This proof-of-concept study aimed to assess the optimal timing, dosing, and duration of vitamin C administration to increase survival and attenuate organ injuries in murine sepsis. Mice were randomized to receive ascorbic acid (AscA) at 1 or 6 h after cecal ligation and puncture (CLP). At each time point, mice randomly received AscA for 4 or 8 d. Mice were assigned to sham and CLP groups, as well as CLP + AscA groups that were treated with AscA at doses of 90, 180, or 360 mg/kg/d. The survival curves diverged significantly when AscA was injected at doses of 180 or 360 mg/kg/d for 8 d, although this was not observed when the treatment was limited to 4 d. AscA at doses of 180 or 360 mg/kg/d for 8 d preserved lung architecture while attenuating the abnormal expression of tight junction proteins. Kidney and liver injuries were evident in CLP mice, with elevated expression of biomarkers and inflammatory mediators; however, exposure to AscA at doses of 180 or 360 mg/kg/d for 8 d improved the histological changes and decreased biomarker expression levels. Very high-dose and prolonged vitamin C administration may potentially play a role in the management of sepsis-associated organ injuries.

Vitamin C has been used as an essential antioxidant to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the 2019 coronavirus disease (COVID-19), but its effect on clinical outcomes remains controversial and inconclusive.

The purpose of this study was to conduct a meta-analysis and systematic review to assess the effects of vitamin C supplementation on the severity of COVID-19 in hospitalized patients.

Web of Science, Embase, Cochrane Library, PubMed, CNKI, CSTJ, Wan fang, and CBM databases were searched for publications between January 2020 and December 2023 that met the inclusion criteria.

The meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. A randomized controlled trial, cohort studies, and retrospective studies in which vitamin C supplementation was supplemented as monotherapy or in combination, compared with placebo, no treatment, or other standard treatment without vitamin C were included.

After screening, 22 studies, with a total of 6831 patients, were selected for assessment. Odds ratios (ORs) with 95% CIs were calculated using fixed- and random-effects models. The meta-analysis showed significant effects of vitamin C on alleviating clinical outcomes in patients with COVID-19 (OR = 0.76, 95% CI = 0.65-0.89, P = .0007) but no shortening of the length of hospitalization (OR = 1.16, 95% CI = -0.13-2.44, P = .08) compared with the control group. Notably, vitamin C supplements significantly reduced the mortality risk (OR = 0.64, 95% CI = 0.51-0.80, P = .0001) and the incidence of severity (OR = 0.59, 95% CI = 0.43-0.80, P = .0006) in COVID-19 patients.

The findings suggest that vitamin C supplements may have a beneficial effect on clinical outcomes, as well as reducing severity and mortality in COVID-19 patients, but more clinical randomized controlled trials are needed to evaluate the role of vitamin C in treating COVID-19.

PROSPERO registration no. CRD42023491517.

It is proven that the blood concentration of antioxidants can impress the severity of viral infections, including COVID-19. However, the lack of a comprehensive study accumulating existing data regarding COVID-19 can be perceived. Therefore, this systematic review is aimed to report the association between the blood concentration of several antioxidants and the overall health condition of COVID-19 patients. We summarized the available data surrounding the serum antioxidant level in COVID-19 patients and COVID-19 outcomes. A systematic search was performed in PubMed, Scopus, Web of Science, and Cochrane, and studies that evaluated the association between antioxidants and COVID-19 outcomes were included. Of 4101 articles that were viewed in the database search, 38 articles were included after the title, abstract, and full-text review. Twenty-nine studies indicated that lower serum antioxidants are associated with worse outcomes, and one study reported no association between serum zinc (Zn) level and COVID-19 outcomes. In most cases, antioxidant deficiency was associated with high inflammatory factors, high mortality, acute kidney injury, thrombosis, intensive care unit (ICU) admission, acute respiratory distress syndrome, cardiac injury, and the need for mechanical ventilation (MV), and there was no significant association between serum antioxidants level and ICU or hospital length of stay (LOS). It seems that higher levels of antioxidants in COVID-19 patients may be beneficial to prevent disease progression. However, clinical trials are needed to confirm this conclusion.

Since November 2021, there have been cases of COVID-19's Omicron strain spreading in competition with Delta strains in many parts of the world. To explore how these two strains developed in this competitive spread, a new compartmentalized model was established. First, we analyzed the fundamental properties of the model, obtained the expression of the basic reproduction number, proved the local and global asymptotic stability of the disease-free equilibrium. Then by means of the cubic spline interpolation method, we obtained the data of new Omicron and Delta cases in the United States of new cases starting from December 8, 2021, to February 12, 2022. Using the weighted nonlinear least squares estimation method, we fitted six time series (cumulative confirmed cases, cumulative deaths, new cases, new deaths, new Omicron cases, and new Delta cases), got estimates of the unknown parameters, and obtained an approximation of the basic reproduction number in the United States during this time period as R 0 ≈ 1.5165 . Finally, each control strategy was evaluated by cost-effectiveness analysis to obtain the optimal control strategy under different perspectives. The results not only show the competitive transmission characteristics of the new strain and existing strain, but also provide scientific suggestions for effectively controlling the spread of these strains.

