WO2021194970A1 - Methods of preventing and treating covid-19 infection - Google Patents

Abstract

A method of preventing COVID-19 infection comprising the steps of: administering hydroxychloroquine; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19. A method of treating an individual infected with COVID-19 comprising the steps of: administering hydroxychloroquine; azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19. The methods can further comprise administering ivermectin in and optionally doxycycline.

Description

METHODS OF PREVENTING AND TREATING COVID-19 INFECTION

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to United States Non-Provisional Patent Application No. 17/114,271, titled ‘'Method of Preventing COVID-19 infection,” filed December 7, 2020, United States Non-Provisional Patent Application No. 16/953,674, titled “Method of Preventing and Treating COVID-19 infection,” filed November 20, 2020, United States Provisional Patent Application No. 63/110,877, titled “Methods of Preventing COVID- 19 Infection with Ivermectin,” filed November 6, 2020, United States Non-Provisional Patent Application No. 17/026,051, titled “Methods of Preventing and Treating COVID-19 Infection,” filed September 18, 2020, United States Provisional Patent Application No. 63/022,371, titled “Method of Treating and Preventing COVID-19 Infection,” filed May 8, 2020, United States Provisional Patent Application No. 63/022,368, titled “Method of Using Vitamin C, Vitamin D, Zinc, and Optionally Hydroxychloroquine, to Prevent COVID-19 Infection,” filed May 8, 2020, United States Provisional Patent Application No. 63/002,494, titled “Method of Using Vitamin C, Vitamin D, Zinc, and Optionally Hydroxychloroquine, to Prevent COVID-19 Infection,” filed March 31, 2020, United States Provisional Patent Application No. 63/001,161, titled “Method of Using Aerosolized Hydroxychloroquine, Vitamin C, and Zinc to Treat Covid-19 Infection,” filed March 27, 2020, United States Provisional Patent Application No. 62/993,345, titled “Method of Treating and Preventing COVID-19 Infection,” filed March 23, 2020, United States Provisional Patent Application No. 62/993,159, titled “Method of Treating COVID-19 infection with Antimicrobials,” filed March 23, 2020, and United States Provisional Patent Application No. 62/993,370, titled “Method of Treating COVID-19 Infection with Antimicrobials,” filed March 23, 2020, the contents of which are incorporated by reference in their entirety. BACKGROUND

[0002] COVID-19 is a novel betacoronavirus that originated in bats in the city of Wuhan, China. This disease has rapidly spread to become a worldwide pandemic, as declared by the World Health Organization (WHO). Symptoms of COVID-19, including fever, myalgia, coughing and shortness of breath, may appear from 2 and 14 days after exposure. Approximately 20% of patients progress to severe illness, including pneumonia, respiratory distress, and even death. Cases in the US have increased five-fold over the last week, alone. The disease is spreading rapidly, and a cure is desperately needed.

[0003] Nucleotide analogues, protease inhibitors and altered cellular bonding due to pH change will maximize host protection by: optimizing levels of gamma interferon and reducing the level of pathogenic microbes in the airways, especially in ‘at risk' patients.

[0004] It is known that single anti-viral agents work poorly when used alone in other chronic viral infections such as Hepatitis C or HIV infection. Therefore, the greater the number of anti-viral agents used in combination, the greater the cure rate.

[0005] Thus, there is a significant unmet need for preventing and treating this viral infection. The present invention addresses this need.

SUMMARY

[0006] In a first embodiment, the invention herein is directed to my method of preventing COVID-19 infection in an individual. The method of prevention comprises the steps of providing an individual that is not infected with COVID-19; administering four antimicrobials to the individual, wherein the antimicrobials comprise: chloroquine or hydroxychloroquine; vitamin C; vitamin D; and zinc; and monitoring the individual’s condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19. [0007] Optionally, the method of prevention comprises administering hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and administering zinc in a daily dosage range of 5 mg to 100 mg.

[0008] Optionally, the method of prevention comprises administering, on day 1: 400 mg of hydroxychloroquine; 3,000 mg of vitamin C; 3,000 IU of vitamin D; and 50 mg of zinc; and administering on day 2: 3,000 mg of vitamin C; 3,000 IU of vitamin D; and 50 mg of zinc.

[0009] Optionally, the method of prevention comprises administering ivermectin in a daily dosage range of 12 mg to 18 mg and, optionally, administering doxycycline in a daily dosage amount of 400 mg.

[0010] In a second embodiment, the invention herein is directed to my method of treating an individual infected with COVID-19. The method of treatment comprises the steps of: providing an individual infected with COVID-19; administering five antimicrobials to the individual, wherein the antimicrobials comprise: chloroquine or hydroxychloroquine; azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

[ 0011] Optionally, the method of treatment comprises administering hydroxychloroquine in daily dosage range of 20 mg to 2,000 mg; administering azithromycin in a daily dosage range of 250 mg to 500 mg; administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and administering zinc in a daily dosage range of 5 mg to 100 mg. [0012] Optionally, the method of treatment comprises the steps of: administering, on day

1: 400 mg of hydroxychloroquine; 500 mg of azithromycin; 3,000 mg of vitamin C; 3,000 IU of vitamin D; and 50 mg of zinc; administering daily, on days 2 to 400 mg of hydroxychloroquine; 250 mg of azithromycin; 3,000 mg of vitamin C; 3,000 IU of vitamin B; and 50 mg of zinc; and administering daily, on days 6 to 10: 400 mg of hydroxychloroquine; 3,000 mg of vitamin C; 3,000 IU of vitamin D; and 50 mg of zinc.

[0013] The method of treatment can further comprise administering daily, on days 6 to 10, administering 250 mg of azithromycin.

[0014] Optionally, the method of treatment comprises administering ivermectin in a daily dosage range of 12 mg to 18 mg and, optionally, administering doxycycline in a daily dosage amount of 400 mg.

BRIEF DESCRIPTION OF THE DRAWINGS [0015] Further advantages of the present invention may become apparent to those skilled in the art with the benefit of the following detailed description of the preferred embodiments and upon reference to the accompanying drawings in which:

[0016] FIG. 1 is a flow chart depicting the steps of a first method of preventing infection of an individual with COVID-19;

[0017] FIG. 2 is a flow chart depicting the steps of a second method of preventing infection of an individual with COVID-19;

[0018] FIG. 3 is a flow chart depicting the steps of a first method of treating an individual infected with COVID-19; [0019] FIG. 4 is a flow chart depicting the steps of a second method of treating an individual infected with COVlD-19;

[0020] FIG. 5 A is a graphical representation of whole genome alignment of SARS-CoV-

2 in patient 1 of Example 6;

[0021] FIG. 5B is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 3 of Example 6;

[0022] FIG. 5C is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 4 of Example 6;

[0023] FIG. 5D is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 6 of Example 6;

[0024] FIG. 5E is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 8 of Example 6;

[0025] FIG. 5F is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 10 of Example 6;

[0026] FIG. 5G is a graphical representation of whole genome alignment of SARS-CoV- 2 in patient 11 of Example 6; and

[0027] FIG. 5H is a graphical representation of whole genome alignment of SARS- CoV-2 in patient 12 of Example 6. DETAILED DESCRIPTION

[0028] As used herein, the following terms and variations thereof have the meanings given below, unless a different meaning is clearly intended by the context in which such term is used.

[0029] The terms ‘"a,” “an,” and “the” and similar referents used herein are to be construed to cover both the singular and the plural unless their usage in context indicates otherwise.

[0030] As used in this disclosure, the term “comprise” and variations of the term, such as “comprising” and “comprises,” are not intended to exclude other additives, components, integers ingredients or steps.

