Composition for the treatment and prevention of at least one symptom of a COVID-19-associated secondary illness in humans

Description

Introduction

[0001] The present invention relates to a sterile, aqueous composition for use in a method for the treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 in humans, comprising the introduction of the composition into the eye.

[0002] COVID-19 is an infectious disease caused by infection with the novel coronavirus SARS-CoV-2. This disease, which primarily affects the respiratory system, was first described in Wuhan at the end of 2019, developed into an epidemic in the People's Republic of China in January 2020, and then spread worldwide as the COVID-19 pandemic.

[0003] The viral infection is usually transmitted via droplets. Under certain circumstances, transmission via aerosols is also possible. The course of the illness is nonspecific, varied, and highly variable.

[0004] One reason for the wide variation in disease progression is thought to be that the weakening of the immune system by the SARS-CoV-2 virus as the primary infection leads to secondary, mostly bacterial, infections that worsen the course of the disease. This hypothesis would also explain why some patients experience no symptoms or only mild cases, while others become critically ill.

[0005] The incubation period for a SARS-CoV-2 infection averages five to six days; however, it can take up to two weeks between infection and the onset of the first symptoms. In rare cases, the first symptoms appear within 24 hours of infection with SARS-CoV-2. The most common symptoms are fever, a dry cough, and fatigue. Less common symptoms include aches and pains, a blocked nose, headache, sore throat, diarrhea, loss of taste or smell, or skin rash or discoloration of the fingers or toes.

[0006] It has been proven that even infected people without symptoms can still be potential carriers of the coronavirus.

[0007] Although COVID-19 is currently the subject of intensive research, apart from the behavioral adjustments recommended by the WHO, there are currently no sufficient means that are efficient for the prevention and treatment of at least one symptom of a secondary illness associated with COVID-19.

[0008] DE 10 2016 125378 A1 discloses eye drops for the prevention of colds. Treatment of Covid-19 or other SARS-mediated viral infections is not disclosed.

[0009] CHU DEREK K ET AL: "Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis", THE LANCET, ELSEVIER, AMSTERDAM, NL, Vol. 395, No. 10242, June 1, 2020 (2020-06-01), pages 1973-1987, XP086202886, ISSN: 0140-6736, DOI: 10.1016 / S0140-6736(20)31142-9; reveals a meta-analysis showing that wearing eye protectors (glasses or face shields) may reduce infection with SARS-CoV-2.

[0010] The RKI article "Are there antiviral substances available for the treatment of COVID-19?", June 19, 2020 (2020-06-19), pages 1-5, XP055956790, DOI: 10.25646 / 6953 URL: https: / / edoc.rki.de / bitstream / handle / 176904 / 6852 / , reveals the treatment methods discussed and used for treating COVID-19-associated symptoms. Eye drops are not discussed.

[0011] Shetty Rohit ET AL: "Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals", Indian Journal of Ophthalmology, Vol. 68, No. 7, June 25, 2020 (2020-06-25), page 1349, XP093241608, IN, ISSN: 0301-4738, DOI: 10.4103 / ijo.IJO_1589 20; reveal various approaches to treating COVID-19 using eye drops, these eye drops containing at least one active ingredient that is attributed with a COVID-19-inhibiting effect. Object of the invention

[0012] The present invention aims to provide an efficient agent for use in a method for the treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 in humans. The invention is intended to enable effective treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 at an early stage, i.e., at the beginning of the infection, and, once the infection has broken out, to mitigate its course and significantly reduce the duration of the illness. The agent is also intended to be cost-effective and easy to apply.

[0013] This problem is solved by the device according to the invention. Description of the invention

[0014] The invention relates to a sterile, aqueous composition for use in the treatment or prevention of at least one symptom of a secondary illness associated with COVID-19 in a human, selected from fever, dry cough, fatigue, body aches and pains, sore throat, diarrhea, headache, loss of taste or smell, discoloration of fingers or toes, skin rash, difficulty breathing or shortness of breath, chest pain or pressure, loss of speech or mobility, muscle pain, back pain, chest pain indicative of pleurisy, decreased total white blood cell count, decreased lymphocyte count, elevated laboratory inflammatory markers (such as CRP and ESR), runny nose, nausea, and pneumonia. where a person is defined as someone who has been diagnosed with SARS-CoV-2 infection by quantitative polymerase chain reaction (PCR), comprising the introduction of the composition into the eye, wherein the composition is introduced into the eye during the person's waking phase and several times at intervals of no more than 2 hours; wherein the composition is a sterile, aqueous composition of a hypotonic solution of NaCl and KCl (275 mOsm / l), further comprising 0.24% thickener, phosphate buffer (disodium phosphate dodecahydrate / sodium dihydrogen phosphate), pH 7.2, and optionally an additional 0.5 wt% Na₂EDTA, wherein the composition is free of pharmaceutical agents, in particular free of decongestants, antihistamines, antibiotics, ephedrine and / or pseudoephedrine.

