L-Arginine Supplementation Improves Reliance on Respiratory Support in Severe COVID-19 Patients

by | Dec 28, 2021 | 2021, Amino Acids, Arginine, COVID-19

Written by Chrystal Moulton, Staff Writer. 71.1% of patients assigned L-arginine versus 44.4% of patients assigned placebo showed reduction in respiratory support (P<0.01).

COVID-19Since the beginning of the pandemic, treatment of COVID-19 has been a critical challenge for hospital systems worldwide 1-3. Clinical evidence has demonstrated that the endothelium is a key target of COVID-19 affecting specifically, amino acid metabolism 4, 5. Researchers observed a decrease in plasma L-arginine levels and enhanced arginase activity in severe cases of COVID-19 6. In the current study, researchers tested oral supplementation with L-arginine versus standard of care in patients with severe COVID-19 infection 7.

This study was designed as a randomized, placebo controlled, double blind clinical trial. 210 patients admitted to the hospital with severe COVID-19 were screened for this trial. Presence of SARS-CoV-2 was confirmed through PCR testing. Patients were included in this trial if they presented all the following conditions: pneumonia confirmed by chest imaging, oxygen saturation of 93% or lower on room air, lymphocytopenia, and ratio of alveolar oxygen partial pressure to fractional inspired oxygen of 300 or less. Eligible patients were randomized to receive one bottle containing 1.66g of L-arginine or one bottle containing placebo. Patients were given their assigned protocol twice a day for the whole duration of hospitalization. Primary endpoint was reduction in respiratory support and secondary outcomes were time to lymphocyte number normalization, length of stay in hospital, and time to obtain a negative result on PCR COVID test. Both primary and secondary endpoints were evaluated at 10 and 20 days after randomization. Follow-up form was completed upon patient discharge or death, whichever occurred first.

Of 210 patients screened for this trial, 101 eligible patients were randomly assigned to either receive L-arginine plus standard of care (N =48) or placebo plus standard of care (N = 53). At the beginning of the trial, all patients were receiving oxygen, with or without non-invasive ventilation. The most common comorbidity was hypertension, coronary heart disease, and diabetes. At day 10 following randomization, 71.1% of patients assigned L-arginine versus 44.4% of patients assigned placebo showed reduction in respiratory support (P<0.01). Multivariate logistical regression showed the magnitude of association between L-arginine supplementation and reduction in respiratory support was 6.6 times higher in patients assigned to the treatment group compared to those assigned to the placebo group (OR= 6.62, P= 0.01). At 20 days post randomization, no significant difference was observed between the placebo group or the treatment group for reduction in respiratory support. Also, ratio of alveolar oxygen to fractional inspired oxygen was significantly better in the L-arginine group compared to placebo 10 days post randomization (P = 0.02) but not 20 days. The only secondary outcome showing statistical significance was length of stay in hospital. Median discharge in the L-arginine group was 25 days compared to 46 days in the placebo group (P <0.001). Multivariable regression analysis maintained the significance of the association between hospital discharge and L-arginine supplementation (HR= 41.6, P<0.0001). Total mortality was 13.9% in the intent-to-treat analysis (L-arginine: 6.3% & Placebo: 20.8%, P=0.035). Four serious adverse events were reported but considered unrelated to study treatment.

Severe COVID patients treated with L-arginine plus standard of care saw a reduction in the need for respiratory support compared to patients assigned the placebo. Furthermore, length of stay in hospital was significantly lower in L-arginine treated patients versus placebo. More clinical trials using a larger sample size will be needed to substantiate these findings.

Source: Fiorentino, Giuseppe, Antonietta Coppola, Raffaele Izzo, Anna Annunziata, Mariano Bernardo, Angela Lombardi, Valentina Trimarco, Gaetano Santulli, and Bruno Trimarco. “Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis.” EClinicalMedicine 40 (2021): 101125.

© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Click here to read the full text study.

Posted December 28, 2021.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. Paules CI, Fauci AS. COVID-19: The therapeutic landscape. Med (N Y). May 14 2021;2(5):493-497. doi:10.1016/j.medj.2021.04.015
  2. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. Jama. May 12 2020;323(18):1824-1836. doi:10.1001/jama.2020.6019
  3. Hall MD, Anderson JM, Anderson A, et al. Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit. J Infect Dis. Jul 15 2021;224(Supplement_1):S1-s21. doi:10.1093/infdis/jiab305
  4. Budinger GRS, Misharin AV, Ridge KM, Singer BD, Wunderink RG. Distinctive features of severe SARS-CoV-2 pneumonia. J Clin Invest. Jul 15 2021;131(14)doi:10.1172/jci149412
  5. Barberis E, Timo S, Amede E, et al. Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2. Int J Mol Sci. Nov 16 2020;21(22)doi:10.3390/ijms21228623
  6. Rees CA, Rostad CA, Mantus G, et al. Altered amino acid profile in patients with SARS-CoV-2 infection. Proc Natl Acad Sci U S A. Jun 22 2021;118(25)doi:10.1073/pnas.2101708118
  7. Fiorentino G, Coppola A, Izzo R, et al. Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis. EClinicalMedicine. Oct 2021;40:101125. doi:10.1016/j.eclinm.2021.101125