ABSTRACT
Introducao: O padrao-ouro para o diagnostico de COVID-19 e o teste molecular que permite a deteccao de acidos nucleicos de SARS-CoV-2 em amostras de swab Nasofaringeo (NPS). A deteccao precoce seguida do isolamento dos individuos infectados desempenha um papel crucial para impedir a propagacao da infeccao e o controle da pandemia. No entanto, a coleta de NPS e invasiva e desconfortavel para os pacientes, requer profissionais de saude especializados e pode ser um risco de infeccao cruzada para esses profissionais. Desta forma, avaliar outras fontes de material biologico, tal como a saliva, e fundamental para facilitar o diagnostico de COVID-19. Objetivo: O objetivo deste trabalho foi avaliar o uso da saliva como amostra biologica para a deteccao do RNA do SARS-CoV-2 e sua estabilidade pos coleta. Material e Metodos: Foram coletadas 954 amostras de saliva (5 mL) e de swab nasofaringeo (NPS) de individuos entre dezembro de 2020 e fevereiro de 2021 e analisadas em diferentes tempos (24h, 48h, 72h, 5 dias e 10 dias) apos a coleta. As amostras de saliva foram armazenadas em temperatura de 2degree a 8degreeC e extraidas puras e diluidas em solucao salina na proporcao 1:1. A extracao do RNA foi realizada em extrator automatico de acidos nucleicos (Extracta, Loccus) e o diagnostico molecular do SARS-CoV-2 foi realizado com o kit Gene FinderTM COVID-19 Plus RealAmp (OSang Healthcare). A idade media dos participantes foi de 37 anos (8 a 83 anos de idade) e a maioria dos individuos 738 (77,3%) foram nao-detectaveis e apenas 216 (22,7%) foram detectaveis para SARS-CoV-2. Entre os detectaveis, 96 (44,4%%) eram do sexo masculino e 120 (55,6%) do sexo feminino. A positividade na saliva foi posteriormente comparada com os resultados do NPS bem como a carga viral ou ciclo de limiar de amplificacao (Ct). Resultados e Discussao: A analise dos testes com a saliva e NPS demonstrou concordancia nos resultados de 210 (97%) pacientes detectaveis para COVID, em apenas 2,7 % (6/216) dos casos o SARS-CoV-2 foi detectado somente no NPS. Todos os participantes com resultado positivo para a RT-PCR apresentaram sintomas relacionados a COVID-19, sendo os mais comuns: tosse seca (19%), dor de cabeca (16%), coriza e dor de garganta (11%) e diarreia (8%). As amostras de salivas apresentaram estabilidade ate o decimo dia apos a coleta do material biologico, sem diferenca de deteccao do RNA viral entre a amostra de saliva pura e saliva diluida. Esses resultados demonstram que as amostras de saliva podem ser transportadas e armazenadas em temperatura de 2degree a 8degreeC, e processadas em ate 10 dias apos a coleta. Conclusao: Os resultados mostraram que a saliva e uma alternativa para a deteccao de SARS-CoV-2. E uma amostra biologica confiavel, nao invasiva, de facil coleta e com resultados similares aos obtidos com amostras de NPS. E uma alternativa que facilitaria a coleta em lugares com baixo suprimento de swabs nasofaringeos e regioes distantes de laboratorios especializados, uma vez que pode ser analisada ate 10 dias apos a coleta. Dessa forma, podemos concluir que a saliva pode ser utilizada com seguranca para o diagnostico de COVID-19. Copyright © 2022
ABSTRACT
Background: Severe aplastic anemia (SAA) is a rare bone marrow failure disorder associated with significant morbidity and mortality. SAA is characterized by severe pancytopenia and a hypocellular (<25%) bone marrow. The standard of care treatment is hemopoietic stem cell transplant or immunosuppressive therapy (IST) for patients (pts) who are ineligible for transplant. IST usually comprises an antithymocyte globulin (ATG) derived from horse or rabbit, and cyclosporine A (CsA). Although IST can be an effective treatment, individual intolerance, insufficient response, relapse, and clonal evolution remain significant limitations. The lack of global availability of the more effective horse ATG also leaves many pts with limited treatment options and poorer