Prevalence Characteristics and Outcomes of Covid 19 Associated Acute Myocarditis

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Method(s): A total of 112 patients with suspected AM from 56963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. Result(s): AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty- one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47;P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). Conclusion(s): AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

MONTAGEM DE UM EVENTO COM IMPLANTAÇÃO DE PROCESSO DE SEGURANÇA QUANTO AO RISCO DE CONTAMINAÇÃO PELA COVID-19

Em virtude ao significativo risco à saúde pública que a COVID-19 representa para o mundo, as empresas comprometidas com a ciência, têm se empenhado para coordenar respostas de prevenção e combate à doença. O comportamento e a capacidade de transmissão da doença propõem desafios físicos e emocionais para população e exige uma grande reorganização das estruturas tradicionais já existentes. Isto não foi diferente com o setor de eventos no Brasil que sofreu significativamente com a queda na realização dos eventos presenciais. Como se pode imaginar, a situação afetou 98% das empresas do setor. E para a retomada no modelo virtual, houve uma grande necessidade de adequação de todos os processos, principalmente o que envolve a segurança da equipe de organização. Estabelecer um protocolo com testes antes da entrada da equipe no local selecionado (centro de convenções). Padronizar um protocolo de segurança diária. Padronizar protocolo de segurança quanto ao uso de EPI, aferição de temperatura, monitoramento de distanciamento social durante trabalho e refeições, sem acesso externo ao local e acomodação em apartamentos individuais. O tipo de EPI foi escolhido de acordo com o nível de precaução necessária, como padrão de contato, produção de gotículas/aerossóis ou precauções para infecções transportadas pelo ar. O procedimento para colocar e remover EPIs deve ser adaptado ao tipo utilizado. As medidas de prevenção e controle foram implementadas por toda a equipe de eventos para evitar ou reduzir ao máximo a transmissão de microrganismos. As regras e orientações para colocação, uso, retirada e descarte correto e seguro dos EPIs foram divulgadas previamente. Executado análise de todos os testes possíveis, sendo que o teste de saliva apresentou especificidade: >99% e sensibilidade: 80%, custo comparado com o mercado, acessível e com resultado em até 24 horas. Elaborado protocolo de segurança quanto ao uso de EPI, aferição de temperatura, monitoramento de distanciamento social e protocolo para casos com resultado de teste positivo na entrada, durante o período de trabalho e saída, com encaminhamento a um hospital de referência para atendimento. Foram realizados 96 testes sendo 48 iniciais e 48 finais tendo todos os resultados negativos (100%). Foram executados 2 testes sorológicos com resultado somente de IgG positivo, sem risco de contaminação. Monitorado continuamente o uso de EPI, aferição de temperatura, possíveis aglomerações. Não foi apresentado resultado positivo durante o evento. Não houve compartilhamento de equipamentos e materiais de uso de trabalho. Com um protocolo de trabalho padronizado, testes validados e executados de forma segura, os envolvidos orientados e respeitando os critérios de segurança, podemos garantir que mesmo havendo risco quanto à contaminação do COVID-19, o evento foi realizado de forma confiável e atingiu seu objetivo, alcançando resultado de 100% com relação à segurança.

