Quelle supplémentation en cas de COVID long ?

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Combining L-Arginine with Vitamin C Improves Long-COVID Symptoms: The Nationwide Multicenter LINCOLN Study
Raffaele Izzo Pharmacol Res . 2022 Jul 19;106360.

Introduction: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms.

Methods: We designed a nationwide multicenter clinical study (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), in which a survey assessing several symptoms that have been associated with Long-COVID was administered to COVID-19 survivors; effort perception was measured using the Borg scale. Patients were divided in two groups, with a 2:1 ratio: the first group included patients treated with L-Arginine + Vitamin C, whereas the second group was treated with a multivitamin combination (alternative treatment). Before administering the survey, patients completed 30 days of treatment.

Results: 1590 patients were initially enrolled, of which 1390 completed the study. Following a 30-day treatment with L-Arginine + Vitamin C, the survey revealed that patients in this treatment group had significantly lower scores compared to the other group. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p<0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm.

Conclusions: Taken together, our findings indicate that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of reducing its typical symptoms and improving effort perception.

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The first group included patients who were treated with 2 vials/day of Bioarginina® C ([b]L-Arginine 1.66 g in association with 500 mg of liposomal Vitamin C[/b], Damor, Naples, Italy). The second group (alternative treatment) was treated with a multivitamin combination (Vitamin B1: 388 mg; Vitamin B2: 443 mg; Nicotinamide:18 mg; Folic Acid: 200 µg; Pantothenic acid: 2493 g; Vitamin B6: 831 mg; Vitamin B12: 416 µg).

[Nutrimuscle-Diététique]

Traduction de l'étude

La combinaison de la L-arginine avec de la vitamine C améliore les symptômes de la COVID-19 : l'étude nationale multicentrique LINCOLN
Raffaele Izzo Pharmacol Res . 19 juillet 2022;106360.

Introduction : Des preuves récentes suggèrent que le stress oxydatif et le dysfonctionnement endothélial jouent un rôle essentiel dans la physiopathologie du COVID-19 et du Long-COVID. Nous avons émis l'hypothèse qu'une supplémentation associant L-Arginine (pour améliorer la fonction endothéliale) et Vitamine C (pour réduire l'oxydation) pourrait avoir des effets favorables sur les symptômes du Long-COVID.

Méthodes : Nous avons conçu une étude clinique multicentrique nationale (LINCOLN : la L-arginine et la vitamine C améliorent le Long-COVID), dans laquelle une enquête évaluant plusieurs symptômes associés au Long-COVID a été administrée aux survivants du COVID-19 ; la perception de l'effort a été mesurée à l'aide de l'échelle de Borg. Les patients ont été divisés en deux groupes, avec un ratio de 2:1 : le premier groupe comprenait des patients traités par L-Arginine + Vitamine C, tandis que le second groupe était traité par une association multivitaminée (traitement alternatif). Avant d'administrer l'enquête, les patients ont suivi 30 jours de traitement.

Résultats : 1590 patients ont été initialement recrutés, dont 1390 ont terminé l'étude. Après un traitement de 30 jours avec L-Arginine + Vitamine C, l'enquête a révélé que les patients de ce groupe de traitement avaient des scores significativement inférieurs à ceux de l'autre groupe. Il n'y avait pas d'autres différences significatives entre les deux groupes. Lors de l'examen de la perception de l'effort, nous avons observé une valeur significativement plus faible (p<0,0001) chez les patients recevant L-Arginine + Vitamine C par rapport au bras de traitement alternatif.

Conclusions : Pris ensemble, nos résultats indiquent que la supplémentation en L-Arginine + Vitamine C a des effets bénéfiques dans le Long-COVID, en termes de réduction de ses symptômes typiques et d'amélioration de la perception de l'effort.

Le premier groupe comprenait des patients traités avec 2 ampoules/jour de Bioarginina® C (L-Arginine 1,66 g en association avec 500 mg de Vitamine C liposomale, Damor, Naples, Italie). Le deuxième groupe (traitement alternatif) a été traité avec une association multivitaminée (Vitamine B1 : 388 mg ; Vitamine B2 : 443 mg ; Nicotinamide : 18 mg ; Acide folique : 200 µg ; Acide pantothénique : 2 493 g ; Vitamine B6 : 831 mg ; Vitamine B12 : 416 µg).

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Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study
Lixue Huang, Lancet May 11, 2022

Background
With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status.
Methods
We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16–Sept 3, 2020), 12 months (Dec 16, 2020–Feb 7, 2021), and 2 years (Nov 16, 2021–Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls.
Findings

2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0–65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0–197·0) for the visit at 6 months, 349·0 days (337·0–360·0) for the visit at 12 months, and 685·0 days (675·0–698·0) for the visit at 2 years.

