Paper Compilation

headache (OR 1.50, 95% CI 1.28-1.75) as symptoms at hospital admission were also associated (all, p <0.01) with a higher number of symptoms after COVID.

https://spiral.imperial.ac.uk/bitstream/10044/1/89844/9/REACT_long_covid_paper_final.pdf

Among the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2%
(95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least
one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This
gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and
2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people (8,771/28,713 [30.5%])
with at least one symptom lasting 12 weeks or more reported having had severe COVID-19
symptoms (“significant effect on my daily life”)

Chronic Inflammation

https://www.healthline.com/health/chronic-inflammation

Scientific Paper Compilation

This blog is accurate as per publishing date 21st November 2020. Scientific literature changes dynamically and evidence will change as time progresses.

Antiseptic Gargles & Betadine

In vitro study from Germany which demonstrated viricidal effects of iodine and alcohol based gargles against SARS-COV2. These two were more effective that other mouthwashes and gargles in inhibiting replication of SARS-COV2 virus.

https://academic.oup.com/jid/article/222/8/1289/5878067

This study compared iodine and alcohol based gargles as well as nasal sinus rinse treatments to inhibit SARS-COV2 virus. Listerine ( alcohol based ) achieved 99.9 % inhibition within a minute and Betadine ( povidone iodine ) required 2 minutes to achieve 99.9 % inhibition.

https://onlinelibrary.wiley.com/doi/10.1002/jmv.26514

Small pilot prospective trial from Malaysia demonstrating SARS-COV2 viral clearance within six days with Betadine gargle three times a day for 30 seconds each. In comparison, essential oil gargle group achieved 80 % clearance, tap water gargle achieved 20 % and no gargling achieved 0 % clearance of virus on repeat RtPCR testing on day 6.

https://clinicaltrials.gov/ct2/show/results/NCT04410159?term=mouth+wash&recrs=e&rslt=With&cond=covid&draw=2&rank=1

Quercetin: Derived from Ayurvedic plant 'Vidanga' and constituent of 'Triphala'

Cell study: Suppression of Hepatitis C virus replication by NS3 Protease inhibition

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2893.2011.01507.x

Cell study: Quercetin inhibits RNA and DNA Polymerase in bacteria

https://link.springer.com/article/10.1007/BF01941188

Cell study: Inhibition of SARS-COV and MERS-COV by Cysteine protease inhibition

https://www.tandfonline.com/doi/full/10.1080/14756366.2016.1265519

Cell study: Zinc Ionophone ( increasing intra-cellular levels of Zinc ) effects of Quercetin

https://pubmed.ncbi.nlm.nih.gov/25050823/

Computer molecular docking study: Quercetin potential inhibitor of SARS-COV2

https://www.sciencedirect.com/science/article/pii/S0141813020339970

Summary:

Quercetin is a Plant based flavanoid readily available in Onions, Apples, Strawberries etc. It has been used in traditional Indian medicine and demonstrates a double action of inhibiting SARS-COV2 virus by Cyteine Protease inhibition as well as Zinc Ionophone action. It should be taken with Zinc and Vitamin C as it appears to work synergistically with them.

Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses

https://pubmed.ncbi.nlm.nih.gov/28629136/

Increasing the intracellular Zn concentration with zinc-ionophores such as PT can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. This study demonstrates that the combination of Zn and PT inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture.

https://pubmed.ncbi.nlm.nih.gov/21079686/

Vitamin D may be a prophylactic and treatment strategy against COVID-19. This meta-analysis of randomized controlled trials indicates a protective effect of vitamin D supplementation against respiratory tract infections.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065835

This pilot study published in BMJ demonstrated quicker resolution and lower fibrinogen levels in patients who received high dose Vitamin D 60,000 IU Cholecalciferol

https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-2020-139065

This small pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19

https://pubmed.ncbi.nlm.nih.gov/32871238/

Magnesium

In this study Patients were administered oral vitamin D3 1000 IU OD, magnesium 150mg OD and vitamin B12 500mcg OD (DMB) upon admission. DMB combination in older COVID-19 patients was associated with a reduction in proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support.

https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v2

Serum magnesium was inversely correlated with hs-CRP which is a marker of inflammation often associated with metabolic syndrome.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685774/

Melatonin

Melatonin's multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses)

https://www.frontiersin.org/articles/10.3389/fmed.2020.00226/full#B51

Scientific paper suggesting how Melatonin counteracts changes related to COVID19 hyperimmune response