[0031] Referring now to the drawings, wherein like reference numerals designate identical or corresponding features throughout the several views. Further, described herein are certain non-limiting embodiments of my pipeline filter assembly for pool filtering and maintenance.

[0032] The following discussion describes in detail multiple embodiments of the invention with several variations of those embodiments. This discussion should not be construed, however, as limiting the invention to those particular embodiments. Practitioners skilled in the art will recognize numerous other embodiments as well.

[0033] In a first embodiment, the present invention is directed to a first method of preventing COVID-19 infection in an individual. The method involves administration of chloroquine or hydroxychloroquine, Vitamin C, Vitamin D, and Zinc. Both methods are discussed in greater detail below. [0034] Referring now to Figure 1, there is shown the first method of prevention. The method of prevention comprises administering four different antimicrobials. The four antimicrobials comprise: ch!oroquine or hydroxychloroquine, vitamin C, vitamin D, and zinc.

10035] Day 1 the individual takes the following, ideal, regimen outlined in Table 1:

Table 1

[0036] Optionally, the method of prevention can comprise administering on day 2: 3,000 mg of vitamin C; 3,000 IU of vitamin D; and 50 mg of zinc.

[0037] Hydroxychloroquine is administered only on day 1. The half-life of hydroxychloroquine is up to 32 days, thus treatment with this drug for one day should be sufficient. However, should the need to prevent the infection or disease last longer than 32 days, repeat dosing can be considered. Accordingly, if necessary, the cycle of day 1 followed by day 2 can be repeated weekly, every_' 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks.

[0038] Vitamin C is administered at 3,000 mg per day ongoing. This 3,000 mg can be broken up into two 1500 mg doses, one taken in the morning and one taken at night.

[0039] Vitamin D is administered at 3,000 IU per day ongoing. This 3,000 IU can be broken up into two 1500 IU doses, one taken in the morning and one taken at night. [0040] Zinc is administered at 50 mg per day ongoing. This 50 mg can be broken up into two 25 mg doses, one taken in the morning and one taken at night.

[0041] Chloroquine or hydroxychloroquine can be administered in a daily dosage range of 20 mg to 2,000 mg. The above amounts recited in the tables are not limiting.

[0042] Vitamin C can be administered in a daily dosage range of 250 mg to 10,000mg. The above amounts recited in the tables are not limiting.

[0043] Vitamin D can be administered in a daily dosage rage of 1,000 IU to 100,000 IU. The above amounts recited in the tables are not limiting.

[0044] Zinc can be administered in a daily dosage of 5 mg to 100 mg. The amount of Zmc can be reduced to 25 mg per day if gastrointestinal upset occurs.

[0045] Zinc, Vitamin C and D help in numerous aspects of viral protection through cellular metabolism, including catalytic activity of enzymes, and play roles in immune function, protein synthesis.

[0046] The chloroquine or hydroxychloroquine can come in various forms: as a pill, liquid solution, lozenges, topical treatment such as a cream or oil, or any other means of delivery. Hydroxychloroquine prevents cytokine release, and cytokine release is what causes anaphylactic flush. Optionally, the hydroxychloroquine is sprayed directly on the users tongue.

[0047] In a second embodiment, the present invention is directed to a second method of prevention that comprises administering three different supplements comprising vitamin C, vitamin D, and zinc, and mixtures thereof, to an individual.

[0048] Referring now to Figure 2, there is shown the second method of prevention. The length of preventative treatment of the present invention can be as long as necessary. However, regardless of the length of treatment, Vitamin C is provided at 10,000mg daily for the first three days of treatment, and then 3000mg daily thereafter. This 10,000 mg of Vitamin C can be broken up into two doses, one taken in the morning and one taken at night. [0049] Vitamin B is provided at 40,000 IU one day every 4 weeks (or however many weeks the preventative treatment lasts). This 40,000 IU of Vitamin D can be broken up into two doses, one taken in the morning and one taken at night. [ 0050] Zinc is provided at 50mg per day ongoing, for the length of the preventative treatment. This 50 mg of Zinc can be broken up into two doses, one taken in the morning and one taken at night.

[0051] On Day 1 (Week I), the patient provides verbal informed consent, the patient reviews prior (previous 3 months) and concomitant medications and the patient receives the three different supplements: Vitamin C, Vitamin D, and Zinc. The patient takes 10,000 mg of Vitamin C, 40,000 IU of Vitamin D, and 50 mg of zinc.

[0052] On Days 2 and 3 (Week 1), the patient takes 10,000 mg of Vitamin C and 50 mg of zinc daily. This 3,000 mg can be broken up into two 1500 mg doses, one taken in the morning and one taken at night. The patient is called on the phone for assessment for potential adverse events (AE) and serious adverse events (SAE), and any COVID-19 symptoms.

[0053] On Days 4-7 (Week 1), the patient takes 3,000 mg of Vitamin C and 50 mg of zinc daily.

[0054] On Day 8 (Week 2), the patient takes 3,000 mg of Vitamin C, 40,000 IU of Vitamin D, and 50 mg of zinc.

[0055] On Days 9-14 (Week 2), the patient takes 3,000 mg of Vitamin C and 50 mg of zinc daily.

[0056] Weeks 3-24 continue with the same protocol identified above for Week 2. [0057] Treatment can be for one day or consecutive or repeated in 2 weeks, 1 month, 6 months or 1 year.

[0058] Optionally, Vitamin C dosage can range from 1000mg to 10,000mg per day, Vitamin D dosage can range from 1000 IU to 40000 IU per day, Zinc (the zinc can be any type or form of zinc) dosage can range from 25-75 mg per day. As noted above, all daily doses of Vitamin C, Vitamin B and Zinc can be broken up into two daily doses, wherein one dose is taken in the rnormng and one dose is taken in the evening. For all protocols provided in this application, when a dosage range is provided, any dosage amount that is included in that range can be administered. Accordingly, the invention is not limited to the dosage ranges disclosed, and includes all dosage amounts contained in those ranges.

[0059] The protocols provided in this application can also include selenium, copper and other vitamins that are deemed appropriate supplements for Vitamin C, Vitamin D or Zinc or, to counteract the negative depletion of certain vitamins, like copper or selenium.

[0060] The Vitamin C, Vitamin D and Zinc, and mixtures thereof, can be administered orally, in the form pills/lozenges, an aerosolized spray, or a food substance such as a liquid drink or yogurt composition. Optionally, the Vitamin C, Vitamin D and Zinc can be administered in the form of a nasal spray or a topical application, such a lotion or spray for administration on the individual's skin.

[0061] In the methods of prevention described above, all, or any combination of, the antimicrobials/supplements disclosed above can be administered m the form of a single small atomizer. The patient sprays the atomizer towards the back of their throat. The spray is administered at least once a day, but preferably twice a day when coughing starts. Use of the atomizer continues as directed by the supervising physician.

[0062] in a second embodiment, the present invention is directed to a first method of treating an individual with infection or disease with five different antimicrobials. The five antimicrobials comprise: hydroxychloroquine, azithromycin, vitamin C, vitamin D and zinc.

Referring now to Figure 3, there is shown the first method of treatment.

