Terapias alternativas para infecções virais causadas pelo SARS-Cov-2

Discutir as potenciais vantagens e desvantagens dos tratamentos alternativos em comparação com as abordagens médicas convencionais e realçar a importância da comunicação colaborativa entre os doentes e os prestadores de cuidados de saúde na tomada de decisões informadas sobre os tratamentos alternativos do vírus SARS-CoV-2.

Métodos

A metodologia de investigação utilizou métodos de análise da literatura, incluindo abordagens bibliográficas e bibliosemânticas. O estudo utilizou métodos teóricos, sistemáticos e estatísticos, incluindo análise, síntese, generalização, interpretação, classificação e meta-aná-lise para explorar tratamentos alternativos para as infecções por SARS-CoV-2, suas inter-relações e tendências estatísticas da incidência.

Resultados

O estudo identifica diversas terapias alternativas para o tratamento das infecções por SARS-CoV-2, destacando a fitoterapia, a acupunctura, a reflexologia, o biohacking, a homeopatia e a magnetoterapia. Sublinha os potenciais benefícios dos remédios à base de plantas como o alho, o gengibre, a camomila e a madressilva, bem como das vitaminas (C, D, B12) e dos minerais (zinco, selénio) na gestão dos sintomas da COVID-19.

Conclusão

Embora ofereçam benefícios holísticos, estas terapias devem ser consideradas com cautela devido ao apoio científico limitado e às potenciais interações. A compreensão cultural, o diálogo paciente-prove-dor e as escolhas informadas são fundamentais para aproveitar o potencial da medicina alternativa juntamente às abordagens convencionais para gerir os desafios da COVID-19.

Medicina alternativa; Infecção por coronavírus; Fitoterapia; Eficácia do tratamento; Resistência

Article	Design/Sample	Mechanisms/Results
Soileymani et al.⁶6. Soileymani S, Naghizadeh A, Karimi M, Zarei A, Mardi R, Kordafshari G, et al. COVID-19: General strategies for herbal therapies. J Evid Based Integr Med. 2022;27:2515690X211 053641. DOI https://doi.org/10.1177/2515690x211053641 https://doi.org/10.1177/2515690x21105364...	This narrative review employed a comprehensive search strategy in PubMed, Scopus, and Google Scholar databases, spanning various types of studies in medicine, pharmacology, toxicology.	This review underscores the potential of natural resources and medicinal herbs as sources for new drug discovery in the prevention and treatment of COVID-19, outlining mechanisms such as immune boosting, hand hygiene, virus binding and entry inhibition, virus replication inhibition, and host-directed therapies, while emphasizing the need for further research to validate these strategies in the fight against the pandemic.
Bijelić et al.⁹9. Bijelić K, Hitl M, Kladar N. Phytochemicals in the prevention and treatment of SARS-CoV-2 - Clinical evidence. Antibiotics. 2022;11(11):1614. DOI https://doi.org/10.3390/antibiotics11111614 https://doi.org/10.3390/antibiotics11111...	This research employed in vitro and in vivo studies on phytochemicals in the context of COVID-19, up until September 2022, with a brief mention of complementary data from preclinical studies.	Currently, promising natural agents for COVID-19 treatment include quercetin, glycyrrhizin, resveratrol, kaempferol, and thymoquinone, with the advantage of generally low side effects associated with natural products, though bioavailability challenges warrant further pharmaceutical technology research for effective drug formulation.
Han et al.¹¹11. Han Z, Zhang Y, Wang P, Tang Q, Zhang K. Is acupuncture effective in the treatment of COVID-19 related symptoms? Based on bioinformatics/network topology strategy. Brief Bioinform. 2021;22(5):bbab110. DOI https://doi.org/10.1093/bib/bbab110 https://doi.org/10.1093/bib/bbab110...	The study utilized a systematic search approach across 6 databases up to December 31, 2020, with specific search terms related to COVID-19, respiratory symptoms, inflammation, and acupuncture techniques to gather relevant data.	The study's bioinformatics and network topology analysis revealed that acupuncture for COVID-19 primarily operates through anti-inflammatory mechanisms, immune system activation, and nervous system modulation, suggesting its potential effectiveness against COVID-19 symptoms and potential additional benefits for patients with cancer, obesity, and cardiovascular disease, but emphasizes the need for further rigorous clinical and basic research for confirmation.
