Introduction

The invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject. It further relates to the use of such a composition in the treatment and/or prevention of COVID-19 disease in a subject, and to a method for the treatment and/or prevention of COVID-19 disease in a subject.

Background

The recent pandemic of infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the COVID-19 disease in millions of people worldwide presents an urgent need for a treatment capable of preventing or attenuating this coronavirus infection. By now a handful of vaccine is available to protect against SARS-CoV-2 infection. In addition, some compounds have been disclosed that may be used in the treatment of COVID-19 or the prevention of a SARS-CoV-2 infection.

WO2021 185874, WO2021185876 and WO2021222584 relate to lactoferrin for use in the treatment and/or prevention of COVID-19 disease in a subject. These documents further disclose the addition of milk fat globular membrane (MFGM) to compositions used in the treatment of COVID-19.

US20210353654 provides compositions and methods for utilizing human milk oligosaccharides, in particular fucosylated human milk oligosaccharides to attenuate or prevent a pathogenic virus infection to a subject.

WO2021 198774 provides sialic acid compositions for use in inhibiting and treating corona virus infection.

Not everybody can or wants to be vaccinated and in view of new variants of SARS- CoV-2 like delta and omicron, there remains an urgent need for improved and/or additional techniques for preventing, treating and ameliorating the symptoms of SARS-Co V-2 infection. Preferably, such techniques are well-tolerated, easily acceptable by the general public and/or easy to implement. As SARS-CoV-2 is a pandemic infectious disease, it is also desirable that such technique or product used therein, is readily available, affordable and / or free of lengthy registration processes. The inventors surprisingly found that a milk protein fraction was very active in blocking the interaction between SARS-CoV-2 spike protein and its human receptor. At the same concentration (in mg/ml) this milk protein fraction had a higher blocking capacity than lactoferrin or human milk oligosaccharides. Accordingly, one or more of the above-mentioned problems may be solved by applying this milk protein fraction.

Summary of the invention

Accordingly, the invention relates to uses and methods as defined in the claims.

In one aspect the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC.

In another aspect the invention relates to the use of a composition comprising milk protein in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the composition comprises SPC.

In yet another aspect, the invention relates to a method for the treatment and/or prevention of COVID-19 disease in a subject, wherein the method comprises the steps of i. providing a composition comprising milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the composition comprises SPC; ii. administering the composition to the subject; and optionally iii. gargling of the composition for at least 2 seconds by the subject prior to swallowing it.

Definitions

As used herein, COVID-19 disease (also referred to as Coronavirus disease 2019) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.

Symptoms of COVID-19 are variable, but often include fever, cough, headache, fatigue, breathing difficulties, and loss of smell and taste. Symptoms may begin one to fourteen days after exposure to the virus. Of those people who develop symptoms noticeable enough to be classed as patients, most (81 %) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are at a higher risk of developing severe symptoms. Some people continue to experience a range of effects (long COVID) for months after recovery, and damage to organs has been observed.

COVID-19 transmits when people breathe in air contaminated by droplets and small airborne particles containing the virus. The risk of breathing these in is highest when people are in close proximity, but they can be inhaled over longer distances, particularly indoors. As such, COVID-19 is considered an infectious disease of the upper respiratory tract.

As used herein the term “reconstituted beverage” relates to a drinkable product that is prepared by dissolving a powder in a liquid such as dissolving an infant formula in water. The drinkable product has a viscosity of less than 200 cP (at 25 °C and a pressure of 1 atmosphere) such as between 1 and 100 cP.

A formula product as used herein refers to a product which upon reconstitution with a liquid, preferably with water, more preferably boiled water, provides a reconstituted drinkable product. The formula product usually is a powder, although in some instances it may be readily dissolvable tablet or cube. Examples of formula products include products that after reconstitution into a reconstituted beverage provide a complete nutrition for a subject such as IFT products, Follow-on-Formula (FOF), and JrGUM products. A formula product has a recommended dosage (i.e. amount) of formula product per subject per day; a recommended number of feeding moments per subject per day and a recommended ratio between the desired amount of the formula product and the desired amount of liquid.

