Evolución clínica en un receptor de trasplante de hígado con la COVID-19: ¿Un efecto benéfico del tacrolimus?
Bibliographic record
Abstract
La enfermedad por coronavirus 2019 (COVID-19) es una enfermedad respiratoria seria causada por el virus SARS-CoV-2. Existe controversia respecto a si los inmunosupresores representan un factor de riesgo para desarrollar una enfermedad más grave. Aquí reportamos el desenlace clínico de tres miembros de una familia que se infectaron de COVID-19, con la presencia y ausencia de diferentes factores de riesgo que han sido descritos en casos de enfermedad grave. Paradójicamente, el receptor de trasplante hepático presentó un desenlace similar comparado con los otros dos miembros de la familia. Mostró un periodo de hospitalización mas corto, con desenlace clínico similar y con menor requerimiento de oxigeno. Esta observación clínica muestra un posible efecto benéfico del tacrolimus en pacientes que presentaron la COVID-19. El tacrolimus presenta una actividad inhibitoria en los coronavirus humanos a través de: 1) Un efecto antiviral al unirse con las proteínas FKBP, con la inhibición subsiguiente de su actividad de peptidil-prolil isomerasa, cuyas actividades enzimáticas promueven la replicación del coronavirus; 2) La regulación de la respuesta inmunitaria a través de la interacción con la calcineurina, que evita la translocación nuclear de su sustrato, el factor nuclear de las células T, lo que inhibe la activación de células T. Esta observación clínica muestra que el receptor de trasplante hepático con la COVID-19 no presenta un peor desenlace comparado con pacientes que tienen otros factores de riesgo para la COVID-19 y pone en evidencia los dos mecanismos relacionados con el tacrolimus. Coronavirus disease 2019 (COVID-19) is a serious respiratory illness caused by SARS-CoV-2. There is controversy about whether their immunosuppressive status is a risk factor or a protective factor for developing severe disease. We report herein the clinical outcome of three family members that had COVID-19 infection, presenting with and without different risk factors that have been described in more severe disease. Paradoxically, the patient with more risks of developing a severe disease, a 64-year-old woman, 2-years liver transplant recipient under treatment with tacrolimus, presented a similar outcome compared to the two other members of the family. She showed shorter hospitalization time, similar clinical outcome with fewer oxygen needs. The present clinical observation raises the question about the possible beneficial effect of tacrolimus in patients with COVID-19. Indeed, tacrolimus (FK-506) have an inhibitory effect on human coronaviruses by: 1) an antiviral effect by binding to the FK-506-binding proteins (FKBP) with a subsequent inhibition of their peptidyl-prolyl cis/trans isomerase (PPIase) activity, which seems to be important for the coronavirus life cycle; and 2) regulating the immune response by the inhibition of the activity of the nuclear factor of activated T-cells (NFAT) required for immunosuppression. The present observation states that liver recipients’ patients with COVID-19 may not have worse outcomes when compared with other patients that have COVID-19 risk factors and puts in evidence the two mechanisms related to tacrolimus.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.090 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".