EXECUÇÃO DE AUDITORIA INTERNACIONAL DE FORMA HIBRIDA DURANTE A PANDEMIA DO COVID-19

Garantir a segurança quanto ao risco de contaminação do COVID-19 durante um processo de auditoria híbrido, com auditores presenciais e on-line. Os efeitos gerados pela pandemia COVID-19, trouxe a necessidade de mudança e adaptação em vários conceitos de negócios e a execução de auditorias externas foi um deles. Tratando-se de um processo com avaliadores internacionais, os efeitos foram ainda maiores devido o fechamento de fronteiras, riscos de contaminação, entre outros itens conhecidos. A preocupação para execução deste procedimento foi garantir que as políticas e as boas práticas minimizassem a exposição a patógenos respiratórios, incluindo o SARS-CoV-2. Desta forma, tendo em vista a grande possibilidade de transmissibilidade, as medidas de prevenção e controle junto aos auditores deste processo foram implementadas em todas as etapas, desde a seleção de auditores pois alguns poderiam apresentar um risco acrescido devido a alguma comorbidade, hospedagem, deslocamento, orientação aos procedimentos a serem utilizados no serviço, durante toda a auditoria e até seu retorno. Estabelecer uma política de segurança durante a execução de visita de acreditação e reacreditação em serviços de bancos de sangue, serviços de transfusão e de terapia celular no padrão AABB/ABHH com auditores presenciais e on line. Padronizar protocolo de segurança, seleção de auditores que não apresentavam nenhuma comorbidade que pudesse acarretar em risco acrescido, treinamentos quanto ao novo fluxo e uso de Equipamentos de Proteção Individual (EPI), fluxo durante os deslocamentos, reuniões, refeições, hospedagem e todo o processo de auditoria. Avaliar a possibilidade de aceitação dos serviços quanto ao recebimento dos auditores presenciais e on line. Analisar a autorização de execução de auditor internacional de forma on lie pela AABB. Foi padronizada a política de segurança, elaboração de procedimento operacional e treinamento de todos os auditores antes da execução da auditoria. Executado levantamento de toda a segurança necessária para execução das visitas de acreditação e reacreditação nos serviços de bancos de sangue, serviços de transfusão e de terapia. Apresentado a política e o procedimento operacional a todos os serviços e com aceite de todos quanto a execução. Executado análise de saúde do auditor antes e durante e no término das auditorias. Implementado fluxo com uso de plataformas on-line para que os auditores internacionais pudessem avaliar os processos em tempo real. Execução de reunião de abertura, fechamento e durante avaliação entre auditores brasileiros e internacionais sem nenhum dano neste fluxo. Executado análise de todos os serviços quanto a mudança na execução de auditoria e o resultado quanto a aprovação foi unanime. Consideramos que a mudança foi necessária, com minimização de riscos, custos e desgastes e aumento quanto a confiabilidade de todos os serviços/clientes quanto a execução, podemos afirmar que este processo foi de caráter positivo e que permanecerá como uma segunda opção dentro deste ciclo. Com um protocolo de trabalho padronizado, testes validados e executados de forma controlada, todos os envolvidos orientados e respeitando os critérios de segurança garantimos que mesmo com um risco quanto a contaminação do COVID-19 todas as auditorias foram executadas de forma confiável tendo resultado de 100% quanto a segurança, confiabilidade, satisfação do cliente e de todos os participantes.

Pancarditis as the Clinical Presentation of Eosinophilic Granulomatosis with Polyangiitis: A Multimodality Approach to Diagnosis

Eosinophilic pancarditis (EP) is a rare, often unrecognized condition caused by endomyocardial infiltration of eosinophil granulocytes (referred as eosinophilic myocarditis, EM) associated with pericardial involvement. EM has a variable clinical presentation, ranging from asymptomatic cases to acute cardiogenic shock requiring mechanical circulatory support (MCS) or chronic restrictive cardiomyopathy at high risk of progression to dilated cardiomyopathy (DCM). EP is associated with high in‐hospital mortality, particularly when associated to endomyocardial thrombosis, coronary arteries vasculitis or severe left ventricular systolic dysfunction. To date, there is a lack of consensus about the optimal diagnostic algorithm and clinical management of patients with biopsy‐proven EP. The differential diagnosis includes hypersensitivity myocarditis, eosinophil granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome, parasitic infections, pregnancy‐related hypereosinophilia, malignancies, drug overdose (particularly clozapine) and Omenn syndrome (OMIM 603554). To our knowledge, we report the first case of pancarditis associated to eosinophilic granulomatosis with polyangiitis (EGPA) with negative anti‐neutrophil cytoplasmic antibodies (ANCA). Treatment with steroids and azathioprine was promptly started. Six months later, the patient developed a relapse: treatment with subcutaneous mepolizumab was added on the top of standard therapy, with prompt disease activity remission. This case highlights the role of a multimodality approach for the diagnosis of cardiac involvement associated to systemic immune disorders.

