FLCCC I-CARE RSV AND FLU TREATMENT PROTOCOL (2023)

A new protocol for patients suffering from Influenza and Respiratory Syncytial Virus (RSV) has been developed in a collaboration led by Dr Paul Marik, Dr Pierre Kory and the Front Line COVID-19 Critical Care Alliance (FLCCC).

In adult patients, COVID-19 (Omicron variant), influenza, and RSV present with a similar constellation of symptoms and physical findings. It may therefore be difficult to distinguish between these infections (particularly COVID-19 and influenza) based on clinical presentation alone.

For advice on how to protect yourself against infection, see I-PREVENT: COVID Protection Protocol. For treatment of COVID-19, see I-CARE: Early COVID Treatment Protocol.


influenza, RSV and COVID-19

The Problem With the Tripledemic Narrative

In a November 18, 2022, Science magazine article, Jon Cohen explained why a simultaneous tripledemic is unlikely:

“Triple threat. Tripledemic. A viral perfect storm. These frightening phrases have dominated recent headlines as some health officials, clinicians, and scientists forecast that SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) could surge at the same time in Northern Hemisphere locales that have relaxed masking, social distancing, and other COVID-19 precautions.

But a growing body of epidemiological and laboratory evidence offers some reassurance: SARS-CoV-2 and other respiratory viruses often ‘interfere’ with each other.

Although waves of each virus may stress emergency rooms and intensive care units, the small clique of researchers who study these viral collisions say there is little chance the trio will peak together and collectively crash hospital systems the way COVID-19 did at the pandemic’s start.

‘Flu and other respiratory viruses and SARS-CoV-2 just don’t get along very well together,’ says virologist Richard Webby, an influenza researcher at St. Jude Children’s Research Hospital. ‘It’s unlikely that they will circulate widely at the same time.’

‘One virus tends to bully the others,’ adds epidemiologist Ben Cowling at the University of Hong Kong School of Public Health. During the surge of the highly transmissible Omicron variant of SARS-CoV-2 in Hong Kong in March, Cowling found that other respiratory viruses ‘disappeared … and they came back again in April’ …

Recent advances in technology … make it easier to detect infections in people and study how multiple viruses behave … Increasingly, researchers are fingering a cause: chemical messengers that infected people produce called, fittingly, interferons.

When a respiratory virus sweeps through a community, interferons can broadly raise the body’s defenses and temporarily erect a population wide immune barrier against subsequent viruses that target the respiratory system.

‘Basically, every virus triggers the interferon response to some extent, and every virus is susceptible to it,’ says immunologist Ellen Foxman at Yale University, who has been exploring interference between SARS-CoV-2 and other viruses in a laboratory model of the human airway.

Rhinoviruses, which cause common colds, can trip up influenza A (the most prevalent flu virus). RSV can bump rhinoviruses and human metapneumoviruses. Influenza A can thwart its distant cousin influenza B.

‘There are a lot of major health implications from viral interference,’ says Guy Boivin, a virologist at Laval University who co-authored a review12 on viral interference earlier this year …

Unlike other immune responses — antibodies, for example — that target specific pathogens an animal has seen in the past, this nonspecific, rapid response [of interferon] is part of what’s known as the immune system’s innate arm.”

Influenza

Influenza characteristically begins with the abrupt onset of fever, nonproductive cough, and myalgia. [1] Other symptoms include malaise, sore throat, nausea, nasal congestion, and headache. Gastrointestinal symptoms like vomiting and diarrhea are usually not part of influenza in adults.

Older adults (≥65 years) and immunosuppressed patients are more likely to have subtle signs and symptoms; they may present without fever and with milder systemic symptoms than other patients; however, older adults have a higher frequency of altered mental status. [1]

To test for influenza, conventional reverse transcription polymerase chain reaction (RT-PCR) assays are preferred, if available; these are the most sensitive and specific tests for diagnosis of influenza virus infection. An alternative diagnostic test for influenza is an antigen detection assay. These assays have low to moderate sensitivity but high specificity.

