ACTIVATING ENDOGENOUS ANTIMICROBIALS TO TREAT SARS-COV-2 INFECTION
Provided herein are methods of treating COVID-19 in a subject in need thereof, comprising administering to the subject a 25-hydroxyvitamin D compound. Also provided herein are hard capsule dosage forms of 25-hydroxyvitamin. In aspects, the 25-hydroxyvitamin D is administered as a controlled release formulation, optionally an extended release oral formulation, such as Rayaldee® extended release calcifediol capsules. Methods of treating SARS-CoV-2 infection including reducing SARS-CoV-2 viral load are provided. Methods of treating SARS-CoV-2 infection including increasing an immune response are provided.
1 . A method of treating a SARS-CoV-2 infection, comprising administering to a subject in need thereof an effective amount of a sustained release formulation of a 25-hydroxyvitamin D compound to treat a SARS-CoV-2 infection,
wherein an effective amount comprises administering to the subject a loading dose of the sustained release 25-hydroxyvitamin D formulation followed by one or more maintenance doses of the 25-hydroxyvitamin D compound, wherein the loading dose is greater than about 500 μg and less than about 1200 μg, and wherein the loading dose provides a serum total 25-hydroxyvitamin D level of at least 60 ng/mL and up to 200 ng/mL within 24 hours,
and wherein the subject's anti-SARS-CoV-2 antibody level is increased by Day 7 of treatment, compared to placebo.
2 .- 13 . (canceled)
14 . The method of claim 1 , wherein the amount is effective to achieve a serum total 25-hydroxyvitamin D level of greater than 100 ng/mL in the subject.
15 . The method of claim 1 , wherein the serum total 25-hydroxyvitamin D level is maintained at an elevated level of greater than 60 ng/mL, for at least 7 days.
16 . The method of claim 1 , wherein the serum total 25-hydroxyvitamin D level is maintained at an elevated level of at least 60 ng/mL, for at least 14 days.
17 .- 19 . (canceled)
20 . The method of claim 1 , wherein the loading dose is at least or about 900 μg of the 25-hydroxyvitamin D compound, and wherein the loading dose raises the subject's serum total 25-hydroxyvitamin D level by 20 ng/mL to 30 ng/mL within 10 hours.
21 . The method of claim 20 , wherein the loading dose is divided over two or three days.
22 . (canceled)
23 . The method of claim 21 , wherein the loading dose is 300 μg per day for the first three days of treatment.
24 . (canceled)
25 . The method of claim 20 , wherein the one or more maintenance doses is greater than about 50 μg of the 25-hydroxyvitamin D compound, and wherein the maintenance doses are administered on a frequency less than daily.
26 . The method of claim 25 , wherein the one or more maintenance doses are administered weekly, twice a week or three times a week.
27 .- 31 . (canceled)
32 . The method of claim 1 , wherein the subject's vitamin D metabolite ratio (VMR, calculated as 100 times the ratio of serum 24,25-dihydroxyvitamin D 3 to serum 25-hydroxyvitamin D 3 ) is in a range of 4 to 12 in a first loading dose period and is in a range of 3 to 11 during a maintenance dosing period.
33 . The method of claim 32 , wherein the subject's VMR is less than 5, or less than 4.8 during a maintenance dosing period.
34 . The method of claim 32 , wherein the subject's VMR remains substantially constant or decreases over a period of at least 28 days, optionally during a maintenance dosing period.
35 . The method of claim 32 , wherein the subject is administered 25-hydroxyvitamin D by extended release, and the subject's rate of change of VMR over a 28 day period is less than the rate of change of VMR that would occur with a bioequivalent amount of the 25-hydroxyvitamin D administered by immediate release.
36 .- 41 . (canceled)
42 . The method of claim 1 , wherein the 25-hydroxyvitamin D compound comprises 25-hydroxyvitamin D 2 or 25-hydroxyvitamin D 3 , or a combination of 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 .
43 . The method of claim 42 , wherein the 25-hydroxyvitamin D compound is 25-hydroxyvitamin D 3 .
44 .- 103 . (canceled)
104 . The method of claim 1 , wherein the loading dose of 25-hydroxyvitamin D is administered in a fasting state; and wherein the subject remains in a fasting state for three hours after the loading dose is administered.
105 .- 159 . (canceled)
160 . A dosing regimen for treating a patient having or suspected of having a SARS-CoV-2 infection, comprising administering to the patient an extended release dosage form comprising a controlled release excipient and a pharmaceutically effective amount of 25-hydroxyvitamin D 3 and wherein the dosage form is administered in a maintenance dosing period in an amount of 30 to 70 μg/day and preceded by a loading dosing period in an amount in a range of 300 to 900 μg/day on days one, two or three of treatment, wherein the patient's vitamin D metabolite ratio (VMR, calculated as 100 times the ratio of serum 24,25-dihydroxoxyvitamin D 3 to serum 25-hydroxyvitamin D 3 ) remains substantially constant or decreases during the maintenance dosing period.
161 . The dosing regimen according to claim 160 , wherein the patient's VMR is in a range of 4 to 12 in the first loading dose period and is in a range of 3-11 during the maintenance dosing period.
162 . The dosing regimen according to claim 160 , wherein the patient's rate of change of VMR over a 28 day period is less than the rate of change of VMR that would occur with a bioequivalent amount of the 25-hydroxyvitamin D administered by immediate release.
163 . The dosing regimen according to claim 160 , wherein the loading dose is administered to the patient subject in a fasting state; and wherein the patient remains in a fasting state for three hours after the loading dose is administered.