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211589/

The possible beneficial effects of melatonin as adjuvant use in COVID-19 in anti-inflammation, anti-oxidation, immune response regulation has been repeatedly demonstrated in respiratory disorder models induced by infections and associated complications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102583/

Curcumin: Derived from Ayurvedic herb Turmeric

Curcumin, has shown beneficial effects on the progression of inflammatory diseases due to its numerous action mechanisms: antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective.

https://www.frontiersin.org/articles/10.3389/fphar.2021.675287/full

Cell Study: Curcumin inhibits Zika and Chikungunya virus. It appears to inhibit viral cell binding to host cells through a membrane effect on enveloped viruses.

https://www.sciencedirect.com/science/article/pii/S0166354216307483

Curcumin strongly inhibits TGEV proliferation and viral protein expression in a dose-dependent manner ( alpha coronavirus family )

https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001466

Computer Molecular docking study: Curcumin theorized to inhibit interaction of SARS-COV2 spike protein with ACE-2 receptor

https://pubs.rsc.org/en/content/articlelanding/2020/ra/d0ra03167d#!divAbstract

Summary:

Curcuminoids, derived from Turmeric have long been known to have antiviral effects. It's likely however that in case of Covid19 , the benefits of Curcumin would extend further with its anti-inflammatory effects, particularly on inhibition of JAK-STAT pathwayas discussed in previous blogs.

Omega 3 Fatty Acids

Omega-3s have anti-thrombotic, anti-inflammatory, anti-arrythmogenic, anti-fibrotic and membrane stabilizing properties

https://www.sciencedirect.com/science/article/pii/S0914508715002300

Coenzyme Q10

Numerous disease processes associated with CoQ₁₀ deficiency can benefit from CoQ₁₀ supplementation, including primary and secondary CoQ₁₀ deficiencies, mitochondrial diseases, fibromyalgia, cardiovascular disease, neurodegenerative diseases, cancer, diabetes mellitus, male infertility, and periodontal disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112525/

Thiamine / Vitamin B1

Thiamine deficiency can result in impaired aerobic respiration and cellular energy production. Although thiamine deficiency is a known cause of lactic acidosis, it has been recently evaluated as a potential contributor to refractory lactic acidosis and organ injury in septic shock and other shock states.

http://jtd.amegroups.com/article/view/34757/html

In this study Thiamine administration within 24 hours of admission in patients presenting with septic shock was associated with improved lactate clearance and a reduction in 28-day mortality compared with matched controls.

http://jtd.amegroups.com/article/view/34757/html

Budesonide Inhaler

This pilot RCT published in reputable British Journal 'The Lancet' demonstrated a statistically significant reduction in hospitalization in patients given budesonide inhaler compared to controls. Dose was 800 mcg twice a day via turbohaler. 1 % patients in treatment arm were hospitalized compared to 14 % in treatment arm. Prior to this there had been other case studies published from Texas, USA which showed beneficial effects of steroid based inhalers for early Covid19. Since systemic steroids have shown reduction of progression and mortality in hospitalized patients, there is certainly a scientific plausibility that an inhalers steroid should also help. Since steroids are immune modulatory but also immune suppresant, I personally use this under cover of an antibiotic such as Doxycycline and reserve it for increased risk patients, patients with pre-existing respiratory airway disease and patients progressing after day ten of illness.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00171-5/fulltext

N- Acetyl Cysteine

Thrombolytic effect of NAC on arterial thrombi

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.027290

Study demonstrating use of IV NAC to reduce inflammation in severely ill COVID19 patient from New York, USA.

https://www.sciencedirect.com/science/article/pii/S1521661620306513

COLCHICINE:

Colchicine exerts anti-inflammatory effect in conditions like gout, pericaridtis and acute coronary syndrome by NRLP inflammazome pathway down regulation. This leads to disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, which prevents activation, degranulation, and migration of neutrophils

Colchicine interferes with intracellular assembly of inflammasome complex present in neutrophils and monocytes, which mediates activation of interleukin-1β and other pro inflammatory cytokines.

Colcorona was a prospective double blinded placebo controlled trial in which patients above the age of 40 were given colchicine within 24 hours of Covid19 diagnosis.

Analysis of the 4,159 patients who had swab confirmed Covid19 shows statistically significant reduction in

-hospitalisation by 25 %

-death by 44 %

-ICU intubation by 50 %

Previous to this GRECO trial was pilot RCT published in JAMA

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593

A statistically significant reduction was seen in this study ( 1.8 % mortality in Colchicine arm vs 14 % mortality in placebo arm )

Colchicine is derived from the plant Colchicium Autumnale, native to Europe and widely regarded as a poisonous plant.

