bims-covind Biomed News
on COVID-19 and Immunology: nutrition and diet
Issue of 2020‒11‒22
twenty-one papers selected by
Aimee Cook
Newcastle University


  1. Molecules. 2020 Nov 16. pii: E5346. [Epub ahead of print]25(22):
    Bae M, Kim H.
      Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.
    Keywords:  COVID-19; infectious disease; selenium; virus; vitamin C; vitamin D
    DOI:  https://doi.org/10.3390/molecules25225346
  2. Nutrients. 2020 Nov 14. pii: E3512. [Epub ahead of print]12(11):
    Malaguarnera L.
      Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the "cytokine storm", promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.
    Keywords:  SARS-CoV2 immunopathology; immunomodulation; prevention; vitamin D
    DOI:  https://doi.org/10.3390/nu12113512
  3. J Community Hosp Intern Med Perspect. 2020 Oct 29. 10(6): 529-536
    Balla M, Merugu GP, Konala VM, Sangani V, Kondakindi H, Pokal M, Gayam V, Adapa S, Naramala S, Malayala SV.
      Importance: As the scientific community is in a marathon in finding out the cure for COVID-19, in this crisis, it is essential for the physicians not to forget about the basics. Due to the pandemic crisis, in many nursing homes and hospitals, there established new policies on decreasing unnecessary medications to minimize cross-contamination. Sometimes these policies are making providers avoid essential drugs such as Vitamins, including Vitamin D. In this paper, we try to emphasize the importance of Vitamin D in COVID-19 and respiratory viral patients.Relevance: Vitamin D helps in decreasing the 'pro-inflammatory cytokines' in the lungs and acts in immunomodulatory function, and 'also it will increase the anti-inflammatory, antiviral responses of the respiratory epithelial cells during infection.'
    Conclusion: Due to the highly contagious nature of COVID-19 and the increased morbidity and mortality with no appropriate therapy and vaccine, one must be cautious and do everything to help COVID-19 patients. In hospitals and other health care settings to decrease cross-contamination, holding other non-essential medications is taking place. Discontinuing Vitamins could increase the mortality and morbidity of those affected, especially in deficient/insufficient individuals. Obtaining serum 25 (OH) D levels in all patients with viral respiratory infections, especially COVID-19, could help in the detection and treatment of Vitamin D deficiency and potentially decrease recovery time and improve outcome. Even though evidence suggests that vitamin D has the anti-inflammatory, antiviral properties, randomized double-blinded controlled trials are needed to verify this further, and to understand Vitamin D and COVID-19 better.
    Abbreviations: Vitamin D receptor-VDR; 25(OH)D- 25 hydroxyvitamin D; 1,25 (OH)D-1,25 dihydroxy Vitamin D; 1α,25-dihydroxy Vitamin D-1,25[OH]2 D or calcitriol; IU- International Units; Interferons stimulated genes- ISG; ARI- acute respiratory infection; RSV- respiratory syncytial virus; RTI- Respiratory tract infections; COPD-Chronic obstructive pulmonary disease; BMI-Basal metabolic index; USA-USA.
    Keywords:  1,25(OH)2 D; 25(OH) D; COVID-19; SARS CoV2; calcitriol; respiratory tract infections; respiratory viruses; vitamin D
    DOI:  https://doi.org/10.1080/20009666.2020.1811074
  4. Biomed Pharmacother. 2020 Nov 11. pii: S0753-3322(20)31139-2. [Epub ahead of print]133 110947
    Din AU, Mazhar M, Wasim M, Ahmad W, Bibi A, Hassan A, Ali N, Gang W, Qian G, Ullah R, Shah T, Ullah M, Khan I, Nisar MF, Wu J.
