Pharmacologic Therapy for COVID-19 Infection.

The COVID-19 pandemic has focused attention on issues of epidemiology, public health, and vaccine design. I submit that attention to COVID-19 pharmacologic therapy needs similar emphasis, including identifying any existing medications that can be repurposed to treat COVID-19 patients.

Opinion of Brazilian physicians on the treatment of COVID-19 / Opinião de médicos brasileiros sobre o tratamento da COVID-19 / Opinión de médicos brasileños sobre el tratamiento de la COVID-19

Objetivo: Investigar a opinião de médicos brasileiros sobre o tratamento precoce da COVID-19 com hidroxicloroquina/ cloroquina e azitromicina em pacientes com suspeita clínica e sobre o tratamento com corticoterapia na fase inflamatória da doença. Métodos: Trata-se de uma pesquisa de opinião, com amostragem por conveniência, com médicos atuantes no Brasil. A coleta dos dados ocorreu no período de 26 de maio a 8 de junho de 2020 (13 dias), por meio de um formulário Google, disponibilizado publicamente nas redes sociais e aplicativos de comunicação. Realizou-se uma análise descritiva dos dados, teste de independência, teste T Student e modelo de regressão logística com análise multivariada. Resultados: A pesquisa contou com 1.020 médicos participantes, com média de 21,9 anos de formado. 72,4% dos participantes apresentaram-se a favor do tratamento precoce com hidroxicloroquina/cloroquina e azitromicina e 89,7% dos médicos apresentaram-se favoráveis ao uso da corticoterapia para o tratamento da fase inflamatória da COVID-19. Constatou-se também que participantes com maior idade, com residência médica, atuantes nas regiões Nordeste e Norte possuíam mais chances de serem favoráveis aos tratamentos. Por outro lado, profissionais especialistas em medicina intensiva, infectologia e pneumologia, além de atuantes nas unidades de terapia intensiva, mostraram-se mais desfavoráveis. Conclusão: A maioria dos médicos investigados nesta pesquisa de opinião mostrou-se a favor do tratamento precoce apresentado e do uso da corticoterapia no tratamento da COVID-19. Já os especialistas em medicina intensiva, infectologia e pneumologia e profissionais atuantes nas Unidades de Terapia Intensiva mostraram-se mais desfavoráveis.

Objective: To investigate the opinion of Brazilian physicians on the early treatment of COVID-19 with hydroxychloroquine/ chloroquine and azithromycin in patients with clinical suspicion and on the treatment with corticosteroid therapy in the inflammatory stage of the disease. Methods: This is an opinion survey conducted with a convenient sample of physicians working in Brazil. Data were collected from May 26 to June 8, 2020 (13 days) through Google forms made publicly available on social media and chat applications. Data underwent descriptive analysis, independence test, Student t-test, and a logistic regression model using multivariate analysis. Results: The survey included 1020 physicians with a mean of 21.9 years since graduation. 72.4% of the participants were in favor of early treatment with hydroxychloroquine/chloroquine and azithromycin and 89.7% of the physicians were in favor of using corticosteroid therapy to treat the inflammatory stage of COVID-19. We also observed that older participants, those who completed medical residency, and those working in the Northeast and North regions were more likely to be in favor of the treatments. On the other hand, professionals specialized in intensive care medicine, infectious diseases and pneumology and working in intensive care units were more opposed. Conclusion: Most physicians in this opinion survey were in favor of the early treatment presented and the use of corticosteroid therapy in the treatment of COVID-19. But specialists in intensive care medicine, infectious diseases and pulmonology, and professionals working in Intensive Care Units were more opposed to them.

