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18COVID-19 И ВИТАМИНЫ: ПРОФИЛАКТИКА И ЛЕЧЕНИЕ ЗАБОЛЕВАНИЯ
Эргашева Зумрад Абдукаюмовна
Андижанский государственный медицинский институт
Во время пандемии COVID-19 произошло увеличение данных о здоровье (правильных и неправильных). Многие перешли на использование витаминов и добавок для борьбы с вирусом. В этой статье мы анализируем клинические испытания витаминов и добавок для лечения и профилактики инфекций COVID-19.
Ключевые слова: COVID-19, пандемия, вирус, витамин, добавки, инфекция, лечение, клиническое испытание.
COVID-19 VA VITAMINLAR: KASALLIKNING OLDINI OLISH VA
DAVOLASH
COVID-19 pandemiyasi davrida sog'liqni saqlashga oid ma'lumotlaming (to'g'ri va noto'g'ri) ko'payishi kuzatilmoqda. Ko'pchilik virusga qarshi kurashish uchun vitamin va qo'shimchalardan foydalanishga o'tishdi. Ushbu maqolada COVID-19 infektsiyalarini davolash va oldini olishda vitaminlar va qo'shimchalar bo'yicha klinik sinovlarni tahlil qilamiz.
Kalit so'zlar: COVID-19, pandemiya, virus, vitamin, qo'shimchalar, infektsiya, davolash, klinik sinov.
COVID-19 AND VITAMINS: PREVENTION AND TREATMENT OF THE
DISEASE
During the COVID-19 pandemic, there has been an increase in health data (correct and incorrect). Many have switched to using vitamins and supplements to fight the virus. In this article, we analyze clinical analysis for vitamins and supplements in the treatment and prevention of COVID-19 infections.
Keywords: COVID-19, pandemic, virus, vitamin, supplements, infection, treatment, clinical analyse.
Introduction. As we continue to keep an eye on COVID-19 and its new strains, now is a great time to strengthen our immune systems to combat the virus. Those of us that have a better nutritional status can fight the disease better than others. If our immune system is working really well, we don't get infected. In general, nutrition affects our entire body. All body processes require enzymes, and many vitamins and minerals help enzymes work better. A number of micronutrients, including vitamins C and D and zinc, have been shown to play key roles in supporting immune function and in reducing risk of respiratory infection. These nutrients can be obtained from the diet and are available as dietary supplements either alone or as part of multivitamin or multinutrient mixtures. There are many other dietary supplements available including, omega-3 fatty acids ('fish oil'), probiotics and plant isolates like garlic. The use of specific dietary supplements in both prevention and acute treatment of infection with SARS-CoV-2 has been promoted by prominent medical entertainment personalities on television and social media since the beginning of the current coronavirus
pandemic. The UK supplement market increased by 19.5% in the period leading up to the national 'lockdown' in early March 2020,6 with a 110% rise in sales of vitamin C and a 93% rise in sales of multivitamin supplements. Likewise, zinc supplement sales increased by 415% over the 7-day period ending 8 March, at the height of COVID-19 concern in the USA. A biologically plausible role exists for certain vitamins and minerals in immune pathways. For example, vitamin D has been suggested to reduce SARS-CoV-2 transmission by enhancing antiviral immunity and to reduce mortality by mitigating the cytokine storm linked with severe COVID-19. Moreover, zinc also supports the function of the immune system9 and may have specific antiviral effects. However, robust evidence to support a role for vitamins and minerals in preventing infection with SARS-CoV-2 is not available. Any such evidence would need to take into account factors such as socioeconomic status, ethnicity and occupational exposure to the virus as well as the requirement of a large sample size and a clear confirmation of infection.
For COVID-19 management in the outpatient setting, the NIH recommended bamlanivimab plus etesevimab [1] or casirivimab plus imdevimab [2] in certain populations as defined by the Emergency Use Authorization (EUA) criteria. [3] Previously, bamlanivimab alone had received an EUA in the outpatient setting. [4] For COVID-19 management in the inpatient setting, the NIH recommended remdesivir, dexamethasone, and/or tocilizumab, depending on oxygen requirements and risk of disease progression. [5] Several other immunomodulators are currently in the pipeline. [6] The Infectious Diseases Society of America, [7] the Society for Critical Care Medicine [8] and the WHO [9] have each published their own set of fluid guideline recommendations that are generally in accordance with the NIH recommendations. The CDC did not recommend specific therapies but instead deferred to the NIH guidance. [10] Whilst there is no universal standard of care at the time of this publication, most institutions have protocolized COVID-19 management, with recommendations evolving with changing evidence.