[0015] Surprisingly, the inventor of the present invention has found that introducing the composition according to the invention into the eye enables efficient treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 in humans.

[0016] Here, the term "SARS-CoV-2" (abbreviation for English: severe acute respiratory syndrome coronavirus , German: Severe Acute Respiratory Syndrome Coronavirus 2), referring to the virus belonging to the coronavirus family. Infection with this virus causes the new respiratory disease COVID-19.

[0017] Here, the term refers to "secondary illness associated with COVID-19"for the treatment or prevention of at least one symptom of a secondary illness associated with COVID-19 in a human being, selected from fever, dry cough, fatigue, body aches and pains, sore throat, diarrhea, headache, loss of taste or smell, discoloration of fingers or toes, rash, difficulty breathing or shortness of breath, chest pain or pressure, loss of speech or movement, muscle pain, back pain, chest pain consistent with pleurisy, decreased total white blood cell count, decreased lymphocyte count, elevated laboratory inflammatory markers (such as CRP and ESR), runny nose, nausea, and pneumonia.

[0018] The secondary infection is usually caused by bacteria. For example, pneumonia caused by... Streptococcus pneumoniae is caused by "COVID-19, a secondary disease associated with SARS-CoV-2"provided it occurs as a subsequent or secondary infection during or after an acute SARS-CoV-2 infection.

[0019] Other known causes of secondary infections within the meaning of the invention are frequently multi-resistant, gram-negative bacteria, such as e.g. Acinetobacter baumannii or Klebsiella pneumoniae. This is particularly dangerous because developing new antibiotics to combat gram-negative bacteria is especially difficult. The substance cefiderocol is one of the very few new antibiotics that show some efficacy in this area.

[0020] Therefore, the composition according to the invention is particularly suitable for the prevention and treatment of secondary infections with bacteria selected from Staphylococcus aureus, Streptococcus pneumoniae, coagulase-negative staphylococci, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Citrobacter spp., Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia.

[0021] In other embodiments, other bacteria, which are found particularly in saliva and droplets, such as meningococci, streptococci, Bordetella pertussis and pneumococci.

[0022] In further embodiments, the composition according to the invention is suitable for the prevention and treatment of secondary infections with fungi (mycoses), such as e.g. Candida spp., Aspergillus spp., Mucorales spp. and Fusarium spp. ; or viruses, such as herpes simplex viruses type I, Epstein-Barr virus, influenza viruses, morbilliviruses, paramyxoviruses, mumps, rubella virus, varicella-zoster viruses, cold viruses (such as harmless coronaviruses like HCoV-HKU1, HCoV-OC43, HCoV-NL63 and HCoV-229E, rhinoviruses, etc.).

[0023] It is certainly astonishing and highly unexpected that introducing the inventive composition into the eye enables efficient treatment and prevention of at least one symptom of a COVID-19-associated secondary illness in humans selected from fever, dry cough, fatigue, body aches and pains, sore throat, diarrhea, headache, loss of taste or smell, discoloration of fingers or toes, rash, difficulty breathing or shortness of breath, chest pain or pressure, loss of speech or movement, muscle pain, back pain, chest pain indicative of pleurisy, decrease in the total number of white blood cells, decrease in the number of lymphocytes, an increase in laboratory inflammatory parameters (such as CRP and ESR), runny nose, nausea and pneumonia.Known applications of aqueous ophthalmic preparations are limited to the local treatment of eye diseases. The use of an ophthalmic preparation for the treatment and prevention of symptoms of a secondary illness associated with COVID-19, which is known not to occur in the eye but typically causes corresponding symptoms in the throat, nose, or lungs of affected individuals, is currently unknown.

[0024] It should therefore be emphasized once again that the treatment of eye diseases or eye symptoms, such as conjunctivitis, is not intended to be included in the present inventive use of the composition.