Objetivo: Investigar la opinión de médicos brasileños sobre el tratamiento precoz de la COVID-19 con la hidroxicloroquina/ cloroquina y la azitromicina en pacientes con sospecha clínica y bajo el tratamiento de corticoterapia en la fase inflamatoria de la enfermedad. Métodos: Se trata de una investigación de opinión con la muestra de conveniencia realizada con médicos de Brasil. La recogida de datos se dio en el periodo entre 26 de mayo y 8 de junio de 2020 (13 días) a través de un formulario Google que ha estado disponible públicamente en las redes sociales y los aplicativos de comunicación. Se realizó un análisis descriptivo de los datos, la prueba de independencia, la prueba T Student y el modelo de regresión logística con el análisis multivariado. Resultados: La investigación tuvo 1.020 médicos participantes, con la media de 21,9 años de término del grado. El 72,4% de los participantes se presentaron a favor del tratamiento precoz con la hidroxicloroquina/cloroquina y la azitromicina y el 89,7% de los médicos se presentaron favorables a la utilización de la corticoterapia para el tratamiento de la fase inflamatoria de la COVID-19. Se constató también que los participantes de más edad, con el curso de residencia medica y que eran de las regiones Noreste y Norte del país eran más favorables a los tratamientos. Los profesionales especialistas de la medicina intensiva, la infectologia y la neumología, además de actuaren en las unidades de cuidados intensivos parecieron más desfavorables. Conclusión: La mayoría de los médicos investigados de esa investigación de opinión se mostró favorable al tratamiento precoz presentado y a la utilización de la corticoterapia para el tratamiento de la COVID-19. Los especialistas de la medicina intensiva, la infectología y la neumología y los profesionales de las Unidades de Cuidados Intensivos se presentaron más desfavorables a los tratamientos.

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19.

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.

Questioning Established Theories and Treatment Methods Related to Iron and Other Metal Metabolic Changes, Affecting All Major Diseases and Billions of Patients.

The medical and scientific literature is dominated by highly cited historical theories and findings [...].

Impact of COVID-19 Pandemic on Surgical Breast Cancer Patients Undergoing Neoadjuvant Therapy: A Multicentric Study.

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.

Durable tracking anti-SARS-CoV-2 antibodies in cancer patients recovered from COVID-19.

Cancer patients are more susceptible to SARS-CoV-2 infection and generally have higher mortality rate. Anti-SARS-CoV-2 IgG is an important consideration for the patients in this COVID-19 pandemic. Recent researches suggested the rapid decay of anti-SARS-CoV-2 antibodies in the general population, but the decline rate of the antibodies in cancer patients was unknown. In this observational study, we reported the clinical features of the 53 cancer patients infected by SARS-CoV-2 from Wuhan, China and tracked the presence of anti-SARS-CoV-2 antibodies in the patients for more than 12 months. We found the duration (days) of anti-SARS-CoV-2 IgG in the patients was significant longer in chemotherapy (mean: 175; range: 75 to 315) and radiotherapy groups (mean: 168; range: 85 to 265) than in non-chemo- or radio-therapy group (mean: 58; range: 21 to 123) after their recovery from COVID-19. We also used single-cell RNA sequencing to track the immunologic changes in a representative patient recovered  from COVID-19 and found that CD8 + effective T cells, memory B cells and plasma cells were persistently activated in the patient undergoing chemotherapy. Together, our findings show that chemotherapy and radiotherapy might be beneficial to extend the duration of anti-SARS-CoV-2 IgG.

Bacterial superinfection in adults with COVID-19 hospitalized in two clinics in Medellín-Colombia, 2020.

COVID-19 represents high morbidity and mortality, its complications and lethality have increased due to bacterial superinfections. We aimed to determine the prevalence of bacterial superinfection in adults with COVID-19, hospitalized in two clinics in Medellín-Colombia during 2020, and its distribution according to sociodemographic and clinical conditions. A cross sectional study was made with 399 patients diagnosed with COVID-19 by RT-PCR. We determined the prevalence of bacterial superinfection and its factors associated with crude and adjusted prevalence ratios by a generalized linear model. The prevalence of superinfection was 49.6%, with 16 agents identified, the most frequent were Klebsiella (pneumoniae and oxytoca) and Staphylococcus aureus. In the multivariate adjustment, the variables with the strongest association with bacterial superinfection were lung disease, encephalopathy, mechanical ventilation, hospital stay, and steroid treatment. A high prevalence of bacterial superinfections, a high number of agents, and multiple associated factors were found. Among these stood out comorbidities, complications, days of hospitalization, mechanical ventilation, and steroid treatment. These results are vital to identifying priority clinical groups, improving the care of simultaneous infections with COVID-19 in people with the risk factors exposed in the population studied, and identifying bacteria of public health interest.

Staying InformED: Top emergency Medicine pharmacotherapy articles of 2020.

The year 2020 was not easy for Emergency Medicine (EM) clinicians with the burden of tackling a pandemic. A large focus, rightfully so, was placed on the evolving diagnosis and management of patients with COVID-19 and, as such, the ability of clinicians to remain up to date on key EM pharmacotherapy literature may have been compromised. This article reviews the most important EM pharmacotherapy publications indexed in 2020. A modified Delphi approach was utilized for selected journals to identify the most impactful EM pharmacotherapy studies. A total of fifteen articles, eleven trials and four meta-analyses, were identified. This review provides a summary of each study, along with a commentary on the impact to the EM literature and EM clinician.