Treatment of inflammatory conditions such as gout with this plant has been documented as far back as 1500 years BC in Egyptian Papyrus scriptures.

This drugs is used to treat acute gout, mediterranean fever and pericarditis. Side effects include abdominal pain, vomitting and diarrhoea, which can be bloody. Colchicine should not be taken by pregnant or lactating women. Also double check with pharmacist and clinician with regards to any drug to drug interactions.

https://www.medrxiv.org/content/10.1101/2021.01.26.21250494v1

https://clinicaltrials.gov/ct2/show/NCT04322682

Aspirin / Acetylsalicylic acid (ASA) has both anti-inflammatory and antithrombotic effects. It inhibits synthesis of prostaglandin by cyclooxygenase; inhibits platelet aggregation; has antipyretic and analgesic activityIn addition, a significant ASA-mediated antiviral activity against DNA and RNA viruses, including different human coronaviruses, has been documented.

https://covid19.elsevierpure.com/en/publications/is-acetylsalicylic-acid-a-safe-and-potentially-useful-choice-for-

Risk of stroke in COVID19 is up to nine times higher than influenza controls.

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30272-6/fulltext

This observational study demonstrated reduced risk of ventilation in hospitalised patients on aspirin

https://pubmed.ncbi.nlm.nih.gov/33093359/

This large Veterans Affairs observational study demonstrated reduced odds of mortality in patients on aspirin despite them having more co-morbidities

https://www.medrxiv.org/content/10.1101/2020.12.13.20248147v1

Famotidine

Famotidine blocks Histamine Type 2 receptors and it has been postulated that histamine pathway may be involved in Covid19 inflammatory pathway

https://www.frontiersin.org/articles/10.3389/fphar.2021.633680/full

Famotidine use in hospitalized patients with COVID-19 was associated with a lower risk of mortality in hospitalized patients with COVID-19 in this observational study.

https://pubmed.ncbi.nlm.nih.gov/32852338/

This systematic review and meta-analysis of five studies for Famotidine showed a statistically significant decrease in the composite outcome for death and intubation.

https://www.medrxiv.org/content/10.1101/2020.09.28.20203463v1.full.pdf+html

This meta analysis of five studies showed that PPI’s were associated with statistically increased risk of secondary infections in Covid19 patients

https://onlinelibrary.wiley.com/doi/full/10.1111/joim.13183

If nothing else, Famotidine will prevent gastric side effects of aspirin and other medications which may need to be prescribed such as steroids and is a safer and more evidence based option than PPI's for that purpose in the context of Covid19 infection.

Ivermectin:

Meta-Analysis of Ivermectin studies conducted my Dr Tessa Giles, Dr Andrew Hill and McMaster university demonstrate a reduction in Covid19 mortality vs controls at all stages of illness in the range of 60-80 % in these studies.. This drug appears to have anti-viral as well as anti-inflammatory effects.

RCT from Bangladesh demonstrating disease reduction and mortality reduction benefits with Ivermectin and Doxycycline

https://clinicaltrials.gov/ct2/show/results/NCT04523831

In this Observational Study from Florida USA, Univariate analysis showed lower mortality in the ivermectin group (25.2% versus 15.0%, OR 0.52, 95% CI 0.29-0.96, P=.03).

https://www.medrxiv.org/content/10.1101/2020.06.06.20124461v2

Ivermectin to prevent infection in health professionals in Argentina

https://clinicaltrials.gov/ct2/show/results/NCT04425850?term=covid&recrs=e&cond=ivermectin&draw=2&rank=4

Ivermectin to prevent COVID19 in close contact / household members for COVID confirmed cases from Egypt

https://clinicaltrials.gov/ct2/show/results/NCT04422561?term=covid&recrs=e&cond=ivermectin&draw=2&rank=7

Ivermectin is an inhibitor of the causative virus (SARS-CoV-2): With a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h in this in vitro study from Australia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129059/

Notably while WHO in its meta-analysis considered data regarding Ivermectin as of insufficient quality to make a strong recommendation, the statistics they present show a 70 % reduction in mortality with 56 fewer deaths in Ivermectin arm per 1000 patients treated vs Placebo.

https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.1

Bromhexine

Scientific Paper discussing importance of TMPRSS2 receptor blockade to stop SARS-COV2 entry into cells

https://www.researchgate.net/publication/343364336_Blocking_serine_protease_TMPRSS2_by_Bromhexine_looking_at_potential_treatment_to_prevent_COVID-19_infection