The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls.
Interpretation
Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.

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Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study
Aranka V Ballering Lancet 400, ISSUE 10350, P452-461, AUGUST 06, 2022

Background
Patients often report various symptoms after recovery from acute COVID-19. Previous studies on post-COVID-19 condition have not corrected for the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection. We aimed to analyse the nature, prevalence, and severity of long-term symptoms related to COVID-19, while correcting for symptoms present before SARS-CoV-2 infection and controlling for the symptom dynamics in the population without infection.
Methods
This study is based on data collected within Lifelines, a multidisciplinary, prospective, population-based, observational cohort study examining the health and health-related behaviours of people living in the north of the Netherlands. All Lifelines participants aged 18 years or older received invitations to digital COVID-19 questionnaires. Longitudinal dynamics of 23 somatic symptoms surrounding COVID-19 diagnoses (due to SARS-CoV-2 alpha [B.1.1.7] variant or previous variants) were assessed using 24 repeated measurements between March 31, 2020, and Aug 2, 2021. Participants with COVID-19 (a positive SARS-CoV-2 test or a physician's diagnosis of COVID-19) were matched by age, sex, and time to COVID-19-negative controls. We recorded symptom severity before and after COVID-19 in participants with COVID-19 and compared that with matched controls.
Findings
76 422 participants (mean age 53·7 years [SD 12·9], 46 329 [60·8%] were female) completed a total of 883 973 questionnaires. Of these, 4231 (5·5%) participants had COVID-19 and were matched to 8462 controls. Persistent symptoms in COVID-19-positive participants at 90–150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90–150 days after COVID-19 diagnosis or matched timepoint.
Interpretation
To our knowledge, this is the first study to report the nature and prevalence of post-COVID-19 condition, while correcting for individual symptoms present before COVID-19 and the symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. Further research that distinguishes potential mechanisms driving post-COVID-19-related symptomatology is required.

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Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial
by Matteo Tosato Nutrients 2022, 14(23), 4984;

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study.

At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5., p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p <0.0001).

l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

[Nutrimuscle-Diététique]

Traduction de l'étude

Effets de la supplémentation en l-arginine plus vitamine C sur les performances physiques, la fonction endothéliale et la fatigue persistante chez les adultes atteints d'un long COVID : un essai contrôlé randomisé en simple aveugle
par Matteo Tosato Nutriments 2022, 14(23), 4984 ;

Le long COVID, une condition caractérisée par la persistance des symptômes et/ou des signes après un épisode aigu de COVID-19, est associé à une performance physique réduite et à un dysfonctionnement endothélial. La supplémentation en l-arginine peut améliorer la fonction endothéliale et musculaire en stimulant la synthèse d'oxyde nitrique. Un essai randomisé en simple aveugle et contrôlé par placebo a été mené chez des adultes âgés de 20 à 60 ans souffrant de fatigue persistante fréquentant une clinique ambulatoire post-aiguë COVID-19. Les participants ont été randomisés 1:1 pour recevoir deux fois par jour par voie orale une combinaison de 1,66 g de l-arginine plus 500 mg de vitamine C liposomale ou un placebo pendant 28 jours. Le résultat principal était la distance parcourue lors du test de marche de 6 minutes. Les critères de jugement secondaires étaient la force de préhension, la dilatation médiée par le flux et la persistance de la fatigue. Cinquante participants ont été randomisés pour recevoir soit de la L-arginine plus de la vitamine C, soit un placebo. Quarante-six participants (âge médian (intervalle interquartile) 51 (14), 30 [65 %] femmes), 23 par groupe, ont reçu l'intervention à laquelle ils ont été affectés et ont terminé l'étude.

A 28 jours, la l-arginine plus vitamine C a augmenté la distance de marche de 6 min (+30 (40,5) m ; placebo : +0 (75) m, p = 0,001) et a induit une plus grande amélioration de la force de préhension (+3,4 (7,5) ) kg) par rapport au placebo (+1 (6,6) kg, p = 0,03). La dilatation médiée par le flux était plus importante dans le groupe actif que dans le groupe placebo (14,3 % (7,3) contre 9,4 % (5,8 ), p = 0,03). À 28 jours, la fatigue a été signalée par deux participants du groupe actif (8,7 %) et 21 du groupe placebo (80,1 % ; p < 0,0001).

La supplémentation en l-arginine plus vitamine C a amélioré les performances de marche, la force musculaire, la fonction endothéliale et la fatigue chez les adultes atteints de long COVID. Ce complément peut donc être envisagé pour restaurer les performances physiques et soulager les symptômes persistants chez cette population de patients.