FMTVDM Quantitative Nuclear Imaging finds Three Treatments for SARS-CoV-2

Introduction: The SARS-CoV-2 pandemic of 2019 represents the third significant infection from a corona virus during the last two decades; this time producing a pandemic with more than a million deaths due to the immune InflammoThrombotic Response (ITR) to the virus. This investigation studied 10 different treatments and 52 treatment combinations to determine if there is an effective treatment regimen for SARS-CoV-2.


Introduction
During the last two decades there have been three major corona viruses that have impacted world health -SARS, MERS and SARS-CoV-2, with SARS-CoV-2 colloquially known as Covid- 19. The later has resulted in a pandemic with more than 34-million cases and over 1-million deaths world-wide due to the InflammoThrombotic Response (ITR) produced by the body's immune response to the virus particularly problematic in those who are either immune naive or have comorbidities associated with a hyper inflammatory response resulting in an increased inflammation and thrombosis [1,2] as shown in Figure 1 [2]. The rapid dissemination of SARS-CoV-2 and the lack of preparedness exposed a weakness in the medical response to such pandemics worldwide. Absent a specific treatment to this virus clinicians have independently set out to investigate a variety of treatments based upon differences in survival rates and response to intubation. However, these efforts have exposed both a haphazard approach to medicine, prescribing treatments in the absence of scientific evidence, as well as the political issues associated with the investigation of SARS-CoV-2 origin and treatment.
The interactions between the multiple components of the immunologic response to disease -in this instance SARS-CoV-2 -and the consequential release of cytokines, interleukins, the complement cascade and clotting factors, result in an InflammoThrombotic Response (ITR) that when not adequately regulated can produce significant inflammation including pulmonary edema and thrombosis.
This investigation looked at 10 different treatments coupled with a) Efforts to reduce the use of ventilators promoting prone positioning or alternative methods of improved oxygenation to reduce ventilator deaths associated with ARDS [3,4], b) Immune system augmentation using associated vitamins and minerals demonstrated to be important for best case scenario immune response [2] along with supplementation of magnesium and other medications [5] to reduce problems Four, a failure to statistically analyze these outcomes in a manner that allows measurement of the effect of each drug and drug combinations.

