Antihipertensivos en pacientes con COVID-19 / Anti hypertensive agents in patients with COVID-19

En 31 de diciembre del 2019 la Organización Mundial de la Salud fue informada por las autoridades sanitarias chinas de la aparición de casos de neumonía de origen desconocido en la ciudad de Wuhan en China. El 7 de Enero de 2020, científicos chinos identificaron a un nuevo coronavirus (temporalmente designado como "2019-nCoV") como el agente etiológico de la enfermedad denominada COVID-19. La secuenciación del genoma del nuevo coronavirus mostró gran similitud con el coronavirus (Covid-1 o SARS-CoV) causante del síndrome respiratorio agudo severo (SARS), ocurrido también en China entre los años 2002-2003. Por este motivo, 2019-nCoV se rebautizó como SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2) y a la fecha es responsable de la actual y grave pandemia que está ocasionando impactos sanitarios y socio-económicos a escala global. Las investigaciones con SARS-CoV establecieron que este virus ingresa a nuestras células utilizando como receptor a la enzima convertidora de angiotensina tipo 2 (ECA 2 o en inglés ACE-2: "angiotensin converting enzyme type 2"). Dado este antecedente también se confirmó que SARS-CoV-2 también utiliza esta misma enzima ya que no se habla de un mecanismo en si para ingresar a sus células blanco, especialmente a nivel de nuestro sistema respiratorio. ECA-2 es una proteasa integrante del sistema renina angiotensina "alterno o no canónico" con importantes acciones regulatorias sobre los sistemas cardiovascular, renal y pulmonar, entre otros. En este contexto, ha surgido preocupación tanto por clínicos como los propios pacientes respecto al estado de pacientes hipertensos con COVID-19 y su vulnerabilidad a infectarse con SARS-CoV-2 dado que algunos trabajos han planteado que ciertos polimorfismos en el gen ECA-2 asociados a hipertensión arterial podrían determinar una mayor expresión de ECA-2. Además, estudios preclínicos han sugerido que ciertos fármacos antihipertensivos (principalmente, inhibidores de ECA y antagonistas del receptor para angiotensina II subtipo 1) también podrían estimular una mayor expresión de ECA-2. Esta revisión tiene por objetivo presentar y discutir los antecedentes en el estado del arte respecto a esta reciente problemática. El análisis crítico de los presentes antecedentes permite concluir que no existe evidencia clínica sólida que permita afirmar que el uso de medicamentos antihipertensivos genere una mayor vulnerabilidad a la infección con SARS-CoV-2. Por lo tanto no se debe descontinuar su uso en pacientes hipertensos en riesgo de infección a SARS-CoV-2 o que padezcan COVID-19.

In December 2019, a new type of coronavirus emerged in the city of Wuhan, China. This novel virus has unleashed a pandemic that has inflicted a considerable impact on public health and the economy and has therefore become a severe concern worldwide. This new virus -named SARS-CoV-2has been rapidly investigated in order to create knowledge aimed at achieving its control. Comparative studies with SARS-CoV virus, responsible for the 2002-2003 pandemic, suggest that SARS-CoV-2 requires the same receptor to bind and infect cells: angiotensin converting enzyme 2 (ACE-2). This hypothesis has been thoroughly supported by a variety of in vitro research and is currently considered a potential therapeutic target. ACE-2 is part of the counter-regulatory renin-angiotensin system, exerting effects in pulmonary, renal and cardiovascular systems. In this context, concerns have arisen in regards to the vulnerability of hypertensive patients against COVID-19, given that there is evidence that may suggest that polymorphisms associated to hypertension may increase the expression of ACE-2. Moreover, preclinical studies have shown that antihypertensive drugs may increase the expression of this enzyme. In this review article, we present the current state of the art on this polemic topic. Our critical analysis suggest that there is no robust clinical evidence supporting the hypothesis that the use of antihypertensive drugs can increase vulnerability to infection with SARS-CoV-2. Therefore, we recommend that the use of these therapeutic agents should not be discontinued in hypertensive patients in risk to or suffering COVID-19.