[0063] Day 1 following positive test (isolation), the individual takes the following regimen outlined in Table 2:

Table 2

[0064] On Day 2-Day 5 the individual takes the following regimen outlined in Table 3:

Table 3

[0065] On Day 6-Day 10, the individual takes the following regimen outlined in Table 4:

Table 4

[0066] Hydroxychloroquine is administered daily, at 200 mg twice daily for days 1-10. [0067] Azithromycin is administered daily, at 500 mg on day 1, and 250 mg days 2-5. Optionally, azithromycin can be administered at 250 mg per day for 5-10 days with a loading dose of 500 mg x day 1 or simply 250 mg on day 1. Azithromycin may be substituted with doxycycline at a daily dosage range of 25 mg to 800 mg, for those unable to take azithromycin. Alternatively, minocycline or antibiotics that inhibit bacterial 50S ribosomal RNA, and mixtures thereof, may be used.

[0068] Optionally, natural products like quercetin and artemesia, and mixtures thereof, may be used, as well as any natural compounds that are used to make hydroxychloroquine or azithromycin, and mixtures thereof. Accordingly, any mixture of any of the above recited compositions may be used.

[0069] Vitamin C is administered at 3,000 mg per day ongoing. This 3,000 mg can be broken up into two 1500 mg doses, one taken in the morning and one taken at night.

[0070] Vitamin D is administered at 3,000 IU per day ongoing. This 3,000 IU can be broken up into two 1500 IU doses, one taken in the morning and one taken at night.

[0071] Zinc is administered at 50 mg per day ongoing. This 50 mg can be broken up into two 25 mg doses, one taken in the morning and one taken at night.

[0072] Chloroquine or hydroxychloroquine can be administered in a daily dosage range of 20 mg to 2,000 mg. The above amounts recited in the tables are not limiting. The chloroquine or hydroxychloroquine can come in various forms: as a pill, liquid solution, lozenges, topical treatment such as a cream or oil, or any other means of delivery. Hydroxychloroquine prevents cytokine release, and cytokine release is what causes anaphylactic flush. Optionally, the hydroxychloroquine is sprayed directly on the users tongue.

[0073] Vitamin C can be administered in a daily dosage range of 250 mg to 10,000mg. The above amounts recited in the tables are not limiting.

[0074] Vitamin B can be administered in a daily dosage rage of 1,000 IU to 100,000 IU. The above amounts recited in the tables are not limiting.

[0075] Zinc can be administered in a daily dosage of 5 mg to 100 mg. The amount of Zinc can be reduced to 25 mg per day if gastrointestinal upset occurs.

[0076] Concurrently with the above treatment, the individual is self-quarantined per CDC recommendations.

[0077] Optionally, for the method of treatment noted above, as the dosages of the hydroxychloroquine, vitamin C, vitamin D and zinc remain the same throughout treatment; all four of those antimicrobials can be administered in the form of a single small atomizer. The patient sprays the atomizer towards the back of their throat. The spray is administered at least once a day, but preferably twice a day when coughing starts. Use of the atomizer continues as directed by the supervising physician.

[0078] For all protocols provided in this application, vitamin C dosage can range from 250 mg to 10,000 mg per day, vitamin D dosage can range from 1000 IU (mg) to 100,000 IU (mg) per day, zinc (which can be any form or type of zinc) dosage can range from 5 mg to 100 mg per day, and hydroxychloroquine dosage can range from 50 mg to 2,000 mg per day for a treatment period of 1 to 10 days treatment. Optionally, hydroxychloroquine can be administered once as single dose. For all protocols provided in this application, when a dosage range is provided, any dosage amount that is included in that range can be administered. Accordingly, the invention is not limited to the dosage ranges disclosed, and includes all dosage amounts contained in those ranges.

[0079] Optionally, the above protocols can include selenium, copper and other vitamins that are deemed acceptable supplements for vitamin C, vitamin D or zinc or to counteract the negative depletion of certain vitamins, which is why copper or selenium are typically used. [0080] Treatment can be for one day or consecutive or repeated in 2 weeks, 1 month, 6 months or 1 year, or weekly for 6 months.

[0081] in a third embodiment, the present invention is directed to a second method of treating COVID-19 infection. Referring now to Figure 4, there is shown the second method of treatment.

[0082] The ivermectin can either be administered while the patient is undergoing the first method of treatment discussed above, or after the patient has undergone 5 to 7 days of the treatment of the method of treatment discussed above.

[0083] The dosage amount for the ivermectin is 12-18 mg/day. The ivermectin can he administered daily, for up to 10 consecutive days, or alternatively, the ivermectin can be adminis tered on day 1, day 3/day 4 and day 7/day 8 of a 10 day period. The 10 day period can ei ther be in conjunction with adminis tration of the treatment of the first method of treatment discussed above, or following the completion of the 5 to 7 days of treatment with the first method of treatment discussed above.

[0084] Ivermectin can be administered in a pill/tablet, a nasal spray, an oral spray, or a topical ointment.

[0085] Optionally, natural products as well as any natural compounds, and mixtures thereof that are used to make ivermectin may be used as an alternative to ivermectin. [0086] Optionally, either the first or the second methods of treating COVID-19 infection can also include administering doxycycline (or any other alternatives listed above and mixtures thereof) to the patient in a dosage amount of 200 mg, by mouth, twice a day, for up to 10 consecutive days.

[0087] Accordingly, combining the first and second methods of treatment discussed above can result in a combined method of treatment that can include the use of hydroxychloroquine, azithromycin, ivermectin, doxycy cline, vitamin C, vitamin D and zinc, taken all at the same time.

[0088] The above protocols can be used to prevent and treat other viruses (not just COVID-19), including other flu and various respiratory viruses, including more benign coronaviruses and rhinoviruses.

[0089] The above protocols can also be used to prevent and treat Autism, Parkinson’s, Alzheimer’s and other neurological diseases.

[0090] EXAMPLES

[0091] Example 1: Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for Prevention of COVID-19 Infection

[0092] Objective: To determine whether treatment with hydroxychloroquine, vitamin C, vitamin D, and zinc in combination will prevent infection with COVID-19 and to assess the safety and tolerability of hydroxychloroquine, vitamin C, vitamin D, and zinc in healthy, high-risk individuals without hypertension, and no evidence of COVID-19 infection.

[0093] Procedure: Day 1: Prescription of study drugs and home health monitoring equipment. The study drugs are hydroxychloroquine 200mg twice a day for 1 day only, vitamin C 3000mg per day ongoing, vitamin D 3000mg per day ongoing, and zinc 50mg per day ongoing per day. The home health monitoring equipment is an electrocardiogram (EKG) which synchs up with a smartphone [0094] Days 2-7: Patient collects the EKG once during this week using the home health equipment

[0095] Weeks 1-23: Patient provides an assessment of any COVID-19 symptoms and continues to collect EKG weekly throughout the remainder of the trial [0096] Week 24: Patient undergoes confirmatory COVID-19 testing which consists of nasopharyngeal (NP) and oropharyngeal (OP) swabs collected according to CDC (Center for Disease Control) protocol. The swabs consist of synthetic fiber swabs with plastic shafts. NP swabs are collected by insertion of a swab into the nostril parallel to the palate. The swab is left in place a few seconds to allow it to absorb secretions. OP swabs are inserted into the oropharynx parallel to the palate, avoiding the tongue. The swab is left in place a few seconds to allow it to absorb secretions. The swabs are then immediately placed in sterile tubes with 2-3mL of viral transport media. The tubes are placed in biohazard bags then boxes and couriered to the local Public Health Lab.