Kladar et al.¹²12. Kladar N, Bijelić K, Gatarić B, Pajić NB, Hitl M. Phytotherapy and dietotherapy of COVID-19 - An online survey results from central part of Balkan Peninsula. Healthcare (Basel). 2022;10 (9):1678. DOI https://doi.org/10.3390/healthcare10091678 https://doi.org/10.3390/healthcare100916...	This prospective cross-sectional study utilized a specially created online survey, hosted on the web page, focusing on sociodemographic characteristics, COVID-19 experiences, therapy with conventional drugs, phytotherapy, dietary supplements, and special diets among participants in the context of the COVID-19 pandemic in the investigated region.	The study findings indicate that the use of medicinal plants as a form of therapy against COVID-19 is widely adopted and perceived as effective and safe, particularly due to its presumed positive impact on the respiratory and immune systems, emphasizing the importance of using high-quality, recognized products, and consulting with medical professionals for optimal benefits.
Li et al.¹³13. Li H, Li Y, Luo C, Liang X, Liu Z, Liu Y, Ling Y. New approach for targeted treatment of mild COVID-19 by honeysuckle through network pharmacology analysis. Comput Math Methods Med. 2022;21:9604456. DOI https://doi.org/10.1155/2022/9604456 https://doi.org/10.1155/2022/9604456...	The study design involved the screening of active components and targets of honeysuckle using the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), predicting pharmacokinetics with SwissADME and pkCSM databases, collecting mild COVID-19 transcriptome data from the Gene Expression Omnibus (GEO) database, and utilizing various bioinformatics tools.	The analysis revealed that seven active ingredients in honeysuckle demonstrated favorable oral absorption and medicinal properties, and both the targets of these active ingredients and differentially expressed genes in mild COVID-19 were significantly associated with immune signaling pathways, particularly showing statistical significance in the expressions of RELA and MAP3K7.
Al-Kuraishy et al.¹⁹19. Al-Kuraishy HM, Al-Gareeb A, Kaushik A, Kujawska M, Batiha GES. Ginkgo biloba in the management of the COVID-19 severity. Arch Pharm (Weinheim). 2022;355(10):e2200188. DOI https://doi.org/10.1002/ardp.202200188 https://doi.org/10.1002/ardp.202200188...	This review critically examines the potential therapeutic role of Ginkgo biloba L. folium extract (EGb) in managing COVID-19, focusing on its anti-inflammatory and antioxidant properties, its mechanisms of action against SARS-CoV-2, and the possibility of utilizing nanosystems for targeted delivery and enhanced efficacy in phytotherapy.	The review highlights that Ginkgo biloba L. folium extract (EGb) may have a potential role in managing COVID-19 by exerting its antiviral effects through mechanisms such as inhibiting the SARS-CoV-2 3-chymotrypsin-like protease, and by mitigating pulmonary inflammatory disorders, including reducing neutrophil elastase activity, proinflammatory cytokine release, platelet aggregation, and thrombosis, suggesting its potential as an adjuvant therapy for COVID-19.
Muscogiuri et al.²⁹29. Muscogiuri G, Barrea L, Di Somma C, Laudisio D, Salzano C, Pugliese G, et al. Sex differences of vitamin D status across BMI classes: An observational prospective cohort study. Nutrients. 2019;11(12):3034. DOI https://doi.org/10.3390/nu11123034 https://doi.org/10.3390/nu11123034...	This study involved 500 participants, comprising 250 males and 250 females, whose body composition was assessed using bioelectrical impedance analysis, and serum 25OHD concentrations were measured via chemiluminescence immunoassay.	The study found that serum 25OH vitamin D (25OHD) concentrations were consistently higher in males compared to females across all body mass index (BMI) categories, with a significant decrease in 25OHD concentrations as BMI values increased.
