4.4. Vitamin C Supplementation against Viral Infection
Vitamin C deficiency status is correlated with an increased susceptibility to severe respiratory infections such as pneumonia [46,47,64,65,66,67,68,69,70,71,72] (Table 3).
In a recent meta-analysis, Hemilä and Louhiala analyzed the effect of vitamin C in preventing and treating pneumonia regardless of the etiology [65]. They reported three studies that show a >80% lower incidence of pneumonia in the vitamin C groups, supporting the potential role of vitamin C in reducing the risk of pneumonia, particularly in individuals with low plasma vitamin C levels [66]. Furthermore, regarding the effect of vitamin C in treating pneumonia, in older patients, lower mortality and reduced severity of disease was found in the vitamin C group, particularly in the most ill patients. However, the authors concluded that the current evidence is too weak to advocate widespread prophylactic use of vitamin C to prevent pneumonia in the general population, and further studies are needed to clarify the population that could have a benefit from vitamin C use. The effect of vitamin C on upper respiratory tract infections, such as the common cold, has also been studied in several trials. Vitamin C supplementation significantly decreases the incidence and the severity of the common cold in people under heavy physical stress [67,68]. In a randomised controlled pilot study, Garaiova et al. have shown a significant reduction in the incidence and duration of upper respiratory tract infection, but no significant differences were observed in the incidence rate ratio or duration of lower respiratory tract infection [69]. A recent meta-analysis comparing vitamin C with placebo demonstrated that administration of extra doses of vitamin C at the onset of a common cold could help reduce the duration by about half a day, shorten the time confined indoors, and relieve the symptoms of a common cold [70].
With the COVID-19 outbreak, vitamin C could play a role in preventing and treating the severe respiratory viral infection caused by SARS-CoV-2. The potential beneficial effect of vitamin C supplementation could be expected also from the depleted vitamin C levels that are present during a severe infection and in critically ill patients [71]. A recent randomised clinical trial (CITRIS-ALI) demonstrated that 96 hours’ infusion of vitamin C compared with placebo in patients with sepsis and ARDS did not improve the primary outcome of organ dysfunction scores, but significantly reduced mortality and significantly increased ICU-free days to 28 and hospital-free days to 60 [72].
Recently, Diao et al. retrospectively reviewed the numbers of total T cells, CD4+, CD8+ T cell subsets in a total of 499 COVID-19 patients and found a significantly reduction of T cells counts. Furthermore, they demonstrated a state of T cell dysfunction (T cell exhaustion) following SARS-CoV-2 infection [73]. Thus, the possibility that vitamin C affects viral respiratory tract infections, also supporting the viral clearance mediated by T cells, could encourage further studies aimed to investigate the role of vitamin C for prevention and treatment of COVID-19 disease.