Cell Study: Demonstrating that in cell lines with TMPRSS2 receptors ( like lung epithelial cells but unlike kidney derived cell lines ) , TMPRSS2 blockers such as Camostat Basilate ( sister drug of Bromhexine only available in Japan ) is more effective than Chloroquine in inhibitting cell entry by SARS-COV2 virus

https://www.nature.com/articles/s41586-020-2575-3_reference.pdf

Editorial article discussing positive as well as one conflicting pre-print article on effect of Bromhexine on SARS-COV2 cell entry.

http://immunopathol.com/Files/Inpress/ipp-14214.pdf

Randomised controlled trial with 39 patients in each arm done in Iran. Patients given Bromhexine had statistically significant reduction in ICU admission and death. Bromhexine group ICU admission was 2 out of 39 (0.05 % ) vs 9 out of 39 ( 23 % ) in placebo group. Death was 0 out of 39 (0 % ) in Bromhexine group vs 5 out of 39 ( 13 % ) in placebo group.

https://bi.tbzmed.ac.ir/Article/bi-23240

Bromhexine is derived from the medicinal plant Adhotada Vascica, used in Ayurveda for respiratory ailments. It is available at Pharmacy as a cough mixture but is unavailable in North America and most of Europe. I recommend that any patients with a cough should preferentially use a Bromhexine containing cough mixture over any other at a dose of 8mg three times a day. Further to that, we await results from larger RCT trials ongoing in China, Mexico and Estonia.

Black Cumin / Nigella Sativa: Derived from Ayurvedic herb 'Kalonji'

Scientific Papers: Hypothesised actions of Thymoquinone on Covid19

https://www.sciencedirect.com/science/article/pii/S2210803320300531

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361316/

https://www.researchgate.net/publication/341537951_Thymoquinone_shield_and_sword_against_SARS-CoV-2

Cell Study: Inhibition of Coronavirus ( not SARS-COV2) by Nigella Sativa

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/

Cell Study: Inhibition of Hepatitis C Virus by Nigella Sativa

https://pubmed.ncbi.nlm.nih.gov/28480371/

Computer simulation study: Nigella Sativa phytoconstituents bind SARS-COV2 targets

https://pubmed.ncbi.nlm.nih.gov/33289456/

Black seed oil might offer a number of benefits to treat COVID-19 such as blocking the entry of the virus into pneumocytes and providing ionophore for enhanced uptake of Zn²⁺ which in turn can enhance host immune response against SARS-CoV-2 as well as inhibit its replication by blocking the viral RdRp

https://www.sciencedirect.com/science/article/pii/S2210803320300531

N. sativa has actions including immune dysfunction, autophagy dysfunction, oxidative stress, inflammation, and the co-morbidities such as diabetes, hyperglycemia, cardiovascular disorders, bacterial infection, and viral infection

https://onlinelibrary.wiley.com/doi/full/10.1002/ptr.6895

Thymoquinone, the main active ingredient of black seed oil, possesses antioxidant, anti-inflammatory, antiviral, antimicrobial, immunomodulatory and anticoagulant activities

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106451/

N sativa exhibited several pharmacological properties including anti-inflammatory, antimicrobial, and immunostimulatory activities

https://www.sciencedirect.com/science/article/pii/S0011393X2030028X

Randomised Placebo controlled prospective Clinical trial testing Nigella Sativa and Honey for Covid19

https://clinicaltrials.gov/ct2/show/NCT04347382

https://www.medrxiv.org/content/10.1101/2020.10.30.20217364v4

Summary:

Kalonji seeds are a natural source of Quercetin, Zinc and Vitamin C along with having an active chemical Thymoquinone which has further anti-viral and anti-inflammatory properties. When Kalonji seeds and honey were tested against placebo in a moderate sized prospective Randomised Controlled Trial organised by Harvard University and conducted in Lahore, it demonstrated statistically significant reduction in ICU admission and death in moderate as well as severe cases of Covid19. Honey and Nigella Sativa group had 4 % mortality with 50 patients in severe group and 107 patients total. Placebo group had 18.87 % mortality with 53 patients in severe group and 103 patients total.

Vitamin C is an essential nutrient involved in a diverse array of immune functions; its supplementation has demonstrated beneficial effects in different types of viral infections. Reduced levels of ascorbate have been found in patients with viral infections , sepsis , sepsis-related ARDS , and other critical illness . During infection, vitamin C is necessary for neutrophil killing , is concentrated within macrophages , is responsible of T cell maturation , and promotes phagocytosis and apoptosis of spent neutrophils.