A reconstituted beverage from a formula product is prepared by admixing a fixed amount of liquid, preferably (warm) water, with a corresponding fixed amount of formula product i.e. recommended ratio or advised ratio or default preparation ratio, or normal value. Once the reconstituted beverage is consumed, its temperature should not be too high in order to avoid burning of the subject’s tongue or mouth.

Hence normally the temperature of the liquid should be 37 °C or below.

As used herein, the term "prevention" in relation to a given disease or disorder means preventing the onset of disease development if none had occurred, preventing the disease or disorder from occurring in a subject that may be predisposed to the disorder or disease but has not yet been diagnosed as having the disorder or disease, and/or preventing further disease/disorder development if already present.

As used herein, the term “treatment” in relation to a given disease or disorder means preventing further disease/disorder development, and I or ameliorating disease symptoms in a subject.

Compositions used according to the invention should be safe and preferably without adverse effects.

As used herein, gargling or to gargle is referring to its normal meaning i.e. to pass air through liquid suspended in the back of the throat, usually for hygienic or therapeutic purposes.

Unless otherwise specified, all amounts are per gram of dry weight of composition. Likewise, wt%, or percentages by weight, are per gram of dry weight of composition.

Brief description of the drawings

In Figure 1 a schematic set-up of the ELISA experiment used to detect blocking of the SARS-CoV-2 spike protein is shown.

In Figure 2, the blocking of heparin by the different milk fractions is shown. A lower optical density (OD, Y-axis) represents more blocking of heparin.

In Figure 3, the blocking of ACE2 by the different milk fractions is shown. A lower optical density (OD, Y-axis) represents more blocking of heparin.

Details of the invention

In one aspect the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC; or alternatively, the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk fat globule membrane (MFGM) and no lactoferrin.

In a first aspect the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC.

In one embodiment, the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the amount of lactoferrin in the SPC is 0.2 wt% or lower (such as 0.1 wt% or lower; 0.05 wt% or lower; or 0.01 wt% or lower) as determined relative to the amount of protein in the SPC and wherein the amount of lactoferrin in the WPC is 1.0 wt% or lower (such as 0.5 wt% or lower; 0.1 wt% or lower; or 0.01 wt% or lower) as determined relative to the amount of protein in the WPC; more preferably in another embodiment, wherein the milk protein comprises SPC and wherein the amount of lactoferrin in the SPC is 0.2 wt% or lower (such as 0.1 wt% or lower; 0.05 wt% or lower; or 0.01 wt% or lower) as determined relative to the amount of protein in the SPC.

In another embodiment, the invention relates to a composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises MFGM and no lactoferrin.

In one embodiment, the composition comprises a therapeutically effective amount of the milk protein.

Both WPC and SPC are the result of separating skimmed milk into a casein-rich and a whey protein-rich fraction; either by renneting (i.e. cheese making), acidification, or microfiltration.

Whey protein concentrate (WPC) is a product obtained by ultrafiltration and/or reverse osmosis and optionally demineralization of acid or cheese whey. By ultrafiltration, a large part of the water, lactose and ash are removed from the product, thereby concentrating the whey proteins. Reverse osmosis can be used to remove water and to further concentrate the WPC. WPC is readily available from several milk processing companies such as FrieslandCampina, Aria, Valio, and Fonterra.

Serum protein concentrate (SPC) is also a concentrated protein product and differs from WPC in the origin of the whey fraction. Instead of acid or cheese whey, the proteins in SPC result from microfiltration of skimmed milk. Said microfiltration results in a concentrated casein retentate fraction and a serum fraction containing most of the whey proteins as the permeate fraction. Conventionally, this permeate fraction is then subjected to ultrafiltration and/or reverse osmosis in order to remove lactose, ash, and water. SPC is readily available from several milk processing companies such as FrieslandCampina, Valio, Aria, and Fonterra. Likewise MFGM is readily commercially available.

In one embodiment, the protein source comprises a mixture of WPC and SPC. These may be mixed in a 5:1 to 1 :5 ratio (by dry weight), preferably in a 2:1 to 1 :2 ratio (by dry weight).

