ABSTRACT
Background: Inflammatory markers are pivotal for the diagnosis of coronavirus disease 2019 (COVID-19) and sepsis. This study compared markers between hospitalised patients with COVID-19 and those with bacterial sepsis. Methods: This retrospective single-centre cohort study included 50 patients with COVID-19 clinical stages II and III and 24 patients with bacterial sepsis. Both groups were treated according to the country's official standards. Leukocytes, C-reactive protein (CRP), ferritin, and D-dimer were registered at the time of patient's admission and 24, 48, and 72 h after initiating intrahospital treatment. Results: Upon admission, marker levels were high, with a significant decrease at 72 h after antibiotic therapy in the sepsis group. The leukocyte count was higher in deceased patients with sepsis. The mean ferritin levels were 1105 mcg/dl for COVID-19 and 525 mcg/dL for sepsis. Higher ferritin levels in COVID-19 (P = 0.001) seemed to be a predictor of higher mortality. Upon admission, the median D-dimer level was 0.68 mg/L for COVID-19 and 3 mg/L for patients with sepsis, whether recovered or deceased. As D-dimer, procalcitonin levels were higher in patients with sepsis (P = 0.001). CRP levels were equally elevated in both entities but higher in deceased patients with COVID-19. Conclusion: Ferritin was the main inflammatory marker for COVID-19, and leukocytes, procalcitonin, and D-dimer were the main markers of sepsis. Markers that were most affected in deceased patients were CRP for COVID-19 and leukocyte for sepsis. The therapeutic implications of these differences require further study.
ABSTRACT
En los últimos meses, las políticas de vacunación para prevenir el COVID-19 han evolucionado a nivel global a medida que la vigilancia farmacológica ha demostrado nuevas evidencias tanto de la eficacia como de los eventos adversos de todas las vacunas disponibles. Las primeras alertas que promovieron cambios en las políticas de vacunación en diferentes países estuvieron relacionadas a casos raros de trombosis severa, que ocurrieron principalmente en mujeres menores de 55 años, usualmente días después de la primera dosis de la vacuna ChAdOx1 nCoV-19 (AZD1222, AstraZeneca) y de la dosis única de la vacuna Ad.26.COV2.S (Johnson & Johnson, J&J/Janssen) (2). La Agencia Europea de Medicamentos (EMA) y la Administración de Medicamentos y Alimentos de Estados Unidos (FDA) recomendaron continuar con el uso de estas vacunas, teniendo en cuenta que los beneficios eran superiores a los riesgos. Sin embargo, algunos países de altos ingresos ordenaron que la vacuna AZD1222 se suministrara solo a personas mayores de 60 años, mientras que otros países pausaron su aplicación indefinidamente. Por otra parte, varios gobiernos de países de bajos y medianos ingresos, siguieron aplicando la vacuna AZD1222 a personas menores de 60 años, ya que realizan la vacunación de sus habitantes con las opciones disponibles. En el caso de las vacunas BNT162b2 (BNT, Pfizer) y mRNA-1273 (Moderna) existen algunos reportes de casos aislados de miocarditis aguda y pericarditis no severas en jóvenes mayores de 16 años, especialmente en varones, típicamente algunos días después de la segunda dosis. Los mecanismos de este evento adverso se encuentran aún en estudio y se desconoce si un segundo refuerzo de estas dos vacunas rRNA podría ocasionar más casos de miocarditis aguda en población susceptible. La recomendación de monitorear y estudiar activamente dichos eventos adversos no parece ser una prioridad en muchos países de bajos y medianos recursos, donde no se han llevado a cabo estudios de farmacovigilancia ni de poscomercialización. Otro problema que obliga a realizar cambios en las políticas es el retraso en la producción como en la distribución de las vacunas. Recientemente, hubo una alerta debido a la insuficiente producción de la segunda dosis de la vacuna Gam-COVID-Vac (Sputnik V), lo cual dejó a varios millones de personas esperando indefinidamente para completar su esquema de inmunización. Unos pocos estudios preliminares sobre la combinación de vacunas en condiciones de escasez están siendo usados para justificar la administración de una vacuna diferente para la segunda dosis. Este hecho ha suscitado debates sobre cuál vacuna debería usarse para completar la inmunización en estos casos. Sin embargo, pese a la carrera contra el tiempo para acabar con la pandemia, es imperativo llevar a cabo más ensayos clínicos y de farmacovigilancia para evaluar la efectividad de estas combinaciones antes de formar parte de políticas públicas de salud en situación de emergencia. La farmacovigilancia posvacuna debe ser sistemática a nivel mundial y también debe llevarse a cabo paralelamente con la vigilancia genómica del SARS-CoV-2 y de sus variantes. Esto permitirá revisar la efectividad y el perfil de seguridad de las vacunas contra el COVID-19 y por ende, formular políticas de vacunación basadas en la evidencia. Alternate abstract: In recent months, vaccination policies against COVID-19 have evolved worldwide as pharmacovigilance provides new evidence on efficacy, and adverse events of all vaccines available. The first alerts that prompted changes in vaccination policies in several countries were related to rare severe thrombosis occurring mainly in women under 55 years old, happening several days after the first dose of the ChAdOx1 nCoV-19 (AZD1222, AstraZeneca) vaccine (1), and the single dose of Ad.26.COV2.S (Johnson & Johnson, J&J/Janssen) vaccine (2). The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) recommended to continue the use of these vaccines, considering that benefits outweighed the risks. However, some high-income countries mandated that the AZD1222 vaccine be given only to people over 60 years old, while other countries paused its use indefinitely. On the other hand, many governments of low-middle income countries continue using the AZD1222 vaccine in people under 60 years of age, as they vaccinate their population with the options they have available. In the case of the BNT162b2 (BNT, Pfizer) and mRNA-1273 (Moderna) vaccines, there are some reports of rare cases of non-severe acute myocarditis and pericarditis in young people older than 16 years, especially men, and typically a few days after the second dose (3). The mechanism for this adverse event of these two mRNA vaccines is still under study, and it is unknown whether a second booster of these vaccines could lead to more cases of acute myocarditis in the susceptible population. The recommendation to actively monitor and study the aforementioned adverse events to determine a cause-effect relation, seems to be under looked in many low-middle income countries where pharmacovigilance or post marketing studies are not being conducted. Another issue forcing policy changes is the vaccine delay in production and delivery. Recently, there was a warning about the insufficient production of the Gam-COVID-Vac (Sputnik V) second dose, leaving several million people awaiting indefinitely to complete the immunization schedule. A few preliminary studies about mixing and matching vaccines in case of shortage, are being used to justify the administration of a different vaccine for second dose. This has raised debates about which vaccines could be used to complete immunization in these cases. However, despite the race against time to end the pandemic, it is imperative to carry out more clinical trials and pharmacological surveillance to evaluate the effectiveness of those combinations before they become part of emergency public health policies. Post-vaccination pharmacovigilance should be systematic worldwide, and should run parallel to genomic surve llance of SARS-CoV-2 and its variants. This will allow to revisit the effectiveness and the safety profile of COVID-19 vaccines, and to provide evidence-based vaccination policies .