[0097] Table 5 provides a schedule of events for Example 1.

require separate informed consent and could possibly include antibody or cytokine testing, and vitals in-clinic to include height, weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate, temperature, and oxygen saturation. [0099] Example 2: Randomized, Double-Blind, Placebo-Controlled Phase IIA Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection [00100] Objectives: Prevention of COVID-19, Lack of COVID-19 symptoms, and assessment of safety and tolerability [00101] Procedure: Screening Period (Days -5 to -1): Prescription of home health monitoring equipment that includes a thermometer, a pregnancy test if applicable, and a daily diary. There are two groups being studied: Arm 1 and Arm 2. [00102] Arm 1 is prescribed the following antimicrobials: hydroxychloroquine 200mg twice a day for 1 day only, vitamin C 3000IU per day for 12 weeks, vitamin D 3000IU per day for 12 weeks, and zinc 50 mg per day for 12 weeks. The zinc can be reduced to 25 mg if GI upset occurs.

[00103] Arm 2 is prescribed the following antimicrobials: Placebo twice a day for 1 day only, vitamin C 3000IU per day for 12 weeks, vitamin D 3000IU per day for 12 weeks, and zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 mg if Gl upset occurs.

[00104] Day 1: Patient is called to teach them how to use the diary in the EDC, discuss the medication regimen, and answer any questions they may have. Patient takes pregnancy test if applicable, collects a temperature reading, completes their diary, and takes the prescribed treatment regimen. Table 6 outlines the prescribed treatment regimen for Day 1.

Table 6

[00105] Day 2: Patient collects a temperature reading, completes their diary, and is called on the phone for assessment of any adverse events or serious adverse events, assessment of any COVlD-19 symptoms, the list of prior and concomitant medications is updated, any questions the patient has are answered, and the patient takes their prescribed treatment regimen. Table 7 outlines the prescribed treatment regimen for Day 2.

Table 7

[00106] Days 3-10: Patient collects a temperature reading, completes their diary, and takes their prescribed treatment regimen. Table 8 outlines the prescribed treatment regimen for Days 3-10.

Table 8

[00107] Day 14: The patient is called for instruction on how to collect a nasal swab and package for shipping, assessment COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have.

[00108] Weeks 3-11 : The patient is called weekly for assessment of any adverse events or serious adverse events, assessment of any COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have. The patient takes weekly temperature readings, completes their diary, and takes the prescribed treatment regimen. During Week 4 the patient is reminded to collect a nasal swab. The prescribed treatment regimen for Weeks 3-11 is shown in Table 9.

Table 9

[00109] Week 12: The patient presents to the clinic for evaluation that includes assessment for adverse events and serious adverse events, updating their list of prior and concomitant medications, a physical exam, nasal swab collection and COV1D-19 sample collection.

[00110] Samples for COVID-19 testing are collected using synthetic swabs with plastic shafts. Nasal swabs are collected and immediately placed into a sterile vial with 2-3 mL of viral transport media. The vials are placed into biohazard bags, boxed up, the box sterilized, and picked up for shipment to the central laboratory. Samples are tested by RT-PCR.

[00111] Table 10 presents the schedule of events for Example 2.

000112] Regarding Table 10: The Zinc may be reduced to 25mg if GI upset occurs, phone/video calls to the patient occur weekly during Weeks 2-11, and vitals in-clinic include height, weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate, temperature, and oxygen saturation. [00113] Statistical Analysis: The treated patients in this study are compared to the placebo group. Measurements include PCR test results, presence or absence of symptoms, and symptom severity. [00114] The change of these measurements from the end to the baseline (post–pre) are used as the primary outcome, for example, μe = μe1 - μe0, where μe1 and μe0 are the outcome of patients from the treatment group at the end and at baseline, respectively. [00115] H₀:Δ≤δ₀ againstH_a:Δ>δ₀ where δ0 is a clinically meaningful threshold to measure the disease symptoms. In this study, that meaningful threshold is calculated as mean change in clinical symptoms as recorded in the diary, from baseline through week 12. Each category in the diary is assigned a number, 0 for None, 1 for Mild, 2 for Moderate and 3 for severe. Each category is analyzed independently and as a group. [00116] Categorical variables are summarized by presenting the number (n) and percent (%) of subjects in each category. All Statistical tests for the analysis are performed using the p<0.05 level of significance. All confidence intervals are one-sided. [00117] Since these are healthcare workers who are exposed to COVID-19 at every shift, efficacy is determined by RT-PCR testing, as well as the presence or absence of symptoms as recorded in the patient diary via EDC.

[00118] Example 3: Use of Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc to treat COVID-19 infection (HAZDPAC)

[00119] Objectives: test the efficacy of hydroxychloroquine, azithromycin, vitamin C, vitamin D, and zinc the treatment of patients with COVID-19 infection and to assess the safety and tolerability of this treatment in patients with COVID-19 infection.

[00120] Procedure: First, the patient is determined to have COVID-19.

[00121] Day 1 following positive test (isolation): The patient takes prescribed regimen outlined in Table 11.

[00122] Day 2-Day 5: The patient takes the prescribed regimen outlined in Table 12.

[00123] Day 6-Day 10: The patient takes the prescribed regimen outlined in Table 13.

[00124] Follow-Up Period: Month 1 (outpatient only AFTER negative test): vital signs are taken that include blood pressure, heart rate, respiratory rate, oxygen saturation. temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00125] Month 3 (outpatient): vital signs are taken that include blood pressure, heart rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00126] Month 6 (outpatient) vital signs are taken that includes blood pressure, heart rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00127] Month 9 (outpatient) vital signs are taken that includes blood pressure, heart rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00128] Month 12 (outpatient) vital signs are taken that includes blood pressure, heart rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00129] COVID-19 sample collection procedure is as follows: nasopharyngeal (NP) and oropharyngeal (OP) swabs are collected according to CDC protocol. The swabs comprise synthetic fiber swabs with plastic shafts. NP swabs are collected by insertion of a swab into the nostril parallel to the palate. The swab is left in place a few seconds to allow it to absorb secretions. OP swabs are inserted into the oropharynx parallel to the palate, avoiding the tongue. The swab is left in place a few seconds to allow it to absorb secretions. NP and OP swabs are immediately placed in sterile tubes with 2-3mL of viral transport media. The tubes are placed in biohazard bags then boxes and couriered to the local Public Health Lab. Table 14 outlines the schedule of events for Example 3.

[00130] Regarding Table 14: Vitals to include height (only at first visit), weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate, temperature, and oxygen saturation. Dosage to be given as in section 8, below

[00131] Table 15 provides a summary of the antimicrobial dosage of Example 3.

[00132] Example 4: Randomized, Double-Blind, Placebo-Controlled Phase IIA Study of Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc to treat COVID-19 Infection

[00133] Objectives: Test the efficacy of hydroxychloroquine, azithromycin, vitamin C, vitamin D, and zinc in the treatment of patients with COVID-19 infection and to assess the safety and tolerability of this treatment m patients with COVID-19 infection.

[00134] Procedure: First, the patient’s diagnosis of COVID-19 infection is confirmed. [00135] Screening Period (Days -3 to -1): Prescription of home health monitoring equipment that includes a thermometer, a pulse oximeter, a pregnancy test if applicable, and a daily diary. There are two groups being studied: Arm 1 and Arm 2.

[00136] Arm 1 is prescribed the following antimicrobials: Hydroxychloroquine 200MG BID for 10 days; Azithromycin 500mg on day 1, 250mg day 2-5; Vitamin C 3000IU for 10 days, then 1500mg for 20 days; Vitamin D 3000IU for 10 days, then 1500IU for 20 days; and Zinc 50mg for 10 days, then 25 mg for 20 days.

[00137] Arm 2 is prescribed the following antimicrobials: Placebo for Hydroxychloroquine BID for 10 days; Placebo for Azithromycin to be taken 2 the on Day 1, then 1 on Days 2-5; Vitamin C 3000mg for 10 days, then 1500mg for 20 days; Vitamin D 3000IU for 10 days, then 1500IU for 20 days; and Zinc 50mg for 10 days, then 25mg for 20 days. Table 16 outlines the prescribed antimicrobials discussed above.

