A Case Report | Virlaza™ Improves Cardiopulmonary Recovery of Post-Covid-19 Patient

Maysa Alves Rodrigues Brandao-Rangel1, Renilson Moraes Ferreira1, Claudio Ricardo Frison1, Dobroslav Melamed2, Boris Brill2, Rodolfo P Vieira1

1- Federal University of São Paulo (UNIFESP), Laboratory of Pulmonary and Execise Immunology, Rua Talim 330, São José dos Campos – SP, Brazil, 12231-280.
2- Libipharm, Research and Development Department, Ben Gurion 70, Rechovot, Israel, 7639461.

Correspondence
Rodolfo P Vieira, Prof. Dr.
rpvieira@unifesp.br
+55 12 99141-0615
Rua Talim 330, Vila Sanches
São José dos Campos – SP
Brazil – 12231-280

Abstract
Coronavirus disease 2019 (COVID-19) affects different organs and a severe pro-inflammatory response, denominated “cytokine storm” have been described as a key underlying mechanism. The lungs are the most affected organ, and a fibrotic response after infection by COVID-19 are often found. This case report demonstrates that 12 days of oral administration of Immune Cov™/Virlaza™, an herbal medicine developed in Israel (based on tinctures and natural antioxidants), was able to accelerate the lung recovery of a moderate/severe post-COVID-19 patient, who present metabolic syndrome, characterized by grade II obesity, dyslipidemia, and hypertension. After 12 days of hospitalization needing high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), awake (nonintubated) proning, the patient was discharged still presenting the following characteristics: 75% of ground-glass opacities of the lungs in CT, severe reduction of the lung function, high levels of fractional exhaled nitric oxide (FeNO), leukopenia and neutrophilia, reduced respiratory muscle strength and peripheral muscle strength. So, a very quick recovery was observed after 12 days of Immune Cov™/Virlaza™, resulting in an improvement to 25% ground-glass opacities of the lungs in computerized tomography (CT), as well as an improvement for all parameters of lung function, FeNO, normalization of blood leukocytes and improvement of respiratory and peripheral muscle strength. So, Immune Cov™/Virlaza™ may be considered as an herbal medicine able to improve the recovery of post-COVID-19 patients and reduce COVID-19 comorbidities.