Respiratory Syncytial Virus (RSV)

RSV is a negative sense RNA virus that is highly infectious, with an R0 of 8-15. Although virtually all individuals have been infected with RSV by two years old, previous infection with RSV does not appear to protect against reinfection, even in patients with high titers of specific antibody. Cell-mediated immunity (CMI) may play an important role in eliminating the virus. [2]

RSV pathogenesis is associated with Th2 polarization of the immune response in the lungs. [3] A formaldehyde-inactivated RSV vaccine administered to toddlers in 1996 was associated with a hospitalization rate of 80% following RSV infection, as compared to 5% in the controls. [3-6] An aberrant Th2-mediated immune response following vaccination was postulated to account for this outcome. [3;4] Furthermore, non-neutralizing antibodies against RSV in seronegative individuals may have primed the patients to develop this aberrant immune response. [3]

During the coronavirus disease 2019 (COVID-19) pandemic, mitigation measures (lockdowns, physical distancing, school closure) were associated with marked reductions in non-COVID-19 respiratory infections in children, including RSV. [7] 2022 has seen a dramatic increase in the number of patients hospitalized with RSV. It is possible that this is related to an increased attack rate following the lockdowns as well as a more robust Th2 response. Prior exposure to SARS-CoV-2 may be associated with a predominant Th2 response. [8;9]

The clinical manifestations of RSV vary with patient’s age, health status, and whether the infection is primary or secondary. [2] RSV is a significant cause of death in infants and young children. Healthy adults are infected with RSV repeatedly throughout their lives and typically have symptoms restricted to the upper respiratory tract. Signs include cough, coryza, rhinorrhea, and conjunctivitis. Compared with other respiratory viruses, RSV is more likely to cause sinus and ear involvement with less prominent fever. [2] RSV is an important and often unrecognized cause of lower respiratory tract infection in older adults and immunocompromised adults.

Diagnosis of RSV is based on a PCR test as well as rapid antigen tests. In adults, the antigen tests have a high specificity however they are less sensitive than PCR-based assays.

Treatment for Influenza and RSV (in order of priority, not all required)

This protocol should also be used in patients with an undiagnosed flu-like illness, i.e., those who have not been tested or those whose tests are negative. We would suggest this treatment protocol in those with diagnosed Respiratory Syncytial Virus (RSV); however, in low-risk patients with mild RSV we would suggest omitting Nitazoxanide/Ivermectin.

1.Naso-Oropharyngeal hygiene. Influenza, SARS-CoV-2 and almost all respiratory viruses replicate primarily in the naso-pharynx. A 1% povidone-iodine nasal spray and a nasal spray with Iota-Carrageenan are potent inhibitors of SARS-CoV-2 and influenza virus, and dramatically alter the course of infections with these viruses. [10-16] The spray should be administered 2-3 times per day. Nasal irrigations with saline as well as neutral electrolyzed water may also be of some benefit. [17;18]

In addition, antiseptic-antimicrobial mouthwashes have been shown in multiple research studies to inhibit replication of multiple respiratory viruses, including SARS-COV-2, influenzae, respiratory syncytial virus, etc. We suggest using a mouthwash/gargle in addition to a nasal spray. We recommend products containing chlorhexidine, povidone-iodine, cetylpyridinium chloride, or the combination of eucalyptus, menthol, and thymol (Listerine™). Gargle with these solutions 2-3 times/day.