[0025] Without being bound to a specific mode of action, it is conceivable that the composition according to the invention, when applied to the eye, can reach the upper nasal cavity via the tear duct or other channels and exert its effect there. Preferably, this can maintain the air supply to the upper nasal cavity. Improved air supply and / or moistening of the mucous membranes prevents or delays the colonization of pathogens and / or can contribute to the death of pathogens already present. The spread of infection, for example, to deeper regions of the respiratory system, can thus be advantageously prevented, mitigated, contained, or prevented. Secondary diseases, such as pneumonia, are advantageously less likely.

[0026] Without being bound to a specific mode of action, it is assumed that in one embodiment, the composition according to the invention reduces secondary infectivity after a SARS-CoV-2 infection by hindering the penetration and establishment of the secondary pathogen. In a preferred embodiment, the composition acts by reducing and / or preventing the dangerous consequences of the viral infection caused by bacteria. In particular, life-threatening pneumonia can be avoided in many cases by the composition according to the invention.

[0027] The WHO recommends, in addition to maintaining social distancing and hygiene measures, the use of face masks to reduce the risk of infection. However, this presents several problems: Firstly, regularly wearing masks creates a warm, humid environment that promotes the growth of viruses, bacteria, and fungi. Since the masks are worn directly over the mouth and nose, these potentially dangerous pathogens can be inhaled, especially if used incorrectly.

[0028] Paradoxically, the poor air quality caused by masks also leads to dry mucous membranes. Without sufficient moisture, pathogens such as viruses, fungi, and bacteria can more easily adhere to the dried-out mucous membranes and multiply in the nose, mouth, and throat.

[0029] This is especially true for mask types where the airflow is redirected in such a way that a significant portion of the breath escapes through the gaps next to the nostrils, past the eyes, which increases the sensitivity of the eyes not only to a potential SARS-CoV-2 infection, but also to secondary infections.

[0030] Therefore, in a further embodiment, the use of the composition according to the invention can also help in the prevention of a COVID-19 associated secondary disease by reducing the susceptibility of the eyes and tear ducts to the pathogens when wearing face masks.

[0031] The preventive use of the composition according to the invention, particularly when wearing face masks, is therefore a further preferred embodiment of the present invention. composition

[0032] The present invention provides a sterile, aqueous composition for use in a method for the treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 in humans. The method comprises introducing the composition into the eye.

[0033] The composition according to the invention is a sterile, aqueous composition of a hypotonic solution of NaCl and KCl (275 mOsm / l), further comprising 0.24% thickening agent, phosphate buffer (disodium phosphate dodecahydrate / Na dihydrogen phosphate), pH 7.2, and optionally an additional 0.5 wt% Na2 EDTA.

[0034] By adjusting the osmolarity accordingly, good tolerability on the eye is achieved.

[0035] Good tolerability means that, as a rule, no significant eye irritation or pain occurs when the composition described here is introduced.

[0036] The pH value of the composition also plays a role in good tolerability in the eye. Compositions with pH values ​​in the range of 6.6 to 10.5 are considered physiologically compatible with the eye. Compositions with pH values ​​above 10.5 or below 6.6 are generally not well tolerated in the eye and can lead to pain, irritation, or both.

[0037] The composition also includes NaCl and KCl. This can advantageously be used to adjust the aforementioned osmolarity.

[0038] The composition includes sodium chloride and potassium chloride. KCl, and especially sodium chloride, are advantageous because they are exceptionally well-tolerated salts that are well-suited for adjusting osmolarity.

[0039] Preferably, the composition comprises the inorganic salt in a concentration of 0.7 to 1.4 wt.% based on the total weight of the composition. More preferably, the composition comprises the inorganic salt in a concentration of 0.7 to 1.2 wt.%, and particularly preferably in a concentration of 0.8 to 1.0 wt.% based on the total weight of the composition. Most preferably, the composition comprises sodium chloride in a concentration of 0.7 to 1.2 wt.% based on the total weight of the composition.

[0040] The salt concentrations mentioned above are advantageous because they possess an osmolarity adapted to the osmotic pressure of the eye. An adapted osmolarity can beneficially contribute to minimizing pain and irritation of the eye that may be caused by the introduction of the composition.