Inpatient Treatment
Patients who were deemed to have failed outpatient treatment and required admission to hospital followed the protocol shown in  1800 individuals who were PCR positive for SARS-CoV-2 were enrolled in the study. Among these individuals physicians began treating 953 with one of four hydroxychloroquine (HCQ) treatment regimens as defined in Tables 3A and 3B. Of these 795 (83.4 %) responded favorable and did not require hospital admission. The remaining 158 (16.6 %) were admitted to hospital. Thirty-nine of these patients were admitted into Phase I of the study along with 301 individuals who had not received treatment as outpatients. The remaining 119 patients who failed HCQ outpatient treatment were admitted to Phase II along with 42 other individuals who had not received prior treatment and required admission. The outcomes of the patient responses to outpatient aminoquinoline treatment are shown in Tables 1,2,6,11. An additional 847 patients did not receive outpatient treatment. Of these 504 (59.5 %) did well; however, 343 (40.5 %) required admission. Of these 301 were assigned to Phase I, and 42 were assigned to Phase II of the study. Three hundred and one patients who had not received outpatient treatment were enrolled in Phase I. The first two horizontal rows show the ten initial single treatment arms -each of which is represented by a specific color that continues throughout the flow diagram. Only treatment arm 11 (Convalescent Plasma) was not provided as an initial treatment as explained in the text of the manuscript. The solid colored arrows from row one (Treatments 1-5) show the next sequential treatment added if the first treatment failed to successfully treat SARS-CoV-2. Failure to successfully treat SARS-CoV-2 after a treatment found in horizontal line two, resulted in an additional treatment being added in horizontal treatment line 3. The connections between the treatments in line two and three are shown by the dashed color line associated with the treatment color in horizontal treatment line two and three. Each treatment box shows the number of patients treated with the treatment regimen and the success of treatment. E.g. In row one, the second Treatment group is Treatment (Tx) 2. This is the combination of Hydroxychloroquine and Doxycycline. Twenty-nine patients received this treatment and all failed with 0 % success. This Treatment group is recorded in red print with solid red arrows leading to multiple second line serial drugs -noted by the solid red arrows -being added to the regimen. One of these red arrows leads straight down to Treatment (Tx) 7 (Tocilizumab) in the second row of drug treatments. Tx 7 is also in red print and the lined arrows leading away from it are dashed red lines. While Tx 7 was also used as a first line drug, the second set of numbers show the outcomes when Tocilizumab is added as an additional second drug. On the first line of second line treatments (Tx), the second group noted reads "4 from Tx 2" meaning there were 4 patients who had received Treatment 2 (Hydroxychloroquine and Doxcycline) who were then treated with the addition of Treatment 7 (Tocilizumab). Of the 38 total patients receiving Tocilizumab as an additional second line treatment 31 (81.6 %) responded favorably to treatment. However, seven did not. Of these seven patients, dashed red arrow lines lead from Tx 7 to a third drug Treatment added to the regimen. One of these red dashed lines flows to the third line of Treatments including Treatment 9 (third from left) in blue print. Treatment (Tx) 9 is Interferon a-2b. In this box you will see the results of Interferon a-2b being used as second and third line Tx. [Its use as a first line treatment is noted in the second line of drug treatments; also in blue print.] Under the 3 rd Tx line the second item reads "2 from Tx 2,7" denoting there were two patients who previously received Treatment 2 then Treatment 7, who were now receiving a third Treatment 9 (Interferon a-2b). As noted four of the patients receiving the triple drug treatment with Interferon a-2b, including the two receiving Treatments 2,7,9; responded successfully (100 %). Tables 7 & 8 provides the tabulated information found in Figure 3. Phase II of the study-initiated treatment focusing on reducing the ITR of SARS-CoV-2 patients. Treatment options consisted of multi-drug combinations or the administration of methylprednisolone. Of the 161-patients enrolled in Phase II, 119 had failed outpatient HCQ treatment and were randomly assigned to receive either a combination treatment of Treatments 5, 7 and 9, or the combination treatment of Treatment 7 and 9. Alternatively patients were randomly assigned to receive Treatment 8. An additional 42-patients who had not received a HCQ outpatient treatment were randomly assigned to these same three groups or to receive treatment 4 or 5. During Phase II of the study only those who initially received treatment 4 or 5 required the addition of a sequential treatment and they were randomly assigned to receive either Treatment 8 or the combination Treatment of 7 and 9. The outcomes of the treatment success for these patients are shown in Table 9.

Quantitative And Serial Determination Of Sars-Cov-2 Severity Prior To Initiating Hospital Treatment Detailed
In Tables 3A & 3B Determination of the severity of SARS-CoV-2 using nuclear imaging has become a major and the newest tool for clinicians [30].
In this study the quantified nuclear imaging method used [26] was the Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) permitting measurement of tissue changes in regional blood flow and metabolism resulting from SARS-CoV-2 and the ITR to the virus as shown in Figure 5. Comparison studies using FMTVDM for other disease states [30] has permitted the differentiation of tissue changes showing progression of changes resulting from increasing regional blood flow and metabolism shown in Figure 6 with progressive worsening of infectious and inflammatory diseases.  FMTVDM quantitative measurements of the severity of SARS-CoV-2 corona virus pneumonia (CVP) associated changes in regional blood flow and metabolism were obtained for each inpatient before and after each period of treatment to determine treatment success. Regions-of-interest (ROIs) were obtained and quantified. The greatest FMTVDM value was reported for each patient study. In this example the greatest FMTVDM measured value was 261. Serial studies were obtained and used to determine measured treatment success. Successful treatment was defined as a reduction in FMTVDM of ≥ 25 or a value of ≤ 150. The results are shown in Tables 4 & 10. Figure 6: Measurement of changes in regional blood flow and metabolism seen with sequential changes in tissue [27].
Quantitative changes in regional blood flow and metabolism resulting from SARS-CoV-2 and the associated InflammoThrombotic Response (ITR) can be non-invasively measured using FMTVDM. Increased FMTVDM values proceeding from 150 to 250 demonstrate progressive worsening of disease. Normal pulmonary tissue is associated with FMTVDM values of less than 150.   Correlational changes seen between FMTVDM, Ferritin and IL-6 over the course of the study are shown in color scale with increased correlations as determined by Pearson's analysis as shown. The correlation between Ferritin and FMTVDM was 0.673, and 0.718 between FMTVDM and IL-6.