Paudyal et al.¹⁰10. Paudyal V, Sun S, Hussain R, Abutaleb MH, Hedima EW. Complementary and alternative medicines use in COVID-19: A global perspective on practice, policy and research. Res Social Adm Pharm. 2022;18(3):2524-8. DOI https://doi.org/10.1016/j.sapharm.2021.05.004 https://doi.org/10.1016/j.sapharm.2021.0...	This narrative commentary addresses the increased demand for complementary and alternative medicines (CAM) during the COVID-19 pandemic and aims to inform healthcare professionals, including pharmacists, about current global practices, policies, research, patient behaviors, and cultural considerations related to CAM use in COVID-19, with a focus on different continents and regions historically associated with diverse CAM practices.	The use of complementary and alternative medicines (CAM) in COVID-19 is widespread and influenced by geographical, cultural, and religious factors, with herbal products often perceived as effective for symptom relief and treatment, despite limited human clinical trial data supporting their efficacy.
Ang et al.¹⁴14. Ang L, Song E, Zhang J, Lee HW, Lee MS. Herbal medicine for COVID-19: An overview of systematic reviews and meta-analysis. Phytomedicine. 2022;102:154136. DOI https://doi.org/10.1016/j.phymed.2022.154136 https://doi.org/10.1016/j.phymed.2022.15...	This study conducted a systematic review of 21 systematic reviews (SRs) analyzing the efficacy of herbal medications for treating COVID-19, using a search of four databases up to October 20, 2021, and assessed the methodological quality of these SRs using the AMSTAR 2 tool.	Although there is a substantial body of evidence suggesting potential benefits, the overall quality of the evidence remains insufficient to make definitive judgments about the effectiveness of herbal medicine therapies, emphasizing the importance of upholding methodological standards in clinical studies and SRs, even in the context of the pandemic.
Fiorino et al.¹⁵15. Fiorino S, Gallo C, Zippi M, Sabbatani S, Manfredi R, Moretti R, et al. Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy. Aging Clin Exp Res. 2020;32(10):2115-31. DOI https://doi.org/10.1007/s40520-020-01669-y https://doi.org/10.1007/s40520-020-01669...	The authors conducted a comprehensive search for reviews describing the characteristics of autoimmune diseases, therapeutic protocols for their treatment, and studies investigating the potential efficacy of vitamins A, D, E, and C in enhancing immune system function, aiming to identify common pathogenetic mechanisms between autoimmune diseases and SARS-CoV-2 infection.	SARS-CoV-2 infection triggers a dysregulated immune response characterized by intense proinflammation leading to cytokine release syndrome (CRS) and acute respiratory syndrome (ARDS), particularly in older individuals, and this review explores the potential of vitamins A, D, E, and C to modulate the immune response, shifting it away from a proinflammatory Th17-mediated profile seen in autoimmune diseases towards a T-cell regulatory phenotype, suggesting a therapeutic role for these micronutrients in restoring normal antiviral immune function and potentially mitigating SARS-CoV-2 infection's severity.
Paul et al.¹⁷17. Paul A, Kumar S, Kaoud TS, Pickett MR, Bohanon AL, Zoldan J, et al. Biomechanical dependence of SARS-CoV-2 infections. ACS Appl Bio Mater. 2022;5(5):2307-15. DOI https://doi.org/10.1021/acsabm.2c00143 https://doi.org/10.1021/acsabm.2c00143...	The authors used hydrogels with varying elastic moduli and conventional tissue culture surfaces to investigate the impact of lung parenchymal tissue stiffness on SARS-CoV-2 infection rates in lung epithelial cells challenged with Spike (S) protein pseudotyped lentiviruses.	The study found that cells on softer and sparser scaffolds, resembling the biomechanical properties of younger lungs, exhibited higher infection rates by both the native SARS-CoV-2 strain and the D614G variant, suggesting that age-related changes in lung biomechanics may not increase susceptibility to SARS-CoV-2 infection, implying that other factors, such as weakened immunity, may contribute to the heightened disease burden observed in older individuals during the pandemic.
