Sedeprovid, a novel vitamin D based substance, plus AlphaH lead to complete recovery from COVID-19 within 48 hours after application in a 7-months old baby, a 1.5-year-old toddler and three further adults

Aim: Coronavirus Disease (COVID-19) is caused by the newly emerged coronavirus SARS-CoV-2. To prevent further spread of SARS-CoV-2 and to provide a possible prophylaxis and treatment option we report about our experience on the application of two preparations with a clinical complete recovery of five patients, including two breastfed babies, from a Coronavirus disease with severe symptoms. Material and methods: Sedeprovid (ImmunoD ® CLS ℗ ) were applied twice a day and AlphaH ℗ 20 ml concentrate was consumed once a day in the morning. The course of disease and symptoms before, during and after treatment were recorded. Results: Prior to treatment, the patients suffered from severe symptoms of confirmed COVID-19 infections, including cough, inappetence, tiredness, bone and body pain, loss of taste and smell and body temperature of ≥39ºC for several days. Within 24 hours after application of ImmunoD ® CLS ℗ and AlphaH ℗ a significant reduction of symptoms and a drop down of maximal body temperature was recorded. A complete recovery with normal body temperature and normal or close to normal activity was documented after 48 hours. No side effects were reported from the patients or the parents. Conclusion: The combination of ImmunoD ® CLS ℗ and AlphaH ℗ might offer a good treatment regimen for COVID-19 infected patients with moderate and severe disease progression before entering or after leaving the ICU ward. In addition, this protocol might be used as a prophylactic therapy option for healthcare providers. We strongly recommend the instant confirmation of these results in a controlled randomized trial for a possible rapid benefit of COVID-19 infected patients.

Strong evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity [4,5]. Especially in viral infection the current vitamin D level can play an important role on the disease course and outcome [6,7].
Latest literature reviews present evidence that Vitamin D supplementation could reduce risk of Influenza and COVID-19 infections and deaths [8].
Furthermore, investigations demonstrated a significant improvement of macrophage function [10]. Preliminary data confirmed attenuated clinical courses of infectious diseases like influenza, HIV and Borna virus infections.
Oxidative stress is mostly involved in inflammation, especially during viral lung epithelial infection, generating free radicals like nitrogen oxide (NO · ), superoxide anion radical (O 2 ·-) and hydroxyl radicals (OH · ) by immune cells [13]. Oxidative stress modulates expression of toll-like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells. Free radicals interfere immediately with the surrounding to modify and inactivate virus and/ or bacteria by the specific oxidation of the lipid membrane and/or proteins called lipid peroxidation [14]. An overwhelm of free radicals is normally controlled by antioxidative reacting enzymes like superoxide dismutase and peroxidases forming reactive oxygen and nitrogen species like peroxynitrite, hydrogen peroxide and lipid peroxides. Any overwhelm of both, free radicals and reactive oxygen and nitrogen radicals, are also able to destroy and/or inactivate the surrounding tissue, cells and organic substances after viral respiratory infection [15]. We have demonstrated that a combination of alpha-ketoglutarate, Vitamin C, 5 -HMF and carnosine (alphaH) decreased effectively the modification of proteins during exposition of cigarette-generated free radicals in vivo and in vitro [16]. Furthermore, we also demonstrated a substantial better outcome during and after surgery in favor of alphaH supplemented lung cancer patients decreasing oxidative modification of lipids and proteins and increasing their energy performance [17].
The aim of applying the combination of the novel substances Sedeprovid and AlphaH ℗ was the immediate exploration of possible positive effects on COVID-19 infected patients.

Material and methods
We used the newly invented and described water soluble transport form of 1,25-D3 (Cholecalciferol) called Sedeprovid, also known as IL-42 (ImmunoD ® CLS ℗ , HG Pharma, Vienna, Austria). AlphaH ℗ is an oral supplement containing following natural compounds namely alpha-ketoglutarate (AKG), vitamin C, 5 -Hydroxymethylfurfural (5-HMF) and carnosine. ImmunoD ® CLS ℗ and AlphaH ℗ were applied to confirmed Coronavirus infected patients according to a prescribed treatment plan. The course of the disease was recorded similar to documented COVID-19 cases in literature. The outcome is reported here.
Sedeprovit (ImmunoD ® CLS ℗ , HG Pharma, Vienna, Austria) was applied twice daily (morning and evening) by diluting the lyophilized preparation of one ampoule with 2 ml of water. The liquid was kept in the mouth for 5 minutes for a sufficient absorption via the buccal mucosa. In case 3 and 4 (7 and 18 months old breastfed baby) one ampoule of ImmunoD was diluted with 1 ml of water and provided with a spray nozzle. Two sprays were given hourly over the day.
Additionally, AlphaH ℗ 20 ml concentrate (HG Pharma, Vienna, Austria) was diluted with 50 ml of water and consumed once daily in the morning. In case 3 and 4 (7 and 18-month-old breastfed baby) 10 ml AlphaH concentrate were mixed with breast milk / baby food and feed twice daily.    2 = medium problems, (less than 50% of the day bedridden) 3 = serious problems, (more than 50% of the day bedridden)