In a preferred embodiment, the milk protein source comprises SPC.

In still another embodiment, more than 60 wt% of the milk protein fraction is WPC/SPC. Preferably, more than 60wt% of the milk protein is SPC, more preferably more than 70% of the milk protein is SPC.

The subject preferably is a human, however other mammals have been reported to be susceptible for a SARS-CoV-2 infection e.g. cats, ferrets, hamsters, non-human primates, minks, tree shrews, raccoon dogs, fruit bats, and rabbits and it is assumed that the invention works for these mammals too.

As is commonly known, viral infections of the respiratory tract may occur in people of all ages, young and old. Severity of such an infection may depend on the state of a subject’s immune system. Subjects with an immune system which is not yet fully developed or a weakened immune system may be more susceptible towards viral infections of the respiratory tract. Accordingly, in one embodiment the composition for use of the current invention is intended for an infant or young child, in another embodiment it is an infant formula. Infant formulae are well known in the art.

The term "infant formula" as used herein refers to a nutritional composition intended for infants and as defined in Codex Alimentarius, (Codex STAN 72-1981 ) and Infant Specialties (incl. Food for Special Medical Purpose) as defined in Codex Alimentarius, (Codex STAN 72-1981 ). It also refers to a foodstuff intended for particular nutritional use by infants during the first months of life and satisfying by itself the nutritional requirements of this category of person (Article 2(c) of the European Commission Directive 2006/141 /EC of 22 December 2006 on infant formulae and follow-on formulae). The infant formulas can encompass the starter infant formulas, the follow-up or follow-on formulas, and young child formulas. Generally a starter formula is for infants from birth as breast-milk substitute, and a follow-up or follow-on formula from the 6th month onwards. So, an infant formula may be dedicated for infants of 0 to 6 months, 6 to 12 months, 12 months an older. A young child formula my be dedicated for children aged 1 - 3 years old.

In another embodiment, the composition for use of the current invention is intended for an adult i.e. an adult nutrition product. In yet another embodiment it is a food supplement. The adult nutrition product can for example be a milk-based product such as a yoghurt drink, a protein bar, or other product. Compositions and forms of adult nutrition products are well known in the art and all variants are suitable as long as they allow the addition of a protein fraction of the invention. Typical examples of suitable adult nutrition products include protein shots comprising protein (15-25 wt%), carbohydrate, fats and optional ingredients such as minerals and vitamins.

In another embodiment the composition for use of the invention is pharmaceutical composition, preferably a pharmaceutical composition for oral administration.

The term “pharmaceutical composition” is defined herein to refer to a mixture (e.g., a solution or an emulsion) containing at least one active ingredient or therapeutic agent (i.e. the milk protein) to be administered to a warm-blooded animal, e.g., a mammal or human, in order to prevent or treat a particular disease or condition affecting the warm-blooded animal.

The term "a therapeutically effective amount" of a compound (i.e. the milk protein) of the present disclosure refers to an amount of the compound of the present disclosure that will elicit the biological or medical response of a subject (patient of subject), for example, reduction or inhibition of an enzyme or a protein activity, or ameliorate symptoms, alleviate conditions, slow or delay disease progression, or prevent a disease, etc. The therapeutically effective dosage of a compound, the pharmaceutical composition, or the combinations thereof, is dependent on the species of the patient, the body weight, age, sex, and individual condition, the disorder or disease or the severity thereof being treated. A physician, clinician or veterinarian of ordinary skill can readily determine the effective amount of the active ingredients necessary to prevent, treat or inhibit the progress of the disorder or disease.

Frequency of dosage may vary depending on the compound used and the particular condition to be treated or prevented. In general, the use of the minimum dosage that is sufficient to provide effective therapy is preferred. Patients may generally be monitored for therapeutic effectiveness using assays suitable for the condition being treated or prevented, which will be familiar to those of ordinary skill in the art.

The milk protein may be obtained from various suitable sources, including, but not limited to, bovine (cow), goat, human, camel, horse and the like. Preferably the milk protein is bovine milk protein, more preferably cow’s milk protein. In some embodiments, the milk may be obtained at various time points before, during and/or after lactation. The milk may be obtained at various time points during the day (for example, morning, evening, midnight). The milk may be obtained at various time points after birth.