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full

Medications which reduce cardiovascular mortality such as medication for raised cholesterol , raised blood pressure or raised sugar appear to have a protective effect for COVID19:

Metformin for Diabetes

The use of statins in hospitalized subjects with COVID-19 was associated with a lower risk of all-cause mortality ( 5.2 % vs 9.4% )

https://www.cell.com/action/showPdf?pii=S1550-4131%2820%2930316-8

Data indicates that statin intake in old, frail people could be associated with a considerable beneficial effect on COVID-19 related clinical symptoms.

https://www.medrxiv.org/content/10.1101/2020.05.11.20096347v1

ACE-I / ARB's for blood pressure

Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers ( approx 4 % vs 11 % )

https://pubmed.ncbi.nlm.nih.gov/32302265/

Fenofibrate

A study in Isreal suggested that Fenofibrate has beneficial effects on COVID19

https://www.pharmaceutical-technology.com/news/study-fenofibrate-covid-19/

Scientific paper hypothesizing how Fenofibrate may be effective

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372998/

Non-Covid Vaccinations

This study demonstrated that low Mumps antibody titres were associated with more severe Covid19 disease

https://mbio.asm.org/content/11/6/e02628-20

This study from Netherlands demonstrated lower incidence of Covid19 in hospital staff who had received Flu vaccine compared to those who had not

https://www.medrxiv.org/content/10.1101/2020.10.14.20212498v1.full-text

These observational studies from Italy showed less prevalence and less severity of Covid19 in populations which had received Influenza vaccination

https://www.mdpi.com/2076-393X/8/3/535/htm

https://onlinelibrary.wiley.com/doi/10.1002/jmv.26120

This observational analysis from Mayo clinic found that uptake of multiple vaccinations were associated with lesser odds of contracting Covid19

https://onlinelibrary.wiley.com/doi/10.1002/jmv.26120

Ivermectin:

Clinical trial results from various countries across the world are showing effective results for both treatment as well as prevention of COVID19. This has now become part of standard treatment in four states in India ( UP, Goa, West Bengal and Assam ) and is already standard treatment in several countries, particularly in South America.

RCT from Bangladesh demonstrating disease reduction and mortality reduction benefits with Ivermectin and Doxycycline

https://clinicaltrials.gov/ct2/show/results/NCT04523831

In this Observational Study from Florida USA, Univariate analysis showed lower mortality in the ivermectin group (25.2% versus 15.0%, OR 0.52, 95% CI 0.29-0.96, P=.03).

https://www.medrxiv.org/content/10.1101/2020.06.06.20124461v2

Ivermectin to prevent infection in health professionals in Argentina

https://clinicaltrials.gov/ct2/show/results/NCT04425850?term=covid&recrs=e&cond=ivermectin&draw=2&rank=4

Ivermectin to prevent COVID19 in close contact / household members for COVID confirmed cases from Egypt

https://clinicaltrials.gov/ct2/show/results/NCT04422561?term=covid&recrs=e&cond=ivermectin&draw=2&rank=7

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129059/

Dosage:

Not recommended under age 2, below weight 15 kg, severe liver disease, seizure disorder and in pregnant or lactating women.

Doxycycline 100 mg twice a day for five days along with Ivermectin once a day for three days two hours after a meal

15 to 30 kg : 6 mg per day

30 to 60 kg: 12 mg per day

60 to 90 kg : 18 mg per day

Above 90 kg: 24 mg per day

Aspirin

Study demonstrated that patients with COVID19 in hospital and on aspirin had reduced mortality vs controls

https://pubmed.ncbi.nlm.nih.gov/33093359/

Famotidine / Famocid / Pepsid

Meta-Analysis and Systematic Review done at AIIMS, India of five international studies for reduced mortality in COVID19

https://www.medrxiv.org/content/10.1101/2020.09.28.20203463v1.full.pdf

In UK, Famotidine is not available over the counter. The following cell study demonstrated that Bismuth salts can inhibit RNA helicase activity of SARS-COV2 virus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271831/

In UK Bismuth Subsalicylate 1-2 tablets four times a day can be considered as a substitute for Famotidine

Pepto Bismol - Boots UK

N - Acetyl - Cysteine

Study demonstrating use of IV NAC to reduce inflammation in severely ill COVID19 patient from New York, USA.