Chemotherapy vs. Immunotherapy in combating nCOVID19: An update.

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.

Médicaments utilisés durant la COVID-19: Examen des données probantes récentes.

OBJECTIF: En réponse à la pandémie actuelle de maladie à coronavirus 2019 (COVID-19), garder les médecins au fait des médicaments qui ont été proposés pour combattre la maladie, et des données probantes à l'appui de leur utilisation. SOURCES D'INFORMATION: Une revue narrative des médicaments les plus fréquemment utilisés pour combattre la COVID-19 a été réalisée, afin de souligner les meilleures données probantes disponibles concernant chaque traitement pharmacologique jusqu'ici. Des recherches ont été effectuées sur PubMed, EMBASE et MEDLINE à l'aide des mots-clés anglais COVID-19 et treatment, ainsi que d'autres mots-clés connexes. Ont été inclus les études pertinentes menées auprès de populations humaines et des cas de patients atteints de la COVID-19, ainsi que les articles et revues relevés à la main. Seuls les articles rédigés en anglais et en chinois ont été retenus. MESSAGE PRINCIPAL: Alors que la prise en charge actuelle des patients atteints de la COVID-19 consiste principalement en soins de soutien, sans accès aux vaccins, les praticiens se sont tournés vers des médicaments utilisés dans d'autres indications. Cela a causé une grande controverse, puisque des données cliniques limitées étayaient l'utilisation de beaucoup de ces traitements, et cela pouvait se répercuter sur la sécurité du patient, l'accès aux médicaments et la santé publique. Par exemple, les médicaments tels que l'hydroxychloroquine et la chloroquine, le lopinavir-ritonavir, les anti-inflammatoires non stéroïdiens, les inhibiteurs de l'enzyme de conversion de l'angiotensine et les antagonistes des récepteurs de l'angiotensine ont capté l'attention des médias en raison de la médiatisation, de la mésinformation ou de la mauvaise interprétation des données de recherche. CONCLUSION: Vu la gravité de la pandémie et les vastes effets éventuels de l'adoption de traitements sûrs et efficaces, cet article se veut être une revue narrative des données probantes actuelles étayant les médicaments les plus utilisés pour le traitement de la COVID-19 afin de permettre aux professionnels de la santé de prendre des décisions éclairées en matière de soins pour les patients qui sont atteints de cette maladie potentiellement mortelle.

Role of community pharmacists in medication management during COVID-19 lockdown.

Preventive and control measures implemented by many countries to mitigate the spread of COVID-19 may negatively impact medication and chronic disease management, which can interfere with achieving patients' therapeutic goals. This study aims to evaluate the effect of the COVID-19 lockdown on these aspects, while exploring the role of community pharmacists. A cross-sectional study was conducted via a web-based questionnaire that targeted individuals who suffer from chronic diseases in Jordan. Participants were recruited by convenience sampling and were asked to self-report their ability to access medication, and the perceived role of community pharmacists. Among the 431 participants, the mean age ± SD (years) was 53.8 ± 13.7 and 60.1% (n= 259) were females. Participants mainly reported difficulties in accessing medication (n=198, 45.9%), reduced supplies or unavailability of medications (n=213, 49.4%), nonadherence to medications due to lack of access (n=98, 22.7%) and high costs (n=85, 19.7%). Participants avoided follow-ups due to a fear of infection (n=367, 82.5%) or prolonged waiting time in clinics (n=322, 74.7%). An increased reliance on the community pharmacy for medical advice was reported by 39.9% (n=172) of the participants, with half of them (n=217, 50.3%) depending on the pharmacists for advice regarding over-the-counter medications and COVID-19-related information (n=119, 27.6%). There is an urgent need to involve community pharmacists in medication and chronic disease management with a focus on patient adherence to ensure the optimal management of such vulnerable patient groups. Future studies to assess the effect of pharmacists' contributions towards enhancing medication/disease management are warranted.

Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): A population-based case-control study.