There are conflicting reports on the antibacterial activity of ascorbate; all at concentrations much higher than the typical in human plasma, but that can be reached in urine. The effect of 10 mM ascorbate (in itself not inhibitory) along with antibiotics, was tested both in Mueller-Hinton broth (MHb) and in synthetic human urine (SHU), against resistant isolates of Escherichia coli from lower urinary infections. The activity of nitrofurantoin and sulfamethoxazole was higher in SHU than in MHb; minimal inhibitory concentrations (MICs) in SHU with ascorbate were below typical urinary concentrations. For other antibiotics, MICs were the same in MHb vs. SHU, with no effect of ascorbate in MHb; but in SHU with ascorbate, MICs of ciprofloxacin and gentamicin also went below reported urinary concentrations, with a lesser effect with norfloxacin and trimethoprim, and none with ampicillin. The effect of ascorbate was independent of oxygen and not related to the susceptibility of each strain to oxidative stress. Ascorbate oxidizes during incubation in SHU, and bacterial growth partially prevented oxidation. These results suggest that 10 mM ascorbate can enhance the inhibitory activity of antibiotics upon resistant strains in urine. Clinical experimentation with ascorbate-antibiotic combinations against urinary infections caused by resistant bacteria is warranted.

The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.

Background: Vitamin C is an essential nutrient that serves as an antioxidant and is known to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the coronavirus disease (COVID-19), but its clinical effects remain controversial. Methods: This study aimed to investigate the therapeutic effect of vitamin C administration on the clinical outcomes of COVID-19 patients through a systematic review and meta-analysis. Results: Nineteen studies were selected, of which 949 participants administered vitamin C were in the intervention group, and 1816 participants were in the control group. All-cause mortality, hospitalization duration, length of intensive care unit stay, and ventilation incidence in COVID-19 patients were analyzed. The intervention group tends to have a lower risk ratio (RR = 0.81, 95% CI: 0.62 to 1.07; I2 = 58%; Q = 40.95; p < 0.01) in all-cause mortality than the control group. However, there were no significant differences in ventilation incidence, hospitalization duration, and length of ICU stay between the two groups. In the subgroup analysis for all-cause mortality, the risk ratio for RCT as study design, combination therapy, of vitamin C was lower than that of the combination therapy with other agents. A moderate dosage showed a lower RR than a higher dose. Conclusion: The results suggest that vitamin C may lower mortality in COVID-19 patients, but further large-scale studies are required to assess the role of vitamin C in the treatment of COVID-19.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), millions of people have died, and the medical system has faced significant difficulties. Our purpose was to perform a meta-analysis to estimate the effect of vitamin C on in-hospital mortality and the ICU or hospital length of stay for patients diagnosed with COVID-19. We conducted a systematic review with meta-analysis in the following databases: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials. We included studies that evaluated the effect of vitamin C supplementation, compared with standard treatment in COVID-19 patients who are ≥18 y of age. Nineteen trials were included in the meta-analysis. In-hospital mortality with and without vitamin C supplementation was 24.1% vs. 33.9% (OR = 0.59; 95%CI: 0.37 to 0.95; p = 0.03), respectively. Sub-analysis showed that, in randomized clinical trials, in-hospital mortality varied and amounted to 23.9% vs. 35.8% (OR = 0.44; 95%CI: 0.25 to 0.76; p = 0.003), respectively. In the non-randomized trials, in-hospital mortality was 24.2% vs. 33.5% (OR = 0.72; 95%CI: 0.38 to 1.39; p = 0.33), respectively. The ICU length of stay was longer in patients treated with vitamin C vs. standard therapy, 11.1 (7.3) vs. 8.3 (4.7) days (MD = 1.91; 95%CI: 0.89 to 2.93; p < 0.001), respectively. Acute kidney injury in patients treated with and without vitamin C varied and amounted to 27.8% vs. 45.0% (OR = 0.56; 95%CI: 0.40 to 0.78; p < 0.001), respectively. There were no differences in the frequency of other adverse events among patients’ treatment with and without vitamin C (all p > 0.05). The use of vitamin C reduces hospital mortality. The length of stay in the ICU is longer among patients treated with vitamin C. In terms of patient safety, vitamin C has an acceptable profile. Low doses of vitamin C are effective and safe. Despite some evidence of the usefulness of vitamin C in modifying the course of COVID-19, it is too early to modify guidelines and recommendations. Further studies, in particular randomized clinical trials, are necessary.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the most dreadful viruses the mankind has witnessed. It has caused world-wide havoc and wrecked human life. In our quest to find therapeutic options to counter this threat, several drugs have been tried, with varying success. Certain agents like corticosteroids, some anti-virals and immunosuppressive drugs have been found useful in improving clinical outcomes. Vitamin C, a water-soluble vitamin with good safety profile, has been tried to reduce progression and im-prove outcomes of patients with coronavirus disease 2019 (COVID-19). Because of its anti-oxidant and immunomodulatory properties, the role of vitamin C has expanded well beyond the management of scurvy and it is increasingly been employed in the treatment of critically ill patients with sepsis, septic shock, acute pancreatitis and even cancer. However, in spite of many case series, observational studies and even randomised control trials, the role of vitamin C remains ambiguous. In this review, we will be discussing the scientific rationale and the current clinical evidence for using high dose vitamin C in the management of COVID-19 patients.