Risk of Post-COVID-19 Dyspnea and Interstitial Lung Disease (ILD) in a Real-World Cohort of Patients Hospitalized with COVID-19 in the United States

Background. While COVID-19 carries substantial morbidity and mortality, the extent of long-term complications remains unclear. Reports suggest that acute lung damage associated with severe COVID-19 can result in chronic respiratory dysfunction. This study: (1) estimated the incidence of dyspnea and ILD after COVID-19 hospitalization, and (2) assessed risk factors for developing dyspnea and ILD in a real-world cohort of patients hospitalized with COVID-19 using US electronic health records (EHR). Methods. Patients in the Optum de-identified COVID-19 EHR database who were hospitalized for COVID-19 (lab confirmed or diagnosis code) between February 20 and July 2020 and had at least 6 months of follow-up were eligible for analysis. Dyspnea and ILD were identified using diagnosis codes. The effects of baseline characteristics and hospitalization factors on the risk of incident dyspnea or ILD 3 to 6 months' post discharge were evaluated. Results. Among eligible patients (n=26,339), 1705 (6.5%) had dyspnea and 220 (0.8%) had ILD 3 to 6 months after discharge. Among patients without prior dyspnea or ILD (n=22,613), 110 (0.5%) had incident ILD (Table 1) and 1036 (4.6%) had incident dyspnea (Table 2) 3 to 6 months after discharge. In multivariate analyses, median (IQR) length of stay (LOS;5.0 [3.0, 9.0] days in patients who did not develop ILD vs 14.5 [6.0, 26.0] days in patients who developed ILD;RR: 1.12, 95% CI: 1.08, 1.15;P=4.34 x 10-10) and age (RR: 1.02, 95% CI: 1.01, 1.03;P=4.63 x 10-3) were significantly associated with ILD. Median (IQR) LOS (5.0 [3.0, 9.0] days in patients who did not develop dyspnea vs 7 [4.0, 14.0] days in patients who developed dyspnea;RR: 1.04, 95% CI: 1.02, 1.06;P=8.52 x 10-4), number of high-risk comorbidities (RR: 1.18, 95% CI: 1.12, 1.24;P=3.85 x 10-9), and obesity (RR: 1.52, 95% CI: 1.25, 1.86;P=2.59 x 10-4) were significantly associated with dyspnea. Conclusion. In a real-world cohort, 4.6% and 0.5% of patients developed dyspnea and ILD, respectively, after COVID-19 hospitalization. Multivariate analyses suggested that LOS, age, obesity, and comorbidity burden may be risk factors for post-COVID-19 respiratory complications. Limitations included sensitivity of diagnosis codes, availability of labs, and care-seeking bias.

Prevalence of Influenza Co-infection in a Real-world Cohort of COVID-19 Patients in the U.S