Table 16

[00138] Treatment Period: Day 1 following positive test (isolation), the patient is video called to ensure they have all study materials and the following is discussed: Use of home health equipment, Subject will take baseline measurements at this time and record it in the diary, Diary and how to transmit its contents, Medication dosing, Subject will take pregnancy test if applicable, Subject will use provided equipment to measure vital signs such as EKG, Oxygen Saturation, and Temperature. The patient takes prescribed regimen outlined in Table 17.

Table 17

[00139] Day 2: The patient completes the AM and PM diary entries, the patient uses the provided equipment to measure vital signs such as EKG, Oxygen saturation, and temperature, and the patient takes the prescribed regimen outlined in Table 18.

Table 18

[00140] Day 3: The patient Is called and asked if they are experiencing any difficulties with swab collection, whether there have been any adverse events and/or serious adverse events, the list of prior and concomitant medications is updated, the patient is asked about symptom resolution or progression, the patient is instructed on how to collect nasal swabs, and the patient then collects the first nasal swab. The patient completes their AM and PM diary entries, and collects their vital signs such as EKG, oxygen saturation and temperature. The patient takes the prescribed regimen outlined in Table 19.

Table 19 [00141] Day 4: The patient completes their AM and PM diary entries, collects their vital signs, and takes the prescribed regimen outlined in Table 20.

Table 20

[00142] Day 5: The patient completes their AM and PM diary entries, collects their vital signs, collects a nasal swab, and takes the prescribed regimen outlined in Table 21.

Table 21

[00143] Day 6: The patient completes their AM and PM diary entries, collects their vital signs, and takes the prescribed regimen outlined in Table 22.

Table 22

[00144] Day 7: The patient is called and asked whether there have been any adverse events and/or serious adverse events, the list of prior arid concomitant medications is updated, the patient is asked about symptom resolution or progression, and the patient then collects a nasal swab. The patient also completes their AM and PM diary entries and collects their vital signs. The patient takes the prescribed regimen outlined in Table 23.

Table 23

[00145] Day 8: The patient completes their AM and PM diary entries, collects their vital signs, and takes the prescribed regimen outlined in Table 24.

Table 24

[00146] Day 9: The patient completes their AM and PM diary entries, collects their vital signs, and takes the prescribed regimen outlined in Table 25.

Table 25

[00147] Day 10: The patient is called reminded to decrease dosage of vitamins C, vitamin D, and zinc tomorrow. The patient is asked whether there have been any adverse events and/or serious adverse events, the list of prior and concomitant medications is updated, and the patient is asked about symptom resolution or progression. The patient also completes their AM and PM diary entries and collects their vital signs. The patient takes the prescribed regimen outlined in Table 26.

Table 26

[00148] Day 11 to Day 13: The patient completes their AM and PM diary entries and takes the prescribed regimen outlined in Table 27.

Table 27

[00149] Day 14: The patient is called and asked whether there have been any adverse events and/or serious adverse events, the patient is asked about symptom resolution or progression, and the patient then collects a nasal swab. The patient also completes their AM and PM diary entries and collects their vital signs. The patient takes the prescribed regimen outlined in Table 28.

Table 28

[00150] Day 15 to Day 30: The patient completes their AM and PM diary entries and takes the prescribed regimen outlined in Table 29.

Table 29

[00151] Follow-Up Period: Month 1 (outpatient only AFTER negative test): Vital signs are taken (BP, HR, RR, oxygen saturation, temperature), the patient is assessed for adverse events and/or serious adverse events, and EKG is administered as well as phy sical exam and a blood draw for CBC/Complete metabolic panel/C-Reactive Protein. The list of prior and concomitant medications is updated and a nasal swab is collected.

[00152] Month 2 (outpatient): Vital signs are collected (BP, HR, RR, oxygen saturation, temperature) the patient is assessed for adverse events and/or serious adverse events, and EKG is administered as well as physical exam and a blood draw for CBC/Complete metabolic panel/C-Reactive Protein. The list of prior and concomitant medications is updated.

[00153] Month 3 (outpatient): Vital signs are taken (BP, HR, RR, oxygen saturation, temperature), the patient is assessed for adverse events and/or serious adverse events, and EKG is administered as well as physical exam and a blood draw for CBC/Complete metabolic panel/C-Reactive Protein. The list of prior and concomitant medications is updated and a nasal swab is collected.

[00154] COVID-19 Sample Collection Procedure is the same as that outlined above in prior Examples. Table 30 outlines the schedule of events for Example 4.

Table 30

[00155] Regarding Table 30: The antimicrobials include hydroxychloroquine 200mg tablets (#20), azithromycin 250mg tablets (#6), vitamin C 750mg capsules (#80), vitamin D 750IU capsules (#80), zinc 12.5mg capsules (#80); the home health equipment includes an EKG (worn continuously), pulse oximeter, and thermometer; the pregnancy test is administered if the patient is a woman of childbearing potential; the patients are called at home to remind them to collect swabs for RT-PCT, ask about AE/SAE, ask about symptoms, and answer any questions; the vitals taken at home include an EKG, oxygen saturation, and temperature; the vitals in-clinic include height (only at first visit), weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate, temperature, and oxygen saturation; and the bloodwork includes CBC, Complete Metabolic Panel, and CRP (details in section 9 Sample Collection).

[00156] Statistical Analysis: The treated patients m this study are compared to the placebo group. Measurements include PCR test results, presence or absence of symptoms, and symptom severity. PCR results will he compared between the groups as positive or negative [00157] In this study, the meaningful threshold is calculated as mean change in clinical symptoms as recorded in the diary, from Day 1 through week 12. Each category in the diary is assigned a number, 0 for None, 1 for Mild, 2 for Moderate and 3 for severe. Each category is analyzed independently and as a group. Ultimately, efficacy is determined based upon reduction and/or progression of symptomatic days, reduction of symptom severity, as well as analysis of the subject’s RT-PCR testing per protocol. These data are compared to an existing database of de-identified Subject data.

[00158] The change of these measurements from the end to the baseline (post-pre) are used as the primary^· outcome, for example, μe = μ_e1 - μ_e0, where μ_e1 and μ_e0 are the outcome of Subjects from the treatment group at the end and at baseline, respectively.

[00159] Categorical variables are summarized by presenting the number (n) and percent (%) of subjects in each category. All Statistical tests for the analysis are performed using the p<0.05 level of significance. All confidence intervals will be one-sided [00160] Sample size was calculated as follows:

[00163] The proportion of the population affected by COVID-19 is 0.005 percent, thus

0.995 percent aren't affected

[00164] The probability of a type II error is 0.05

100165] Thus:

[00166] n= log 0.050

100167] log 0.995

[00168] n 97.647

[00169] A sample size of 600 was used.

[00170] Example 5: Successful Treatment of COVID-19 Infected Outpatients and Prophylaxis of Immediate Associates

[00171] Objective: to successfully treat COVID-19 infected outpatients and prophylaxis of immediate associates.