Abdelgawad et al.¹⁸18. Abdelgawad SM, El Hassab MA, Abourehab MAS, Elkaeed EB, Eldehna WM. Olive leaves as a potential phytotherapy in the treatment of COVID-19 disease; A mini-review. Front Pharmacol. 2022;13:879118. DOI https://doi.org/10.3389/fphar.2022.879118 https://doi.org/10.3389/fphar.2022.87911...	This study reviewed recent research to identify olive leaves as a potential co-therapy supplement for the treatment and improvement of clinical manifestations in COVID-19 patients.	The review highlighted that olive leaves, rich in phenolic compounds and triterpenoids with reported anti–SARS-CoV-2 properties, along with their established in vivo anti-inflammatory, analgesic, antipyretic, immunomodulatory, and antithrombotic activities, have the potential to be a co-therapy supplement for the treatment of COVID-19 and its associated symptoms, particularly in controlling the inflammatory cytokine storm and disseminated intravascular coagulation in patients.
Pranskuniene et al.²⁰20. Pranskuniene Z, Balciunaite R, Simaitiene Z, Bernatoniene J. Herbal medicine uses for respiratory system disorders and possible trends in new herbal medicinal recipes during COVID-19 in Pasvalys District, Lithuania. Int J Environ Res Public Health. 2022;19(15):8905. DOI https://doi.org/10.3390/ijerph19158905 https://doi.org/10.3390/ijerph19158905...	The survey was conducted using the deep interview method. The respondents mentioned 60 species of medicinal plants from 29 different families used for the treatment and prevention of respiratory system disorders (for cough mostly, 51.70% of all indications).	The study found that during the COVID-19 pandemic in the Pasvalys district of Lithuania, herbal medicines were commonly used for the treatment and prevention of respiratory system disorders, primarily for cough, with 60 species of medicinal plants mentioned, but a significant proportion of these plants were not included in European Medicines Agency monographs, indicating potential safety concerns and the need for adherence to safety guidelines when considering herbal remedies for COVID-19 symptoms.
Holford et al.²⁴24. Holford P, Carr AC, Jovic TH, Ali SR, Whitaker IS, Marik PE, et al. Vitamin C - An adjunctive therapy for respiratory infection, sepsis and COVID-19. Nutrients. 2020;12(12):3760. DOI https://doi.org/10.3390/nu12123760 https://doi.org/10.3390/nu12123760...	The literature review aimed to investigate the potential therapeutic benefits of vitamin C in the prevention and treatment of respiratory infections, including COVID-19, through both oral and intravenous administration, with a focus on its impact on reducing infection incidence, duration, and severity.	Vitamin C, due to its antioxidant, anti-inflammatory, and immunomodulating effects, may have potential therapeutic benefits in preventing and ameliorating COVID-19 infection, particularly when administered orally or intravenously in certain doses, by reducing the incidence and duration of respiratory infections and improving outcomes, including reduced mortality and hospital stays in severe cases, warranting further clinical trials.
Feyaerts et al.²⁵25. Feyaerts AF, Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? Nutrition. 2020; 79-80:110948. DOI https://doi.org/10.1016/j.nut.2020.110948 https://doi.org/10.1016/j.nut.2020.11094...	This article discusses the potential use of vitamin C, both as prophylaxis at a relatively low dose and as an intravenous high-dose regimen for severe COVID-19 cases, based on evidence of its ability to reduce mediators like interleukin-6 and endothelin-1.	The authors suggest that elevated levels of mediators like interleukin-6 and endothelin-1 in severe COVID-19 cases may contribute to the disease's characteristics, and there is evidence that high doses of vitamin C can reduce these mediators, supporting the potential benefit of using vitamin C at low doses for prophylaxis and high doses for severe COVID-19 cases.
