Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

Calvani, Riccardo; Gervasoni, Jacopo; Picca, Anna; Ciciarello, Francesca; Galluzzo, Vincenzo; Coelho-Júnior, Hélio José; Mario, Clara Di; Gremese, Elisa; Lomuscio, Sara; Paglionico, Annamaria; Santucci, Lavinia; Tolusso, Barbara; Urbani, Andrea; Marini, Federico; Marzetti, Emanuele; Landi, Francesco; Tosato, Matteo

doi:10.3390/ijms24065078

Cited by 7 publications

(3 citation statements)

References 66 publications

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“…However, the persistent hyper-inflammatory state and immune dysregulation which is common among virus-free PASC patients, arginine supplementation may prove beneficial to this group. In PASC pathology, the markers of NO• bioavailability are low; accordingly, oral supplementation of these patients with l -arginine + vitamin-C for 4 weeks could significantly elevate serum l -arginine levels and thereby increase NO• bioavailability 419 . In another human RCT ( n = 50), oral supplementation of l -arginine (1.66 g/d) + vit-C (500 mg/d) for 4 weeks restored physical performance, endothelial function, fatigue, and relieved persistent symptoms in PASC patients 415 .…”

Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

View full text Add to dashboard Cite

show abstract

“…After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID-19 [119].…”

Section: L-arginine With Vitamin Cmentioning

confidence: 99%

A Significance of Endothelial Dysfunction in Long COVID-19 for The Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease

Yanai,

Adachi,

Hakoshima

et al. 2024

Preprint

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Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

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“…Some studies reported the beneficial effects of vitamin C and L-arginine on walking capacity, muscle strength, endothelial function and fatigue in adults with Long COVID [155,156]. Considering their effects on aerobic and anaerobic performance in patients with cardiopulmonary diseases including HF or heart transplant, their potential efficiency in combination with a physical activity rehabilitation program may be one of the key medical strategies for Long COVID patients.…”

Section: Long Covid-potential Management Directionsmentioning

confidence: 99%

Unmasking Pandemic Echoes: An In-Depth Review of Long COVID’s Unabated Cardiovascular Consequences beyond 2020

Luchian,

Higny,

Benoit

et al. 2023

Diagnostics

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At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or ‘post-acute COVID-19 syndrome’ emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients’ quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients’ prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

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Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

Cited by 7 publications

References 66 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

A Significance of Endothelial Dysfunction in Long COVID-19 for The Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease

Unmasking Pandemic Echoes: An In-Depth Review of Long COVID’s Unabated Cardiovascular Consequences beyond 2020

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