Remarks:
Please write down what you think is important to note that day. Include other symptoms such as cough, runny nose, chills, loss of smell and / or taste.

Co-Morbidities: Diabetes
Chonic Obstructive Pulmonary Disease Hypertension Table 4. Explanation of applied scoring scale

Discussion
Recent literature reviews report about the evidence that Vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths [8].
Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response.
Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic antimicrobial effect [4,18].
The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract [19] by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Vitamin D constitutes a prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents [4].
Vitamin (1,25-D) acts as an immune system modulator [20]. Nearly all cells display a specific vitamin D receptor (VDR), including B and T lymphocytes (both resting and activated), monocytes [10] and dendritic cells [20]. The deficiency impairs significantly regulatory T-cells [21]. Vitamin D exerts its immunomodulatory activity on both mononuclear and polynuclear cell lines through its effects on the VDR22. Vitamin D tends to favor a mononuclear phenotype, increasing VDR expression on monocytes and macrophages [22,23]. Circulating vitamin D levels have a direct influence on macrophages, increasing their "oxidative burst" potential (maturation and production of cytokines, acid phosphatase and hydrogen peroxide) [6,24], and prevent excessive expression of inflammatory cytokines. Vitamin D also facilitates neutrophil motility and phagocytic function [25].
After the outbreaks of H1N1 influenza in 2009, Edlich et al. [26] strongly recommended that all health care workers and patients be tested and treated for vitamin D deficiency to prevent exacerbation of respiratory infections. Vitamin D also reduces the production of proinflammatory cytokines, which may reduce the risk of cytokine storm in H1N1 infection [27].
Each of the forms of vitamin D is hydrophobic and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein (VDBP). The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours. Therefore, the urgent supplementation to achieve this prophylactic and therapeutic effect of 1,25-D3 (Cholecalciferol) is complicated due to its natural lipophilic structure.
Factors that regulate vitamin D metabolism are of main importance. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate [28].
Pro-hormone 25OHD is a lipophilic molecule that is transported in the circulation bound primarily to vitamin D binding protein (DBP). While the association between 25OHD and DBP is pivotal for renal handling of 25OHD and endocrine synthesis of 1,25(OH)2D, what is the role of DBP for extra-renal synthesis of 1,25(OH)2D? [29].
The question of utmost importance in this context is, how the VDBP-bound Vitamin D in the blood stream tissue-specifically reaches the intracellular VDR in the effector cell in need of Vitamin D reaction? What is the key receptor for distribution into the different tissues?
The answer might be, that Vitamin D binding protein is a sparsely glycosylated serum protein responsible for highly specific binding and tissue-specific delivery of vitamin D and its metabolites. In addition, it is also an actin scavenger, and the precursor to the immunomodulatory protein. Vitamin D binding protein has been proposed to have significant roles in C5a chemotaxis [30], osteoclast development and possibly in macrophage activation/recruitment [31].
In addition, a significant increase in VDBP and 25(OH)D(3) in human BALF 24 h after allergen challenge, suggests a role for these factors in the asthmatic late-phase reaction [35,36]. Concerning the immune system, it could be demonstrated, that the membrane immunoglobulin (MIg) of B lymphocytes displays physicochemical and immunological properties indistinguishable from those of Gc (group-specific component). In addition, evidence suggests that this vitamin D3-binding protein is involved in the linkage between MIg and actin and may therefore be important in signal transduction [37].
More recently, it could be shown that activated T cells express CYP27B1 and convert 25(OH)D3 to 1,25(OH)2D3 in sufficiently high concentrations to affect vitamin D-responsive genes when cultured in serum-free medium [38]. Furthermore, flow cytometry and representative confocal microscopy images revealed increased DBPuptake of activated T cells compared to naïve T cells [38].
Furthermore, an inhibitory effect of 25(OH)D3 on the Th17 response is mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics [39].
Unfortunately, VDBP has a broad genotypic and phenotypic variety. Therefore, standardized scientific research is complex.