outcomes. In addition, pts with SAA often require transfusions which can be burdensome and negatively impact their quality of life. Eltrombopag (ETB) is indicated for use in pts with SAA who have had an insufficient response to IST (FDA PI, 2014) or are refractory to IST (EMA SmPC, 2015). More recently in the USA, ETB may also be used in combination with IST as first-line (1L) treatment (FDA PI, 2018). Aims: To assess the efficacy and safety of ETB + CsA (without ATG) as 1L therapy in adult pts with SAA. Methods: SOAR (NCT02998645) is a Phase 2, single-arm, multicenter, open-label study. Treatment-naive pts with SAA received ETB + CsA for 6 months;responders continued CsA therapy for an additional 24 months (later reduced to 18 months). The primary efficacy endpoint was overall response rate (ORR) by 6 months. ORR was defined as the proportion of pts with complete response ([CR] = absolute neutrophil count [ANC] ≥1000/μL AND platelet count ≥100,000/μL AND hemoglobin ≥10 g/dL) plus the proportion of pts with partial response ([PR] = any 2 of the following counts: ANC ≥500/μL;platelet count ≥20,000/μL;automated reticulocyte count ≥60,000/μL, but not sufficient for a CR). CR and PR were confirmed by 2 assessments ≥7 days apart;transfusion restrictions were also applied. For the primary endpoint to be considered ‘clinically meaningful’ at least 17/54 pts treated were required to have a response. Other endpoints included ORR by 3 months, ORR at 6 months (ie, confirmed response at the 6-month visit), and transfusion independence, which was defined as transfusion not being required in a period of ≥28 days for platelet transfusions and ≥56 days for red blood cell (RBC) transfusions. Results: Pts (N=54) had a median (interquartile range [IQR]) age of 55.0 (40.0-67.0) years and 63.0% were male. The majority of pts were White (40.7%) or Asian (40.7%). The median (IQR) duration of exposure to ETB and CsA was 5.7 (2.5-5.8) months and 5.7 (2.4-8.1) months, respectively, and the median (IQR) daily ETB dose was 150.0 (100.0-150.0) mg/day. In the full analysis set, the primary endpoint was met, with 25/54 pts having a CR or PR by 6 months (ORR 46.3%;95% confidence interval [CI], 32.6-60.4%). Of the 25 responders, 2 (3.7%) achieved a CR by 6 months. ORR by 3 months was 40.7% (95% CI, 27.6-55.0%;n=22/54), and ORR at 6 months was 37.0% (95% CI, 24.3-51.3%;n=20/54). 70.4% of all pts qualified for ≥1 period of RBC and/or platelet transfusion independence by 6 months, including all 25 (100%) responders and 13/29 (44.8%) non-responders (Fig. 1). 40.7% of all pts (responders: 68.0%;non-responders: 17.2%) qualified for ≥1 period of RBC transfusion independence (corresponding percentages for platelet transfusion independence were the same as for the combined RBC and/or platelet endpoint). Adverse events (AEs) occurred in 52/54 (96.3%) pts;45 (83.3%) pts experienced treatment-related AEs (TAEs), 23 (42.6%) of whom had a grade ≥3 TAE. The most common all-grade AEs were increased blood bilirubin (40.7%), nausea (29.6%), increased alanine aminotransferase (22.2%), and diarrhea (22.2%). Seven (13.0%) pts discontinued treatment due to grade ≥3 AEs. There were 8 on-treatment deaths (aplastic anemia [n=3];COVID-19, hemorrhage, multi-organ dysfunction syndrom , pyrexia, and thrombosis [all n=1]);no deaths were considered treatment-related. Conclusion: Data from the SOAR study indicate that ETB + CsA may be beneficial for pts with SAA ineligible for transplant who cannot access or tolerate ATG. All responders and almost half of non-responders qualified for ≥1 period of transfusion independence by 6 months, suggestive of a decreased transfusion burden. No new safety signals were identified. [Formula presented] Disclosures: Vallejo: Novartis: Honoraria;Sanofi: Honoraria;Pfizer: Honoraria. Finelli: Takeda: Consultancy;Celgene BMS: Consultancy, Research Funding, Speakers Bureau;Novartis: Consultancy, Speakers Bureau. Calado: Agios: Membership on an entity's Board of Directors or advisory committees;AA&MDS International Foundation: Research Funding;Alexion Brasil: Consultancy;Instituto Butantan: Consultancy;Novartis Brasil: Honoraria;Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees. Peffault De Latour: Novartis: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria, Research Funding;Amgen: Research Funding;Alexion: Consultancy, Honoraria, Research Funding;Apellis Pharmaceuticals Inc: Consultancy, Honoraria;Swedish Orphan Biovitrum AB: Consultancy, Honoraria. Kriemler-Krahn: Novartis: Current Employment. Haenig: Novartis: Current Employment. Maier: Novartis: Current Employment. Scheinberg: Alexion pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;BioCryst Pharmaceuticals: Consultancy;Roche: Consultancy;Abbvie: Consultancy. OffLabel Disclosure: In the United States, eltrombopag is a thrombopoietin receptor agonist indicated in combination with standard immunosuppressive therapy (ATG + CsA) for the first-line treatment of adult and pediatric patients aged 2 years and older with severe aplastic anemia (SAA). It is also indicated for the treatment of patients with SAA who have had an insufficient response to immunosuppressive therapy. The SOAR trial aims to assess the efficacy and safety of eltrombopag + CsA (without ATG) as first-line therapy in adult patients with SAA.
ABSTRACT
COVID-19 is an infectious disease caused by the virus SARS-CoV-2, which was first described at the end of 2019. Since then, it has affected a growing portion of the world's population because of its high transmissibility. Most patients are asymptomatic or present with mild symptoms, but approximately 5-10% of cases can develop more serious manifestations, such as severe acute respiratory syndrome, acute kidney injury, shock, myocardial injury and even death. These features seem to occur more commonly in patients with essential hypertension, diabetes mellitus, obesity and chronic pulmonary disease. However, there are few studies that clarify the natural history of the disease and its broad clinical spectrum owing to the fact that it is a new entity. Since individuals with malignancies tend to present some degree of immunological deficiency and are more prone to opportunistic infections, especially those being treated with immunosuppressive drugs, it is possible that this group has a higher incidence of COVID-19. The current recommendations of oncology specialists advise to postpone treatments and to use less toxic drugs when possible. However, we still do not know how much these measures will affect in cancer mortality. Also, the incidence of COVID-19 in this population remains undetermined. We do not know if infectious symptoms are a good parameter to motivate these therapeutic changes or if there is benefit to test asymptomatic patients. In this context, this research submitted 100 patients with hematological malignancies or solid tumors on chemotherapy at the Ribeirão Preto Medical School of the University of São Paulo's Hospital, asymptomatic for COVID-19, to RT PCR to determine the SARS-CoV-2 infection incidence in this population. Only two patients were diagnosed with COVID-19. Both had gastrointestinal cancer. One of them developed symptoms, but none presented severe manifestations. Both had their treatment postponed initially and reinitiated after the appropriate period of isolation. Hence, we believe that it's reasonable not to test every asymptomatic patient when the resource for that is scarce, prioritizing those at greater risk of infection and those more prone to severe outcomes as long as the appropriate preventive measures are being taken. Disclosures: Calado: Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees;Agios: Membership on an entity's Board of Directors or advisory committees;Instituto Butantan: Consultancy;Alexion Brasil: Consultancy;AA&MDS International Foundation: Research Funding;Novartis Brasil: Honoraria.