The amount of SPC and I or WPC, preferably of SPC may vary e.g. depending on the age, weight, condition, and sex of the subject. In one embodiment the daily dosage of SPC and/or WPC, preferably of SPC is in the range of 0.1 g/day to 100 g/day. In another embodiment, the concentration of SPC and/or WPC, preferably of SPC is between 0.1 wt% and 35 wt% (relative to the weight of the composition). In still another embodiment the concentration of SPC and/or WPC, preferably of SPC is between 1 wt% and 70 wt% relative to the dry weight of the composition.

The milk protein as used in the different aspects and embodiments of the invention may comprise WPC in addition to SPC. In one embodiment it comprises SPC and lactoferrin. In yet another embodiment it comprises SPC, WPC and lactoferrin. Preferably the composition as used in the different aspects and embodiments of the invention is suitable for oral administration, more preferably, it is a liquid. The composition as used in the invention may comprise other milk components, preferably milk components that have been reported to be useful in the treatment of COVID-19, such as one or more compounds selected from the group consisting of human milk oligosaccharides, milk fat globular membranes (MFGM), and sialic acid, as described elsewhere herein.

As used herein, sialic acid, includes compounds rich in N-acetyl Neuraminic acid (NANA) such as gangliosides.

Human milk oligosaccharides are also known as human milk glycans, oligomers of monosaccharides that can be found in high concentrations exclusively in human breast milk. Human milk oligosaccharides promote the development of the immune system, can reduce the pathogen infections and improve brain development and cognition. Human milk oligosaccharides (HMOs) form the third most abundant solid component of human milk, after lactose and fat. HMOs are present in a concentration of 9.9-24.9 g/L. Approximately 200 structurally different human milk oligosaccharides are known. The composition of human milk oligosaccharides in breast milk is individual to each mother and varies over the period of lactation. The dominant oligosaccharide in 80% of all women is 2’-fucosyllactose (2’ FL), which is present in human breast milk at a concentration of approximately 2.5 g/L. Other oligosaccharides include lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), and lacto-N-fucopentaose (LNFP). (Bode, L. (2012). "Human milk oligosaccharides: every baby needs a sugar mama". Glycobiology. 22 (9): 1147-1162. doi:10.1093/glycob/cws074). Preferably the HMOs are selected from the group consisting of 2’FL, 3FL, LNT, LNnT, LNFP, 3’GL, 3’SL, and 6’SL.

The composition as referred to in the different aspects and embodiments of the invention may be administered to the subject i. during, before and/or after a SARS- CoV-2 vaccine administration; and/or ii. during, before and/or after a SARS-CoV-2 infection.

Preferably it is administered during and/or before a SARS-CoV-2 infection, more preferably before such an infection.

It is believed that mucosal tissue in the upper respiratory tract is in contact with the milk protein when the subject is drinking I consuming a composition as referred to in the different aspects and embodiments of the invention. Without wishing to be bound by theory, it is believed that this contact triggers the subject’s immune system to provide more resistance towards viral infections. So, in one embodiment the composition comprising milk protein is gargled for at least 2 seconds prior to swallowing it, preferably at least 5 seconds, by the subject in need thereof to enhance the contact between the composition and the oral mucosal tissue. Alternatively, it is gargled for at least 10 seconds. In alternative embodiment, the composition may be gargled without swallowing it afterwards. As used herein, to “gargle” refers to washing one's mouth and throat with a liquid that is kept in motion by breathing through it with a gurgling sound, or kept in motion by moving one’s tongue or cheeks while the liquid is in one’s mouth or oral cavity.

The different embodiments of the invention as described above, equally apply to the other aspects of the invention as listed below.

In another aspect the invention relates to the use of a composition comprising milk protein in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the composition comprises SPC.

In still another aspect the invention relates to the use of a composition comprising MFGM in the treatment and/or prevention of COVID-19 disease in a subject wherein the composition does not comprise lactoferrin.

