The LUSZ COVID-19 Severity Index: A Prognostic and Predictive Score of Mortality for Hospitalized Patients With Covid-19 (LUSZ_SCORE)

The LUSZ COVID-19 Severity Index: A Prognostic and Predictive Score of Mortality for Hospitalized Patients With Covid-19.

The coronavirus disease 2019 (COVID-19) has spread rapidly and caused a global pandemic, as defined by the WHO, within a short period of time. The prognostic of disease severity is still a challenge and early identification of risk factors to be involved in its progression is of high importance. The scoring of variables related to worse outcomes is key for a targeted and/or advanced protocol. Besides, the need for a predictive-wide model is mandatory for hospitalized unvaccinated patients to avoid any delay in the characterization of severe illness and the development of complications. The LUSZ COVID-19 Severity Index was developed as a predictive tool based on >100 risk factors/biomarkers, that could effectively identify high-risk patients and prevent mortality.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Other: LUSZ P

Detailed Description

The scientific community is in urgent need of reliable biomarkers related to COVID-19 disease progression, in order to stratify high-risk patients. The rapid disease spread necessitates the immediate categorization of patients into risk groups following diagnosis, to ensure optimal resource allocation. Novel biomarkers are needed to identify patients who will suffer rapid disease progression to severe complications and death. The identification of novel biomarkers is strictly related to the understanding of viral pathogenetic mechanisms, as well as cellular and organ damage. Effective biomarkers would be helpful for screening, clinical management, and prevention of serious complications.

Indeed, previous studies suggested and developed predictive scores (CALL, Chosen, HA2T2, ANDC, ABC2-SPH, ICOP, SEIMC, IRS, NLP, APACHE II, GRAM, and others) that estimate the severity of the disease, the risk of needing invasive mechanical ventilation (IMV) among patients with COVID-19 and the risk of mortality. Many scores including so many relevant parameters have been used to predict the status of a patient. In addition to comorbidities, age, etc., some hematological parameters, including white blood cell (WBC), lymphopenia, c-Reactive Protein (CRP), and some biochemical parameters, such as lactate dehydrogenase (LDH), creatine kinase (CK), and troponin were reported to be associated with COVID-19 severity. In fact, the patient's initial laboratory scoring is useful but not sufficient to avoid mortality: high neutrophil count (>0.7 × 103/μL), lymphopenia (<0.8 × 103/μL), elevated CRP (>4.75 mg/dL), and elevated LDH (>593 U/L) were the most important predictors of mortality. Another prognostic marker the lymphocyte-to-CRP ratio (LCR), was also helpful. A rise in the NLR and a decline in LCR correlates with the severity of COVID-19. Specifically, a low LCR at presentation was seen to predict ICU admission and the need for invasive ventilation. Patients critically ill with COVID-19 had a hyperinflammation, the associated biomarkers may be beneficial for risk stratification. Many studies found other associations with serum CRP, procalcitonin (PCT), D-dimer, and serum ferritin. Subsequent studies demonstrate that the inflammatory response plays a critical role in COVID-19, and inflammatory cytokine storm increases the severity of COVID-19. In fact, the serum levels of IL-6 can effectively assess disease severity and predict outcomes in patients with COVID-19. So, these prognostic models have been introduced to guide treatment and resource management.

In this study, we aimed to specify high-risk factors and biomarkers of fatal outcomes in hospitalized subjects with coronavirus depending on many variables analysis, and also to compare the efficacy of targeted treatments (antiviral, antiretroviral, immunosuppressive antagonist, etc.) in order to help clinicians better choose a therapeutic strategy.

The population had been divided into groups according to the WHO Ordinal Clinical Severity Scale on which the LUSZ SCORE was applied; The percentage of mortality, in and out of the hospital, the length of stay in the hospital, the pulmonary inflammatory lesions and their distribution, the SARS-CoV-2 IgM and IgG variations at admission, the inflammatory markers, the complete blood count, the coagulation factors and enzymes, proteins and electrolytes profile, glucose and lipid profile, and others were measured before and after LUSZ scoring. The establishment of this novel predictive scoring model of disease progression may help identify patients with COVID-19 who may subsequently develop a critical illness. Thus, we can improve the therapeutic effect and reduce the mortality of COVID-19 with more accurate and efficient use of medical resources, which helps to deliver proper treatment according to each case.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Nehman Makdissy, Professor; Phone Number: +96171210250; Email: nehman.makdissy@ul.edu.lb

Study Locations

• Lebanon
  • North
    • Tripoli, North, Lebanon, 961
      • Recruiting
      • Lebanese University
      • Contact: Nehman Makdissy, Professor; Phone Number: +96171210250; Email: nehman.makdissy@ul.edu.lb
      • Sub-Investigator: Samar El Hamoui, PhD
      • Sub-Investigator: Nadine El Ghotme, PhD
      • Sub-Investigator: Wissame Daher, MSc DMAH
      • Sub-Investigator: Bassam BouDeleh, MSc DMAH
      • Sub-Investigator: Assaad Assaad, MSc DMAH
      • Sub-Investigator: Fatmeh Matar, MSc CompSci
      • Sub-Investigator: Rania Baida, PhD
      • Sub-Investigator: Sara Chaar, Msc DMAH
    • Zgharta, North, Lebanon
      • Recruiting
      • SZUMC
      • Contact: Fadi Fenianos, MD; Phone Number: +9613191528; Email: hop.sz@hotmail.com
      • Contact: Mareine Douiehy, MSc; Phone Number: +9613777484; Email: hop.sz@hotmail.com
      • Principal Investigator: Fadi Fenianos, MD, ID
      • Sub-Investigator: Mareine Douiehy, MSc Head QC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