Ahmad et al.²⁶26. Ahmad SR. Vitamin C for COVID-19 treatment: Have we got enough evidence? Front Nutr. 2022;9:892561. DOI https://doi.org/10.3389/fnut.2022.892561 https://doi.org/10.3389/fnut.2022.892561...	The study investigates the potential applications of vitamin C as a prevention and treatment for COVID-19, focusing on its immune-modulatory mechanisms, antioxidant properties, and its potential to reduce oxidative damage and mitigate cytokine attacks.	The study suggests that vitamin C exhibits antioxidant and antiviral effects, making it a promising option for combating SARS-CoV-2 infections, but emphasizes the need for further research, including randomized controlled trials (RCTs) and large cohort studies, to confirm its effectiveness, especially in combination with other drugs, intravenous administration, and for critically ill patients.
Hui et al.²⁷27. Hui LL, Nelson EAS, Lin SL, Zhao JV. The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study. Eur J Clin Nutr. 2022;76(4):588-91. DOI https://doi.org/10.1038/s41430-021-00993-4 https://doi.org/10.1038/s41430-021-00993...	The authors used genetic tools derived from a genome-wide association study (GWAS) of plasma vitamin C levels in a sample of 52,018 people of European ancestry selected on the basis of an F-statistic > 10 as strong tools.	Genetically predicted circulating levels of vitamin C were not found to be associated with the susceptibility to severe COVID-19, COVID-19 hospitalization, any COVID-19 infection, or pneumonia, suggesting limited support for the use of vitamin C in the prevention and treatment of these conditions through these pathways, unless high-dose vitamin C infusion operates through distinct biological mechanisms.
Barrea et al.²⁸28. Barrea L, Verde L, Grant WB, Frias-Toral E, Sarno G, Vetrani C, et al. Vitamin D: A role also in long COVID-19? Nutrients. 2022;14(8):1625. DOI https://doi.org/10.3390/nu14081625 https://doi.org/10.3390/nu14081625...	In this review, data were summarized using a narrative approach, drawing from clinical expertise and interpretation of available evidence in peer-reviewed journal literature. PubMed and Google Scholar were searched using relevant terms including COVID-19, long COVID-19, mechanisms, risk, SARS-CoV-2, symptoms, and vitamin D.	The COVID-19 pandemic has seen rising cases and lingering symptoms among patients, particularly those with long-term sequelae, and vitamin D deficiency has been associated with increased severity and mortality in COVID-19 cases, highlighting its immunomodulatory role and potential as a cost-effective and safe supplement in COVID-19 treatment.
Subramanian et al.³⁰30. Subramanian S, Griffin G, Hewison M, Hopkin J, Kenny RA, Laird E, et al. Vitamin D and COVID-19-Revisited. J Intern Med. 2022;292(4):604-26. DOI https://doi.org/10.1111/joim.13536 https://doi.org/10.1111/joim.13536...	This is a narrative review but informed by a PubMed literature search that included as search terms ‘COVID-19 and vitamin D’ and with emphasis on reports published since January 2021.	The evidence for the impact of vitamin D deficiency on COVID-19 risk and severity is largely indirect, and future studies should consider the dose and formulation of vitamin D, with calcifediol potentially being more effective for both prevention and treatment of acute respiratory infections, while regular low-dose daily supplementation to prevent deficiency should be encouraged.
Shakoor et al.³¹31. Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas. 2021;143:1-9. DOI https://doi.org/10.1016/j.maturitas.2020.08.003 https://doi.org/10.1016/j.maturitas.2020...	A total of 35 relevant studies specifically on COVID-19 and nutrition or diet components were identified.	The potential benefits of vitamins C, D, E, zinc, selenium, and omega-3 fatty acids in supporting the immune system and COVID-19 patients, particularly in the elderly population, are discussed, and higher dosages of vitamins D, C, and zinc are suggested for possible positive effects during COVID-19 infection, although clinical trials are needed to confirm their effectiveness in COVID-19 patients, along with the exploration of other immunomodulatory micronutrients like vitamin B.