2Elderberry. Black elderberry (Sambucus nigra) has traditionally been used to treat cold and flu symptoms. Elderberries contain a great variety of flavones, isoflavones, flavanols, anthocyanins, phenolic acids, lectins, and many vitamins. The active chemicals include anthocyanins, primarily cyanidin 3-glucoside and cyanidin 3-sambubioside, which have been shown to have immune-modulating effects as well as antiviral properties, including against coronaviruses and influenza viruses. [19;20] The active compounds have been demonstrated to bind to H1N1 virions, blocking host cell entry and/or recognition. [21] Oral ingestion of elderberry results in detectable levels of these anthocyanins in blood plasma. A recent meta-analysis demonstrated that supplementation with elderberry was found to substantially reduce upper respiratory symptoms in patients with influenza. [22] We therefore recommend the use of elderberry syrups or supplements, following the dosing recommendations on the package. A triple combination containing elderberry, Vitamin C, and Zinc may be a convenient approach. Elderberries should be used with caution in patients with autoimmune diseases such as multiple sclerosis, lupus erythematous and rheumatoid arthritis as this nutraceutical may activate the immune system worsening symptoms of the autoimmune disease.[23] Elderberries have not been reported to have drug-food interactions,[24] however caution is suggested with the with use immunosuppressant drugs including those use in transplant patients as elderberry may increase cytokines thereby interfering with effectiveness of these drugs.[23] Insufficient evidence is available for use during pregnancy or breastfeeding. [23] Elderberry fruit extracts have most often been used by adults in doses up to 1200 mg daily orally for 2 weeks. Elderberry is available in many different types of products, including syrups, tablets, and mouth rinses. Don’t consume green, unripe, uncooked elderberries. They contain toxins and can be poisonous.

3. Vitamin C. Vitamin C has important anti-inflammatory, antioxidant, and immune-enhancing properties, including increased synthesis of type I interferons. [25-30] Vitamin C increases interferons and the innate antiviral response mediated by RIG-I-mediated signal transduction pathways. [31] The effects of Vitamin C on the course of upper respiratory tract infections have long been recognized. [32]

We recommend a dose of 500-1000 mg taken four times daily. Oxidant injury plays a major role in the pathogenesis of RSV lung disease; [33] a combination of antioxidants including Vitamin C, NAC, and melatonin may therefore play a major role in ameliorating this disease.

4. Nitazoxanide (NTZ): NTZ is an oral antiparasitic drug having activity against many protozoa and helminths and – like ivermectin – has been shown to have antiviral, anti-inflammatory, and immune-modulatory effects. [14;15] NTZ has broad spectrum antiviral activity that includes influenza virus, respiratory syncytial virus (RSV), and SARS-CoV-2 [15-18] Nitazoxanide appears to be highly effective against influenza. NTZ inhibits replication of a broad range of influenza viruses, including neuraminidase inhibitor-resistant strains, blocking the maturation of viral hemagglutinin at the post-translational level. [19]

The US Nitazoxanide Influenza Clinical Study Group randomized 622 patients for at least one respiratory symptom, and one constitutional symptom of influenza within 48 hours of symptom onset to receive either nitazoxanide 600 mg, nitazoxanide 300 mg, or placebo twice daily for 5 days. [20] The median duration of symptoms for participants receiving placebo was 116·7 h (95% CI 108·1–122·1) compared with 95·5 h (84·0–108·0; p=0·0084) for those receiving 600 mg nitazoxanide and 109·1 h (96·1–129·5, p=0·52) for those receiving 300 mg nitazoxanide (median difference of 21.2 hr for the 600 mg group). Adverse events were similar between the three groups. It is interesting to note that the duration of symptoms was significantly shorter in the NTZ group that was viral culture negative.

It should be noted that while NTZ is relatively cheap in almost all countries in the world (approx. $0.31 per tablet), the main distributor in the US (Alinia™) charges exorbitant prices (> $500 for 6 tablets). We, therefore, suggest that 500 mg or 600 mg tablets be ordered from a compounding pharmacy in the US or a reliable pharmacy abroad.

