LARGE BODY OF EVIDENCE supports a central role for lowering levels of low-density lipoprotein cholesterol (LDL-C) in the prevention of atherosclerotic cardiovascular disease. Randomized controlled trialshaveestablishedthatstatin-mediated reductions in LDL-C have a favorable effect on the incidence of cardiovascular events. 1-6 As a result, LDL-C lowering has become an integral component of therapeutic strategies in the prevention of cardiovascular disease. 7 In particular, the use of statins has become widespread. Recent studies have reported that highdosestatintherapyresultsinanincrementalbenefitcomparedwithamoderatelipidlowering strategy. 8-11 Some investigators havesuggestedthatstatinsalsohavepleiotropic properties, such as modulation of inflammationwithinthearterialwall,that maycontributetotheirbeneficialeffect. 12-14 Accordingly,mostauthoritiesandcurrent national guidelines emphasize reduction in LDL-C as the primary target for lipidlowering therapy.

IMPORTANCE There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. OBJECTIVE To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. INTERVENTION Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. OUTCOMES The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. RESULTS A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care.

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At 3 T, the effective wavelength of the RF field is comparable to the dimension of the human body, resulting in B 1 standing wave effects and extra variations in phase. This effect is accompanied by an increase in B 0 field inhomogeneity compared to 1.5 T. This combination results in nonuniform magnetization preparation by the composite MLEV weighted T 2 preparation (T 2 Prep) sequence used for coronary magnetic resonance angiography (MRA). A new adiabatic refocusing T 2 Prep sequence is presented in which the magnetization is tipped into the transverse plane with a hard RF pulse and refocused using a pair of adiabatic fast-passage RF pulses. The isochromats are subsequently returned to the longitudinal axis using a hard RF pulse. Coronary magnetic resonance angiography (MRA) at 1.5 T has shown promise for the assessment of significant coronary artery disease in proximal and mid segments of the coronary arteries (1). However, low signal-to-noise ratio (SNR) limits the utilization of this imaging technique for more distal and branching vessels at 1.5 T (1). At a higher magnetic field strength, an improved SNR is expected. However, the enhanced effect of magnetic field susceptibility leads to off-resonance effects, while B 1 inhomogeneity, tissue dielectric constants, body dielectric resonances, and increased specific absorption rate (SAR) are additional limitations that must be considered at higher magnetic field strength (2-8). Therefore, to take full advantage of higher field strength and clinically realize the improved SNR, a careful sequence design that minimizes these effects is necessary.Three-dimensional (3D), free-breathing coronary MRA techniques can be used to image the tortuous path of the coronary arterial tree with improved SNR relative to twodimensional (2D) approaches. However, 3D imaging results in a lower contrast between the coronary blood and the myocardium. To overcome this problem, the use of contrast agents (9 -12) or magnetization preparation schemes (13-17) have been proposed. T 2 Prep is used in 3D coronary imaging to increase the contrast between the coronary arterial blood-pool and the surrounding tissue (13,17,18). However, increased B 1 and B 0 inhomogeneities at higher magnetic field strength pose significant challenges to uniform T 2 preparation of the magnetization across the imaged volume, thereby limiting the value of coronary MRA in general. Therefore, a novel T 2 preparation scheme in which adiabatic pulses are used to achieve B 1 and B 0 insensitive contrast enhancement was developed. Numerical simulations and an in vivo study were performed to characterize the efficacy of the technique. METHODS Background