Varikasuvu et al.³²32. Varikasuvu SR, Thangappazham B, Vykunta A, Duggina P, Manne M, Raj H, et al. COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther. 2022;20(6):907-13. DOI https://doi.org/10.1080/14787210.2022.2035217 https://doi.org/10.1080/14787210.2022.20...	A total of 6 RCTs with 551 COVID-19 patients were included.	The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z = 2.33, p = 0.02, I2 = 48%). Conclusively, COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events, and RT-PCR positivity.
Tabatabaeizadeh et al.³⁶36. Tabatabaeizadeh SA. Zinc supplementation and COVID-19 mortality: a meta-analysis. Eur J Med Res. 2022;27(1):70. DOI https://doi.org/10.1186/s40001-022-00694-z https://doi.org/10.1186/s40001-022-00694...	A systematic search has conducted for manuscripts through PUBMED/Medline and Google Scholar up to September 2021. Based on the heterogeneity a fixed-effect or random-effect model, the OR and 95% CI were used to assess the combined risk.	After assessment, five studies with 1506 participants in case and control groups were included in meta-analysis. The OR for one study was not estimable, and the pool OR was estimated for other studies with 1398 participants. The meta-analysis showed that zinc supplementation in cases led to a significant lower risk of mortality when it was compared with the control group; pooled OR (95% CI) was 0.57 [0.43, 0.77] (P < 0.001).
Borges et al.³⁷37. Borges L, Gennari-Felipe M, Dias BB, Hatanaka E. Melatonin, zinc, and vitamin C: Potential adjuvant treatment for COVID-19 patients. Front Nutr. 2022;8:821824. DOI https://doi.org/10.3389/fnut.2021.821824 https://doi.org/10.3389/fnut.2021.821824...	The review included peer-reviewed randomized controlled trials (RCTs) and observational studies in any language that assessed COVID-19 patients treated with melatonin, zinc, or vitamin C.	The review highlights that while nutritional supplementation with melatonin, zinc, and vitamin C is often cost-effective and associated with anti-inflammatory and antioxidative properties, most randomized controlled trials (RCTs) involving these supplements for COVID-19 are still in development, with inconclusive data from relatively small sample sizes and early terminations of trials.
Boretti⁴⁰40. Boretti A. Zinc augments the antiviral potential of HCQ/CQ and ivermectin to reduce the risks of more serious outcomes from COVID-19 infection. J Trace Elem Med Biol. 2022;71:126954. DOI https://doi.org/10.1016/j.jtemb.2022.126954 https://doi.org/10.1016/j.jtemb.2022.126...	The manuscript proposes a statistical analysis of the works with Zn for COVID-19 infection.	The review of Zinc (Zn) supplementation for COVID-19 infection indicates that Zn supplementation may reduce the risks of serious outcomes from COVID-19 infection, particularly when taken in conjunction with antiviral drugs, with a range of risk reduction from 37% in late treatment to 78% in sufficiency.
Pisoschi et al.⁴¹41. Pisoschi AM, Pop A, Iordache F, Stanca L, Geicu OI, Bilteanu L, et al. Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Eur J Med Chem. 2022; 232:114175. DOI https://doi.org/10.1016/j.ejmech.2022.114175 https://doi.org/10.1016/j.ejmech.2022.11...	This review synthesizes existing literature to discuss the potential roles of vitamins in reducing oxidative stress, countering cytokine storms, and their direct antiviral activities in the context of viral infections, including SARS-CoV-2, with a focus on timing, dosage, and potential interactions among these micronutrients.	This review highlights the role of antioxidants, including vitamins, in mitigating oxidative stress, reducing cytokine storms, and potentially exerting direct antiviral effects in viral infections such as SARS-CoV-2, emphasizing their ability to lower oxidative stress markers, alleviate cytokine storms, and potentially reduce disease severity by modulating pro-inflammatory cytokines and countering hyperinflammation.