https://www.sciencedirect.com/science/article/pii/S1521661620306513

Listerine ( Alcohol based ) mouthwash gargle

In vitro study from Germany which demonstrated viricidal effects of alcohol based mouthwashes against SARS-COV2

https://academic.oup.com/jid/article/222/8/1289/5878067

Listerine Antiseptic is an alcohol formulation that historically has claimed numerous antimicrobial properties is highly effective at inactivating HCoV in solution. Even at the lowest contact time of 30 s it inactivated greater than 99.99% of HCoV in this study from Germany

https://academic.oup.com/jid/article/222/8/1289/5878067

Small prospective trial from Malaysia demonstrating SARS-COV2 viral clearance with mouth wash and gargles three times a day for 30 seconds each

https://clinicaltrials.gov/ct2/show/results/NCT04410159?term=mouth+wash&recrs=e&rslt=With&cond=covid&draw=2&rank=1

Favipiravir

Three completed trials from Russia, Egypt and Iran, results of which have not yet been published as off 24th October 2020

https://clinicaltrials.gov/ct2/results?cond=favipiravir&term=covid&cntry=&state=&city=&dist=&Search=Search&recrs=e

Solidarity Trial / WHO : 30 countries

This trial shows that the four study repurposed antiviral drugs Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-β1a are not effective for COVID19.

https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1.full-text

It is now my opinion that :

-Considering that the only effective treatment of severe COVID19 is steroid Dexamethasone and even that in the recovery trial reduced mortality in single digit percentages only, clearly the optimum time to treat this condition is early. Overall in recovery trial, UK, 21.6% patients allocated dexamethasone died and 24.6% patients allocated usual care died within 28 days. The effect was more pronounced for severely ill patients with trend towards harm in patients with early minor illness. The numbers were statistically significant partly due the large study size so while steroids are a welcome and important weapon in our fight against this disease, they are by no means a ‘cure’.

https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1

-Ivermectin should now be added to the regime in case of COVID19 symptoms or high risk contact such as close family member testing positive, in addition to the supplements and drugs already on my previous blog prescriptions

-Along with staying well hydrated, drinking plenty of fluids and using humidifiers / steam to maintain healthy mucous membranes, patients should gargle with listerine thrice a day, particularly in case of infection or raised risk.

-Case for supportive treatments such as NAC, famotidine ( with aspirin ) continues to strengthen

-Jury is still out on the efficacy of oral antiviral Favipiravir. There have been some initial concerns with regards to tolerability due to gastric side effects.

Covid-19 Inflammatory Pathways

Covid19 is an illness in which viral replication phase lasts 7-10 days. The disease is complicated however with hyper-inflammation ( often called cytokine storm ) and thrombo-inflammation which can result in poor outcomes. Effective treatments needs to reduce and contain the various inflammatory pathways which lead to this complication.

CAF-IBB Protocol for early Treatment of Covid19: Four of the six medications are anti-inflammatories working through different mechanism.

https://drsrawat.blogspot.com/2020/09/prescription-for-early-mild-covid19.html

Colchicine: NLRP

Aspirin: COX

Famotidine: Histamine type 2

Ivermectin: Antiviral

Budesonide: Glucocoticoid Agonist

Bromhexine: Antiviral

NLRP Inflammazome Pathway:

Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Pathway.

NLRP proteins are part of the innate immunity and detect conserved pathogen characteristics such as peptidyglycan.

Inhibitors: Mefenamic Acid, Colchicine, Aspirin, Glyburide

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01021/full

https://www.frontiersin.org/files/Articles/552689/fimmu-11-01021-HTML/image_m/fimmu-11-01021-g001.jpg

https://www.researchgate.net/publication/350734989_Repurposing_Mefenamic_Acid_in_the_Management_of_COVID-19

Colchicine

Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, which prevents activation, degranulation, and migration of neutrophils

May interfere with intracellular assembly of inflammasome complex present in neutrophils and monocytes, which mediates activation of interleukin-1β

Cyclooxegenase Pathway:

Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid.

Pharmaceutical inhibition of COX can provide relief from the symptoms of inflammation and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin exert their effects through inhibition of COX

Aspirin

Inhibits synthesis of prostaglandin by cyclooxygenase; inhibits platelet aggregation; has antipyretic and analgesic activity

Histamine Type 2 Pathway

Scientific Hypothesis explaining how Histamine pathway may be involved in Covid19 inflammatory pathway

https://www.frontiersin.org/articles/10.3389/fphar.2021.633680/full

Famotidine blocks Histamine Type 2 receptors

Glucocorticoid Agonists

Budesonide inhaled

Prednisolone oral

Methyl Prednisone i.v

Controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level

In-Patient medication for severe resistant Covid19 use the follwing pathways to reduce inflammation:

Interleukin 6

Tocizulamab / Actemra and Sarilumab / Kevzara

Human monoclonal antibody has been shown to inhibit IL-6-mediated signaling.