Background. Over 29 million people have been infected with COVID-19 in the U.S. alone. While COVID-19 carries serious morbidity and mortality, potential for co-infection with other respiratory infections remains unclear. We aimed to: (1) estimate co-infection prevalence of COVID-19 and influenza, and (2) compare demographics and clinical outcomes of co-infected patients to those of COVID-19 singly-infected patients using U.S. electronic health records (EHR). Methods. Patients in the Optum De-identified COVID-19 EHR database diagnosed with COVID-19 (lab-confirmed or ICD code) between February 2020 and January 2021 were eligible. Influenza co-infection was defined as an influenza diagnosis (lab-confirmed or ICD code) within ±10 days of COVID-19 diagnosis. We report co-infection prevalence for all COVID-19 patients and for a subset of hospitalized COVID-19 patients. Results. Among all COVID-19 patients (N = 549,532), 1,794 (0.3%) were co-infected with influenza. Among the hospitalized subset (N = 80,192), 242 (0.3%) were co-infected with influenza. In sensitivity analyses restricting to lab-confirmed influenza, co-infection prevalence was 0.1% overall and 0.2% among hospitalized patients. No meaningful differences were observed in baseline demographics between co-infected and singly-infected patients. Among hospitalized patients, univariate analysis suggested higher likelihood of invasive ventilation (12.8% vs. 9.8%;p=0.14), respiratory failure (56.2% vs. 46.6%, p< 0.01), and ICU stay (27.3% vs. 23.1%, p=0.13), but no meaningful difference in mortality (13.3% vs. 13.0%, p=0.97), for co-infected as compared to singly-infected COVID-19 patients. Conclusion. In a real-world cohort, we observed a low proportion (0.3%) of COVID-19 patients co-infected with influenza. Co-infected patients had similar baseline characteristics but higher likelihood of hospitalization severity as compared to singly-infected COVID-19 patients. Limitations include low prevalence of circulating influenza and potential missing data bias.

Risk Factors for COVID-19 Disease Severity Using Electronic-Health Records in a Real-World Cohort in the United States

Background. Over 32 million cases of COVID-19 have been reported in the US. Outcomes range from mild upper respiratory infection to hospitalization, acute respiratory failure, and death. We assessed risk factors associated with severe disease, defined as hospitalization within 21 days of diagnosis or death, using US electronic health records (EHR). Methods. Patients in the Optum de-identified COVID-19 EHR database who were diagnosed with COVID-19 in 2020 were included in the analysis. Regularized multivariable logistic regression was used to identify risk factors for severe disease. Covariates included demographics, comorbidities, history of influenza vaccination, and calendar time. Results. Of the 193,454 eligible patients, 36,043 (18.6%) were hospitalized within 21 days of COVID-19 diagnosis, and 6,397 (3.3%) died. Calendar time followed an inverse J-shaped relationship where severe disease rates rapidly declined in the first 25 weeks of the pandemic. BMI followed an asymmetric V-shaped relationship with highest rates of disease severity observed at the extremes. In the multivariable model, older age had the strongest association with disease severity (odds ratios and 95% confidence intervals of significant associations in Figure). Other risk factors were male sex, uninsured status, underweight and obese BMI, higher Charlson Comorbidity Index, and individual comorbidities including hypertension. Asthma and overweight BMI were not associated with disease severity. Blacks, Hispanics, and Asians experienced higher odds of disease severity compared to Whites. Conclusion. Odds of hospitalization or death have decreased since the start of the pandemic, with the steepest decline observed up to mid-August, possibly reflecting changes in both testing and treatment. Older age is the most important predictor of severe COVID-19. Obese and underweight, but not overweight, BMI were associated with increased odds of disease severity when compared to normal weight. Hypertension, despite not being included in many guidelines for vaccine prioritization, is a significant risk factor. Pronounced health disparities remain across race and ethnicity after accounting for comorbidities, with minorities experiencing higher disease severity.

Evolution of Treatment Patterns for Patients Hospitalized with COVID-19 in the United States