The polymorphisms of DBP have been associated with susceptibility or resistance to a large number of chronic conditions, such as osteoporosis [40][41][42], type 1 and type 2 diabetes [43], thyroid autoimmunity [44], inflammatory bowel disease [45], and chronic obstructive lung disease [46]. Furthermore, it plays a role in infectious diseases [47][48][49]. It was also reported that the polymorphisms in the vitamin D receptor (VDR) and VDBP genes appeared to be responsible for host susceptibility to human tuberculosis [50].
Therefore, it is crucial to choose the right transporter to get the best effectiveness of Vitamin D related response in infectious disease.
We recently reported a newly developed dimeric compound, namely cholecalciferol-N-acetyl-galactosamine-Vitamin D binding protein (VitD~dgVDBP) and its positive and non-toxic effects in mice after intravenous injection compared to a sham group [9], effectively increasing the vitamin D level.
In addition, VitD~dgVDBP (Il-42) showed a higher macrophage activation and lower oxidative burst than VitD free dgVDBP and VDBP. This may result from a synergistic effect through a better presentation / exposition of protein bound Vitamin D to macrophages [10]. This form has shown to have no side effects, even in high doses and neither as oral or iv.-application form, in animals [9] and humans [11,12].
There is little awareness, that Vitamin C can have an adverse effect on infections, if not combined with the recoverage substance Alphaketoglutarate (AKG) [66].
Alpha-Ketoglutaric acid is the is one of two ketone derivatives of glutaric acid. Its anion, α-ketoglutarate also called 2-oxoglutarate, is an important biological compound. It is the keto acid produced by deamination of glutamate and is widely known as an intermediate in the Krebs cycle. But, this is only a small range of its function. AKG, an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. It functions as an energy donor, a precursor in the amino acid biosynthesis, a signaling molecule, as well as a regulator of epigenetic processes and cellular signaling via protein binding. ΑKG is an obligatory co-substrate for 2-oxoglutarate-dependent dioxygenases (OGDD), which catalyze hydroxylation reactions on various types of substrates [67]. It regulates the activity of prolyl-4 hydroxylase, which controls the biosynthesis of collagen, a component of bone tissue. ΑKG also affects the functioning of prolylhydroxylases, which, in turn, influences the function of the hypoxia-inducible factor [68,69], an important transcription factor in cancer development and progression. Additionally, it affects the functioning of enzymes that influence epigenetic modifications of chromatin: ten-eleven translocation hydroxylases involved in DNA demethylation and the Jumonji C domain containing lysine demethylases, which are the major histone demethylases. Thus, it regulates gene expression [70].
Most important, AKG is the obligate co-substrate of Fe(II)/2oxoglutarate-dependent dioxygenases (OGDD), a superfamily of enzymes that catalyze the oxidative decarboxylation of AKG producing succinate and CO2 from O 2 [70].
We first described the beneficial and additive effect of this combination. Recent confirming findings have been released and are under review [71].
We used the newly invented and described water soluble transport immune-competent form of 1,25-D3 (Cholecalciferol) called Sedeprovid, also known as IL-42 (ImmunoD ® CLS ℗ , HG Pharma, Vienna, Austria) for the treatment of five conclusive patients. Additionally, we also added the AlphaH concentrate to reduce known oxidative stress side effects of infections.
Prior to treatment the patients suffered from severe symptoms of confirmed Covid-19 infections, like cough, inappetence, tiredness, bone and body pain and body temperature of 39ºC or above for several days.
Within 24 hours after application of ImmunoD and AlphaH, patients and parents reported a significant reduction of symptoms and a drop down of maximal body temperature. After 48 hours the patients and parents reported a progressive recovery with regained energy and normal or close to normal activity over the day.
No side effects were reported from the patients or parents.

Conclusion
This novel treatment regimen might offer a good opportunity for the treatment of patients with moderate to severe symptoms before entering or after leaving the ICU ward. This protocol might also be used for critically ill patients during ICU stay and even be implemented as prophylactic program for healthcare providers.
Therefore, we strongly recommend the instant confirmation of these results in a controlled randomized trial for possible rapid benefit of Covid-19 infected patients and simultaneously a prophylactic program for healthcare providers.