CN-122003606-A - Biomarkers for therapeutic management and/or prediction of disease progression, severity and/or outcome for respiratory viral infections

Abstract

The present invention relates to a method for the therapeutic management and/or prediction of disease progression, severity and/or outcome in a patient suffering from an respiratory viral infection. The method comprises the steps of providing a first sample isolated from the patient and a second sample isolated from the patient at a time point after the first sample is isolated from the patient, wherein the first and second samples are isolated within 96 hours (4 days) after consultation with medical personnel, determining the level of one or more endothelial biomarkers in the first and the second samples, wherein the one or more endothelial biomarkers is soluble Fms-like tyrosine kinase-1 (sFlt-1) or a fragment thereof, C-terminal pro-endothelin-1 (CT-proET-1) or a fragment thereof, and/or adrenomedullin precursor (pro) or a fragment thereof, and wherein a lower or equal level of the one or more endothelial biomarkers in the second sample compared to the first sample indicates that the patient is not at risk of an adverse clinical outcome for at least 28 days. The invention also relates to a kit for carrying out the method of the invention.

Inventors

• Andre Schwabe
• Sasha Johannes
• Yang Wimmer
• Michael. K. Mansur

Assignees

• B.R.A.H.M.S有限公司

Dates

Publication Date

20260508

Application Date

20241009

Priority Date

20240604

Claims (20)

1. 1. A method for therapeutic management and/or prediction of disease progression, severity and/or outcome in a patient suffering from an infection with a respiratory virus, the method comprising the steps of: a. providing a first sample isolated from the patient, B. Providing a second sample isolated from the patient at a point in time after the first sample is isolated from the patient, C. Wherein the first and the second sample are separated within 96 hours (4 days) after consultation of medical personnel, D. Determining the level of one or more endothelial biomarkers in said first and said second samples, wherein said one or more endothelial biomarkers is soluble Fms-like tyrosine kinase-1 (sFlt-1) or a fragment thereof, C-terminal pro-endothelin-1 (CT-proET-1) or a fragment thereof and/or adrenomedullin precursor (proADM) or a fragment thereof, and E. wherein a lower or equal level of the one or more endothelial biomarkers in the second sample as compared to the first sample is indicative of the patient not being at risk of an adverse clinical outcome for at least 28 days.
2. 2. The method of claim 1, wherein a lower or equal level of the one or more endothelial biomarkers in the second sample as compared to the first sample indicates that the patient is not at risk of an adverse clinical outcome associated with a need to replenish oxygen for at least 28 days.
3. 3. The method of the preceding claims, wherein a lower or equal level of the at least one additional biomarker and/or the one or more endothelial biomarkers in the second sample as compared to the first sample indicates that the patient does not need to be supplemented with oxygen for at least 28 days.
4. 4. The method of any one of the preceding claims, wherein the first sample and the second sample are obtained by a first medical staff member following a clinic visit to the patient after symptoms of the respiratory viral infection appear.
5. 5. The method of any one of the preceding claims, wherein the patient is hospitalized.
6. 6. The method of any one of the preceding claims, wherein the patient is admitted to and/or not admitted to an Intensive Care Unit (ICU).
7. 7. The method according to any of the preceding claims, wherein the patient is admitted to an Intensive Care Unit (ICU), preferably after first contact with medical personnel.
8. 8. The method of any one of the preceding claims, wherein A. The first sample is obtained within 24 hours (1 day) after admission to the hospital and/or after consultation in the medical staff, and/or B. The second sample is obtained 72 to 96 hours (day 4) after admission to the hospital and/or after consultation with the medical staff.
9. 9. The method according to any of the preceding claims, wherein the patient is infected with a coronavirus, preferably a SARS coronavirus, more preferably a SARS-CoV2 coronavirus.
10. 10. The method of any one of the preceding claims, wherein an adverse event is death within at least 28 days after the first sample is obtained.
11. 11. The method of any one of the preceding claims, wherein the adverse event is an adverse respiratory and/or infectious clinical outcome requiring oxygen support and intensive therapy for at least 28 days.
12. 12. The method of the preceding claim, wherein the bad breath and/or infectious clinical outcome is Intensive Care Unit (ICU) therapy, mechanical ventilation, and/or other infections.
13. 13. The method of any one of the preceding claims, wherein the patient is infected with coronavirus and the adverse event is a COVID scale score deterioration (e.g., COVID scale score deterioration to: > 4) and/or maintenance of hospitalization on or after day 4 post-admission.
14. 14. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises sFlt-1 or a fragment thereof, and -Wherein the level of sFlt-1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -A level of sFlt1 or fragment thereof of +.81.3 pg/l±20% determined in the first sample indicates that the patient is not at risk of poor clinical outcome for at least 28 days.
15. 15. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises sFlt-1 or a fragment thereof, and -Wherein the level of sFlt1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -A level of sFlt-1 or fragment thereof of +.81.3 pg/l ± 20% determined in the first sample indicates that the patient is not at risk of an adverse clinical outcome associated with the need for supplemental oxygen for at least 28 days.
16. 16. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises sFlt1 or a fragment thereof, and -Wherein the level of sFlt1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -The level of sFlt1 or fragment thereof measured in the first sample of +.81.3 pg/l±20% indicates that the patient is not at risk of mortality for at least 28 days (and preferably does not require oxygen support).
17. 17. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises sFlt-1 or a fragment thereof, and -Wherein the level of sFlt-1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -A level of sFlt-1 or fragment thereof of +.81.3 pg/l ± 20% determined in the first sample indicates that the patient does not need oxygen support and is not at risk of mortality and additional infection for at least 28 days after consultation with the medical staff.
18. 18. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises C-terminal pro-endothelin-1 (CT-proET-1) or fragments thereof, and -Wherein the level of CT-proET-1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -A level of CT-proET-1 or fragment thereof of +.87.4 pmol/l±20% determined in the first sample indicates that the patient is at risk of having a poor clinical outcome for at least 28 days.
19. 19. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises CT-proET-1 or a fragment thereof, and -Wherein the level of CT-proET-1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -A level of CT-proET-1 or fragment thereof of +.87.4 pmol/l±20% determined in the first sample indicates that the patient is not at risk of an adverse clinical outcome associated with the need to replenish oxygen for at least 28 days.
20. 20. The method of any one of the preceding claims, wherein the one or more endothelial biomarkers determined in the first and the second samples comprises CT-proET-1 or a fragment thereof, and -Wherein the level of CT-proET-1 or a fragment thereof in the second sample is lower or equal compared to the first sample, and -The level of CT-proET-1 or fragment thereof measured in the first sample being +.87.4 pmol/l±20% indicates that the patient is not at risk of mortality (and preferably does not require oxygen support) for at least 28 days.