[0041] The composition preferably further comprises a thickening agent. The thickening agent is particularly preferably selected from polyethylene glycol (PEG); propylene glycol; polyvinylpyrrolidone; polyvinyl alcohol; cellulose; cellulose derivatives, such as carboxymethylcellulose and hydroxypropylmethylcellulose; xanthan gum; carbomers; guar gum derivatives, such as hydroxypropyl guar; hyaluronic acid and its derivatives, as well as mixtures thereof. Thickening agents selected from the group consisting of hyaluronic acid, PEG, and hydroxypropylmethylcellulose are most preferred. The addition of a thickening agent to the composition is advantageous because it allows the viscosity of the composition to be influenced. Advantageously, an increase in viscosity results in a longer contact time between the composition and the eye.

[0042] Another advantage of adding thickening agents is their ability to bind water and provide lubrication. The addition of thickening agents allows the solution to wet the cornea particularly well and adhere to the tissue surface for longer than without them. In particular, prolonged adhesion to the mucous layer of the tear film can be achieved. This effect is known as mucoadhesion. This results in an additionally longer contact time with the eye.

[0043] Preferably, the thickening agent is present in the composition in an amount of 0.1 to 10 wt.% based on the total weight of the composition. More preferably, the thickening agent is present in the composition in an amount of 0.15 to 5 wt.% based on the total weight of the composition, and most preferably, the composition contains the thickening agent in an amount of 0.2 to 1 wt.% based on the total weight of the composition.

[0044] The composition is free of pharmaceutical active ingredients, in particular free of decongestants such as antihistamines; antibiotics; analgesics such as paracetamol, ibuprofen and / or acetylsalicylic acid and their derivatives; ephedrine, pseudoephedrine and / or others. In one embodiment, the composition is free of hydroxychloroquine, interferons and / or trehalose.

[0045] A composition free from one or more of the following is particularly preferred.

[0046] Active ingredients: Acetylcysteine; Ambroxol; Horehound; Angelica root; Anise oil; Benzocaine; Bittersweet nightshade; Bromhexine; Cajeput oil; Camphor; Carbocysteine; Cineole; Clenbuterol; Clobutinol; Codeine; Caffeine; Chlorphenamine; Dextromethorphan; Dihydrocodeine; Dimetindene; Diphenylpyraline; Doxycycline; Doxylamine; Dropropizine; Ivy leaves; Marshmallow; Gentian root; Ephedrine; Eucalyptus oil; Vervain; Eucalyptus leaves; Indigo root; Pine needle oil; Guaifenesin; Elderflower; Hydrocodone; Iceland moss; Nasturtium herb; Pine needle oil; Conifer oil; Arborvitae tips; Levomenthol; Linden flowers; Horseradish root; Metamfepramone; Menthol; Myrtle oil; Myrtol; Naphazoline; Noscapine; Oxymetazoline; Oxytetracycline; Paracetamol; Pelargonium root; Pentoxyverine; Peppermint oil; Pheniramine; Phenylephrine; Pseudoephedrine; Sorrel herb; Primroses; Primrose flowers with calyx; Echinacea; Ribwort plantain herb; Sweet orange oil; Turpentine oil; Thyme; Thyme herb; Thyme oil; Thymol; Tramazoline; Triprolidine;Tyrothricin; Vitamin C; Willow bark; Xylometazoline; Lemon oil.

[0047] In another embodiment, the composition additionally contains one of the aforementioned active ingredients in order to obtain a synergistic effect between the effect of the composition and that of the active ingredient.

[0048] Furthermore, the composition preferably comprises a buffer system. The addition of a buffer system is advantageous because it ensures that the pH value of the composition, as described above, does not change or hardly changes when mixed with tear fluid upon application to the eye. The composition particularly preferably comprises a phosphate buffer system. Phosphate buffer systems are generally well tolerated physiologically and are therefore advantageous.

[0049] Preferably, the composition comprises further excipients. Preferred excipients are, for example, gelling agents, preservatives, complexing agents, and enzymes.

[0050] Preferably, the composition may contain a complexing agent. Suitable complexing agents are, for example, EDTA, such as in the form of its disodium salt, or citrate. The composition may also contain several complexing agents. Complexing agents are advantageous because they can bind divalent ions. This can, for example, prevent the precipitation of calcium phosphate, magnesium phosphate, or other divalent phosphates or salts from the composition. Calcification of the cornea (for example, through the formation of sparingly soluble calcium phosphate compounds) can thus be advantageously prevented.