Alshammari et al.⁴²42. Alshammari MK, Fatima W, Alraya RA, Alzahrani AK, Kamal M, Alshammari RS, et al. Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature. J Infect Public Health. 2022;15(11):1225-33. DOI https://doi.org/10.1016/j.jiph.2022.09.011 https://doi.org/10.1016/j.jiph.2022.09.0...	This review examines clinical studies, compositions, and patent literature related to selenium's potential in preventing and treating COVID-19, focusing on its mechanisms of action and the development of selenium-based compositions and dosage forms for COVID-19 management.	Clinical studies and patent literature suggest that selenium monotherapy and its combinations with various nutritional supplements and drugs could be effective in COVID-19 management, emphasizing a correlation between COVID-19 and selenium deficiency, which opens avenues for novel selenium-based compositions and dosage forms for COVID-19 treatment, while recognizing the importance of considering selenium's narrow therapeutic window and chemical interactions in formulation.
Rayman et al.⁴³43. Rayman MP, Taylor EW, Zhang J. The relevance of selenium to viral disease with special reference to SARS-CoV-2 and COVID-19. Proc Nutr Soc. 2023;82(1):1-12. DOI https://doi.org/10.1017/s0029665122002646 https://doi.org/10.1017/s002966512200264...	In this review, the association between selenium (Se) status and COVID-19 outcomes were investigated based on available data and serum samples from COVID-19 patients in Chinese cities with varying Se statuses.	The review highlights the historical significance of selenium (Se) in reducing the severity of viral infections and presents evidence of a significant association between COVID-19 cure rates and background Se status in Chinese cities, suggesting additional mechanisms beyond selenoprotein optimization.
Darand et al.⁴⁴44. Darand M, Hassanizadeh S, Martami F, Shams S, Mirzaei M, Hosseinzadeh M. The association between B vitamins and the risk of COVID-19. Br J Nutr. 2023;130-1:155-63. DOI https://doi.org/10.1017/s0007114522003075 https://doi.org/10.1017/s000711452200307...	This study analyzed data from 9189 adult participants aged 20 to 69 years from the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study, utilizing a validated FFQ to assess dietary intakes, and employed multivariable logistic regression analysis.	The study found that higher dietary intake of vitamin B5 was associated with a 47% reduction in the odds of COVID-19, and moderate intake of vitamin B12 was linked to a protective effect against COVID-19, while no significant associations were observed for dietary intake of vitamin B1, B2, B3, B9, and B-complex in relation to COVID-19 incidence.
Islam et al.⁴⁵45. Islam MT, Quispe C, Martorell M, Docea AO, Salehi B, Calina D, et al. Dietary supplements, vitamins and minerals as potential interventions against viruses: Perspectives for COVID-19. Int J Vitam Nutr Res. 2022;92(1):49-66. DOI https://doi.org/10.1024/0300-9831/a000694 https://doi.org/10.1024/0300-9831/a00069...	This study is a review of the latest publications on the modulatory effects of natural antiviral dietary supplements, vitamins, and minerals on immunity, focusing on their potential use as adjuvant therapy alongside antiviral medicines in the management of COVID-19 disease.	The review suggests that various dietary supplements, such as black seeds, garlic, ginger, cranberry, orange, omega-3 and -6 polyunsaturated fatty acids, vitamins (e.g., A, B vitamins, C, D, E), and minerals (e.g., Cu, Fe, Mg, Mn, Na, Se, Zn), have demonstrated anti-viral effects against respiratory viruses, including coronaviruses, and could be used as adjuvant therapy alongside antiviral medicines in managing COVID-19 disease.

Advantages	Disadvantages
Holistic approach: considers overall well-being and immune system support.	Limited scientific evidence to support efficacy and safety for SARS-CoV-2.
Potential for personalized care based on individual needs.	Delay in seeking proven, evidence-based conventional treatments.
Perceived lower occurrence of side effects.	Potential interactions with conventional medications.

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[1] *Correspondence: risto_jo@tkut.in.ne