This study aims first to assess the efficacy, safety, and effectiveness of the LUSZCOVID-19 therapy consisting of a comparative study of three different treatmentapproaches: antiviral, antiretroviral, and immunosuppressive IL-6 receptor antagonist,and second to identify high-risk factors and biomarkers associated with fatal outcomes inhospitalized COVID-19 patients. The study seeks to validate a novel predictive scoringmodel for disease progression and evaluate the impact of these treatments on mortality,admission to the intensive care unit (ICU), and time to recovery.
The ongoing COVID-19 pandemic has posed significant challenges worldwide, necessitating
the evaluation of various treatment options to mitigate disease severity and improve
patient outcomes. This study aims to conduct a comparative therapeutic analysis of
antiviral, antiretroviral, and immunosuppressive treatments in hospitalized COVID-19
patients, named here the COVID-19 LUSZ Therapeutic Stduy. By assessing the efficacy and
effectiveness of these treatment modalities, as well as considering high-risk factors,
biomarkers, and disease progression, we seek to provide valuable insights into their
relative benefits and inform evidence-based therapeutic strategies.
Hypothesis:
Our hypothesis is that certain antiviral, antiretroviral, and immunosuppressive
treatments can effectively mitigate disease progression and improve clinical outcomes in
hospitalized COVID-19 patients with different degrees of illness severity as classified
by the WHO Ordinary Severity Scale (WOSS) adjusted to LUSZ scoring. We postulate that the
choice of treatment may depend on the presence of high-risk factors and the underlying
immune response, as reflected by biomarker profiles.
Study Design:
This study will adopt a prospective comparative design, analyzing medical records of
hospitalized COVID-19 patients from multiple healthcare facilities and evaluating the
disease progression. The inclusion criteria will encompass patients diagnosed with
COVID-19 and receiving either antiviral, antiretroviral, or immunosuppressive treatments.
Patients with comorbidities, varying levels of disease severity, and different treatment
durations will be included to reflect real-world clinical scenarios.
Data Collection:
Key variables of interest will include patient demographics, medical history, disease
severity at admission, laboratory results, radiology results, treatment regimen,
treatment duration, and clinical outcomes. High-risk factors such as advanced age,
immunocompromised status, and comorbidities will be specifically analyzed. The pulmonary
inflammatory lesion, biomarkers, including inflammatory markers, cytokines, and viral
load, will be assessed at various time points to evaluate treatment response and disease
progression.
Analysis:
Descriptive statistics will be employed to summarize patient characteristics, treatment
modalities, and clinical outcomes. Comparative analysis will be performed to assess the
efficacy and effectiveness of antiviral, antiretroviral, and immunosuppressive
treatments. Statistical methods, such as chi-square tests, t-tests, Kaplan-Meier survival
analysis, and regression analysis, will be utilized to examine associations between
treatment regimens and clinical outcomes. Subgroup analyses will be conducted to evaluate
treatment response based on high-risk factors and biomarker profiles, applying the LUSZ
score.
Targets and Significance:
The primary targets of this study are to compare the therapeutic effects of antiviral,
antiretroviral, and immunosuppressive treatments in hospitalized COVID-19 patients and
identify potential predictors of treatment response. By elucidating the relative benefits
and limitations of these treatment modalities, we aim to contribute to evidence-based
clinical decision-making, enhance patient care, and optimize resource allocation.
Additionally, this study will provide valuable insights into the interplay between
high-risk factors, biomarkers, and disease progression, which can aid in the development
of personalized treatment approaches for COVID-19 patients.
In conclusion, this comparative LUSZ therapeutic study in hospitalized COVID-19 patients
will provide valuable evidence regarding the efficacy and effectiveness of the LUSZ
COVID-19 therapy. By considering high-risk factors, biomarkers, and disease progression,
we aim to shed light on the optimal treatment strategies for different patient
populations. The findings of this study have the potential to inform clinical practice,
improve patient outcomes, and contribute to the ongoing efforts to combat the COVID-19
pandemic.
Drug: Lopinavir / Ritonavir
Kaletra is a medication that is produced by AbbVie, a pharmaceutical company based in the
United States. It is FDA approved for the treatment of HIV-1 infection in adults and
pediatric patients. Kaletra contains two active ingredients, lopinavir, and ritonavir,
which work together to inhibit the replication of the HIV virus.
Administration dose and duration of treatment: Patients will receive a loading dose
(800/200, daily) of lopinavir 400 mg plus ritonavir 100 mg orally every 12 h for 10 days
or until discharge, if sooner.
Other Name: Kaletra
Drug: Remdesivir (RDV)
Remdesivir is provided by the United States as an FDA-approved drug, an antiviral
medication developed by Gilead Sciences, and has been authorized for emergency use and
approved for the treatment of COVID-19 in certain countries, including the United States.
Administration dose and duration of treatment: intravenously as a 200-mg loading dose on
day 1, followed by a 100-mg once daily on days 2-10 or until hospital discharge or death.