[0051] Preferably, the complexing agent(s) is / are present in the composition at a total concentration of 0.001 to 1 wt.%. More preferably, the complexing agent(s) is / are present in the composition at a total concentration of 0.005 to 0.5 wt.%.

[0052] Preferred gelling agents include the thickening agents mentioned above and may alternatively or additionally include one or more of the following substances: alginates, agar-agar, carrageenan, furcellaran, gellan gum; pectin and pectin derivatives; gum arabic; methylcellulose; ethylcellulose; methylethylcellulose; hydroxypropylcellulose; gelatin; modified starch. The addition of a gelling agent may be advantageous to increase viscosity. Thus, the gelling agents may advantageously serve to prepare the composition as an ointment or gel.

[0053] Preferred preservatives include, for example, thiomersal, organic mercury compounds, phenylmercury, benzalkonium chloride, quaternary ammonium compounds, quaternary ammonium salts, chlorhexidine, benzyl alcohol, or mixtures thereof. If preservatives are present, they are preferably in the range of 0.0005 to 5% by weight of the total weight of the composition; more preferably in the range of 0.005 to 1% by weight of the total weight of the composition. Preservatives are advantageous because they increase the shelf life of the composition. However, they can also be disadvantageous because they may cause intolerances and / or allergic reactions in the eye in sensitive individuals.

[0054] The composition may include enzymes. Preferred enzymes include lysozyme and / or catalase. Catalase is most preferred. If enzymes are included, the composition preferably comprises between 100 and 300 enzyme units (U / ml) of the enzyme, and particularly preferably between 120 and 200 U / ml of the enzyme. One enzyme unit (U) corresponds to one micromole of substrate conversion per minute. One catal corresponds to the amount of enzyme that converts one mole of substrate per second (mol / s). One U thus corresponds to 1 / 60 of a microcatal (µcat).

[0055] Preferably, the osmolarity of the composition is not affected, or only minimally affected, by the addition of thickening agents or other excipients.

[0056] Preferably, the composition is in the form of an aqueous solution, an emulsion, a suspension, an ointment, or a gel. Preferably, the composition is prepared for application as an aqueous solution, emulsion, suspension, ointment, or gel. The method of preparing the aforementioned application forms is known to those skilled in the art.

[0057] The sterilization of the composition is carried out according to procedures and methods known to those skilled in the art, such as autoclaving or sterile filtration. Type of treatment / application

[0058] The term "Symptom of a secondary illness associated with COVID-19"According to the present invention, the following symptoms are associated with COVID-19: fever, dry cough, fatigue, body aches and pains, sore throat, hoarseness, diarrhea, headache, loss of taste or smell, discoloration of fingers or toes, skin rash, difficulty breathing or shortness of breath, chest pain or pressure, loss of speech or movement, muscle pain, back pain, chest pain in the sense of pleurisy, decrease in the total number of white blood cells, decrease in the number of lymphocytes, an increase in laboratory inflammatory parameters (such as CRP and ESR), runny nose, nausea and pneumonia.

[0059] The composition is particularly preferred for use in a procedure for the treatment and prevention of olfactory and / or gustatory disorders, fever, cough, sore throat, rhinitis (runny nose) or mixed forms thereof.

[0060] The term "prevention or treatment of at least one symptom" means that at least one of the aforementioned symptoms is alleviated, stopped or prevented.

[0061] Prevention or treatment of secondary diseases not associated with COVID-19, i.e., diseases in which a COVID-19 infection has not preceded or is occurring simultaneously and / or no SARS-CoV-2 infection is taking place in the population, is not part of the invention.

[0062] The population is defined by the detection of SARS-CoV-2 infection in individuals who have tested positive for the virus using a polymerase chain reaction (PCR), preferably a quantitative real-time polymerase chain reaction (RT-PCR), via a throat or nasal swab. A particularly preferred test method for detecting SARS-CoV-2 infection using real-time polymerase chain reaction (RT-PCR) is described in the publication by Corman et al., Eurosurveillance, published on January 23, 2020.

[0063] In other embodiments, detection can also be carried out using a bowel swab and PCR test.

[0064] In a preferred method, the composition is introduced into the eye during the waking phase of the person and several times at intervals of at most 2 h, preferably at intervals of at most 1.5 h, preferably at intervals of at most 1 h, particularly preferably at intervals of at most 0.5 h.