Some group scientists [11-14] say that aside from interventional trials involving vitamins and supplements in COVID-19, data have also been published regarding serum levels of vitamins, minerals, and nutrients and their role in COVID-19.89,90 Most of the data involve vitamin D levels. A full review of deficiencies in COVID-19 is beyond the scope of this article, but representative studies are discussed below to better contextualize supplementation in COVID-19. Interested readers can find a more in-depth analysis on this topic in the cited review articles. Several retrospective studies found a relationship between vitamin D levels and COVID-19 positivity rate. Amongst patients aged >70 years old, one study showed that patients positive for COVID-19 had significantly lower median vitamin D levels compared to those negative for COVID-19 (9.3 ng/mL versus 23.1 ng/mL, respectively; p=0.037). Similarly, another study found positive COVID-19 tests were associated with deficient vitamin D status (defined as <20 ng/mL) at the time of testing (relative risk 1.77, 95% CI 1.12-2.81; p=0.02). Moreover, a third study demonstrated an association between low vitamin D levels (defined as <30 ng/mL) and an increased likelihood of COVID-19 infection (p<0.001) [15-17].
Additional retrospective studies found vitamin D was also related to the severity and outcomes of COVID-19. Amongst patients who were positive for COVID-19, in both inpatient and outpatient settings and equally treated at a single site in Germany, those who had vitamin D deficiency (<12 ng/mL) had significantly higher hospitalization rates (p=0.004), required intensive oxygen therapy (p<0.001), and had significantly higher rates of invasive mechanical ventilation and/or death (p<0.001) or death alone (p<0.001). Insufficient
levels of vitamin D (<20 ng/mL) were also associated with higher rates of invasive mechanical ventilation and/or death (p=0.004) or death alone (p=0.2). In contrast, another study did not show a difference in mortality between vitamin D deficiency (<30 nmol/L) and replete inpatient adults >65 years old in the United Kingdom. However, vitamin D deficiency was associated with significantly higher ventilation requirements (p=0.042). In an Italian study, patients with severe vitamin D deficiency (<10 ng/mL) had higher median respiratory intermediate care unit stays compared to those with vitamin D levels >10 ng/mL (8 versus 12.5 days). Additionally, those with severe vitamin D deficiency had higher mortality rates (50% versus 5%; p=0.019). Minimal data exist regarding supplements or vitamins, besides vitamin D; however, there are some data on selenium and potassium. In one study, 64.7% of COVID-19 non-survivors had selenium levels <45.7 pg/L, whereas 39.3% of COVID-19 survivors had these levels. Additionally, the COVID-19 non-survivors had significantly lower selenium serum levels than the survivors (p<0.001). In another study of 197 inpatients with COVID-19, those who were normokalaemic (K >3.5 mmol/L) had significantly fewer complications (including respiratory failure, sepsis, liver damage, respiratory distress and cardiac damage) than those with severe hypokalaemia (K <3 mmol/L) (p=0.006). Additionally, normokalaemic patients were less likely to be critically ill compared to severely hypokalaemic patients (p=0.03) [18-22].
Vitamin D is critical for bone and mineral metabolism. Because the vitamin D receptor is expressed on immune cells such as B cells, T cells, and antigen-presenting cells, and because these cells can synthesize the active vitamin D metabolite, vitamin D also has the potential to modulate innate and adaptive immune responses. Vitamin D has previously been proposed to have antiviral effects, which led to a theoretical benefit of its use as an adjuvant in treating COVID-19 infections [23,24]. Several retrospective studies have addressed an observed correlation between low serum vitamin D levels and severity of the course of COVID-19 disease symptoms, which is evaluated later in this paper [25-28]. Amongst the vitamin D interventional trials assessed in this review, calcifediol use showed significant decreases in intensive care unit (ICU) admission rates, from 50% without therapy to 2% with therapy (p<0.001) [29]. Additionally, patients receiving high-dose cholecalciferol showed significantly more negative SARS-CoV-2 tests prior to week 3 (p=0.018). A retrospective study involving various dosing strategies of cholecalciferol was associated with decreased risk of COVID-19-related mortality (p<0.001). With regard to vitamin D levels, in the SHADE study, the cholecalciferol group had achieved significantly higher vitamin D levels (>50 ng/mL) compared to the placebo group (p<0.001) by day 14. Most often we get our vitamin D through the sun, but throughout this time, Palacios said, taking a supplement is a good idea. She added that studies have shown that low levels of vitamin D have been associated with a greater risk of developing respiratory conditions in adults and children. In fact, studies have begun to show that people with vitamin D deficiencies are at a higher risk of getting infected by the COVID-19 virus.