      In December 2019, a pneumonia outbreak of unknown etiology was reported which caused panic in Wuhan city of central China, which was later identified as Coronavirus disease (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CDC) and WHO. To date, the SARS-CoV-2 spread has already become a global pandemic with a considerable death toll. The associated symptoms of the COVID-19 infection varied with increased inflammation as an everyday pathological basis. Among various other symptoms such as fever, cough, lethargy, gastrointestinal (GI) symptoms included diarrhea and IBD with colitis, have been reported. Currently, there is no sole cure for COVID-19, and researchers are actively engaged to search out appropriate treatment and develop a vaccine for its prevention. Antiviral for controlling viral load and corticosteroid therapy for reducing inflammation seems to be inadequate to control the fatality rate. Based on the available related literature, which documented GI symptoms with diarrhea, inflammatory bowel diseases (IBD) with colitis, and increased deaths in the intensive care unit (ICU), conclude that dysbiosis occurs during SARS-COV-2 infection as the gut-lung axis cannot be ignored. As probiotics play a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotics might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function.
    Keywords:  COVID-19; Colitis; Gut microbiome; IBD; ICU; Probiotics
    DOI:  https://doi.org/10.1016/j.biopha.2020.110947
  5. Front Immunol. 2020 ;11 574029
    Cerullo G, Negro M, Parimbelli M, Pecoraro M, Perna S, Liguori G, Rondanelli M, Cena H, D'Antona G.
      From Pauling's theories to the present, considerable understanding has been acquired of both the physiological role of vitamin C and of the impact of vitamin C supplementation on the health. Although it is well known that a balanced diet which satisfies the daily intake of vitamin C positively affects the immune system and reduces susceptibility to infections, available data do not support the theory that oral vitamin C supplements boost immunity. No current clinical recommendations support the possibility of significantly decreasing the risk of respiratory infections by using high-dose supplements of vitamin C in a well-nourished general population. Only in restricted subgroups (e.g., athletes or the military) and in subjects with a low plasma vitamin C concentration a supplementation may be justified. Furthermore, in categories at high risk of infection (i.e., the obese, diabetics, the elderly, etc.), a vitamin C supplementation can modulate inflammation, with potential positive effects on immune response to infections. The impact of an extra oral intake of vitamin C on the duration of a cold and the prevention or treatment of pneumonia is still questioned, while, based on critical illness studies, vitamin C infusion has recently been hypothesized as a treatment for COVID-19 hospitalized patients. In this review, we focused on the effects of vitamin C on immune function, summarizing the most relevant studies from the prevention and treatment of common respiratory diseases to the use of vitamin C in critical illness conditions, with the aim of clarifying its potential application during an acute SARS-CoV2 infection.
    Keywords:  COVID-19; athletes; frail elderly subjects; immune function; non-communicable diseases; pneumonia; viral infections; vitamin C supplementation
    DOI:  https://doi.org/10.3389/fimmu.2020.574029
  6. Metabol Open. 2020 Nov 13. 100066
    Kritis P, Karampela I, Kokoris S, Dalamaga M.
      The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proved effective. COVID-19 pathophysiology involves the activation of three main pathways: the inflammatory, the coagulation and the bradykinin cascades. Here, we highlight for the first time the joint potential therapeutic role of bromelain and curcumin, two well-known nutraceuticals, in the prevention of severe COVID-19. Bromelain (a cysteine protease isolated from the pineapple stem) and curcumin (a natural phenol found in turmeric) exert important immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. Their anti-inflammatory properties include inhibition of transcription factors and subsequent downregulation of proinflammatory mediators. They also present fibrinolytic and anticoagulant properties. Additionally, bromelain inhibits cyclooxygenase and modulates prostaglandins and thromboxane, affecting both inflammation and coagulation, and also hydrolyzes bradykinin. Interestingly, curcumin has been shown in in silico studies to prevent entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells as well as viral replication, while a recent experimental study has demonstrated that bromelain may also inhibit viral entry into cells. Notably, bromelain substantially increases the absorption of curcumin after oral administration. To the best of our knowledge, this is the first report highlighting the significance of bromelain and, most importantly, the potential preventive value of the synergistic effects of bromelain and curcumin against severe COVID-19.