5.  Ivermectin. In-vitro (test tube) studies suggest that ivermectin has broad antiviral activity against RNA viruses including influenza virus. [34-36] It is likely that ivermectin has clinical efficacy in patients with influenza. However, there is no (published) clinical data on the use of ivermectin in the treatment of influenza. We, therefore, recommend ivermectin as part of a multi-drug regimen when nitazoxanide is not available. We suggest a dose of 400 ug/kg/day for 5 days. Ivermectin is best taken with a meal. This drug should be avoided in pregnancy and in patients taking calcineurin inhibitors (cyclosporine and Prograf).

6.  Zinc.  Zinc is essential for innate and adaptive immunity, with zinc deficiency being a major risk factor for influenza. [37-39] Due to competitive binding with the same gut transporter, prolonged high-dose zinc (> 50mg day) should be avoided, as this is associated with copper deficiency. [40] Commercial zinc supplements contain 7 to 80 mg of elemental zinc and are commonly formulated as zinc oxide or salts with acetate, gluconate, and sulfate; 220 mg zinc sulfate contains 50 mg of elemental zinc. A dose of 50-90 mg/day of elemental zinc is recommended. [37-39]

7.  N-acetylcysteine (NAC)NAC is the precursor of reduced glutathione. NAC penetrates cells where it is deacetylated to yield L-cysteine, thereby promoting glutathione (GSH) synthesis. [41] NAC has a broad range of antioxidant, anti-inflammatory, and immune-modulating mechanisms, and has demonstrated benefit in both experimental models and in patients with COVID-19, influenza, and RSV infections. [41-50] A dose of 600-1200 mg orally twice a day is suggested.

8.  Sunlight and photobiomodulation (PBM)PBM is referred to in the literature as low-level light therapy, red light therapy, and near-infrared light therapy. Our forefathers roamed the earth and were exposed to sunlight on a daily basis, likely with profoundly important health benefits. [51] The spectral radiance of solar radiation extends from 10 nm to about 3000 nm i.e., the spectrum from ultraviolet (10 -400 nm), visible (400-700 nm with red light 600-700 nm), near-infrared radiation (750-1500 nm (NIR-A)) and mid-infrared radiation (1500- 3000 nm (NIR-B)).

Sunlight has great therapeutic powers. Indeed, during the 1918 influenza pandemic, “open-air treatment of influenzae” appeared to be the most effective treatment for seriously ill patients reducing hospital mortality from 40% to about 10%. [52] The Surgeon-General of Massachusetts reported that “plenty of air and sunshine” was highly effective for the treatment of influenzae pneumonia. He reported that “very little medicine was given after the value of plenty of air and sunshine had been demonstrated.” Further, he commented: “from being discouraged, the medical staff became enthusiastic, and the patients were treated with the confidence that at last something had been found which would give good results.”

Apart from UV radiation stimulating Vitamin D synthesis, red and NIR-A radiation have a profound effect on human physiology, notably acting as a mitochondrial stimulant and increasing ATP production. [53] Furthermore, IR light profoundly modulates inflammatory pathways and inflammatory genes. [53;54]

Based on this data, we suggest that patients expose themselves to about 30 mins of midday sunshine. When this is neither feasible nor practical, patients can expose themselves to red and NIR radiation emitted from LED panels or incandescent lamps.

9. MelatoninMelatonin is a potent antioxidant with important anti-inflammatory effects. We suggest a dose of 5-10 mg at night. [55-61] Slow- or extended-release preparations are preferred, as this minimizes the risk of bad dreams. If 10 mg is not well tolerated, cut the dose to 5 mg, and slowly increase as tolerated.

10. Symptomatic treatments. In patients who are highly symptomatic, over-the-counter “flu” preparations with acetaminophen, antihistamines, and a decongestant are suggested.

Not recommended:

1.  Tamiflu. The Tamiflu saga (summarized below) highlights the fraud, deception, and abuse perpetrated by Big Pharma and the agencies (FDA) with which they conspire.