Vitamin C (ascorbic acid) is a water-soluble vitamin that is thought to have beneficial effects in patients with severe and critical illnesses. It is an antioxidant and free radical scavenger that has anti-inflammatory properties, influences cellular immunity and vascular integrity, and serves as a cofactor in the generation of endogenous catecholamines. Because humans may require more vitamin C in states of oxidative stress, vitamin C supplementation has been evaluated in numerous disease states, including serious infections and sepsis. Because SARS-CoV-2 infection may cause sepsis and acute respiratory distress syndrome (ARDS), the potential role of high doses of vitamin C in ameliorating inflammation and
vascular injury in patients with COVID-19 is being studied. Vitamin C, a water-soluble vitamin, plays various roles, including supporting connective tissues through collagen synthesis, wound healing, and enhancing the immune system through its bactericidal properties and antibody boosting [30]. It has previously been proposed as having a theoretical benefit in immune defence against COVID-19 infection, based on its known properties and hypothetical, inconsistent evidence supporting its role in symptom mitigation in the common cold [31-33]. Additionally, various studies have demonstrated the positive effects of vitamin C against Epstein-Barr virus, enterovirus/rhinovirus-induced acute respiratory distress syndrome, and severe sepsis and in mechanically ventilated patients with acute respiratory distress syndrome in the ICU [34-36]. IV vitamin C was investigated based on variable evidence of its use in critically ill patients and showed no mortality benefit but some symptom management benefit [37]. One study involving high-dose vitamin C in the setting of COVID-19 demonstrated a significantly longer hospital stay than the non-vitamin C arm. Additionally, there were no significant differences in mortality or ICU length of stay. Vitamin C, alone and in combination with zinc, showed no significant decreases in COVID-19-related symptoms compared to no study intervention. This vitamin has been hailed for years as a go-to source for aiding the immune system. Palacios said vitamin C is vital for the health of leukocytes, a type of white blood cells that help fight infections. It's particularly important during a pandemic. She recommends adults take a supplement of 1000 mg twice every day. She also recommended consuming foods rich in vitamin C. These foods include the classics of orange juice and oranges as well as other citric fruits and vegetables including grapefruit, strawberries, tomatoes and cranberries.
Magnesium has previously been shown to increase 25-hydroxyvitamin D levels when they are <30 ng/mL at baseline; [38] thus, if vitamin D helps protect against COVID-19, magnesium could in turn also be beneficial. So far, magnesium has only been studied in combination with vitamins B and D. The combination therapy showed significant decreases in oxygen support (including ICU support) (p=0.006); however, there were no significant differences in the outcome of oxygen support, excluding any ICU support [39].
Vitamin B12 has been observed to play a fundamental role in gut microbiome [40], which can affect the innate immune response [41]. Some data report that SARS-CoV-2 RNA was found in the stool of patients testing positive for COVID-19, implying that there could be involvement of the gut-lung axis in COVID-19 infections. Additionally, one study demonstrated that the faecal microbiome of patients testing positive for COVID-19 was significantly altered compared to a control group [42]. Similar to magnesium, vitamin B has only been studied in combination with vitamin D and magnesium. As stated above, this combination therapy showed significant decreases in oxygen support (including ICU support) (p=0.006); however, there were no significant differences in the outcome of oxygen support, excluding any ICU support.
Increased intracellular zinc concentrations efficiently impair replication in a number of RNA viruses. Zinc has been shown to enhance cytotoxicity and induce apoptosis when usedin vitrowith a zinc ionophore (e.g., chloroquine). Chloroquine has also been shown to enhance intracellular zinc uptake in vitro. The relationship between zinc and COVID-19, including how zinc deficiency affects the severity of COVID-19 and whether zinc supplements can improve clinical outcomes, is currently under investigation. Zinc levels are difficult to measure accurately, as zinc is distributed as a component of various proteins and nucleic acids. The proposed immune-related mechanism of action of zinc is through enhancement of the innate anti-infective properties of basophils, eosinophils, and neutrophils
[43]. Some weak evidence supports the use of zinc in mitigating symptoms of the common cold [44-46]. Additionally, zinc has demonstrated inhibition of RNA polymerase in vitro but this has not been studied in SARS-CoV-2 [47,48]. Zinc supplementation has been minimally studied in COVID-19; however, one trial demonstrates that zinc, both alone and in combination with vitamin C, showed no significant decreases in COVID-19-related symptoms compared to no study intervention [49]. Zinc is crucial for normal development and functioning of cells mediating part of the immune system. She added that studies have shown that increased concentrations of zinc can inhibit the replication of viruses like poliovirus and SARS-coronavirus.
ALA is an anti-inflammatory and antioxidant. It has previously been shown to decrease the levels of serum inflammatory cytokines and inflammatory-related symptoms in patients with acute coronary syndrome, liver transplantation, and kidney-pancreas combined transplantation [50-53]. Only one study investigated the use of ALA in COVID-19, and this study demonstrated no significant differences in the Sequential Organ Failure Assessment (SOFA) score by day 7 of therapy or mortality [54]. SOFA is a validated scoring system used to predict mortality in ICU patients [55].
Conclusion. At this time, studies involving vitamins and supplements do not provide enough evidence to justify their use over other established pharmacological therapies and prevention techniques that have been proven for use in COVID-19 management and prevention. Additionally, current data regarding vitamin D levels and COVID-19 suggest that low vitamin D levels are associated with increased risk of COVID-19 infection as well as with more complications during infection and higher rates of death. However, from these data alone, it cannot be deducted that vitamin D supplementation is beneficial in the setting of COVID-19 infections. More data are needed regarding other vitamins and minerals to deduct further effects of serum levels on COVID-19. It should also be noted that this article cited several vitamins and their clinical analysis in relation to COVID-19. The findings of several scientists were analyzed. Hopefully, this article will be an impetus for in-depth research.
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