Background. COVID-19 remains a threat to public health, with over 30 million cases in the US alone. As understanding of optimal patient care has improved, treatment guidelines have continued to evolve. This study characterized real-world trends in treatment for US patients hospitalized with COVID-19, stratified by whether patients required invasive ventilation. Methods. US patients diagnosed and hospitalized with COVID-19 between March 23 and December 31, 2020, in the Optum de-identified COVID-19 electronic health record (EHR) data set were identified. Both drug and procedure codes were used to ascertain medications, and both procedure and diagnostic codes were used to detect invasive ventilation during hospitalization. Medication trends were estimated by computing proportions of hospitalized patients receiving each drug weekly during the study period. Results. In this cohort of 71,366 hospitalized patients, the largest observed change in care was related to chloroquine/hydroxychloroquine (HCQ) (Figure). HCQ usage peaked at 87% of patients receiving invasive ventilation (54% without ventilation) in the first week of this study (March 23-29), but declined to < 5% of patients, regardless of ventilation status, by the end of May. In contrast, dexamethasone usage was 10% at baseline in patients receiving ventilation (1% without ventilation) and increased to a steady state of >85% of patients receiving ventilation ( >50% without ventilation) by the end of June. Similarly, remdesivir usage increased sharply from a baseline of 2% of patients and continued to rise to a peak of 79% of patients receiving invasive ventilation (44% without ventilation) in November before declining. Conclusion. Meaningful shifts in treatments for US patients hospitalized with COVID-19 were observed from March through December 2020. A dramatic decline was observed for HCQ use, likely owing to safety concerns, while usage of dexamethasone and remdesivir increased as evidence of their efficacy mounted. Across medications, usage was substantially more prevalent among patients requiring invasive ventilation compared with patients with less severe cases.

Increased Risk of Thrombosis in Patients with Myeloproliferative Neoplasms Compared with the General Population Hospitalized with COVID-19