Successful Treatment Outcomes for Inpatients
Successful treatment outcomes were defined using the quantitative measurements of FMTVDM with a reduction of ≥ 25, or a level of < 150, Ferritin levels < 270 ng/ml for men and < 160 ng/ml for women, and an IL-6 level of < 5 pg/ml.

Additional Diagnostic Studies
12-lead electrocardiograms were obtained every three days with measurement of QTc intervals. The final analysis of any electrocardiogram and treatment decision was made by Cardiology.
Additional telemetry monitoring provided interval monitoring and information. Additional blood work was routinely performed with morning labs except for the initial blood work obtained at the time of admission. In addition to Ferritin and IL-6 levels patients had daily CBCs with differential, liver and renal function along with fasting glucose levels. Due to the volume of blood obtained, venous samples were obtained in micro vacutainers. Additional testing was performed per hospital protocol.

Medication Inpatient Treatment Arms
During Phase I of the study patient treatment arms were different dependent upon whether the patient was intubated (Table 3B) and unable to take medications orally or not (Table   3A). Patients who were intubated and later extubated continued to receive the intubated medications to maintain consistency.
Randomization of treatments was limited only by the exclusion of Treatment 5 from intubated patients, as Treatment 5 (Primaquine) is only available orally. One intubated patient was randomly assigned to treatment 5 and was subsequently re-randomized to another treatment group providing for intravenous administration of treatment. Additionally, convalescent plasma (Treatment 11) was not used as a first line treatment. It was included by randomized assignment as a second or third line treatment.
Random assignment of Treatments was done at each site. Further

Other Treatments
In addition to these treatments, patients also received immune support and bronchodilator treatment according to their treatment schedules in Tables 3A or 3B. Further treatments were determined by other medications the patients might have already been receiving or required by hospital protocol. The use of Esmolol [5] for heart rate and QTc regulation was determined by Cardiology.
Patients were also given 5000 units of subcutaneous Heparin every 12-hours to reduce formation of thrombi. This agent was selected over other anticoagulants due to the easy of reversal with Protamine Sulfate within minutes .

Oxygen and Respiratory Support
Every effort was made to avoid intubation and reduce further ARDS [3,4]. When ventilators were used the tidal volume was restricted to 5cc/kg Ideal Body Weight (IDW) with use of paralytic agents to prevent the patient from over breathing the ventilator. Per protocol other modalities included prone positioning, supplemental oxygen and Extracorporeal Membrane Oxygenation (ECMO) were given priority as shown in Table 5.

Infectious Disease Physician
Primarily responsible for treating SARS-CoV-2 infection and addressing secondary infections.

Cardiologist
Maintain the satisfactory patient rhythm and address any electrolyte and QTc abnormalities focusing on the use of b-1 selective agonist [5]. Attention to be given to complement cascade clotting and glycoprotein IIb/IIIa issues resulting from ITR. The Cardiologist is also to be at the patient's bedside when adenosine is delivered during FMTVDM imaging.

ICU-Pulmonologist
Guarantee adequate oxygenation, control of ventilator tidal volumes, prone positioning, nebulizer treatments including Atrovent and any other medications, provided by nebulizer. The ICU-Pulmonologist is responsible for determining intubation and extubation of patients.

Pharmacist
Guarantee that all medications are properly prepared with instructions for the rate of delivery and any and all monitoring needed to assure the safest and most effective delivery of the medications.