In yet another aspect, the invention relates to a method for the treatment and/or prevention of COVID-19 disease in a subject, wherein the method comprises the steps of i. providing a composition comprising milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the composition comprises SPC; ii. administering the composition to the subject and optionally iii gargling the composition for at least 2 seconds by the subject prior to swallowing it, preferably at least 5 seconds.

As indicated above, in step iii, the composition may also only be gargled, without being swallowed. In another aspect, the invention relates to a method for the treatment and/or prevention of COVID-19 disease in a subject, wherein the method comprises the steps of i. providing a composition comprising MFGM wherein the composition does not comprise lactoferrin; ii. administering the composition to the subject and optionally iii gargling the composition for at least 2 seconds by the subject prior to swallowing it, preferably at least 5 seconds.

As indicated above, in step iii, the composition may also only be gargled, without being swallowed.

As used herein, when a composition is said to “not comprise lactoferrin” this in one embodiment, refers to the composition not comprising a therapeutically effective amount of lactoferrin, preferably a composition not comprising lactoferrin is free of lactoferrin. In one embodiment, the composition for use or method or use according to the invention does not comprise lactoferrin.

It must also be noted that, as used in the specification and the appended claims, the singular form "a", "an," and "the" comprise plural referents unless the context clearly indicates otherwise. For example, reference to a component in the singular is intended to comprise a plurality of components.

Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

Except in the examples, or where otherwise expressly indicated, all numerical quantities in this description indicating amounts of material or conditions of reaction and/or use are to be understood as modified by the word "about" in describing the broadest scope of the invention. Practice within the numerical limits stated is generally preferred. Also, unless expressly stated to the contrary: percent, "parts of," and ratio values are by weight; the description of a group or class of materials as suitable or preferred for a given purpose in connection with the invention implies that mixtures of any two or more of the members of the group or class are equally suitable or preferred; description of constituents in chemical terms refers to the constituents at the time of addition to any combination specified in the description, and does not necessarily preclude chemical interactions among the constituents of a mixture once mixed; the first definition of an acronym or other abbreviation applies to all subsequent uses herein of the same abbreviation and applies, mutatis mutandis, to normal grammatical variations of the initially defined abbreviation; and, unless expressly stated to the contrary, measurement of a property is determined by the same technique as previously or later referenced for the same property.

The invention is hereinafter illustrated with reference to the following, non-limiting, examples.

Examples

A Biomol SARS-CoV-2 Inhibitor Screening Kit (ELISA) was used to check different milk fractions for their capacity to bind SARS-CoV-2 spike protein. This kit allows to screen compounds that inhibit the binding of the viral protein SARS-CoV-2 Spike Protein (RBD) to its human receptor. SARS-CoV-2 contains 4 structural proteins, including Envelope (E), Membrane (M), Nucleocapsid (N) and Spike (S), which is a transmembrane protein, composed of two subunits S1 and S2. The S1 subunit contains a receptor binding domain (RBD), which binds to Angiotensin-Converting Enzyme 2 (ACE2) or heparin. The SARS-CoV-2 Inhibitor Screening Kit contains key reagents required to facilitate identification of SARS-CoV-2 inhibitors. This inhibitor screen is based on a colorimetric ELISA kit, which measures the binding of the RBD of the Spike S protein from SARS-CoV-2 to its human receptor ACE2. This assay allows to identify and characterize the effect of different inhibitory molecules including antibodies or chemicals on the prevention of binding of SARS-CoV-2 virus to any ACE2-expressing cells, (https://www.biomol.com/). This kit was used in accordance with manufacturer’s instructions.

Briefly, 1 ug/ml spike protein was coated on the ELISA plate overnight at 4 degrees C.

Each different milk fraction was preincubated with Heparin (16 ug/mL) or ACE2 (1 ug/mL) for 1 h at room temperature.

After washing the ELISA plate, the preincubated milk ingredients with ACE2 or heparin were added to the ELISA plate and incubated for 1 h at 37 degrees C. After washing, HRP labeled streptavidin was added and the plate was incubated at room temperature for 1 h. 3,3',5,5'-Tetramethylbenzidine (TMB) buffer was added after washing away non bound streptavidin and the plate was incubated for 5m in at room temperature. The reaction was stopped by adding stop solution (2M H2SO4) and Optical Density (OD) was measured at 450nm with an ELISA reader.