Description

Biomarkers for therapeutic management and/or prediction of disease progression, severity and/or outcome for respiratory viral infections Technical Field The present invention relates to the fields of treatment guidance, medical risk assessment, clinical diagnosis and prognosis, and corresponding methods and products. The present invention relates to a method for the therapeutic management and/or prediction of disease progression, severity and/or outcome in a patient suffering from an respiratory viral infection, comprising the steps of (a.) providing a first sample isolated from said patient, (b.) providing a second sample isolated from said patient at a time point after the first sample is isolated from said patient, (c.) wherein the first and the second sample are isolated after admission and/or within 96 hours (4 days) after consultation of a person, (d.) determining the level of one or more endothelial biomarkers in the first and the second sample, wherein the one or more endothelial biomarkers is soluble Fms-like tyrosine kinase-1 (sFlt-1) or a fragment thereof, C-terminal pro-endothelin-1 (CT-pro-1) or a fragment thereof and/or an adrenomedullin precursor (proADM) or a fragment thereof, and (e.) wherein a lower level of the one or more endothelial biomarkers in the second sample compared to the first sample indicates that there is at least an equal clinical risk of the one or more endothelial biomarkers in the patient 28. The present invention also relates to a method for treatment management of a patient suffering from an infection with an respiratory virus, the method comprising assessing whether said patient requires oxygen support, comprising the steps of (a.) providing a first sample isolated from said patient, (b.) providing a second sample isolated from said patient at a time point after isolation of the first sample from said patient, (c.) wherein the first and the second sample are isolated after admission and/or within 96 hours (4 days) after consultation with medical personnel, (d.) determining the level of one or more endothelial biomarkers in the first and the second sample, wherein the one or more endothelial biomarkers is soluble Fms-like tyrosine kinase-1 (sFlt-1) or a fragment thereof, C-terminal pro-endothelin-1 (CT-proET-1) or a fragment thereof, and/or an adrenomyelon precursor (proADM) or a fragment thereof, and (e.) wherein a lower level of the one or more biomarkers in the second sample compared to the first sample indicates that the level of the one or more biomarkers does not require at least equal endothelial support in the patient 28 days. The invention also relates to a method for predicting disease progression, severity and/or outcome in a patient suffering from a coronavirus infection, wherein the method comprises (a) providing a sample from said patient, (b) determining the level of one or more biomarkers in said sample, (C) wherein the one or more biomarkers comprise one or more of soluble Fms-like tyrosine kinase-1 (sFlt-1) or a fragment thereof, a C-terminal endothelin-1 precursor (CT-proET-1) or a fragment thereof, an adrenomedullin precursor (proADM) or a fragment thereof and/or Procalcitonin (PCT) or a fragment thereof, (d) wherein said level of the one or more biomarkers in the sample is indicative of a risk of poor clinical outcome within 28 days. The invention also relates to a method for predicting disease progression, severity and/or outcome in a patient suffering from a coronavirus infection, wherein a low risk level of one or more biomarkers or fragments thereof in said sample on day 1 indicates that the patient is not at risk of an adverse clinical outcome within 28 days, and/or wherein a low risk ratio (ratio day 4/day 1) of the levels of one or more biomarkers or fragments thereof in said sample measured on day 4 and day 1 indicates that the patient is not at risk of an adverse clinical outcome within 28 days. The invention also relates to a kit for performing a method for therapeutic management and/or prediction of disease progression, severity and/or outcome in a patient suffering from a respiratory viral infection, the kit comprising detection reagents for determining the level of one or more biomarkers in a sample from said patient, reference data for the risk of a patient for a poor clinical outcome within 28 days, optionally detection reagents for determining the presence of a respiratory viral infection, and optionally detection reagents for determining the level of at least one additional biomarker or fragment thereof. Background Severe Acute Respiratory Syndrome (SARS) is a virus-mediated respiratory disease, first discovered in 2002, usually caused by coronavirus (CoV) infection. From scientific reports, it is speculated that all human covs may be of human-animal co-occurrence. Once humans are infected, viruses can spread rapidly through spray transmission and intimate human-to-human contact, ultimately resulting in epidemic scenarios and even p