[Formula presented] Background: Coronavirus disease-2019 (COVID-19) is an inflammatory, multisystem infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) and is associated with increased risk of thrombosis, particularly among critically ill patients. The myeloproliferative neoplasms (MPNs) include Philadelphia chromosome-negative (Ph-negative) MPNs polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), and Philadelphia-chromosome positive chronic myeloid leukemia (CML). Patients with MPNs, especially PH-negative, have increased risk of thrombotic complications. Given the increased propensity of thrombosis and prognostic significance of thrombosis in both COVID and MPNs, defining the risk of thrombotic complications in this patient population compared to the general population is important. Methods: Using an institutional database within the Mass General Brigham integrated health network, we retrospectively analyzed 63 consecutive patients with MPN who were ≥ 18 years old and tested positive for SARS-COV-2 infection based on polymerase chain reaction (PCR) testing from March 1, 2020 to January 1, 2021. We compared patients admitted to the hospital in our “MPN cohort” with patients admitted to the hospital from a separate COVID-19 (non-MPN cohort) Mass General Brigham registry of 1114 consecutive patients who tested positive for SARS-COV-2 infection based on PCR testing from March 13, 2020 to April 3, 2020. Care was taken to ensure the cohorts were mutually exclusive. The 90-day primary outcome for MPN cohort was a composite of all-cause death, any thrombosis (composite of arterial and venous thromboembolism [VTE]), International Society on Thrombosis and Haemostasis (ISTH) defined major and clinically relevant non-major bleeding. To identify risk factors for primary outcome in MPN cohort we used a multivariable logistic regression using age, sex, hospital admission status, MPN type, cytoreduction for MPN, hypertension, smoking status, baseline anticoagulation (AC), prior thrombosis (stroke, myocardial infarction or VTE) as co-variables. The 90-day outcomes of interest in our MPN vs non-MPN cohort analysis were any thrombosis, death, ISTH major and clinically relevant non-major bleeding and readmission for any reason. To assess impact of MPN status in hospitalized patients in our MPN vs non-MPN comparison, we used a multivariable logistic regression using age, sex, race, Hispanic ethnicity, ICU admission, treatment with steroids and/or Remdesivir, baseline AC and aspirin use, prior thrombosis (stroke, myocardial infarction or VTE), diabetes, heart failure, admission hematocrit, platelet count and D-dimer as co-variables. Continuous variables were compared using student t-test and categorical variables were compared using Fischer's Exact Test with a p value of < 0.05 considered significant. Results: Of the 63 patients with MPN (23 with PV, 17 ET, 4 PMF, 15 CML, 4 other), 27 (43%) were admitted to the hospital for COVID-19 and 5 (8%) required ICU admission. The mean age of all MPN patients was 66, 84% were White, 8% Black and 10% Hispanic. Primary 90-day outcome occurred in 12 (19%) of MPN patients. In multivariable analysis, only admission to hospital was associated with increased odds of composite (aOR 21.11, 95% CI 2.38 - 546.40), Figure 1A. In patients with (n = 27) and without MPN (n = 399) who were admitted to the hospital, patients with MPN were older (mean age 70 vs 61, p = 0.0076), more likely to be White (89% vs 54%, p = 0.0004) and less likely to be Hispanic (7% vs 29%, p = 0.0158), less likely to be admitted to the ICU (19% vs 43%, p = 0.0138), and more likely to be treated with corticosteroids (30% vs 14%, p = 0.025) or remdesivir (41% vs 13%, p < 0.0001). After multivariable logistic regression, diagnosis of MPN was significantly associated with increased odds of thrombosis (aOR 5.38, 95% CI 1.15-25.38) and readmission (aOR 6.28, 95% CI 1.60-24.88), but not bleeding (aOR 3.51, 95% CI 0.62-18.87) or death (aOR 4.29, 95% CI 0.95-18.9 ), Figure 1B. Conclusions: Thrombotic complications are common in patients with MPN and COVID-19, particularly if hospitalized for COVID-19. After multivariable analysis, MPN patients admitted for COVID-19 had a significantly increased risk of thrombotic complications compared with non-MPN patients. [Formula presented] Disclosures: Al-Samkari: Dova/Sobi: Consultancy, Research Funding;Novartis: Consultancy;Argenx: Consultancy;Rigel: Consultancy;Amgen: Research Funding;Agios: Consultancy, Research Funding;Moderna: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding;BMS: Consultancy, Research Funding;Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees;Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fathi: Agios/Servier: Consultancy, Other: Clinical Trial Support;BMS: Consultancy, Other: Clinical Trial Support;AbbVie: Consultancy, Other: Clinical Trial Support;Pfizer: Consultancy;Trillium: Consultancy;Kura: Consultancy;Blueprint Medicines Corporation: Consultancy;Genentech: Consultancy;Novartis: Consultancy;Trovagene: Consultancy;Daiichi Sankyo: Consultancy;Novartis: Consultancy;Morphosys: Consultancy;Kite: Consultancy;Foghorn: Consultancy;Takeda: Consultancy;Amgen: Consultancy;Seattle Genetics: Consultancy;NewLink Genetics: Consultancy;Forty Seven: Consultancy;Ipsen: Consultancy. Goldhaber: Bayer: Consultancy, Research Funding;Boehringer-Ingelheim: Consultancy, Research Funding;BMS: Research Funding;Boston Scientific BTG EKOS: Research Funding;Daiichi: Research Funding;Janssen: Research Funding;Pfizer: Consultancy, Research Funding;Agile: Consultancy. Piazza: Portola: Research Funding;Bayer: Research Funding;Amgen: Research Funding;BMS: Research Funding;Janssen: Research Funding;BSC: Research Funding. Hobbs: Celgene/Bristol Myers Squibb: Consultancy;Novartis: Consultancy;Merck: Research Funding;Constellation Pharmaceuticals: Consultancy, Research Funding;Bayer: Research Funding;Incyte Corporation: Research Funding;AbbVie.: Consultancy.