ICU Nurse and Staff
Guarantee that all medications are delivered according to instructions and not on an alternate delivery (e.g. q 8 hours, means every 8-hours, not three times a day).

Nuclear Technologist
Guarantee that all nuclear cameras are quantitatively calibrated at the beginning of the day. Make certain each patient's FMTVDM study falls at the same time of the patient's treatment regimen eliminating differences due to medications, movement, et cetera.

Others
Additional clinical personnel including Gastroenterologists, Nephrologists and Endocrinologists, along with ancillary personnel should be added to the SARS-CoV-2 clinical staff should patients have gastrointestinal, renal, or specific diabetic needs or concerns.

Statistical Analysis
Analysis of results included descriptive statistics including mean + standard deviations, Confidence Intervals (CI), range, and analysis between groups and group effects using student T-testing, Pearson's correlation, and one-way analysis of variance (ANOVA) using both Tukey and Bonferoni analysis for a more conservative analysis with statistical correction using Bartlett's statistic.

Results
From 16 April 2020 through 5 August 2020, 1800 study participants seen by clinicians in 7 countries and 23 study sites who tested positive for SARS-CoV-2 by PCR were enrolled for evaluation and treatment of SARS-CoV-2 and the ITR to the virus as shown in

Outpatient Outcomes
As patients entered the study, Figure 2 shows that they were initially seen as outpatients and divided into two groups. The first group of 847 (47%) people included those whose clinicians did not think they required treatment. Of these 504 (59.5 %) were determined to be recovering on follow up evaluation 3-5 days  Table 6 was 74.2 to 97.9 %. Among patients successfully treated as outpatients, Figure 2 shows the percentages following each of the four treatment groups that were deemed to have successfully responded to aminoquinoline outpatient treatment, including 28.3 % of cases from Treatment 1; 21.4 % from Treatment 2; 23.8 % from Treatment 3; and 26.5 % from Treatment 4 including Primaquine. Table 5: Proven and proposed treatments based upon mechanism of action.

Viral Attachment and Replication
Innate T-cell Cytotoxic Response Oxygenation and ARDS** Adaptive Humoral (Antibody) Response.
Ascorbic Acid (Vit. C) Improved immune response. Improved immune response Atrovent β-2 bronchodilator to increase airway diameter and reduce bronchial secretions without the increase in heart rate and potential QTc prolongation associated with b-1 agonists.

Azithromycin
Inhibition of viral protein translation.

Clindamycin
Inhibition of viral protein translation.

Convalescent Plasma
Provides passive immunity reducing potential ITR although the increased fibrinogen levels associated with plasma transfusions may increase thrombus formation.
Cyanocobalamin (Vit. B12) Improved immune response and reduction of inflammatory homocysteine.
Improved immune response and reduction of inflammatory homocysteine.

Doxycycline
Inhibition of viral protein translation.
Folate (Vit. B9) Improved immune response and reduction of inflammatory homocysteine.
Improved immune response and reduction of inflammatory homocysteine.
Inhibits glycoprotein IIb/IIIa thereby interfering with thrombus formation.

Hydroxychloroquine
Inhibits viral attachment at ACE2 receptor site.
Reduces the production of pro-inflammatory cytokines.

Hydroxychloroquine
Enhances entry of zinc through zinc ionophore.

Hydroxychloroquine
Increases cytosol pH to reduce removal of viral envelope required for replication.
Increases cellular pH decreasing major histocompatability complex (MHC) viral antigen presentation to b-cells thereby decreasing release of inflammatory cytokines.

Hydroxychloroquine
Enhances production of Type I Interferons.

Interferon a-2b
Interferes with viral replication.
Reduction of IL-6 levels.
Reduction of IL-6 levels.

Magnesium
Improved immune response and reduction of QTc prolongation potential.
Improved immune response and reduction of QTc prolongation potential.
Oxygen (supplemental) other than ventilator.* [Prone positioning, BiPAP, Reduced inflammatory stretching of alveoli and subsequent worsening of ARDS.