Since the first pandemic scare of this century (H5N1 avian influenza in 2004), governments have been stockpiling the neuraminidase inhibitors zanamivir (Relenza) and especially oseltamivir (Tamiflu) in vast quantities. [62] The UK, US, and many other countries hold enough stocks of these antivirals to offer courses of treatment to a quarter of their population. Of 28 European states that have published a pandemic response plan, all but one (Poland) make oseltamivir the mainstay of their response.

These recommendations were based on a 2003 pooled analysis by Laurent Kaiser and colleagues, which was based on 10 randomized controlled trials, of which only two had been published. [63] Most of the data supporting oseltamivir’s claim to reduce lower respiratory tract complications had never seen the light of day (another example of Big Pharma playing the fraudulent Disinformation Playbook). [64] The BMJ and Cochrane reviewers contacted the authors of the 2003 paper but were told they did not have the data on the missing eight studies. [62] So the Cochrane team went to the source, the manufacturer, Roche. The company refused to release the data unless the reviewers signed a confidentiality agreement with a secrecy clause. [62] This they weren’t prepared to do, as it could stop them reporting their findings. So began a campaign of public pressure that lasted four years.

A freedom of information request shook loose 20,000 pages of incomplete oseltamivir data from the European Medicines Agency in 2011. Later in 2011, Roche finally relented and released 77 full clinical study reports of oseltamivir trials. Importantly, none of the trials was independent of the drug’s manufacturer; in addition, all were against placebo rather than against standard drugs for relieving symptoms, such as acetaminophen. [65] Furthermore, many of the published studies were ghost-written and in many instances it was impossible to work out who actually carried out the research. [65;66]

A Cochrane review in 2014 that used the newly released data found insufficient evidence to support claims that oseltamivir reduced lower respiratory tract complications or impeded viral transmission. [67;68] There was no significant reduction in risk of pneumonia, bronchitis, otitis media, sinusitis, or any complication classified as serious and no reduction in the risk of hospitalization. The reviewers also raised new questions about the drug’s harm profile; the use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults, and vomiting in children.

An additional analysis demonstrated that Oseltamivir had no protective effect on mortality among patients with 2009A/H1N1 influenza. [69] Furthermore, data suggests that Tamiflu does not have antiviral properties but rather acts as an antipyretic (fever reducer). [62] As treatment with Tamiflu only suppresses symptoms, “then infected people could be going to work and school feeling fine, while passing on the flu virus.” [62] Despite these data,  pandemic stockpiles are still being scrupulously topped up and the “influenza pandemic”  response plans of the UK and US have not changed in over a decade (another example of the Pharma-Government fraudulent collaboration). [62]

2.  Patients with upper respiratory tract infections should NOT empirically be treated with antibiotics unless they develop a documented complicating bacterial infection.