[0065] Thus, during a 16-hour waking period, the composition is administered at least 8 times, preferably at least 10 to 11 times, particularly preferably at least 16 times, and particularly preferably at least 32 times. For shorter waking periods, the number of applications decreases accordingly, and for longer waking periods, the number of applications is increased.

[0066] In another embodiment, consecutive increases in the time interval between two applications are also possible. A possible administration schedule is therefore, for example, as follows: During waking hours of 12 to 20 hours, the eye drops are initially applied at half-hour intervals. If effective, this interval can then be extended to once per hour or every two hours.

[0067] However, the interval between two applications should generally not exceed 2 hours, as otherwise the positive effect of the treatment is lost. Therefore, conventional treatment intervals with eye drops described in the prior art, such as 2-3 treatments per day or one treatment every 3 to 6 hours, are not suitable for the treatment effect according to the invention against symptoms of a secondary illness associated with COVID-19.

[0068] The use of the eye drops should not be discontinued too early and should ideally be continued throughout the entire SARS-CoV-2 infection of the patient or, especially in preventive cases, throughout the entire SARS-CoV-2 infection event in the population.

[0069] According to the present invention, "introducing the composition into the eye" means any method of application known to those skilled in the art. This includes, for example, instilling drops into the eye, instilling drops into the conjunctival sac, washing the eye, rinsing the eye, spraying the eye, applying cream to the cornea, applying gels or ointments to the cornea, and other known methods of application.

[0070] Preferably, a volume of 15 to 250 µl or one to five drops of the composition are introduced into the eye within a time interval, particularly per application. Particularly preferably, a volume of 30 to 150 µl of the composition or one to three drops of the composition are introduced into the eye within a time interval.

[0071] In a preferred method, the composition is introduced into the eye at the first occurrence of symptoms of a secondary illness associated with COVID-19, such as loss of smell and / or taste, fever (from 38.5°C and up to 40.4°C body temperature in adults, in further embodiments more than 40.5°C body temperature in adults), cough, sore throat, runny nose, or mixtures thereof.

[0072] In another embodiment, the composition is introduced into the eye at the first occurrence of more vague symptoms such as a scratchy throat, chills, elevated temperature (up to 38.4°C body temperature in adults), general malaise, headache or body aches, fatigue, sneezing, blocked nose and / or a runny nose, especially if these symptoms occur during a SARS-CoV-2 infection.

[0073] Such early application can advantageously prevent, shorten or stop the course of the disease with a secondary infection and thus contribute to a rapid cure.

[0074] Ideally, the application should begin before the actual onset of a cold. Early or even preventative application is advantageous because it can lead to a rapid improvement in symptoms. This, in turn, reduces the likelihood of a secondary illness, such as pneumonia.

[0075] The preventive application is advantageously started as soon as a COVID-19 infection occurs in the population and continued until the infection is considered to have ended.

[0076] During this period, the composition is applied to the eye at least every half hour, at least every hour, at least every 1.5 hours, or at least every 2 hours while the patient is awake. Preferably, the composition is applied to both eyes.

[0077] For application to the eye, the composition can preferably be formulated as eye drops, an eye wash, an eye spray, an eye ointment, or an eye gel. This allows for easy application.

[0078] The present invention also relates to the treatment of patients with COVID-19 using the aforementioned compositions. The patient group consists of humans, and in particular, the patient group belongs to one of the populations mentioned.

[0079] People who test positive for SARS-CoV-2 using RT-PCR belong to the patient group.

[0080] Likewise, the present invention also relates to the use of the described composition for the treatment and prevention of at least one symptom of a secondary illness associated with COVID-19 in humans, comprising the introduction of the composition into the human eye. Examples Example 1

[0081] In the event of the first occurrence of a sore throat during the 2020 Corona pandemic in Germany, with an average infection rate of more than 100 new infections per 100,000 people, the following sterile composition is instilled into both eyes of the patient: Composition I: hypotonic solution of NaCl and KCl (275 mOsm / l), 0.24% thickener, phosphate buffer (disodium phosphate dodecahydrate / sodium dihydrogen phosphate), pH value 7.2.

[0082] The passage between the nasal cavity and the eye is not blocked in the patient at the start of treatment.

[0083] The medication is applied during the 15-hour waking period at 1.5-hour intervals, ten times daily. Three drops of the solution are instilled into each eye.