Primaquine
Inhibits entry of Virulent Newcastle Disease (VND) virus.

Primaquine
Inhibits viral RNA replication and protein translation.

Pyridoxine (Vit. B6)
Improved immune response and reduction of inflammatory homocysteine.
Improved immune response and reduction of inflammatory homocysteine.

Zinc
May reduce ACE2 receptor activity.

Zinc
Interferes with RdRP and polyprotein transcription.
Zinc Improved immune response. Improved immune response.
***Originally included in study design with prior pre-clinical studies in animals suggesting a possible mechanism of action inhibiting ARDS with H5N1 virus. Excluded from study after IRB review and consideration of concerns for angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Included in this table for completeness.
****RdRP = RNA dependent RNA polymerase. The outpatient failures represented 11.5 % of the Phase I patients and 73.9 % of those in Phase II. Table 2 shows the severity of SARS-CoV-2 upon admission for patients who did and did not receive outpatient therapy. There were no statistical differences between those who were admitted and failed aminoquinoline treatment and those who received no pre-hospital treatment. The results of the two groups are pooled together in Table 4. Outpatients did not undergo diagnostic measurement of FMTVDM, Ferritin or IL-6 to quantitatively measure treatment results. Their physicians subjectively determined their outcomes.

Phase I outcomes-analysis of sequential single drug treatments added in queue.
Of the 501 patients admitted to hospital, 340 (67.9 %) were I, and II Treatments, were not altered due to glucose; liver and renal function tests, or QTc, and they consequently will not be discussed further here.

Treatment
As shown in Figure  Interferon a-2b.   Table 7 show the flow and treatment results of patients who were enrolled in Phase I of the study after failing to improve as outpatients without treatment. As shown in Figure   2, 301 (88.5 %) of the Phase I patients were individuals who had received no outpatient treatment and were admitted to hospital for further evaluation and treatment. This group of patients is Table 7. Patients enrolled without prior outpatient treatment were randomly assigned to one of nine first line treatments, and one of ten when more than one treatment was added to the treatment regimen. This tenth treatment was defined as Treatment 11 (Convalescent Plasma). The original tenth treatment (Losartan) noted in Table 5 was thought to have a potential benefit based upon animal models but was excluded by the IRB given concerns about the potential increase in ACE2 receptors and lack of further potential information when the study was initiated.
Of the 301 patients in this part of Phase I, 38 (12.6 %) were randomly assigned to Treatment 1 (Hydroxychloroquine, Azithromycin Methylprednisolone leaving only 2 to require a third drug including one who received Treatment 7 (Tocilizumab) and one who received Four (13.8 %) of the 29 patients received Treatment 7 (Tocilizumab) as the second drug with a 50 % response rate. The two patients who did not respond to the combination of Treatment 2 and 7, both responded to Treatment 9 (Interferon a-2b). Ten  Of the 301 patients in this part of Phase I, 39 (13 %) were initially started on Remdesivir (Treatment 6). Of these 11 (28.2 %) responded to Remdesivir as the first line drug treatment leaving 28 (71.8 %) requiring a second drug to be added to Remdesivir.
Of the 11 who did respond, 6 (54.5 %) were from Belgium. Of the 28 people who did not respond to Remdesivir, 7 received  Table 8. As shown in Table 7 Table 9 shows the details of Phase II.

Treatment
One hundred nineteen patients who had received Treatments

Treatment 4
No pre-hospital treatment patients 9 0 (0 %)   Table   9. In addition to the three treatments focusing on the immune ITR response to SARS-CoV-2, these patients were also randomized to (Interferon a-2b) added (in red) to the regimen. In all 7 (100 %) of the cases, patients were successfully treated. Note: ## Treatment designations include the sequence by which treatment drugs were added; e.g. Treatment 1,6 means the first treatment was Treatment 1 followed by the addition of Treatment 6; Treatment 4, (7,9) means the first Treatment was Treatment 4 followed by the addition of combination Treatments 7 and 9.