The more fluorescence, the more binding, and hence less blocking. See Figure 1 for an schematic set-up of the experiment.

The tested milk fractions:

• Lactoferrin at 2.5 and 5 mg of lactoferrin per mL

• WPC at 2.5 and 5 mg protein per mL

• SPC at 2.5 and 5 mg protein per mL

• Human Milk Oligosaccharide (HMOs) at 1 and 5 mg HMO per mL (HMOs is the mixture of human milk oligosaccharides as present in human milk).

• Milk Fat Globular Membrane (MFGM) at 0.25 and 0.5 mg phospholipids per mL

All milk fractions were obtained from FrieslandCampina.

Bovine Serum Albumin (BSA) at 5 mg protein per mL was used as a protein loading control, to show that not every protein blocks that interaction.

All ingredients blocked the interaction between the viral spike protein and its human receptors (BSA did not, as expected - negative control). As illustrated in Figures 2 and 3 showing the interaction with Heparin and ACE2, respectively.

The results show that of the milk fractions tested, SPC is most effective in blocking an interaction between the spike protein and Heparin or ACE2 as human receptor.

The lactoferrin content in SPC was determined to be 1 .69 mg lactoferrin per gram of total protein. Accordingly, the 2.5 mg/mL SPC sample comprised 4.225ug of lactoferrin and the 5.0 mg/mL SPC sample comprised 8.45ug of lactoferrin per mL, or in other words about 0.2 % of the protein in SPC was lactoferrin.

The lactoferrin content in WPC was determined to be 8.17 mg lactoferrin per gram of total protein. So, the 2.5 mg/mL WPC sample comprised 20.425ug and the 5.0 mg/mL WPC sample comprised 40.85ug of lactoferrin per mL, or in other words about 1 % of the protein in WPC was lactoferrin.

It was also noted that SPC and WPC were more effective than lactoferrin in blocking the interaction with heparin.

Considering i) all these samples were used at the same protein concentration and ii) the lactoferrin content in SPC and WPC is 0.2 and 1 % of total protein, respectively. It was concluded that components other than lactoferrin which are present in SPC and WPC are responsible for blocking the interaction between spike protein and heparin because the very low level of lactoferrin cannot contribute to more than 1 % of the blocking.

Moreover, the fact that SPC and WPC showed difference responses in the ELISA test, proves that there are differences between these milk fractions from a chemical point of view. In other words, the composition of SPC is not the same as the composition of WPC.

These results show that milk components can act against the binding of SARS-Cov-2 to human cells and may block the entry of the virus in the cell, in particular SPC and WPC, preferably SPC. Unexpectedly, SPC and WPC were more effective as compared to lactoferrin. This was surprising as lactoferrin was known to be effective in defending against viral and bacterial infections.