    Keywords:  ACE2, angiotensin-converting enzyme 2; COVID-19; COVID-19, coronavirus disease 19; COX-2, cyclooxygenase-2; NF-κB, nuclear factor kappa B; PG, prostaglandin; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2; STAT-3, signal transducer and activator of transcription 3; TMPRSS-2, trans-membrane serine protease 2; TXA2, thromboxane A2; bromelain; curcumin; nutraceuticals
    DOI:  https://doi.org/10.1016/j.metop.2020.100066
  7. Metabolism. 2020 Nov 17. pii: S0026-0495(20)30298-5. [Epub ahead of print] 154434
    Smolders J, van den Ouweland J, Geven C, Pickkers P, Kox M.
      
    Keywords:  COVID-19; Coronavirus; Cytokines; Inflammation; SARS-CoV-2; Vitamin D
    DOI:  https://doi.org/10.1016/j.metabol.2020.154434
  8. Curr Pharm Des. 2020 Nov 17.
    Wijayasinghe YS, Bhansali P, Viola RE, Kamal MA, Poddar NK.
      Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the prevention or treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-β-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anti-coronaviral research that has been published during last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies.
    Keywords:  COVID-19; Coronavirus; Natural products; Phytochemicals; SARS-CoV-2; Traditional Medicine
    DOI:  https://doi.org/10.2174/1381612826666201118111151
  9. Front Nutr. 2020 ;7 562051
    Kumrungsee T, Zhang P, Chartkul M, Yanaka N, Kato N.
      
    Keywords:  COVID-19; cardiovascular diseases; carnosine; diabetes; inflammasome; oxidative stress; pneumonia; vitamin B6
    DOI:  https://doi.org/10.3389/fnut.2020.562051
  10. Sci Rep. 2020 Nov 19. 10(1): 20191
    Jain A, Chaurasia R, Sengar NS, Singh M, Mahor S, Narain S.
      COVID-19 is characterized by marked variability in clinical severity. Vitamin D had recently been reviewed as one of the factors that may affect the severity in COVID-19. The objective of current study is to analyze the vitamin D level in COVID-19 patients and its impact on the disease severity. After approval from Ethics Committee, M.L.B Medical College the current study was undertaken as continuous prospective observational study of 6 weeks. Participants were COVID-19 patients of age group 30-60 years admitted during the study period of 6 weeks. Study included either asymptomatic COVID-19 patients (Group A) or severely ill patients requiring ICU admission (Group B). Serum concentration of 25 (OH)D, were measured along with serum IL-6; TNFα and serum ferritin. Standard statistical analysis was performed to analyze the differences. Current Study enrolled 154 patients, 91 in Group A and 63 patients in Group B. The mean level of vitamin D (in ng/mL) was 27.89 ± 6.21 in Group A and 14.35 ± 5.79 in Group B, the difference was highly significant. The prevalence of vitamin D deficiency was 32.96% and 96.82% respectively in Group A and Group B. Out of total 154 patients, 90 patients were found to be deficient in vitamin D (Group A: 29; Group B: 61). Serum level of inflammatory markers was found to be higher in vitamin D deficient COVID-19 patients viz. IL-6 level (in pg/mL) 19.34 ± 6.17 vs 12.18 ± 4.29; Serum ferritin 319.17 ± 38.21 ng/mL vs 186.83 ± 20.18 ng/mL; TNFα level (in pg/mL) 13.26 ± 5.64 vs 11.87 ± 3.15. The fatality rate was high in vitamin D deficient (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients. As per the flexible approach in the current COVID-19 pandemic authors recommend mass administration of vitamin D supplements to population at risk for COVID-19.
    DOI:  https://doi.org/10.1038/s41598-020-77093-z
  11. Nutr J. 2020 Nov 18. 19(1): 124
    Khubber S, Hashemifesharaki R, Mohammadi M, Gharibzahedi SMT.