[0084] The patient's sore throat subsided the very next day. After approximately 5 days, the patient was completely symptom-free. Example 2

[0085] Composition II: same as Composition I, but additionally containing 0.5 wt% Na2 EDTA.

[0086] If a blocked nose first occurs during the Corona pandemic 2020 in Germany with an average infection rate of more than 50 new infections per 100,000 people, the sterile composition II will be dripped into both eyes of the patient.

[0087] The medication is applied during the 16-hour waking period at 2-hour intervals, i.e., eight times a day. Three drops of the solution are instilled into each eye.

[0088] The patient's nose was clear again the very next day. The patient was completely symptom-free after approximately 6 days. Example 3

[0089] Upon first experiencing symptoms during the 2020 COVID-19 pandemic in Germany, a patient undergoes a PCR test (throat swab) for SARS-CoV-2 and tests positive. The patient complains of a scratchy throat, mild fever, and a dry cough.

[0090] The following sterile composition is instilled into both eyes of the patient: Composition I: hypotonic solution of NaCl and KCl (275 mOsm / I), 0.24% thickener, phosphate buffer (disodium phosphate dodecahydrate / Na dihydrogen phosphate), pH 7.2.

[0091] The treatment begins on day 1 during the waking hours (16 hours), initially with 6 applications every 0.5 hours, followed by thirteen applications for 1 hour. From day 2 onwards, treatment is carried out every 2 hours during the waking hours (approximately 14-16 hours) (approximately 8 applications per day). Three drops of the solution are instilled into each eye.

[0092] The patient's sore throat subsided on the second day. After approximately five days, the dry cough disappeared. The patient remained completely symptom-free for the next 14 days.

Claims

1. A sterile, aqueous composition for use in the treatment or prevention of at least one symptom of a secondary disease associated with COVID-19 in a human, selected from fever, dry cough, fatigue, pain in the limbs, sore throat, diarrhea, headache, loss of sense of taste or smell, discolorations of fingers or toes, skin rash, breathing difficulties or shortness of breath, pain or feeling of pressure in the thoracic region, loss of ability to speak or move, muscular pains, back pain, chest pain associated with pleurisy, reduction in the total white blood cell count, reduction of the number of lymphocytes, an increase of laboratory inflammation parameters (such as CRP and ESR), common cold, nausea and a pulmonary inflammation (pneumonia), wherein the human is characterized in that in him or her a SARS-CoV-2 infection has been detected by means of a quantitative polymerase chain reaction (PCR), comprising administration ofthe composition into the eye, wherein the composition is applied into the eye during the waking phase of the human and a multiple timesat intervals of at most 2 h; wherein the composition is a sterile, aqueous composition of a hypotonic solution of NaCl and KCl (275 mOsm / l), furthermore comprising 0.24 % by weight of a thickener, phosphate buffer (di-sodium phosphate dodecahydrate / Na-dihydrogen phosphate), pH value 7.2, and optionally in addition 0.5 % by weight Na2EDTA, wherein the composition is free of active pharmaceutical ingredients, in particular free of active decongestantingredients, antihistamines, antibiotics, ephedrine and / or pseudoephedrine.

2. The composition for use according to claim 1, wherein the human is defined by the fact that he or she is part of a population in which the number of the detected SARS-CoV-2 infections is higher than 100 per 100,000 residents.

3. The composition for use according to one of the preceding claims, wherein the composition comprises a thickener selected from polyethylene glycol, polyvinyl pyrrolidone, cellulose, cellulose derivatives, xanthan, carbomer, hyaluronic acid and the derivates thereof, as well as mixtures thereof.

4. The composition for use according to one of the preceding claims, wherein the composition is applied into the eye during the waking phase of the human and multiple times with a period of time of at most 1.5 h in between, preferably with an interval of at most 1 h.

5. The composition for use according to one of the preceding claims, wherein a volume of 15 to 250 µl of the composition per administration is applied into the eye; wherein the composition is preferably applied into both eyes.

6. The composition for use according to one of the preceding claims, wherein the composition is applied into the eye, when a symptom of a secondary disease associated with COVID-19, such as smell and / or taste disorders, fever, cough, sore throat, tickle in the throat, common cold (runny nose), fatigue or combinationsthereof, occurs for the first time and / or in the case of a contact with a person being proven to be infectedwith SARS-CoV-2.