BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible.Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%.A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed.ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives.Funded by The Bill & Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.
BackgroundAtypical clinical and imaging findings in Reversible Posterior Leukoencephalopathy Syndrome are recognized with increasing frequency.Case reportWe report a case of an adult in his 5th decade immunosupressed with methilprednisolone, tacrolimus and micophenolate who two months after renal transplantation, multiple infections and an episode of humoral rejection became hypertensive with severe headaches, visual field abnormalities, seizures, left hemiparesis and hemineglect.Computed Tomography scan of the brain showed a hypo dense lesion in the left occipital lobe. Ischemic stroke was diagnosed and aspirin and permissive hypertension were indicated. Twelve hours later he developed left sided motor seizures and cortical blindness. Magnetic Resonance Image showed hyper intensity in T2 and FLAIR in both occipital lobes and a small area of cortical restricted diffusion in Diffuson Weighted Images in the left occipital lobe. With a diagnosis of Reversible Posterior Leukoencephalopathy Syndrome his blood pressure was controlled with intravenous labetalol, and two days later the neurologic findings returned to baseline and most Computed tomography findings resolved.ConclusionThis case underscores that in the appropriate setting Reversible Posterior Leukoencephalopathy Syndrome should be suspected and the clinician should not be misled by atypical clinical or imaging findings. In contrast to other pathologies that resemble Reversible Posterior Leukoencephalopathy Syndrome, with the right and timely treatment, signs, symptoms and images can be completely reversible.
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