Cardiovascular outcomes in hospitalized patients with COVID-19 and history of cancer: A CORONA-VTE analysis

Background: In hospitalized patients with COVID-19, active cancer has been identified as a potential risk factor for adverse cardiovascular outcomes, including thrombosis. However, the impact of COVID-19 on outcomes in patients with a remote history of cancer is poorly understood. We evaluated hospitalized patients with a history of remote cancer and COVID-19 to examine whether a history of cancer contributes to 30-day major adverse cardiovascular outcomes among patients with COVID-19. Methods: Using a retrospective cohort of 1114 patients from CORONAVTE (Registry of Arterial and Venous Thromboembolic Complications in Patients With COVID-19), we looked at 399 hospitalized patients diagnosed with polymerase chain reaction (PCR)-confirmed COVID-19 within a large heath care network that consists of two large academic medical centers and several community hospitals. Twenty-six patients with active cancer or receiving cancer treatment within 1-year of COVID-19 diagnosis and five patients with unknown cancer history were excluded.We assessed 46 patients with a history of cancer and 322 patients without any history of cancer. The primary endpoint was the frequency of adjudicated major adverse cardiovascular outcomes, defined as myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and mortality. Results: Among the 46 hospitalized patients with COVID-19 and a history of cancer, 23.9% were non-white and 43.48% women. Compared to patients without any history of cancer, patients with a history of cancer were older (median 59.0 vs. 75.5 years, p<0.001) and had higher BMI (median 26.4 vs. 29.6 kg/m2, p<0.05). Patients with a history of cancer had higher rates of underlying CVD than those without (42.4% vs. 23.2%). Rates of major adverse cardiovascular events were similar in patients with and without a history of cancer (28.3% vs. 23.6%, respectively). Those with a history of cancer had a higher mortality rate (28.9% vs. 11.2%, p<0.05). Acute Respiratory Distress Syndrome (ARDS) and preexisting CVD were independently associated with mortality in this patient cohort (OR 19.7, 95% CI 7.5-51.7 and OR 2.9, 95% CI 1.2-6.9). History of remote cancer was not independently associated with mortality (OR 2.39, 95% CI 0.93-6.15, p=0.07). Conclusion: Our findings indicate that a history of remote cancer is not independently associated with increased mortality in hospitalized COVID-19 patients. These data suggest that the cause of death among hospitalized patients with COVID-19 and history of cancer is most likely multifactorial, with a strong contribution from cardiovascular disease.