      Coronavirus disease 2019 (COVID-19) is the current major health crisis in the world. A successful strategy to combat the COVID-19 pandemic is the improvement of nutritional pattern. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g., allicin and alliin) and flavonoid (e.g., quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main structural protease of SARS-CoV-2. The formation of hydrogen bonds between this serine-type protease and garlic bioactives in the active site regions inhibits the COVID-19 outbreak. The daily dietary intake of garlic and its derived-products as an adjuvant therapy may improve side effects and toxicity of the main therapeutic drugs with reducing the used dose.
    Keywords:  Allicin; Antiviral; COVID-19; Garlic; Quercetin; SARS-CoV-2
    DOI:  https://doi.org/10.1186/s12937-020-00643-8
  12. Evid Based Complement Alternat Med. 2020 ;2020 7493281
    Niu W, Wu F, Cui H, Cao W, Chao Y, Wu Z, Fan M, Liang C.
      "Three formulas and three medicines," which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, Qingfei Paidu decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, have been proven to be effective in curbing coronavirus disease 2019 (COVID-19), according to the State Administration of Traditional Chinese Medicine. The aims of this study were to identify the active components of "Three formulas and three medicines" that can be used to treat COVID-19, determine their mechanism of action via angiotensin-converting enzyme 2 (ACE2) by integrating network pharmacological approaches, and confirm the most effective components for COVID-19 treatment or prevention. We investigated all the compounds present in the aforementioned herbal ingredients. Compounds that could downregulate the transcription factors (TFs) of ACE2 and upregulate miRNAs of ACE2 were screened via a network pharmacology approach. Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2. Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to search for possible molecular mechanisms of these compounds. In conclusion, traditional Chinese medicine (TCM) plays a pivotal role in the prevention and treatment of COVID-19. Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.
    DOI:  https://doi.org/10.1155/2020/7493281
  13. Front Nutr. 2020 ;7 580504
    Sahin E, Orhan C, Uckun FM, Sahin K.
      The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 caused a major global pandemic and continues to be an unresolved global health crisis. The supportive care interventions for reducing the severity of symptoms along with participation in clinical trials of investigational treatments are the mainstay of COVID-19 management because there is no effective standard therapy for COVID-19. The comorbidity of COVID-19 rises in obese patients. Micronutrients may boost the host immunity against viral infections, including COVID-19. In this review, we discuss the clinical impact potential of supplemental nutrients as adjuncts of therapy in high-risk COVID-19 for obese patients.
    Keywords:  SARS-CoV-2; cytokines; inflammation; micronutrients; nutrition
    DOI:  https://doi.org/10.3389/fnut.2020.580504
  14. Med Hypotheses. 2020 Nov 11. pii: S0306-9877(20)33251-5. [Epub ahead of print] 110360
    Diep PT.
      
    DOI:  https://doi.org/10.1016/j.mehy.2020.110360
  15. Futur J Pharm Sci. 2020 ;6(1): 104
    Rajagopal K, Varakumar P, Baliwada A, Byran G.
      Background: In early 2020, many scientists are rushing to discover novel drugs and vaccines against the coronavirus, and treatments for COVID-19, because coronavirus disease 2019 (COVID-19), a life-threatening viral disease, affected first in China and quickly spread throughout the world. In this article, in silico studies have been performed to explore the binding modes of chemical constituents for natural remedies like Curcuma longa (turmeric) and Andrographis paniculata against COVID-19 (PDB ID 5R82) targeting coronavirus using Schrodinger suit 2019-4. The molecular docking studies are performed by the Glide module, in silico ADMET screening was performed by the QikProp module, and binding energy of ligands was calculated using the Prime MM-GB/SA module.Results: The chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone are significantly binding with the active site of SARS CoV-2 main protease with Glide score more than - 6 when compared to the currently used drugs hydroxychloroquine (- 5.47) and nelfinavir (- 5.93). When compared to remdesivir (- 6.38), cyclocurcumin from turmeric is significantly more active. The docking results of the compounds exhibited similar mode of interactions with SARS CoV-2. Main protease and the residues THR24, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, MET165, HIE164, PHE181, and THR54 play a crucial role in binding with ligands.