Renal changes and acute kidney injury in covid-19: a systematic review

SUMMARY OBJECTIVE We aimed to present a review of renal changes in patients with COVID-19. METHODS We performed a systematic review of the literature to identify original articles regarding clinical, laboratory, and anatomopathological kidney changes in patients infected with SARS-CoV-2 published until May 7, 2020. The search was carried out across PubMed, Scopus, and Embase using the keywords "COVID-19", "coronavirus", "SARS-CoV-2", "kidney injury" and "kidney disease". Fifteen studies presented clinical and laboratory renal changes in patients with COVID-19, and three addressed anatomopathological changes. DISCUSSION Acute kidney injury (AKI) was a relevant finding in patients with COVID-19. There were also significant changes in laboratory tests that indicated kidney injury, such as increased serum creatinine and blood urea nitrogen (BUN), proteinuria, and hematuria. The presence of laboratory abnormalities and AKI were significant in severely ill patients. There was a considerable prevalence of AKI among groups of patients who died of COVID-19. Histopathological analysis of the kidney tissue of patients infected with SARS-CoV-2 suggested that the virus may directly affect the kidneys. CONCLUSION Although COVID-19 affects mainly the lungs, it can also impact the kidneys. Increased serum creatinine and BUN, hematuria, proteinuria, and AKI were frequent findings in patients with severe COVID-19 and were related to an increased mortality rate. Further studies focusing on renal changes and their implications for the clinical condition of patients infected with the novel coronavirus are needed.

RESUMO OBJETIVO Apresentar uma revisão sobre as alterações renais nos pacientes com COVID-19. MÉTODOS Foi realizada uma revisão sistemática de literatura para buscar estudos referentes a pacientes com alterações renais clínicas, laboratoriais e anatomopatológicas durante a infecção por SARS-CoV-2. A busca foi realizada nas bases de dados eletrônicos PubMed, Scopus e Embase, com as palavras-chaves: "COVID-19", "coronavirus", "Sars-CoV-2", "kidney injury" e "kidney disease", para identificar artigos originais publicados na literatura até 07 de maio de 2020. Quinze estudos trouxeram alterações renais clínicas e laboratoriais dos pacientes com COVID-19, e três abordaram análises anatomopatológicas. DISCUSSÃO A Lesão renal aguda (LRA) foi um achado relevante nos pacientes com COVID-19. Houve também alterações significativas nos exames laboratoriais que indicam lesão renal, como o nível de creatinina e ureia séricas, proteinúria e hematúria. As alterações laboratoriais e a LRA foram importantes nos pacientes que desenvolveram o quadro grave da doença. Há considerável prevalência de LRA nos grupos de pacientes que vieram a óbito. Na análise histopatológica de pacientes com SARS-CoV-2 foram encontrados achados renais sugestivos que o vírus poderia ter efeitos diretos sobre o rim. CONCLUSÃO A COVID-19 é uma doença que, apesar de acometer principalmente os pulmões, também acomete os rins. Aumento das escórias nitrogenadas, hematúria, proteinúria e LRA foram achados frequentes em pacientes com quadros graves da COVID-19. Esses achados foram relacionados a maior mortalidade. É necessária a realização de mais estudos com enfoque nas alterações renais e suas implicações no quadro clínico causadas pelo novo coronavírus.

Susceptibility of the elderly to SARS-COV-2 infection: ace-2 overexpression, shedding, and antibody-dependent enhancement (ADE)

The world is currently facing a serious SARS-CoV-2 infection pandemic. </mac_aq>This virus is a new isolate of coronavirus, and the current infection crisis has surpassed the SARS and MERS epidemics</mac_aq> that occurred in 2002 and 2013, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing </mac_aq>5,000 deaths and spreading across more than 130 </mac_aq>countries worldwide. The spreading capacity of the virus clearly demonstrates the potential threat </mac_aq>of respiratory viruses to human health, thereby reiterating to the governments around the world that preventive </mac_aq>health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of the patients need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of the elderly, especially individuals who are older than 60 years of age, and have comorbidities, including hypertension, diabetes, and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow less susceptible and are not considered as a risk group. Therefore, in this review, we discuss some possible molecular and cellular mechanisms by virtue of which the elderly subjects may be more susceptible to severe COVID-19. Toward this, we raise two main </mac_aq>points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 </mac_aq>receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe that these points are pivotal for a better understanding of the pathogenesis of severe COVID-19, and must be carefully addressed by physicians and scientists in the field.