BACKGROUND: The objectives of this study were to identify risk factors for severe coronavirus disease 2019 (COVID-19) and to lay the basis for risk stratification based on demographic data and health records. METHODS AND FINDINGS: The design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the national database followed by entry to a critical care unit or death within 28 days or a death certificate with COVID-19 as underlying cause. Up to 10 controls per case matched for sex, age, and primary care practice were selected from the national population register. For this analysis-based on ascertainment of positive test results up to 6 June 2020, entry to critical care up to 14 June 2020, and deaths registered up to 14 June 2020-there were 36,948 controls and 4,272 cases, of which 1,894 (44%) were care home residents. All diagnostic codes from the past 5 years of hospitalisation records and all drug codes from prescriptions dispensed during the past 240 days were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio 21.4 (95% CI 19.1-23.9, p = 8 × 10-644). Univariate rate ratios for conditions listed by public health agencies as conferring high risk were 2.75 (95% CI 1.96-3.88, p = 6 × 10-9) for type 1 diabetes, 1.60 (95% CI 1.48-1.74, p = 8 × 10-30) for type 2 diabetes, 1.49 (95% CI 1.37-1.61, p = 3 × 10-21) for ischemic heart disease, 2.23 (95% CI 2.08-2.39, p = 4 × 10-109) for other heart disease, 1.96 (95% CI 1.83-2.10, p = 2 × 10-78) for chronic lower respiratory tract disease, 4.06 (95% CI 3.15-5.23, p = 3 × 10-27) for chronic kidney disease, 5.4 (95% CI 4.9-5.8, p = 1 × 10-354) for neurological disease, 3.61 (95% CI 2.60-5.00, p = 2 × 10-14) for chronic liver disease, and 2.66 (95% CI 1.86-3.79, p = 7 × 10-8) for immune deficiency or suppression. Seventy-eight percent of cases and 52% of controls had at least one listed condition (51% of cases and 11% of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past 9 months and with at least one hospital admission in the past 5 years (rate ratios 3.10 [95% CI 2.59-3.71] and 2.75 [95% CI 2.53-2.99], respectively) even after adjusting for the listed conditions. In those without listed conditions, significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses, and prescriptions provided an additional 1.07 bits (C-statistic 0.804). A limitation of this study is that records from primary care were not available. CONCLUSIONS: We have shown that, along with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over.

COVID pandemic as an opportunity for improving mental health treatments of the homeless people.

BACKGROUND: Homeless population has been severely affected by the COVID-19 pandemic. Their living conditions, comorbidity with different pathologies and a greater frequency of mental disorders, make this population vulnerable. METHOD: We implemented a program of serial visits in a hostel for confined homeless of the city council social services, for the monitoring and treatment of mental disorders and substance abuse problems. Accompanied by serial phone and email contacts. RESULTS: A highly significant percentage (63%) had mental disorders or substance abuse, requiring pharmacological intervention, and 37% began follow-up in resources of the Mental Health and Addiction network of the Psychiatric Service at the end of the program. Hospital emergency service visits were drastically reduced. None of them were infected with COVID-19. An individualized Social plan was drawn up in order to reintegrate them with support in the community. CONCLUSIONS: The Results have been really positive, meeting all the objectives and opening up developing new programs in the future, in the pandemic outbreak and out of it.

An audit of end-of-life symptom control in patients with corona virus disease 2019 (COVID-19) dying in a hospital in the United Kingdom.

BACKGROUND: The literature contains limited information on the problems faced by dying patients with COVID-19 and the effectiveness of interventions to manage these. AIM: The aim of this audit was to assess the utility of our end-of-life care plan, and specifically the effectiveness of our standardised end-of-life care treatment algorithms, in dying patients with COVID-19. DESIGN: The audit primarily involved data extraction from the end-of-life care plan, which includes four hourly nursing (ward nurses) assessments of specific problems: patients with problems were managed according to standardised treatment algorithms, and the intervention was deemed to be effective if the problem was not present at subsequent assessments. SETTING/PARTICIPANTS: This audit was undertaken at a general hospital in England, covered the 8 weeks from 16 March to 11 May 2020 and included all inpatients with COVID-19 who had an end-of-life care plan (and died). RESULTS: Sixty-one patients met the audit criteria: the commonest problem was shortness of breath (57.5%), which was generally controlled with conservative doses of morphine (10-20 mg/24 h via a syringe pump). Cough and audible respiratory secretions were relatively uncommon. The second most common problem was agitation/delirium (55.5%), which was generally controlled with standard pharmacological interventions. The cumulative number of patients with shortness of breath, agitation and audible respiratory secretions increased over the last 72 h of life, but most patients were symptom controlled at the point of death. CONCLUSION: Patients dying of COVID-19 experience similar end-of-life problems to other groups of patients. Moreover, they generally respond to standard interventions for these end-of-life problems.

Emerging pharmacological therapies for ARDS: COVID-19 and beyond.

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.