IL-6 is produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes (eg, rheumatoid arthritis)

IL-6 is a pleiotropic proinflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts

IL-6 has been shown to be involved in diverse physiological processes (eg, T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation

Interleukin-6 receptor antagonist; changes in clinical trials observed include decreased C-reactive protein level to within normal range, decreased values in other pharmacodynamic parameters (eg, rheumatoid factor, erythrocyte sedimentation rate, amyloid A), and increased hemoglobin value

IL6 Inhibition and Dietary ways to reduce IL6

https://drsrawat.blogspot.com/2021/01/hyper-inflammation-and-blood-clotting.html

JAK-STAT2:

Baricitnib / Olumiant

Janus kinases (JAKs) pathways inhibitor; JAK consists of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoieses and immune cell function

Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which modulate intracellular activity including gene expression; baricitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs

JAK-STAT Inhibition and dietary reduction of JAK-STAT inflammation

https://drsrawat.blogspot.com/2020/12/jak-stat-pathwaythe-connection-between.html

INFORMATION & DISCLAIMER:

The information on this this blog reflects my opinions as per time of publishing. Scientific information and evidence changes dynamically. The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique situation.

The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique case. Patient confidentiality must be upheld at all times and any patients wishing to discuss specific medical scenarios on social media are requested to do so anonymously in 'third party' sense.

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INFORMATION & DISCLAIMER:

I obtained my primary medical education from India and post graduate MD in Family Medicine from the United Kingdom. After working in the NHS for 15 years, I moved to Canada five years ago. As a Family Physician, my specialty is engaging patients, interpreting medical information for them, guiding them through their health journey, promoting wise health choices and encouraging early detection and management of disease. The information on this blog is accurate as per time of publishing and patients should check the main blog for updates. Scientific information and evidence changes dynamically and my opinions would change accordingly. The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique case. Patient confidentiality must be upheld at all times and any patients wishing to discuss specific medical scenarios on social media are requested to do so anonymously in 'third party' sense.

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Long Haulers

Following study found that Three quarters of a group of patients who received care for coronavirus at Bristol’s Southmead Hospital were still suffering ongoing symptoms three months later. It should be noted that several of the items on this prescription show promise in reducing or eliminating chronic inflammatory symptoms of COVID19 infection.

https://www.nbt.nhs.uk/news-media/latest-news/southmead-hospital-publishes-pioneering-research-long-term-effects

It is fair to say that while a lot of these treatments can be explained scientifically and are backed by good quality in vitro , in vivo, animal study and observational study data . Most of these do not have scientific data rigorous enough to gain inclusion into national or WHO guidelines. The decision on whether to take a certain medication depends upon risk and benefit analysis. I would argue that when considering vitamins, minerals and health foods available over the counter, the body of scientific evidence need not be as rigorous since these items have already been deemed safe enough to be available without prescription. Large propensity matched observational studies can yield data as reliable as RCT's and when managing a potentially fatal disease such as Covid19 , many clinicians would find it unethical to test a medication vs placebo.

As with most serious viral illnesses, it is unlikely that we will find a 'silver bullet' or 'cure' for Covid19. The condition itself is a complex interplay of infection, host immune response, pre-existing inflammation, thrombogenic tendencies and general resilience to oxidative stress. It is much more likely that an approach of managing the condition in a multi faceted method will be more successful.

With the wealth of scientific knowledge we have today, I do not feel it is reasonable to instruct patients to just isolate themselves and wait to see if they will run into complications. Primary Care Medicine has always been about early intervention and treatment to reduce complications, and these same principles apply to early treatment of Covid19 as well. I request that you share this article widely so that more people with a Covid19 diagnosis are able to make an informed choice about their treatment options.

The use of medication using TMPRSS2 inhibition to deny cell entry of SARS-COV2 virus into lung epithelial cells is gaining traction among the medical research community.

A recent study concluded in Iran with collaboration from University of Toronto demonstrated a statistically significant reduction in ITU admission and death in Covid19 patients. This was a small study in which Bromhexine and Control ( not given Bromhexine) groups had 39 patients each.