[00172] Procedure: Prospective COVID-19 infected individuals were diagnosed using a Pangea DNA/RNA Shield^TM Collection Tube to obtain a nasopharyngeal swab and PCR +ve patients were entered into the study. They were immediately commenced on a 10 day course of Hydroxychloroquine (200 mg, twice a day, for 10 days), Azithromycin extended release (500mg on day 1, then 250 mg a day for days 9-10). zinc (50mg a day for days 1 -10), Vitamin D (3000IU a day for days 1-10) and Vitamin C (3000mg a day for days 1-10). Some individuals lived alone; otherwise immediate partners and family deemed to be most exposed were given a prophylactic which comprised hydroxychloroquine 200 mg twice a day on day 1 only with Zinc, Vitamin C and Vitamin D for given at the same doses as above for days 1-10. [00173] Results: In 11 families a total of 21 family members were identified to be PCR COVID-19 positive index cases and were treated with the above treatment protocol while 22 exposed associates with negative PCR were given the above prophylaxis protocol. This is shown below in Table 31. All 21 index cases were cured of COVID-19 infection as judged by the repeat swab PCR on day 10 and accompanying symptom resolution. None of the 22 highly exposed associates developed COVID-19 infection when retested on day 10 (day 14 in Family 10) in spite of close co-habitation with the infected index cases. Table 31 documents the results from families that received a 10-day course of daily HCQ (200mg bd), AZ extended release (500mg dayl, then 250 mg), zinc (50mg), Vitamin D (3000IU) and Vitamin C (3000mg)

Table 31

[00174] Apart from the families a further 11 single infected individuals found to be swab PCR positive were treated with the above treatment protocol. This is shown below in Table 32. Ail were also successfully cured of the infection.

Table 32

[00175] A further 9 individuals recently closely exposed to Covid-19 infected persons were given the prophylaxis protocol outlined above. The prophylactic worked very well with no exposed person acquiring the infection. This is shown in Table 33.

Table 33

[00176] Discussion: it was demonstrated that a 10 day combination of hydroxychloroquine, azithromycin (for 5 days only), zinc with vitamin D and vitamin C, can result in uniform cure of COVID-19 infection when used in an outpatient population. The prophylaxis treatment noted above for those closely exposed to proven, infected patients can completely prevent spread of COVID-19. This combination of test-and-treat permits abolishing of new outbreaks of infection such as a ‘next wave’ - by avoiding quarantine to treat the infected and give prophylactics to surrounding staff and family.

[00177] In conclusion, this is an effective anti-Covid-19 therapy as well as an effective prophylactic combination capable of arresting the spread of coronavirus infection throughout the community. This is achieved by treating the index case and the surrounding associates of the patient as early as possible after infection is identified and then treating the people they live with and close associates.

[00178] Example 6: Presence of the SARS-CoV-2 by NGS of Fecal Samples

[00179] Objective: In view of the large percentage of SARS-CoV -2 detectible by RT-

PCR in stools of infected patients, the objective was to identify the presence of the SARS- CoV-2 by NGS of fecal samples from symptomatic study participants positive for SARS- CoV-2 by nasopharyngeal sample RT-PCR, in addition to asymptomatic individuals (with or without prior nasopharyngeal sample RT-PCR). The objective was also to execute whole genome analysis to characterize SARS-CoV-2 mutational variations to identify potentially significant nucleotide changes. [00180] Procedure: Study participants (n = 14) underwent testing for SARS-CoV-2 from fecal samples by whole genome enrichment NGS. Following fecal collection (Zymo Research Shield Fecal Collection Tubes), RNA was extracted (Qiagen Allprep Power Viral Kit), reverse transcribed (New England Biolabs NEBNext 1st and 2nd Strand Synthesis Modules), library prepped (Illumina Nexerta Flex for Enrichment), enriched (llumina Respiratory Virus Oligo Panel), and sequenced on Illumina’ s NextSeq 550 System.

Sequences were then mapped to the SARS-CoV-2 Wuhan-Hu-1 (MN90847.3) complete genome utilizing One Codex’s SARS-CoV-2 bio informatics analysis pipeline. SARS-CoV-2 positive samples were further analyzed for mutational variants that differed from the reference genome. Of the 14 study participants, 12 also had their nasopharyngeal swabs tested for SARS-CoV-2 by RT-PCR.

[00181] Results: The results from patients that had their stool samples tested by whole genome enrichment NGS, and their nasopharyngeal swabs tested by RT-PCR for the presence of SARS-CoV-2 were evaluated. Of the 14 study participants, ten were symptomatic and tested positive for SARS-CoV-2 by RT-PCR, two asymptomatic individuals tested negative, and two other asymptomatic individuals did not undergo RT-PCR testing (Table 34). Patients 5 and 7, which tested positive by RT-PCR from nasopharyngeal swabs, were treated with the protocol from Example 5 above (Hydroxychloroquine, Azithromycin, vitamin C, vitamin D, and zinc for 10 days prior to fecal collection). Similarly, after positive nasopharyngeal swab, patient 13 was treated with vitamin C, vitamin D, and zinc for 10 days (the same protocol as noted above in Example 5) before fecal collection. The concordance of SARS-CoV-2 detection by enrichment NGS from stools among positive non-treated patients tested by RT-PCR nasopharyngeal analysis was 100% (7/7). Patient 8, who did not undergo nasopharyngeal analysis, tested positive for SARS-CoV-2 by NGS. The three patients (5, 7, 13) that received treatment prior to providing fecal samples, all tested negative by NGS. Asymptomatic patients 2 and 9, who tested negative by nasopharyngeal swab, were also negative by NGS, as was asymptomatic patient 14. Table 34 outlines the symptoms and SARS-CoV-2 testing results.

Table 34

[00182] All fecal samples analyzed by enrichment NGS from positive patients by RT- PCR, achieved 100% genome coverage of SARS-CoV-2 except for patient 3 which had 45%, and patient 10 which had 93% coverage. Table 35 outlines the enrichment NGS metrics.

Table 35

[00183] The total number of SARS-CoV-2 mapped reads for patients 1, 3, 4, 6, 8, 10, 11, and 12 were 465645, 5984, 131582, 793603, 496852, 5929, 1270734, and 38256 respectively. The mean read depths of SARS-CoV-2 for patients 1, 3, 4, 6, 8, 10, 11, and 12 were 1129.8x, 31.7x, 318.6x, 1924, 6x, 1206.7x, 15.5x, 3075.3x, and 92, 7x, and respectively. The read depths at specific coordinates along the SARS-CoV-2 genome for each patient are captured in Figures 5A-5H. Whole genome alignment of SARS-CoV-2 in patients 1, 3, 4, 6, 8, 10, 11, and 12 (respectively) as identified by One Codex’s SARS-CoV-2 analysis pipeline. The x-axis depicts the genomic coordinates as aligned to the MN908947.3 reference genome, and the y-axis represents the read depth at specific loci.

[ 00184] Following alignment and mapping of SARS-CoV-2, patient genomes were compared to the Wuhan-Hu-1 (MN90847.3) SARS-CoV-2 reference genome via One Codex’s bio informatics pipeline to identify mutational variations. This analysis identified nucleotide variants at positions nt241 (C → T) and nt23403 (A → G) across all positive patients, and variants at positions nt3037 (C → T) and nt25563 (G → T) in seven of the eight patients (Table 3). Interestingly, patients 8, 11, and 12 harbored the same set of variants, as did patients 4 and 6 (who were kindred). Unique variants not identified in any of the other individuals were detected in patients 1, 3, 6, and 10, with patient 3 harboring the most distinct SARS-CoV-2 genome with eight unique variants, followed by patient 1 with seven. Collectively, there were thirty-three different mutations among the patients in which SARS- CoV-2 was detected by whole genome enrichment NGS. Table 36 outlines the SARS-CoV-2 genomic positions, variant changes, and frequencies across the positive patient cohort.