Collectively Looking at Phase I And II to Evaluate
The Statistical Significance of The 52-Treatment Regimens.
The cumulative 52 Treatment regimens resulting from the 10 individual Treatments applied in Phases I and II provided the measureable outcomes of the various drug treatments and treatment combinations that were then statistically compared as shown in Table 10. Following the protocol established for determining when a treatment should be abandoned due to worsening of the patient as defined by an increase in FMTVDM of greater than 25 units, no treatments were abandoned. While some treatments provided no definable measureable benefit, their absence of detriment was defined as a possible stabilization of the patient to which additional treatment was then added per protocol.

Cov-2 Treatment(S)
The results of the sequential addition of treatment to prior treatment(s) resulted in 52-treatment combinations from the 10 Treatment Arms that were then statistically analyzed to determine treatment outcomes. Given an absence of statistical differences (p=NS) several treatments were combined for further statistical analysis as "Triple Drug Treatment." These combinations included a) Treatment 1 (Hydroxychloroquine, Azithromycin) to which two of the following Treatments 6-9 and 11 were added sequentially, b) Treatment 2 (Hydroxychloroquine, Doxycycline) to which two of the following Treatments 7-9, 11 were added sequentially,

c) Treatment 3 (Hydroxychloroquine, Clindamycin -No
Primaquine) to which two of the following Treatments 7-9, 11 were added sequentially, and finally d) Treatment 4 (Hydroxychloroquine, Clindamycin, Primaquine) to which two of the following Treatments 7-9 were added sequentially. When multiple ANOVA was applied to FMTVDM, Ferritin and IL-6, the absolute and measured changes in response to treatments were statistically significant at p < 0.0001.   Table 4 and  Table 8.

Quantitatively Finding Sars-COV-2 Treatment Response
The measured changes in IL-6 over the course of treatment for the various combinations of treatments are shown in Table   8. Differences between IL-6 and FMTVDM are displayed in red.
Like Ferritin, the changes in IL-6 lag behind those measured with FMTVDM although the lag is less pronounced than that of Ferritin. in Ferritin levels than FMTVDM or IL-6 as shown in Figure 6 & Table   6 where variability is standard deviation squared. The graphic displays the quantified mean standard ± deviation of FMTVDM, Ferritin and IL-6 measurements made on the day of admission (Day 0) as well as on Days 4, 7, and 10 where changes in SARS-CoV-2 infection and ITR were measured following sequential changes in treatment. Successful treatment outcomes were defined using the quantitative measurements of FMTVDM with a reduction of ≥ 25, or a level of ≤ 150, Ferritin levels < 270 ng/ml for men and < 160 ng/ml for women, and an IL-6 level of < 5 pg/ml. The tabulated results are shown in Tables 4 & 10. Each of the three deaths occurred on different treatments. When patient outcomes were initially analyzed to determine if there was a specific treatment -either outpatient or inpatient -that was associated with a difference in time to extubation or time to discharge, patients were evaluated looking at both outpatient and inpatient treatment regimens. As shown in Tables 10 & 12 there were obvious differences associated with specific treatments that were statistically significant at p < 0.0001.

Entered
Phase I

Rx 2
Failure Entered Phase II

Rx 3
Failure Entered Phase I

Rx 3
Failure Entered Phase II    The results were then clustered together based upon common factors as shown in Table 12 Table 12 for patients who had received prior aminoquinoline treatment as an outpatient, the time for recovery and discharge from hospital was approximately one week, and slightly more than two weeks for those who had not received outpatient treatment. There was no statistically significant difference (p = 0.5216) between the four treatments groups targeting the immune ITR associated with SARS-CoV-2, with each resulting in successful treatment and discharge on an average of 7-8 days.