1. Introduction
Coronavirus disease 2019 (COVID-19) develop in response to infection to coronavirus 2, denominated as Sars-Cov-2 [1]. COVID-19 affects several organs in different severities and the respiratory [2], hematological [3] and musculoskeletal [4] systems are centrally affected. In fact, severe pro-inflammatory response is described as key mechanism for organ-damage induced during COVID-19 [5]. Some factors are key predictive factors for the development of severe forms of COVID-19 [6]. Among then, metabolic syndrome (MS), obesity, dyslipidemia, diabetes, and hypertension are considered critical negative predictive factors [6]. So, it is well established that specially MS individuals present more severe pneumonia and respiratory failure, increased hospitalization rate and duration and elevated mortality [6]. In addition, pre-clinical studies reinforce the hypothesis that the impairment of lung function observed in obese individuals may be attributed to obesity-induce lung fibrosis [7, 8]. Concerning the hematological system, a classical clinical state characterized by leukopenia and neutrophilia has been reported in COVID-19 patients, while its severity was also associated with worse prognosis [9]. So far, COVID-19 survivals remained presenting deteriorated function of organs and systems, which deserve special attention, once the duration of these sequalae are unknown [4]. In fact, fatigue, extreme loss of muscle mass and strength are being reported by 63% of the post-COVID-19 patients [4]. Therefore, pharmacological, and non-pharmacological strategies are urgently necessary to improve and speed up the recovery of such patients. Thus, this present case report, demonstrate the effects of an Israeli herbal medicine, the Immune Cov™/Virlaza™ on respiratory, hematological, and muscular response. Immune Cov™/Virlaza™ is a tincture-based 10% concentration of all components (Clove Glycerin Extract, Eucalyptus Glycerin Extract, Basil Glycerin Extract, Sage Glycerin Extract, Maritime Pine Glycerin Extract, Clove Ethyl Alcohol Extract, Eucalyptus Ethyl Alcohol Extract, Maritime Pine Ethyl Alcohol Extract, Basilica Ethyl Alcohol Extract, Sage Ethyl Alcohol Extract).
2. Case presentation
A 50-year-old man, without any history of previous respiratory diseases, with historic of two cardiovascular surgeries (mamarian and safena), presenting grade II obesity (BMI 35.91), flu-like symptoms, fatigue and breathlessness, partial oxygen saturation (SpO2%) of 80%, laboratory diagnosis and computerized tomography (CT) of the lungs (>75% ground-glass opacities) characterizing acute respiratory distress syndrome (ARDS), who was additionally diagnosed with coronavirus disease 19 (COVID-19) by RT-PCR. After twelve days of hospitalization, under treatment with antibiotic (Amoxicillin 500mg/2x/day and Clavulanate Potassium 125mg/2x/day), corticosteroid (Prednisone 20mg/day) and sodium enoxaparin (100mg/day), the patient has been discharged from the hospital, with a new CT still presenting 75% of ground-glass opacities of the lungs. The main complaints of the patient after hospital discharge were acute fatigue and breathlessness for minimal effort, after standing of a chair, for example. So, the following evaluations were performed before and after 12 days of use of Immune Cov™/Virlaza™ (20 drops, 2x/day): the SpO2% was evaluated at rest, the lung function by spirometry (Masterscreen, Jaeger, Germany), according to ATS/ERS recommendations by using force maneuver [10], the whole blood analysis (red and white cells), the levels of exhaled nitric oxide, the maximal inspiratory (MIP) and expiratory (MEP) pressure, and the hand grip strength. The results demonstrated that 12 days of Virlaza™ resulted in improvement of: lung function, notably on forced vital capacity (FVC; 1.91 L x 2.31 L; 41.2% x 61.7% of predicted), forced expiratory volume in the first second (VEF1; 1.51 L x 1.68 L; 40.4% x 55.9% of predicted), inspiratory vital capacity (VC In; 1.59 L x 1.63 L, 36.3% x 46.7% of predicted), forced expiratory flow 25% (FEF25%; 0.47 L/s x 0.58 L/s, 35.8% x 58.3% of predicted), forced expiratory flow 50% (FEF50%; 1.42 L/s x 1.62 L/s, 37.4% x 41.9% of predicted), forced expiratory flow 75% (FEF75%; 2.91 L/s x 3.58 L/s, 48.3% x 49.7% of predicted), peak expiratory flow (PEF; 2.99 L/s x 3.97 L/s, 36.4% x 38%). Importantly, the CT revealed a significant reduction in ground-glass opacities, reducing from >75% to 25% after 12 days of Immune Cov™/Virlaza™ (Figure 1). The levels of fractional exhaled nitric oxide (FeNO) which reflects the pulmonary inflammation, was initially of 28 parts per billion (ppb) to 11 ppb after treatment with Immune Cov™/Virlaza™. SpO2% also presented significant recovery, once SpO2 of 92% was initially measured after hospital discharge reaching a SpO2 of 99% after 12 days of treatment with Immune Cov™/Virlaza™. The hematological response was also improved by Immune Cov™/Virlaza™ (platelets 250x103/mm3 x 350x103/mm3; total leukocytes 5,37/mm3 x 9,77/mm3; neutrophils 87% x 52.2%; lymphocytes 11% x 38%; eosinophils 0.9% x 0%; monocytes 2% x 0.1%; basophils 0.02% x 0.01%). The strength of respiratory muscles also presented improvement after treatment with Immune Cov™/Virlaza™, where MIP was -100 cmH2O x -120 cmH2O and MEP 40 cmH2O x 60 cmH2O. Concerning the peripheral muscle strength measured by hand grip strength, the results demonstrated that Immune Cov™/Virlaza™ improved hand grip strength on right (28.9 Kg x 36.2 Kg) and left (19.8 Kg x 23.1 Kg) hand. Therefore, the present case study reveals beneficial effects of Immune Cov™/Virlaza™ on clinical and functional parameters of severe post-COVID-19 patient, significantly improving several aspects of their recovery.
3. Discussion
In the present study, we observed the effectiveness of Immune Cov™/Virlaza™ accelerating the recovery of an obese middle-aged man who developed a moderate/severe form of COVID-19. The results obtained after 12 days of Immune Cov™/Virlaza™ treatment accelerated the recovery of lung function, lung structure, reduced lung inflammation and improved systemic leukopenia and neutrophilia, as well as the respiratory and peripheral muscle strength.
This case report demonstrates a severe acute lung injury in response to Sars-Cov-2 infection, characterized by bilateral infiltrates affecting more than 75% of the lungs, oxygen saturation below 80% (at hospital), where the patient, still presented at a thoracic CT presenting 75% of ground-glass opacities 12 hours after hospital discharge. Of note, in our daily clinical practice and according to the literature, it was reported that such affection of >75% of ground-glass opacities of the lungs, normally can be normalized only after 2-3 months [11]. So, its is plausible to affirm the efficacy of Immune Cov™/Virlaza™ facilitating the recovery of the lungs concerning the bilateral inflammatory infiltrates, visualized through the extensive area >75% of ground-glass opacities. This anti-inflammatory effect of Immune Cov™/Virlaza™ for the lungs is additionally supported by its effects dampen the levels of fractional exhaled nitric oxide (FeNO), which is a classical marker of pulmonary inflammation and nitrosative stress and has been linked to pathophysiology and severity of COVID-19 [12, 13]. Importantly, such improvement observed in CT was functionally proven once it was followed by an incredibly significant enhancement in all parameters of the lung function, as presented in the case presentation session above. Again, our clinical practice and the literature is demonstrating that even after 3 months, post-COVID-19 patients are still presenting alterations in lung function [14]. Furthermore, such reduction in ground-glass opacities and improvement in the lung function was reflected by improvement in oxygen saturation, which remained at 99% after the 12 days of treatment with Immune Cov™/Virlaza™. Concerning the importance of systemic inflammation in COVID-19 pathophysiology and during the recovery from COVID-19 [2, 3, 4], this case report also pointed out that 12 days of treatment with Immune Cov™/Virlaza™ simply reestablished the levels of platelets and of total and differential leukocytes to normal numbers, demonstrating not only a pulmonary but also a positive systemic effect for post-COVID-19 patients. Finally, around 63% of all post-COVID-19 patients report fatigue and breathlessness [4]. In this sense, a growing number of studies are reporting wasting of peripheral muscle mass and strength [15] as well as in respiratory muscle strength [16], which are key factor interrelated with the development of fatigue and breathlessness. Once more, the literature is demonstrating that even asymptomatic and mild COVID-19 patient are displaying fatigue and breathlessness [4], which are sequelae completely dampen by Immune Cov™/Virlaza™.

