month were conducted from 11/2020-1/2021. Capillary blood from round 1 and 2 was tested for IgG antibodies against SARS-CoV-2 spike proteins with a qualitative chemiluminescent ELISA (spike-only assay). In a subsample of participants (n=82) at round 2, a second assay was performed that measured IgGs reactive to SARS-CoV-2 nucleocapsid protein (nucleocapsid-containing assay). Round 1 biospecimen collections occurred prior to vaccination in all participants. Vaccination status at round 2 was determined via self-report. SETTING: The Minneapolis/St. Paul, Minnesota metropolitan area. PARTICIPANTS: HCW age 18-80 years. EXPOSURES: Round 1 recent SARS-CoV-2 infection assessed via a spike-only assay and participant self-report. OUTCOMES: Round 2 SARS-CoV-2 infection assessed via the nucleocapsid-containing assay. Area under the curve (AUC) was computed to determine the discriminatory ability of round 2 IgG reactivity to nucleocapsid for identification of recent infection determined during round 1. RESULTS: Participants had a mean age of 40 (range=23-66) years, 83% were female, 46% reported vaccination prior to the round 2 testing. Round 1 seroprevalence was 9.5%. Among those not recently infected, when comparing vaccinated vs. unvaccinated individuals, elevated levels of spike 1 (p<0.001) and spike 2 (p=0.01) were observed while nucleocapsid levels were not statistically significantly different (p=0.90). Among all participants, nucleocapsid response predicted recent infection with an AUC(95%CI) of 0.93(0.88,0.99). Among individuals vaccinated >10 days prior to antibody testing, the specificity of the nucleocapsid-containing assay was 92% and while the specificity of the spike-only assay was 0%. CONCLUSIONS AND RELEVANCE: An IgG assay identifying reactivity to nucleocapsid protein is an accurate predictor of natural infection among vaccinated individuals while a spike-only assay performed poorly. In the era of SARS-CoV-2 vaccination, seroprevalence studies monitoring natural infection will require assays that do not rely on spike-protein response alone.

15.
J Infect Dis ; 223(8): 1339-1344, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33476387

RESUMO

Coronavirus disease 2019 (COVID-19) outcomes are linked to host immune responses and may be affected by antiviral therapy. We investigated antibody and cytokine responses in ACTT-1 study participants enrolled at our center. We studied serum specimens from 19 hospitalized adults with COVID-19 randomized to treatment with remdesivir or placebo. We assessed severe acute respiratory syndrome coronavirus 2 antibody responses and identified cytokine signatures, using hierarchical clustering. We identified no clear immunologic trends attributable to remdesivir treatment. Seven participants were initially seronegative at study enrollment, and all 4 deaths occurred in this group with more recent symptom onset. We identified 3 dominant cytokine signatures, demonstrating different disease trajectories.


Assuntos
COVID-19/imunologia , COVID-19/mortalidade , Imunidade/imunologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/imunologia , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/análogos & derivados , Alanina/imunologia , Alanina/uso terapêutico , Anticorpos Antivirais/imunologia , Antivirais/imunologia , Antivirais/uso terapêutico , COVID-19/virologia , Citocinas/imunologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Masculino , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Tratamento Farmacológico da COVID-19
16.
N Engl J Med ; 384(9): 795-807, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33306283

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Azetidinas/uso terapêutico , Tratamento Farmacológico da COVID-19 , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Azetidinas/efeitos adversos , COVID-19/mortalidade , COVID-19/terapia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Respiração Artificial , Sulfonamidas/efeitos adversos , Resultado do Tratamento
17.
medRxiv ; 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-32793921

RESUMO

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals and some patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. Limited data are available on the point prevalence of SARS-CoV-2 infection in symptom-free U.S. healthcare workers (HCW). METHODS: A cross-sectional convenience sample of symptom-free HCWs from the metropolitan area surrounding Minneapolis and St. Paul, Minnesota was enrolled between April 20 th and June 24 th , 2020. A participant self-collected nasopharyngeal swab (NPS) was obtained. SARS-CoV-2 infection was assessed via polymerase chain reaction. Participants were queried about their willingness to repeat a self-collection NPS for diagnostic purposes. We had >95% power to detect at least one positive test if the true underlying prevalence of SARS-CoV2 was ≥1%. RESULTS: Among n=489 participants 80% were female and mean age±SD was 41±11. Participants reported being physicians (14%), nurse practitioners (8%), physician's assistants (4%), nurses (51%), medics (3%), or other which predominantly included laboratory technicians and administrative roles (22%). Exposure to a known/suspected COVID-19 case in the 14 days prior to enrollment was reported in 40% of participants. SARS-CoV-2 was not detected in any participant. Over 95% of participants reported a willingness to repeat a self-collected NP swab in the future. CONCLUSIONS: The point prevalence of SARS-CoV-2 infection was likely <1% in a convenience sample of symptom-free Minnesota healthcare workers from April 20 th and June 24 th , 2020. Self-collected NP swabs are well-tolerated and a viable alternative to provider-collected swabs to preserve PPE.

18.
Mayo Clin Proc ; 95(9): 1946-1954, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32861338

RESUMO

On May 1, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow use of the antiviral drug remdesivir to treat patients with severe coronavirus disease-2019 (COVID-19). Remdesivir is an investigational drug studied in clinical trials for COVID-19 and is available to children and pregnant women through compassionate-use access but is not yet FDA approved. In early May, the US Department of Health and Human Services began to distribute remdesivir, donated by Gilead Sciences, Inc., to hospitals and state health departments for emergency use; multiple shipments have since been distributed. This process has raised questions of how remdesivir should be allocated. The Minnesota Department of Health has collaborated with the Minnesota COVID Ethics Collaborative and multiple clinical experts to issue an Ethical Framework for May 2020 Allocation of Remdesivir in the COVID-19 Pandemic. The framework builds on extensive ethical guidance developed for public health emergencies in Minnesota before the COVID-19 crisis. The Minnesota remdesivir allocation framework specifies an ethical approach to distributing the drug to facilities across the state and then among COVID-19 patients within each facility. This article describes the process of developing the framework and adjustments in the framework over time with emergence of new data, analyzes key issues addressed, and suggests next steps. Sharing this framework and the development process can encourage transparency and may be useful to other states formulating and refining their approach to remdesivir EUA allocation.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/provisão & distribuição , Infecções por Coronavirus/tratamento farmacológico , Alocação de Recursos para a Atenção à Saúde/ética , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/provisão & distribuição , Alanina/provisão & distribuição , Betacoronavirus , COVID-19 , Drogas em Investigação/provisão & distribuição , Humanos , Minnesota , Pandemias , SARS-CoV-2 , Estados Unidos , United States Food and Drug Administration
19.
N Engl J Med ; 383(19): 1813-1826, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32445440

RESUMO

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Método Duplo-Cego , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Respiração Artificial , SARS-CoV-2 , Fatores de Tempo , Adulto Jovem , Tratamento Farmacológico da COVID-19
20.
Open Forum Infect Dis ; 7(1): ofaa010, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993451

RESUMO

We evaluated the association between infectious disease consultation and bloodstream infection outcomes, including methicillin-resistant Staphylococcus aureus, Candida, and Pseudomonas. No infectious diseases consultation was associated with over 4-fold increased hazard of death at 3 months and 6-fold increased hazard of death in hospital.

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