List of Numbered embodiments

1A. A composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the amount of lactoferrin in the SPC is 0.2 wt% or lower as determined relative to the amount of protein in the SPC and wherein the amount of lactoferrin in the WPC is 1 .0 wt% or lower as determined relative to the amount of protein in the WPC; more preferably wherein the milk protein comprises SPC and wherein the amount of lactoferrin in the SPC is 0.2 wt% or lower as determined relative to the amount of protein in the SPC. B. A composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises MFGM and no lactoferrin. . A composition for use in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC. . The composition for use of anyone of embodiment 1 A, 1 B, or 2 wherein i. the subject is a human subject; ii. the composition is intended for an infant or young child; iii. the composition is intended for an adult; and I or iv. the composition is a pharmaceutical composition. . The composition for use of any of the preceding embodiments wherein the milk protein is bovine milk protein. . The composition for use of any of the preceding embodiments wherein i. the daily dosage of SPC and/or WPC, preferably of SPC is in the range of 0.1 g/day to 100 g/day; ii. the concentration of SPC and/or WPC, preferably of SPC is between 0.1 wt% and 35 wt%; and/or iii. the concentration of SPC and/or WPC, preferably of SPC is between 1 wt% and 70 wt% relative to the dry weight of the composition. . The composition for use of any of the preceding embodiments wherein the milk protein comprises SPC and it further comprises Whey Protein Concentrate (WPC) and I or lactoferrin. . The composition for use of any of the preceding embodiments wherein the composition further comprises one or more compounds selected from the group consisting of human milk oligosaccharides, milk fat globular membranes (MFGM), and sialic acid. . The composition for use of any of the preceding embodiments wherein the composition is administered to the subject: i. during, before and/or after a SARS-CoV-2 vaccine administration; and/or ii. during, before and/or after a SARS-CoV-2 infection. 0. The composition for use of any of the preceding embodiments wherein the composition is a liquid and the composition is gargled for at least 2 seconds by the subject prior to swallowing it, preferably at least 5 seconds. Use of a composition comprising milk protein in the treatment and/or prevention of COVID-19 disease in a subject, wherein the composition comprises milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC. The use of embodiment 11 wherein the composition is a liquid and wherein it is gargled for at least 2 seconds by the subject prior to swallowing it, preferably at least 5 seconds. The use of embodiment 11 or 12 wherein i. the subject is a human subject; ii. the composition is intended for an infant or young child; iii. the composition is intended for an adult; and I or iv. the composition is a pharmaceutical composition. The use of any one of embodiments 11 - 13, wherein the milk protein is bovine milk protein. The use of any one of embodiments 11 - 14, wherein i. the daily dosage of SPC and/or WPC, preferably of SPC is in the range of 0.1 g/day to 100 g/day; ii. the concentration of SPC and/or WPC, preferably of SPC is between 0.1 wt% and 35 wt%; and/or iii. the concentration of SPC and/or WPC, preferably of SPC is between 1 wt% and 70 wt% relative to the dry weight of the composition. The use of any one of embodiments 11 - 15, wherein the milk protein further comprises Whey Protein Concentrate (WPC) and I or lactoferrin. The use of any one of embodiments 9 - 16, wherein the composition further comprises one or more compounds selected from the group consisting of human milk oligosaccharides, milk fat globular membranes (MFGM), and sialic acid. The use of any one of embodiments 11 - 17, wherein the composition is administered to the subject: i. during, before and/or after a SARS-CoV-2 vaccine administration; and/or ii. during, before and/or after a SARS-CoV-2 infection. A method for the treatment and/or prevention of COVID-19 disease in a subject, wherein the method comprises the steps of i. providing a composition comprising milk protein and the milk protein comprises Serum Protein Concentrate (SPC) and/or Whey Protein Concentrate (WPC); preferably wherein the milk protein comprises SPC; ii. administering the composition to the subject.

20. The method of embodiment 19 wherein the composition is a liquid and wherein the composition comprises a further step of iii gargling the composition for at least 2 seconds by the subject prior to swallowing it, preferably at least 5 seconds.

21 . The method of embodiment 19 or 20 wherein i. the subject is a human subject; ii. the composition is intended for an infant or young child; iii. the composition is intended for an adult; and I or iv. the composition is a pharmaceutical composition.

21 . The method of any one of embodiments 19 - 20 wherein the milk protein is bovine milk protein.

22. The method of any one of embodiments 19 - 21 wherein i. the daily dosage of SPC and/or WPC, preferably of SPC is in the range of 0.1 g/day to 100 g/day; ii. the concentration of SPC and/or WPC, preferably of SPC is between 0.1 wt% and 35 wt%; and/or iii. the concentration of SPC and/or WPC, preferably of SPC is between 1 wt% and 70 wt% relative to the dry weight of the composition.

23. The method of any one of embodiments 19 - 22 wherein the milk protein further comprises Whey Protein Concentrate (WPC) and I or lactoferrin.

24. The method of any one of embodiments 19 - 23 wherein the composition further comprises one or more compounds selected from the group consisting of human milk oligosaccharides, milk fat globular membranes (MFGM), and sialic acid.

25. The method of any of embodiments 19 - 24 wherein the treatment is a prophylactic treatment.