This is a prospective cohort study with data on patients collected and followed up from March 28, 2020, from the SZUMC (as one single medical center; this study will be applied to other centers). All included patients were diagnosed by polymerase chain reaction (PCR) test taken from a nasopharyngeal sample, throat sputum, saliva, urine, stool, or bodily fluid. Analyses were realized upon admission as well 8-10 days after admission. All patients were followed by the principal investigator of the study. The collection of data from each patient in terms of laboratory data, treatments, and outcomes was verified by the principal investigator through the review of clinical records. Selected patients were divided into groups according to the WHO ordinal clinical severity scale.

Description

Inclusion Criteria: (1) admission to hospital, (2) fulfills WHO case definition, including a positive PCR for COVID-19 from any specimen (e.g., nasopharyngeal, throat, saliva, urine, stool, other bodily fluid), (3) not received any therapy (radiotherapy, chemotherapy, corticotherapy, hormonotherapy, immunotherapy, anti-inflammatory, antibiotics, antiparasitic, antiviral, antibacterial, convalescent plasma, monoclonal antibodies, or other treatments such as hydroxychloroquine and azithromycin) before admission and samples' collection, and (4) Spo2 < 90%.

Exclusion Criteria: (1) Non-SARS-CoV-2, (2) active indication and use for one of the investigational products (e.g., HIV positive if antiretroviral agents were used), (3) allergy or hypersensitivity to one of the investigational products (Lopinavir/Ritonavir, Remdesivir, Tocilizumab) or other contraindication, (4) progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments, (5) received any therapy (radiotherapy, chemotherapy, hormonotherapy, immunotherapy, anti-inflammatory, antibiotics, antiparasitic, antiviral, antibacterial, convalescent plasma, monoclonal antibodies, or other treatments such as hydroxychloroquine and azithromycin) before admission and samples' collection, (6) weight loss during the last 2 years, (7) abdominal surgeries, (8) pregnancy, and (9) SpO2 superior or equal to 90%, and (10) vaccinated individuals were excluded.

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Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
LUSZ WOSS-3; hospitalized COVID-19 patients classified as WOSS-3 (as per the WHO Ordinal Severity Scale) who didn't need oxygen therapy	Other: LUSZ P; LUSZ protocol applied to WOSS in-hospitalized Covid-19 patients: a Corticosteroid Therapy-enhanced Standard Care (CTSC), a standard care enhanced by corticosteroid (methylprednisolone) treatment.
LUSZ WOSS-4; hospitalized COVID-19 patients classified as WOSS-4 (as per the WHO Ordinal Severity Scale) who needed oxygen therapy by mask or traditional nasal cannula	Other: LUSZ P; LUSZ protocol applied to WOSS in-hospitalized Covid-19 patients: a Corticosteroid Therapy-enhanced Standard Care (CTSC), a standard care enhanced by corticosteroid (methylprednisolone) treatment.
LUSZ WOSS-5; hospitalized COVID-19 patients classified as WOSS-5 (as per the WHO Ordinal Severity Scale) who needed oxygen therapy NIMV or HFNC	Other: LUSZ P; LUSZ protocol applied to WOSS in-hospitalized Covid-19 patients: a Corticosteroid Therapy-enhanced Standard Care (CTSC), a standard care enhanced by corticosteroid (methylprednisolone) treatment.
LUSZ WOSS-6; hospitalized COVID-19 patients classified as WOSS-6 (as per the WHO Ordinal Severity Scale) who needed oxygen therapy IMV & intubation	Other: LUSZ P; LUSZ protocol applied to WOSS in-hospitalized Covid-19 patients: a Corticosteroid Therapy-enhanced Standard Care (CTSC), a standard care enhanced by corticosteroid (methylprednisolone) treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival / Mortality	Occurence of survival or death	1 day to 3 years
LOS	Time to recovery in-hospital (the length of stay (LOS))	up to 3 months
IMV	incidence of mechanical ventilation and incidence of serious adverse effects	during the first 3 days of hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Status	Clinical status at days 8-10 by radiology and laboratory assessments	up to 3 years

Collaborators and Investigators

• Sponsor: Lebanese University
• Collaborators: Hospital Saydet Zgharta University Medical Center
• Investigators: Study Chair: Nehman Makdissy, Professor, Lebanese University

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2020
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; treatment; immunosuppressive; comorbidities; inflammation; covid-19; antiviral; IL6; antagonist; score; antiretroviral; LUSZ; WHO ordinal severity scale
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: The COVID-19 LUSZ SCORE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No