Table 36

[00185] Discussion: Although previous studies have identified SARS-CoV-2 in fecal collections by RT-PCR, this study was able to report whole genome sequencing (WGS) of SARS-CoV-2 from stool samples. SARS-CoV-2 was identified in patients that tested positive by nasopharyngeal swab RT-PCR analysis and unique genomes in 62.5% of the NGS positive patients was observed. The overall homology among the genomes was high (99.97%), with variations identified in the ORF regions 1a, 1b, S, 3a, 8, and N. Of particular interest, was the adenine to guanine change in the S protein at position nt23403 which converts aspartic acid to glycine (D → G).

[00186] Conclusion: Next generation sequencing identified the SARS-CoV-2 whole genome sequence in 100% of patients with positive nasopharyngeal RT-PCR and did not detect it in treated patients, or those with negative rt-PCR. These results highlight the importance of metagenomic analysis of the SARS-CoV-2 viral genome.

[00187] Example 7: Randomized, Double-Blind, Placebo-Controlled Phase HA Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection

[00188] Objectives: Prevention of COVID-19, Lack of COVID-19 symptoms, and assessment of safety and tolerability [00189] Procedure: Screening Period (Days -7 to -1): Prescription of home health monitoring equipment that includes a thermometer, a pregnancy test if applicable, and a daily diary. There are two groups being studied: Arm 1 and Arm 2.

[00190] Arm 1 is prescribed the following antimicrobials: hydroxychloroquine 200mg twice a day for 1 day only, vitamin C 300QIU per day for 12 weeks, vitamin D 3000IU per day for 12 weeks, and zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 mg if GI upset occurs. The hydroxychloroquine is to be taken first thing in the morning as soon as subject has eaten and again right before bed, and must be separated from vitamin dose by at least 2 hours.

[00191] Arm 2 is prescribed the following antimicrobials: Placebo twice a day for 1 day- only, vitamin C 3000IU per day for 12 weeks, vitamin D 3000IU per day for 12 weeks, and zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 mg if GI upset occurs.

[00192] Day 1: Patient is called to teach them how to use the diary in the EDC, discuss the medication regimen, and answer any questions they may have. Patient takes pregnancy- test if applicable, collects a temperature reading, completes their diary, and takes the prescribed treatment regimen. Table 37 outlines the prescribed treatment regimen for Day 1.

Table 37

[00193] Day 2: Patient collects a temperature reading, completes their diary, and is called on the phone for assessment of any adverse events or serious adverse events, assessment of any COVlD-19 symptoms, the list of prior and concomitant medications is updated, any questions the patient has are answered, and the patient takes their prescribed treatment regimen. Table 38 outlines the prescribed treatment regimen for Day 2.

Table 38

[00194] Days 3-10: Patient collects a temperature reading, completes their diary, and takes their prescribed treatment regimen. Table 39 outlines the prescribed treatment regimen for Days 3-10.

Table 39

[00195] Day 14: The patient is called for instruction on how to collect a nasal swab and package for shipping, assessment COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have.

[00196] Week 3: The patient is called for assessment of any adverse events or serious adverse events, assessment of any COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have. The patient takes a temperature reading, completes their diary, and takes the prescribed treatment regimen. [00197] Table 40 outlines the treatment regime for week 3.

Table 40

[00198] Week 4: The patient is called for assessment of any adverse events or serious adverse events, assessment of any COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have. The patient takes a temperature reading, completes their diary, and takes the prescribed treatment regimen. The patient also collects a nasal swab.

[00199] Table 41 outlines the treatment regime for week 4.

Table 41

[00200] Weeks 5-11: The patient is called weekly for assessment of any adverse events or serious adverse events, assessment of any COVID-19 symptoms, updating their list of prior and concomitant medications, and answering any questions they may have. The patient takes a weekly temperature reading, completes their diary, and takes the prescribed treatment regimen.

[00201] Table 42 outlines the treatment regime for weeks 5-11.

[00202] Week 12: The patient presents to the clinic (or video conference) for evaluation that includes assessment for adverse events and serious adverse events, updating their list of prior and concomitant medications, a physical exam, nasal swab collection and COVlD-19 sample collection.

[00203] Samples for COVTD-19 testing are collected using synthetic swabs with plastic shafts. Nasal swabs are collected and immediately placed into a sterile vial with 2-3 mL of viral transport media. The vials are placed into biohazard bags, boxed up, the box sterilized, and picked up for shipment to the central laboratory. Samples are tested by RT-PCR.

[00204] Table 43 presents the schedule of events for Example 7.

Table 43

[00205] Regarding Table 43: The Zinc may be reduced to 25mg if GI upset occurs, phone/ video calls to the patient occur weekly during Weeks 2-11, and vitals in-clinic include height, weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate, temperature, and oxygen saturation.

[00206] Statistical Analysis: The treated patients in this study are compared to the placebo group. Measurements include PCR test results, presence or absence of symptoms, and symptom severity.

[00207] The change of these measurements from the end to the baseline (post-pre) are used as the primary outcome, for example, μe = μe1 - μe0, where μe1 and μe0 are the outcome of patients from the treatment group at the end and at baseline, respectively.

[00208] H₀:Δ≤δ₀ against H_a:Δ>δ₀ whereδ₀ is a clinically meaningful threshold to measure the disease symptoms. In this study, that meaningful threshold is calculated as mean change in clinical symptoms as recorded in the diary, from baseline through week 12. Each category in the diary is assigned a number, 0 for None, 1 for Mild, 2 for Moderate and 3 for severe. Each category is analyzed independently and as a group. [00209] Categorical variables are summarized by presenting the number (n) and percent (%) of subjects in each category. All Statistical tests for the analysis are performed using the p<0.05 level of significance. All confidence intervals are one-sided. [00210] Since these are healthcare workers who are exposed to COVID-19 at every shift, efficacy is determined by RT-PCR testing, as well as the presence or absence of symptoms as recorded in the patient diary via EDC.

[00211] Example 8: Method of Treating COVID-19 Infection with Ivermectin (ZIVERDOX)

[00212] A total of 6 patients infected with COVID-19 were treated as follows:

[00213] Day 1: 12-18 mg/day ivermectin, 200 mg, Doxycycline twice a day, 250- 10,000mg/ day Vitamin C, 1,000-100,000 IU/day Vitamin D, and 5mg-100mg/day Zinc [00214] Days 2 and 3: 200 mg Doxycycline twice a day, 250-10,000mg/ day Vitamin C, 1,000-100,000 IU/day Vitamin D, and 5mg-100mg/day Zinc

[00215] Day 4: 12-18 mg/day ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc [00216] Days 5, 6 and 7: 200 mg Doxycycline twice a day, 250-10,000mg/day Vitamin C, 1,000-100,000 IU/day Vitamin D, and 5mg-100mg/day Zinc

[00217] Day 8: 12-18 mg/day Ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc [00218] Days 9 and 10: 200 mg Doxycycline twice a day, 250-10,000mg/ day Vitamin C, 1,000-100,000 IU/day Vitamin D, and 5mg-100mg/day Zinc [00219] All 6 patients tested positive for COVID-19 antibodies at day 5

[00220] All 6 patients tested negative PCR at days 5-7.

[00221] Basic information about the 6 patients is shown in Table 44.

Table 44 [00222] Example 9: Study evaluating method of prevention (ZINCD+H)

[00223] As of January 14, 2021, a total of 91 individuals have been treated with the method of prevention of the claimed invention. These 91 individuals were high risk either from potential exposure at work or from living with people who had tested positive for COVID-19. Of those 91 individuals, 59 individuals gave consent for the test information to be released. Of those 59 individuals, 56 individuals had negative test results, two individuals had positive test results but were asymptomatic, and one individual had an invalid test result after receiving the prevention protocol.