4. Conclusion
Consent
Written and verbal consent was obtained from the patient for this case report.

Conflict of interest
MARBR, RMF and CRF have no conflict of interest related to this study. DM and BB declares that they are the owners of Libipharm™. RPV declares he have received consulting fee from Libipharm.

Figure Legend
Figure 1 – In panel A (A.1 to A.5) the images referred to after treatment with Immune Cov™/Viralza™, while in panel B (B.1 to B.5) the images referred to before treatment with Immune Cov™/Viralza™.

Figure 1 – Thorax CT before and after Virlaza™ for 12 days.

Figure 1 – In panel A (upper panel) the images demonstrate approximately 50%-75% of ground-glass opacities in the whole lung parenchyma, while in panel B (lower panel) the images demonstrate approximately 25%-50% of ground-glass opacities in the whole lung parenchyma.
All data obtained during the current study are not publicly available due to confidential issues but are available from the corresponding author on reasonable request.

Data Availability
References
The results demonstrated that Immune Cov™/Viralza™ accelerates the recovery of lung structure, function, and inflammation, reduces systemic inflammation, and improves the respiratory muscle strength and the peripheral muscle strength. Therefore, Immune Cov™/Viralza™, an herbal medicine, should be urgently considered for treatment and recovery of COVID-19 survivals.

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