Reference List

  1. Dolin R. Seasonal influenza in adults: Clinical manifestations and diagnosis. https://www uptodate com [ 2022  [cited 2022 Nov. 15];
  2. Barr FE, Graham BS. Respiratory syncytial virus infection: Clinical features and diagnosis. https://www uptodate com [ 2022  [cited 2022 Nov. 15];
  3. Acosta PL, Cabellero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clinical and Vaccine Immunology 2016; 23:189-195.
  4. Boelen A, Andeweg A, Kwakkel J, Lokhorst W, Dormans J. Both immunisation with formalin-inactivated respiratory syncytial virus (RSV) vaccine and a mock antigen vaccine induce severe lung pathology and a Th2 cytokine profile in RSV-challenged mice. Vaccine 2000; 19:982-991.
  5. Thomas S, Smatti MK, Ouhtit A, Cyprian FS, Thani AA. Antibody-dependnet enhancement and the role of complement system in disease pathogenesis. Molecular Immunology 2022; 152:172-182.
  6. Gimenez HB, Chrisholm S, Dornan J, Cash P. Neutralizing and enhancing activities of human respiratory syncytial virus-specific antibodies. Clinical and Diagnostic Laboratory Immunology 1996;(3):-280.
  7. Van Brusselen D, De Troeyer K, ter Haar E, Vander Auwera A, Poschet K, Van Nuijs S et al. Bronchiolitis in COVID-19 times: a nearly absent disease? Eur J Pediatr 2021; 180:1969-1973.
  8. Roman M, Calhoun WJ, Hinton KL, Avendano LF, Simon V, Escobar AM et al. Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. Am J Respir Crit Care Med 1997; 156:190-195.
  9. Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Type 1 and Type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 2003; 168:633-639.
  10. Choudhury IM, Shabnam N, Ahsan T, Kabir S, Ahsan SM. Effect of 1% povidone iodine mouthwash/gargle, nasal and eye drop in COVID-19 patient. Bioresearch Communications 2021; 7.
  11. Eccles R, Meier C, Jawad M, Weinmullner R, Grassauer A. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold. Respiratory Research 2010; 11:108.
  12. Koenighofer M, Lion T, Bodenteich A, Grassauer A, Unger H, Mueller CA. Carrageenan nasal spray in virus conformed common cold: individual patient data analysis of two randomized controlled trials. Mutlidisciplinary Respiratory Medicine 2014; 9:57.
  13. Eccles R, Winther B, Johnston SL, Robinson P, Trampisch M, Koelsch S. Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial. Respiratory Research 2022; 16:121.
  14. Leibbrandt A, Meier C, Konig-Schuster M, Weinmullner R, Kalthoff D, Graf P et al. Iota-Carrageenan is a potent inhibitor of Influenza A virus infection. PloS ONE 2010; 5:e14320.
  15. Hemila H, Chalker E. Carrageenan nasal spray may double the rate of recovery from coronavirus and influenza virus infections: Re-analysis of randomized trial data. Pharmacol Res Perspect 2021; 9:e00810.
  16. Meister TL, Briggemann Y, Todt D, Muller JA, Grob R. Virucidal efficacy of different oral rinses against severe acute respiratory syndrome coronavirus 2. J Infect Dis 2020; 222:1289-1292.
  17. Baxter AL, Schwartz KR, Johnson RW, Swartout KM. Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients. Ear, Nose & Throat Journal 2022.
  18. Gutierrez-Garcia R, De La Cerda-Angeles JC, Cabrera-Licona A, Delgado-Encisco I. Nasopharyngeal and oropharyngeal rinses with neutral electrolyzed water prevents COVID-19 in front-line health professionals: A randomized, open-label, controlled trial in a general hospital in Mexico City. Biomedical Reports 2022; 16:11.
  19. Mocanu ML, Amariei S. Elderberries – A source of bioactive compounds with antiviral action. Plants 2022; 11:740.
  20. Boroduske A, Jekabsons K, Riekstina U, Muceniece R, Rostoks N, Nakurte I. Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro. Industrial Crops & Products 2021; 165:113438.
  21. Roschek B, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 2009; 70:1255-1261.
  22. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complementary Therapies in Medicine 2019; 42:361-365.
  23. Martini N. Elderberry. J Prim Health Care 2021; 13:91-92.