Duration is generally 5 days or until hospital discharge, whichever is first, but may
extend to up to 10 days based on clinical response: For inpatients not requiring IMV
and/or ECMO: 5 days; if clinical improvement is not demonstrated, treatment may be
extended up to 10 days total. For inpatients requiring IMV and/or ECMO: 10 days.
Other Name: Veklury
Drug: Tocilizumab
Actemra is an FDA-approved brand name for Tocilizumab, a monoclonal antibody that targets
the interleukin-6 (IL-6) receptor, an immunosuppressive drug produced by Roche. It
belongs to a class of medications known as IL-6 receptor antagonists and is designed to
suppress the activity of the immune system. By blocking IL-6 receptor signaling, Actemra
helps reduce inflammation and is used in the treatment of various autoimmune conditions
and cytokine release syndrome.
Administration dose and duration of treatment: TCZ was administered 8 mg/kg intravenously
(800 mg per infusion) as a single 60-minute intravenous infusion for 4 Weeks initially.
The second infusion (400 mg) after 24 h may be administered based on clinical response in
case of respiratory worsening, or 8 mg/kg at T0 followed by 8 mg/kg after 12 h.
Other Name: Actemra
Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
(1) Methylprednisone (120mg/24h/IV) followed by 80mg/day (7days), and if necessary,
continued with 40mg/day; or a pulse therapy (patient in critical state (360mg/day/IV) for
3 serial days, followed by 80mg/day (7days), and if necessary, continued with a dose of
40mg/day. (2) Standard Care: Normal Saline 0.9% (500cc/24h); vitamins [D (Oravil,
100.000IU/2ml PO STAT), C (10g/250cc in normal saline, 60drops/min/day), B (BECOZYME, 6
ampoules IV STAT)]; Omeprazole (RISEK, 40 mg/day IV); Paracetamol (PREFALGAN, 1g IV each
8h 3 times per day), Ketoprofen (PROFENID, 100mg/12h); Ceftriaxone (ROCEPHIN, 2g/day for
3 consecutive days), Doxycycline (VIBRAMYCIN, 100mg/12h PO for 8 days), Ivermectin
(12mg/day for a period of 5 days); TOPLEXIL (Syrup, 10cc/each 8h) or SINECOD (Syrup,
15cc/each 8h); ATORVASTATIN (20mg/day); LOVENOX (40mg/12h if <80kg, or 60mg/12h if
>80kg). Tranquillizers: NORMOCALM (400mg/night), XANAX (10mg/day), SEROQUEL (25mg/night),
DEPIA (2mg/day), to be administered orally
Other Name: CTSC
Eligibility Criteria for Hospitalized Patients:
Inclusion criteria:
- Age ≥ 18 years.
- Gender-neutral
- Fulfills WHO case definition, including a positive PCR for COVID-19 from any
specimen (e.g., nasopharyngeal, throat, saliva, urine, stool, and other bodily
fluid).
- 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.
- Spo2 < 90%.
- Moderate to severe COVID-19 cases as defined by WHO ordinal severity scale and
clinical and radiological findings.
- The time frame of symptom onset within the past 7 days.
- Participants provide informed consent.
- The study has received ethical approval from the institutional review board: All
clinical investigations on human samples will be conducted according to the
principles expressed in the Declaration of Helsinki, as revised in 2008
(http://www.wma.net/e/policy/b3.htm). All donors should provide written informed
consent, and samples have to be collected in accordance with ethical codes. The
study protocol was approved by the institutional review committee of the SZUMC
(MA-LE-E-60/2022).
Exclusion criteria:
- Non-SARS-CoV-2.
- Active indication and use of one of the investigational products (e.g., HIV positive
if antiretroviral agents were used).
- Allergy or hypersensitivity to one of the investigational products
(Lopinavir/Ritonavir, Remdesivir, Tocilizumab) or other contraindication.
- Progression to death is imminent and inevitable within the next 24 hours,
irrespective of the provision of treatments.
- 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.
- Weight loss during the last 2 years.
- Abdominal surgeries.
- Pregnancy.
- SpO2 ≥ 90%.
- Vaccinated individuals were excluded.
- Severe renal impairment (eGFR < 30 mL/min).
- Liver dysfunction (Child-Pugh score ≥ 10).
All included patients should be diagnosed by polymerase chain reaction (PCR) test to be
taken from a nasopharyngeal sample, throat sputum, saliva, urine, stool, or bodily fluid.
Analyses are to be conducted upon admission as well as 8-10 days after admission. All
patients will be followed by the principal investigator of the study. The collection of
data from each patient in terms of laboratory data, treatments, and outcomes will be
verified by the principal investigator through the review of clinical records. Selected
patients will be divided into groups according to the WHO ordinal clinical severity
scale.
SZUMC
Zgharta, North, Lebanon
Lebanese University
Tripoli, Lebanon
Nehman Makdissy, Professor
+96171210250
nehman.makdissy@ul.edu.lb
Nehman Makdissy, Professor, Study Chair
Lebanese University