    Conclusion: Based on in silico investigations, the chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone, significantly binding with the active site of SARS CoV-2 main protease, may produce significant activity and be useful for further development.
    Keywords:  Andrographis paniculata; Coronavirus (COVID-19); Curcuma longa (turmeric); Docking studies; MM-GBSA
    DOI:  https://doi.org/10.1186/s43094-020-00126-x
  16. Comput Biol Med. 2020 Nov 03. pii: S0010-4825(20)30433-9. [Epub ahead of print]128 104102
    Natesh J, Mondal P, Penta D, Abdul Salam AA, Meeran SM.
      BACKGROUND: Coronavirus disease-2019 (COVID-19) is an infectious pandemic caused by SARS-CoV-2. SARS-CoV-2 main protease (Mpro) and spike protein are crucial for viral replication and transmission. Spike protein recognizes the human ACE2 receptor and transmits SARS-CoV-2 into the human body. Thus, Mpro, spike protein, and ACE2 receptor act as appropriate targets for the development of therapeutics against SARS-CoV-2. Spices are traditionally known to have anti-viral and immune-boosting activities. Therefore, we investigated the possible use of selected spice bioactives against the potential targets of SARS-CoV-2 using computational analysis.METHODS: Molecular docking analysis was performed to analyze the binding efficiency of spice bioactives against SARS-CoV-2 target proteins along with the standard drugs. Drug-likeness properties of selected spice bioactives were investigated using Lipinski's rule of five and the SWISSADME database. Pharmacological properties such as ADME/T, biological functions, and toxicity were analyzed using ADMETlab, PASS-prediction, and ProTox-II servers, respectively.
    RESULTS: Out of forty-six spice bioactives screened, six bioactives have shown relatively better binding energies than the standard drugs and have a higher binding affinity with at least more than two targets of SARS-CoV-2. The selected bioactives were analyzed for their binding similarities with the standard drug, remdesivir, towards the targets of SARS-CoV-2. Selected spice bioactives have shown potential drug-likeness properties, with higher GI absorption rate, lower toxicity with pleiotropic biological roles.
    CONCLUSIONS: Spice bioactives have the potential to bind with the specific targets involved in SARS-CoV-2 infection and transmission. Therefore, spice-based nutraceuticals can be developed for the prevention and treatment of COVID-19.
    Keywords:  COVID-19; Drug-likeness; Molecular docking; Nutraceuticals; SARS-CoV-2; Spices
    DOI:  https://doi.org/10.1016/j.compbiomed.2020.104102
  17. Front Immunol. 2020 ;11 590716
    Chowdhury P, Barooah AK.
      Innate immunity impairment led to disruption in cascade of signaling pathways upregulating pro-inflammatory cytokines, diminish interferons, depleted natural killer cells and activate reactive oxygen species production. These conditions severely affected body's ability to fight against infectious diseases and also plays a pivotal role in disease progression. Here, in emphasis is on nutritional immunity for regulating effective innate immune response for combating against infectious diseases like novel coronavirus disease (COVID 19). Drawing from discoveries on in-vitro experiments, animal models and human trials, tea polyphenols, micronutrients, and vitamins has the potential to modulate and enhance innate immune response. This article provides a comprehensive review on tea (Camellia sinensis L) infusion (a hot water extract of dried processed tea leaves prepared from young shoots of tea plant) as an innate immunity modulator. Tea infusion is rich in polyphenols; epigallocatechin gallate (EGCG) and theaflavin (TF), major green and black tea polyphenols, respectively. Studies showed their immunomodulatory competence. Tea infusions are also rich in alkaloids; caffeine and its intermediates, theophylline and theobromine, which have anti-inflammatory properties. Tea plant being an acidophilic perennial crop can accumulate different micronutrients, viz., copper (Cu), iron (Fe), manganese (Mn), selenium (Se), and zinc (Zn) from growing medium, i.e., from soil, which led to their considerable presence in tea infusion. Micronutrients are integral part of innate immune response. Overall, this review presents tea infusion as an important source of nutritional immunity which can enhance innate immune response in order to mitigate the unprecedented COVID-19 pandemic.