  24. Sprouce AA, van Breemen RB. Pharmacokinetic interactions between drugs and botanical dietary supplements. Drug Metab Dispos 2016; 44:162-171.
  25. Marik PE. Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) for the treatment of sepsis. Focus on ascorbic acid. Nutrients 2018; 10:1762.
  26. Marik PE. Vitamin C for the treatment of sepsis: The scientific rationale. Pharmacol Therapeut 2018; 189:63-70.
  27. Colunga Biancatelli RM, Berrill M, Marik PE. The antiviral properties of vitamin C. Expert Rev Anti Infect Ther 2020; 18:99-101.
  28. Miranda-Massari JR, Toro AP, Loh D, Rodriguez JR, Borges RM. The effects of vitamin C on the multiple pathological stages of COVID-19. Life 2021; 11:1341.
  29. Holford P, Carr AC, Zawari M, Vizcaychipi MP. Vitamin C intervention for Critical COVID-19: A pragmatic review of the current level of evidence. Life 2021; 11:1166.
  30. Kim Y, Kim H, Bae S, Choi J, Lim SY, Lee N. Vitamin C is an essential factor on the anti-viral immune response through the production of interferon-alpha/beta at the initial stage of Influenza A virus (H3N2) infection. Immune Network 2013; 13:70-74.
  31. Cai Y, Li YF, Tang LP, Tsoi B, Chen M, Chen H et al. A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. BioMed Research International 2015; 2015:675149.
  32. Ely JT. Ascorbic acid role in containment of the world avian flu pandemic. Experimental Biology & Medicine 2007; 232(7):847-851.
  33. Hosakote YM, Jantzi PD, Esham DL, Spratt H, Kurosky A. Viral-mediated in hibition of antioxidant enzymes contributes to the pathogenesis of severe Respiratory Syncytial Virus bronchiolitis. Am J Respir Crit Care Med 2011; 183:1550-1560.
  34. Caly L, Wagstaff KM, Jans DA. Nuclear trafficking of proteins from RNA viruses: Potential targer for antivirals? Antiviral Res 2012; 95:202-206.
  35. Jans DA, Wagstaff KM. Ivermectin as a broad-spectrum host directed anti-viral: The real deal. Cells 2020; 9:2100.
  36. Gotz V, Magar L, Dornfeld D, Giese S, Hoper D, Jans DA et al. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Scientific Reports 2016; 6:23138.
  37. Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients 2017; 9(6).
  38. Hemila H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. J Royal Soc Med Open 2017; 8:1-7.
  39. Calder PC. Nutrition, immunity and COVID-19. BMJ Nutrition, Prevenion & Health 2020; 3(e000085).
  40. Willis MS, Monaghan SA, Miller ML, McKenna RW. Zinc-induced copper deficiency. A report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005; 123:125-131.
  41. De Flora S, Balansky R, La Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J 2020.
  42. Shi Z, Puyo CA. N-Acetylcysteine to combat COVID-19: an evidence review. Therapeutics and Clinical Risk Management 2020; 16:1047-1055.
  43. Assimakopoulos SF, Aretha D, Kominos D, Dimitropoulou D, Lagadinou M. N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study. Infectious Diseases 2021; 53(11):847-854.
  44. Kumar P, Osahon O, Vides DB, Hanania N, Minard CG. Severe glutathione deficiency, oxidative stress and oxidant damage in adults hospitalized with COVID-19: implications for GlyNac (Glycine and N-acetylcysteine) supplementaion. Antioxidants 2022; 11(50).
  45. Altay O, Arif M, Li X, Yang H, Aydin M, Alkurt G. Combined metabolic activators accelerates recovery in mild-to-moderate COVID-19. Adv Sci 2021;202101222.
  46. Izquierdo JL, Soriano JB, Gonzalez Y, Lumbreras S. Use of N-Acetylcysteine at high doses as an oral treatment for patients with COVID-19. Science Progress 2022; 105.
  47. Mata M, Sarrion I, Armengot M, Carda C, Martinez I, Melero JA et al. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: Effectiveness of N-Acetylcysteine. PloS ONE 2012; 7:e48037.
  48. Chi L, Shan Y, Cui Z. N-acetyl-L-cysteine protects airway epithelial cells during respiratory syncytial virus infection against mucin synthesis, oxidative stress, and inflammatory response and inhibits HSPA6 expression. Analytical Cellular Pathology 2022; 2022:4846336.