DEFINING THE FREQUENT EXACERBATOR PHENOTYPE DURING A PANDEMIC IN COPD

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Prior-year exacerbation history is the best predictor of future exacerbations and forms part of the global clinical guidelines for management of COPD patients. Frequent exacerbators (FEs) are patients who have >=2 moderate-to-severe exacerbations in a year. They have a high risk of poor outcomes and may benefit from close monitoring and therapeutic interventions. Clinical trials of novel COPD treatments that reduce exacerbations also select for patients who meet the FE definition. During the COVID-19 pandemic, the COPD exacerbation rate has declined dramatically, complicating the use of prior-year exacerbation frequency for identifying FEs. An alternate approach is to extend the observation period from one to two previous years;however, the impact of this change on the prognostic value of exacerbation history is not well understood. The aim of this study was to compare the prevalence of FEs in subsequent years when a two-year vs. one-year exacerbation history is used to identify FEs. METHODS: We used US national claims data (IQVIA Pharmetrics Plus) from 2015-2019 to identify COPD patients aged >=40 years on standard-of-care combination therapy and with 1-3 years of follow-up. Two patient groups were created;those with ≥2 exacerbations over a continuous 12-month period within two years preceding follow-up [group A] and those with ≥2 exacerbations in the year preceding follow-up [group B, a subset of group A]. Exacerbations were defined as COPD-related ER visits or hospital admissions and prescription fills for an antibiotic or an oral corticosteroid burst. We compared baseline characteristics and proportions of FEs in each follow-up year between groups A and B. RESULTS: Of the 41,998 COPD patients who met the inclusion criteria, 14,972 (35.6%) were in group A and 9,781 (23.3%) were in group B. Patients in groups A and B had comparable age and gender distributions. In years 1, 2 and 3 of follow-up, 41.7%, 38.6% and 38.0% of group A patients and 48.9%, 44.8% and 43.5% of group B patients had >=2 exacerbations. Overall, group A patients had a lower rate of exacerbations during follow-up (0.87 per patient-year (PY), 95% CI: 0.86-0.88) compared to group B patients (1.00 per PY, 95% CI: 0.99-1.01). Among patients with 3 years of follow-up, the proportions of FEs in group A vs. B were: 38.2% vs. 45.6% in year 1, 22.4% (58.6% of year 1 FEs) vs. 28.5% (62.6% of year 1 FEs) in year 2 and 15.7% (70.1% of year 2 FEs) vs. 20.5% (71.9% of year 2 FEs) in year 3. CONCLUSIONS: 41.7% of group A patients and 48.9% of group B patients were FEs in year 1 of follow-up. In both groups, the overall prevalence of FEs was consistent in each year of follow-up and the FE phenotype remained stable over the three years of follow-up. CLINICAL IMPLICATIONS: A two-year exacerbation history may be an acceptable alternative to the prior-year history to guide patient management while pandemic measures continue to impact typical patient behaviors and exacerbation rates. DISCLOSURES: Employee relationship with Genentech Inc. Please note: Current Added 04/01/2021 by Parul Dayal, source=Web Response, value=Salary Employee relationship with Genentech, Inc. Please note: 03/2021 to current Added 04/29/2021 by Colin Dimond, source=Web Response, value=Salary No relevant relationships by Matthew Kent, source=Web Response Employee relationship with Genentech Please note: June 2020 - ongoing Added 04/29/2021 by Divya Mohan, source=Web Response, value=Salary Employee relationship with GSK Please note: Aug 2015 - May 2020 Added 04/29/2021 by Divya Mohan, source=Web Response, value=Salary Employee relationship with Genentech Please note: 2019-present Added 04/27/2021 by Shemra Rizzo, source=Web Response, value=Salary Stockholder relationship with Roche Please note: 2019-present Added 04/27/2021 by Shemra Rizzo, source=Web Response, value=stocks Employee relationship with Genentech Please note: 4 years Added 04/27/2021 by Xiaoying Yang, source=Web Response, value=Salary

SARS-CoV-2 neuropathology: Evidence from a post-mortem autopsy series in Padova, Italy

Introduction: SARS-CoV-2 is a novel strain of Coronavirus that mainly targets the respiratory tract, but with important implications also for the CNS. Data deriving from autopsy studies supports the neuroinvasive potential of SARS-CoV-2, even though infection appears to be limited to sparse cells within the brainstem and was not associated with the severity of neuropathological changes. Objectives: In the following study, we assess the neuropathological changes of 14 patients who died following a diagnosis of Sars-CoV-2 infection in Padova, Italy from March 2020 to January 2021. Methods: The cerebrum, cerebellum, brainstem, cranial nerves and meninges were sampled and histopathological evaluation was performed by histochemistry and immunohistochemistry for GFAP, CD8, CD61, CD68 and HLA-DR antibodies. SARS-CoV-2 proteins and RNA were investigated through immunohistochemistry, RTPCR and in-situ hybridization. Results: Small vessel thromboses were identified in two patients, while fresh territory ischaemic lesions were identified in three patients. Astrogliosis and microglial activation were more pronounced at the level of the brainstem in all subjects. SARS-CoV-2 proteins were found within the brainstem and meninges of 4 patients. In one patient, SARS-CoV-2 proteins and RNA were identified throughout the whole rostrocaudal extent of the brainstem and basal ganglia, with prominent involvement of neurons and oligodendrocytes in the mesencephalon, rostral pons and medulla. Conclusion: Although limited by the number of our cohort, the study contributes to define the neuroinvasive potential of SARS-CoV-2 within the CNS. In line with available literature, SARS-CoV-2 invasion does not appear to correlate with the severity of neuropathological changes.