    Keywords:  coronavirus; cytokines; innate immunity; micronutrients; nutritional immunity; tea polyphenols; vitamins
    DOI:  https://doi.org/10.3389/fimmu.2020.590716
  18. J Thorac Dis. 2020 Oct;12(10): 6054-6069
    Al-Romaima A, Liao Y, Feng J, Qin X, Qin G.
      In December 2019, the coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered. Since its emergence, COVID-19 has been outbreaking rapidly worldwide, where the virus has so far caused the death of hundreds of thousands and infected more than a million, what has been called a pandemic by the World Health Organization (WHO). According to the WHO-Coronavirus disease 2019 Situation Report-142, by June 10, 2020, there are 7,145,539 confirmed cases and 408,025 deaths. There is an urgent need to develop a suitable specific medicine against this novel coronavirus; therefore, scientists and researchers around the world are making great efforts endeavoring to discover an efficient specific medication for COVID-19 treatment. Given the similarity of the novel coronavirus with previous epidemic viruses, namely, the acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), previously tested drugs could potentially work against the novel coronavirus. In this narrative review, we aim to summarize and discuss the effectiveness of current Western medicine and traditional Chinese medicine options for COVID-19 treatment based on the overview of the scientific literature. Some Western medicines including remdesivir, chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, and arbidol, as well as some traditional Chinese medicine (TCM) such as Qingfei Paidu decoction, Yupingfeng, Lianhua Qingwen, and TCM injections have revealed a relative activity against SARS-CoV-2 in vitro, in observational studies, and in clinical trials. However, further extensive studies and clinical trials including double-blind and randomized clinical trials, with a higher number of patients, are necessary to confirm the activity of these medicines. There are several ongoing trials conducted on the drugs of COVID-19, and the results are urgently needed to make a suitable treatment recommendation.
    Keywords:  Coronavirus disease 2019 (COVID-19); coronavirus; traditional Chinese medicine (TCM); treatment
    DOI:  https://doi.org/10.21037/jtd-20-1810
  19. EMBO Mol Med. 2020 Nov 14. e13424
    Marfia G, Navone S, Guarnaccia L, Campanella R, Mondoni M, Locatelli M, Barassi A, Fontana L, Palumbo F, Garzia E, Ciniglio Appiani G, Chiumello D, Miozzo M, Centanni S, Riboni L.
      The severity of coronavirus disease 2019 (COVID-19) is a crucial problem in patient treatment and outcome. The aim of this study is to evaluate circulating level of sphingosine-1-phosphate (S1P) along with severity markers, in COVID-19 patients. One hundred-eleven COVID-19 patients, and forty-seven healthy subject were included. The severity of COVID-19 was found significantly associated to anemia, lymphocytopenia, and significant increase of neutrophil-to-lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C-reactive protein (CRP), and D-dimer. Serum S1P level was inversely associated with COVID-19 severity, being significantly correlated with CRP, LDH, ferritin, and D-dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient's outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID-19 patients. Restoring abnormal S1P levels to a normal range, may have the potential to be a therapeutic target in patients with COVID-19.
    Keywords:  COVID-19; coronavirus; intensive care unit; prognostic biomarker; sphingosine-1-phosphate
    DOI:  https://doi.org/10.15252/emmm.202013424