  49. Mata M, Morcillo E, Gimeno C, Cortijo J. N-acetyl-l-cysteine (NAC) inhibits mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV). Biocemical Pharmacology 2011; 82:548-555.
  50. Zhang RH, Li CH, Wang CL, Xu MJ, Xu T, Wei D et al. N-acetyl-L-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury. International Immunopharmacology 2014; 22:1-8.
  51. Heiskanen V, Pfiffner M, Partonen T. Sunlight and health; shifting the focus from vitamin D3 to photobiomodulation by red and near-infrared light. Ageing Research Reviews 2022; 61:101089.
  52. Hobday RA, Cason JW. The open-air treatment of pandemic influenza. Am J Public Health 2022; 99 Suppl.2:S236-S242.
  53. Hamblin MR. Mechanisms and application of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 2017; 4:337-361.
  54. Aguida B, Pooam M, Ahmad M, Jourdan N. Infrared light therapy relieves TLR-4 dependent hyper-inflammation of the type induced by COVID-19. Communicative & Integrative Biology 2021; 14(1):-200.
  55. Gandolfi JV, Di Bernardo AP, Chanes DA, Martin DF, Joles VB, Amendola CP et al. The effects of melatonin supplementation on sleep quality and assessment of the serum melatonin in ICU patients: A randomized controlled trial. Crit Care Med 2020.
  56. Castillo RR, Quizon GR, Juco MJ, Roman AD, de Leon DG, Punzalan FE et al. Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series. Melatonin Res 2021; 3:297-310.
  57. Ramiall V, Zucker J, Tatonetti N. Melatonin is significantly associated with survival of intubated COVID-19 patients. medRxiv 2021.
  58. Farnoosh G, Akbaariqomi M, Badri T, Bagheri M, Izadi M. Efficacy of a low dose of melatonin as an adjunctive therapy in hospitalized patients with COVID-19: A randomized, double-blind clinical trial. medRxiv 2021.
  59. Hasan ZT, AlAtrakji MQ, Mehuaiden AK. The effect of melatonin on thrombosis, sepsis and mortality rate in COVID-19 patients. International Journal of Infectious Diseases 2022; 114:79-84.
  60. Farnoosh G, Akbariqomi M, Badri T, Bagheri M, Izadi M, rezaie E. Efficacy of a low dose of melatonin as an adjunctive therapy in hospitalized patietns with COVID-19: A randomized, double-blind clinical trial. Archives of Medical Research 2021.
  61. Darban M, Malek F, Memarian M, Gohari A, Kiani A, Emadi A. Efficacy of high dose vitamin C, melatonin and zinc in Iranian patients with acute respiratory sydrome due to Coronavirus infection: A pilot randomized trial. Journal of Cellular & Molecular Anesthesia 2021; 6:164-167.
  62. Dyer O. What did we learn from Tamiflu? BMJ 2020; 368:m626.
  63. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of Oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2002; 163:1667-1672.
  64. The Disinformation Playbook. https://www ucsusa org/resources/disinformation-playbook [ 2018  [cited 2022 Nov. 15];
  65. Loder E, Tovey D, Godlee F. The Tamiflu trials. Progress towards data sharing but many battles still to fight. BMJ 2014; 348:g2630.
  66. Cohen D. Complications: tracking down the data on oseltamivir. BMJ 2009; 339:b5387.
  67. Jones JT, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database of Syst Rev 2014; 4:CD008965.
  68. Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348:g2545.
  69. Heneghan CJ, Onakpoya I, Jones MA, Doshi P, Hama R, Spencer EA et al. Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data. Health Technology Assessment 2016; 42.



Comments

Pages

Archive

Show more

Popular posts from this blog

Best 6 Retirement Villages in Malaysia 2024

Glutathione vs NAD: What's the Difference?

6 Best Cloud Kitchens in Kuala Lumpur and Selangor 2024

6 Best NMN Supplements To Buy In 2024

12 Best SME Business Loans in Malaysia 2024

Estate Planning in Malaysia: Importance, Process, Will vs Trust, and Challenging a Will

FLCCC I-Care Early Treatment Protocol (2023)

10 Best E Wallets in Malaysia 2024

FLCCC I-Recover Protocol: Post Vaccine Treatment Protocol (2023)

Best 7 Executive MBAs in Malaysia 2022