Discussion
This study addressed several key issues important in defining the treatment of SARS-CoV-2, including the prevalence of those who did not require treatment in the outpatient setting as well as those who responded to treatment as outpatients using aminoquinoline treatments. Following failure to recover from SARS-CoV-2 -with or without outpatient treatment -patients were hospitalized for treatment. During the inpatient treatment patients were evaluated to determine what treatments or combinations of treatments provided a statistically significant treatment effect (Table 10)  Ferritin results showed a greater variability and thus less reliability.
IL-6 changes required 7-days to become statistically significant. As we believe this study demonstrates, successful treatment of SARS-CoV-2 requires diligent attention to addressing the ITR sooner than later and adjusting treatments based upon measured tissue and blood response.

It is important to clinically distinguish between Cytokine
Release Syndrome (CRS) and InflammoThrombotic Response (ITR). At first glance the biochemical responses appear to be similar with increases in both Ferritin and Interleukin-6 levels; however CRS defines the syndrome following car T-cell treatments where the body's immune system is being attacked by human interventiontreatment. In an ITR [2] as shown in Figure 1, the person's immune system is responding to an infectious process. In people with  there are other measures frequently discussed when looking at patient success or treatment failure. These include intubation rate, extubation rate, deaths and days to discharge. Among patients admitted and treated in this study several key points standout regarding these later factors. First, the more rapidly treatment is initiated to bring the ITR under control, the more successful the patients treatment course will be and the more likely they will not be intubated and if intubated, the more rapidly they will be extubated. They will also leave the hospital statistically sooner.
Secondly, the use of a multidrug treatment to address the ITR and/ or the use of substantial dosing of methylprednisolone -requiring a careful titration off the steroid -to reduce the ITR, will result in the patient responding to treatment significantly faster with earlier discharge. The patients who took one of the HCQ treatments as outpatients and were subsequently admitted for further treatment, at first appeared to have failed treatment; however, it was these individuals that had the fastest response when ITR therapies were initiated and they were discharged soonest. In contrast, patients

Limitations
This research can only address the outcomes of people seen by a medical doctor. It cannot address patients treated by physicians in the outpatient setting without being seen by the physician and undergoing PCR screening with a positive result, consequently it cannot determine how many people were symptomatic or asymptomatic at drive through PCR testing sites and their outcomes.
This study also cannot speak to smaller facilities that lacked the personnel and equipment to do the testing required for this study.
The decision of who was selected at each study site was determined on site along with the randomization of treatments. Individuals who were intubated prior to receiving treatment were excluded from Treatment Arm 5 (Primaquine) although this only involved one patient. Finally, once admitted and the outpatient treatment for SARS-CoV-2 was discontinued, there may have been some residual impact from the aminoquinolines due to the long half-life of these drugs; however, when compared with those who entered the study who had not received aminoquinolines there was no difference in outcomes.

Conclusion
This study established a rigorous assertive approach to treating and modifying SARS-CoV-2 treatments every three days. Rather than allowing patients to be treated with any given regimen for an extended period of time -given the absence of successful clinical trials and treatment -this study focused on rapidly adjusting treatment based upon measured changes in disease; specifically FMTVDM, Ferritin and IL-6 levels, in addition to conventional treatment monitoring. Using FMTVDM provided earlier measurement of treatment response allowing physicians the opportunity to act sooner to change treatments based upon tissue response to treatment. By taking this approach, treatments were added in 3-day intervals significantly reducing the time to treatment response. The lessons from Phase I lead to multi-drug regimens in Phase II following the same assertive approach. We believe the benefit of bronchodilator therapy and immune support beginning on day 1 cannot be underestimated both from an immune function and QTc cardiac perspective. The answer to the question,

Is there a treatment for SARS-CoV-2 is yes however it depends upon
where the patient is in the course of the disease. Accordingly patient treatment should focus on the stage of infection and immune response as shown in Figure 9. In the outpatient setting more than a quarter of the patients required no treatment as they were either asymptomatic or deemed to have very low risk and recovered without treatment. More than 40% of the outpatients were treated with an aminoquinoline and appear to have successfully been

Acknowledgment
FMTVDM is patented #9566037 to and owned by first author and was made available and provided without cost for the study.
There are no other funding sources to report.