[00224] In view of the above, it can be said that 58 out of the 59 individuals were successfully treated with the prevention protocol. That is a success rate of about 98%.

[00225] Table 45 details the information presented above. In Table 45, the results are color coded as follows:

Table 45

[00226] As shown above, the prevention protocol of the claimed invention is extremely effective.

[00227] Example 10: Study Evaluating Methods of Treatment and Prevention

[00228] In a second selection of studies, 25 different households/infection events were momtored/treated, where at least one person tested positive for COVID-19, and at least one housemate/family member/attendee was treated with a prevention protocol of the claimed invention. Specifically, there were 155 individuals total in the 25 households/events, with 75 of those 155 individuals testing positive for COVID-19, and the remaining 80 individuals were given at least one of the prevention protocols of the claimed invention.

[00229] The treatment protocol was HAZDPAC = Hydroxychloroquine, azithromycin, vitamin C, vitamin D and zinc administered as noted above in Example 3.

[00230] The prevention protocols included:

[00231] ZIVERDOX = Ivermectin, doxycyclin, vitamin C, vitamin D, and zinc administered as discussed above in Example 8.

[00232] ZTNCD = zinc, vitamin C, and vitamin D administered as noted above.

[00233] ZINCD+H = zinc, vitamin C, vitamin D, and hydroxychloroquine administered as noted above. Table 46 documents all of the data summarized above.

[00235] In all 25 households/events, all 80 individuals who were treated with the prevention protocols tested negative for COVID-19 via PCR at 3 months post exposure and tested negative for the presence of antibodies. Accordingly, none of the housemates/attendees in all 25 households/events ever became infected with COVID-19, despite living with at least one, and some cases multiple, infected individuals,

[00236] Having thus described the invention, it should be apparent that numerous structural modifications and adaptations may be resorted to without departing from the scope and fair meaning of the instant invention as set forth herein above and described herein below by the claims.

[00237] While particular forms of the invention have been illustrated and described, it will also be apparent to those skilled in the art that various modifications can be made without departing from the spirit and scope of the invention.

[00238] Although the present invention has been described in considerable detail with reference to certain preferred embodiments, other embodiments are possible. The forgoing description is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. The steps disclosed for the present methods, for example, are not intended to be limiting nor are they intended to indicate that each step is necessarily essential to the method, but instead are exemplary steps only. Therefore, the scope of the appended claims should not be limited to the description of preferred embodiments/methods contained in this disclosure. All references cited herein are incorporated by reference. Insofar as the description above and the accompanying drawings disclose any additional subject matter that is not within the scope of the claims below, the inventions are not dedicated to the public and the right to file one or more applications to claim such additional inventions is reserved.

Claims

WHAT IS CLAIMED IS:

1. A method of preventing COVID-19 infection in an individual, the method comprising the steps of: a) providing an individual that is not infected with COVID-19; b) administering four antimicrobials to the individual, wherein the antimicrobials comprise: i) administering chloroquine or hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg: ii) administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; iii) administering vitamin D in a daily dosage range of 1,000 IU to 100,0001U; and iv) administering zinc in a daily dosage range of 5 mg to 100 mg. v) monitoring the individuals condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

2. The method of claim 1, wherein step b) comprises: a) administering, on day 1 : i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C: iii) 3,000 IU of vitamin B; and iv) 50 mg of zinc; and b) administering on day 2: i) 3,000 mg of vitamin C; ii) 3,000 IU of vitamin D; and iii) 50 mg of zinc.

3. The method of claim 1, wherein step b) further comprises before step v), administering ivermectin in a daily dosage range of 12 mg to 18 mg.

4. The method of claim 1, wherein step b) further comprises before step v), administering doxycycline in a daily dosage amount of 400 mg.

5. A method of preventing COVID-19 infection in an individual, the method comprising the steps of: a) providing an individual that is not infected with COVID-19; b) administering four antimicrobials to the individual, wherein the antimicrobials comprise: i) hydroxychloroquine; ii) vitamin C; iii) vitamin D; and iv) zinc; and c) monitoring the individuals condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

6. The method of claim 6, wherein step b) comprises: a) administering hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; b) administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; c) administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and d) administering zinc in a daily dosage range of 5 mg to 100 mg.

7. The method of claim 6, wherein step b) further comprises administering ivermectin in a daily dosage range of 12 mg to 18 mg.

8. The method of claim 6, wherein step b) further comprises administering doxycyeline in a daily dosage amount of 400 mg.

9. The method of claim 6, wherein step b) comprises: a) administering, on day 1 : i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc; and b) administering on day 2: i) 3,000 mg of vitamin C; ii) 3,000 IU of vitamin D; and iii) 50 mg of zinc.

10. A method of treating an individual infected with COVID-19, the method comprising the steps of: a) providing an individual infected with COVID-19; b) administering five antimicrobials to the individual, wherein the antimicrobials comprise: i) administering hydroxychloroquine in a daily dosage range of 200 mg to 1,000 mg; ii) administering azithromycin in a daily dosage range of 250 mg to 500 mg; iii) administering vitamin C in a daily dosage range of 1,000 mg to 10,000 mg; iv) administering vitamin D in a daily dosage range of 3,000 IU to 40,000 IU; and v) administering zinc in a daily dosage range of 25 mg to 75 mg. c) monitoring the individuals condition over a pre-determined period of time to determine whether the individual is no longer infected with COVlD-19.

11. The method of claim 10, wherein step b) further comprises vi) administering ivermectin in a daily dosage range of 12 mg to 18 mg.

12. The method of claim 10, wherein step b) further comprises administering doxycycline in a daily dosage amount of 400 mg.

13. The method of claim 11, wherein step b) comprises: a) administering, on day 1: i) 400 mg of hydroxychloroquine; ii) 500 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; b) administering daily, on days 2 to 5: i) 400 mg of hydroxychloroquine; ii) 250 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; and c) administering daily, on days 6 to 10: i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc.

14. The method of claim 15, wherein step c) of administering on days 6 to 10 further comprises administering 250 mg of azithromycin.

15. A method of treating an individual infected with COVID-19, the method comprising the steps of: a) providing an individual infected with COVID-19; b) administering five antimicrobials to the individual, wherein the antimicrobials comprise: i) hydroxychloroquine; ii) azithromycin; iii) vitamin C; iv) vitamin D; and v) zinc; and c) monitoring the individuals condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

16. The method of claim 15, wherein step b) further comprises step administering ivermectin in a daily dosage range of 12 mg to 18 mg.

17. The method of claim 15, wherein step b) further comprises administering doxvcyc!ine in a daily dosage amount of 400 mg.

18. The method of claim 15, wherein step b) comprises: a) administering hydroxychloroquine in a daily dosage range of 200 mg to 1,000 mg; b) administering azithromycin in a daily dosage range of 250 mg to 500 mg; c) administering vitamin C in a daily dosage range of 1,000 mg to 10,000 mg; d) administering vitamin D in a daily dosage range of 3,000 IU to 40,000 IU; and e) administering zinc in a daily dosage range of 25 mg to 75 mg.

19. The method of claim 13, wherein step b) comprises: a) administering, on day 1 : i) 400 mg of hydroxychloroquine; ii) 500 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; b) administering daily, on days 2 to 5: i) 400 mg of hydroxychloroquine; ii) 250 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; and c) administering daily, on days 6 to 10: i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C: iii) 3,000 IU of vitamin B; and iv) 50 mg of zinc.

20. The method of claim 19, wherein step c) of administering daily, on days 6 to 10, further comprises administering one dose of 250 mg of azithromycin.