Primary endpoint results were reported as following:

1. No patient died (0%) in the treatment group, while five patients died (12.8%) in the standard group

2. Among patients in the treatment arm with bromhexine, two patients were admitted to ICU (5.1%) while in the standard arm, eleven patients (28.2%) were transferred to ICU

3. Among patients in bromhexine arm, one patient received mechanical ventilation (2.6%), while in the standard arm nine patients (23.1%) were intubated and underwent mechanical ventilation

Secondary and lab endoints were reported a following:

1. Dyspnea ( breathlessness ) remained in 3.4% in the treatment group vs 48.3% in the standard group

2. Cough remained in the treatment group 6.9% vs 40.0% in the standard group

3. Lassitude / fatigue between two groups were observed as 6.9% vs 34.5%,

4. Inflammatory marker CRP was positive in 87.9% and 91.7% of patients in treatment and standard arms respectively, before the initiation of any treatment. Re-checking CRP two weeks after treatment showed complete improvement in CRP in 100% of patients in the bromhexine group while CRP remained positive in 83.3% of patients in the standard treatment arm.

The conclusion of the study is quoted as following :

' The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy.'

Pilot RCT on effect of Bromhexine on Rx of early COVID19

It is intriguing that a medication derived from an Ayurvedic plant used for centuries to treat cough and respiratory ailments is now being tested against this novel zoonotic virus. According to an article in

http://www.wjpmr.com/ Review ArticleISSN 2455-3301

Adhatoda vasika (also called vasika) is an ayurvedic medicinal plant used for a cough, asthma, nasal congestion, bleeding disorders, allergic conditions, upper respiratory infections etc. Bromhexine is an modern expectorant, mucolytic and bronchodilator drug, which is a synthetic form of alkaloid vasicine found in adhatoda vasica. Anti-viral property is described among its many qualities. Currently there are four ongoing trials to investigate this medication against SARS-COV2 in Russia, Mexico, Slovenia and China.

The story of how this approach came about is interesting and detailed in the nature journal article linked below. Chloroquine had been shown to inhibit SARS-COV2 virus in cell lines, however the same effect was not being seen in clinical studies which prompted further investigation. The cell lines being used were 'Vero Cell Lines' which are derived from kidney epithelial cells of an African green monkey. Scientists postulated that this may not be representative of what transpires within human lung cells.

Chloroquine / HCQ block entry of SARS-COV2 virus into cells by altering acidity / Ph at site of entry. It seems however that the virus has an alternate Ph independent method of entering lung cells which is dependant upon transmembrane serine protease enzyme TMPRSS2.

TMPRSS2 was identified as a site which is present in lung cells but not kidney cells, which SARS-COV2 virus may be using to enter lung cells.

Using DNA technology, TMPRSS2 was expressed on Vero Cell lines as second arm and Lung Epithelial cells were used in the third arm of the experiment. First arm was the original Vero Cell lines which do not express TMPRSS2. Camostat Mesylate, which can be described as a sister drug of Bromhexine only currently available in Japan was compared vs Chloroquine and Hydroxychloroquine in the three cell lines for action against SARS-COV2. Both Camostat Mesylate and Bromhexine HCL inhibit TMPRSS2 dependent entry of virus into cells. Bromhexine however has better lung deposition than Camostat pharmacologically.

As can be seen on page 4 of the paper, while Chloroquine / HCQ were effective vs SARS-COV2 in Vero Cell lines, in lung epithelial lines and in lines with TMPRSS2 receptors , these became ineffective while TMPRSS2 receptor blocker Camostat Mesylate was effective in blocking viral entry into cells.Interestingly, in the cell viability assay, higher doses of Chloroquine / HCQ were toxic to host cells, which TMPRSS2 inhibitors were not.

https://www.nature.com/articles/s41586-020-2575-3_reference.pdf

Further research into early use of this cheap, safe, over the counter drug for COVID19 needs to be encouraged and supported.

INFORMATION & DISCLAIMER:

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Prescription

Patient's name:

Today's date:

Diagnosis: Mild / Early COVID19 in patient at increased risk of progression

1.Molnupiravir ( Molulow ) 200 mg capsule: Take four capsules orally twice a day for five days. Quantity: 40 capsules

2.Fluvoxamine (Fluvoxin ) 100 mg tablet: Take half tablet (50mg) at night on day 1. Half tab (50 mg ) oral twice a day with food on day 2. One tab (100 mg ) twice a day with food for 7-10 further days Quantity: 15 tablets

3.Budesonide (Budecort) 400 rotacap: One powder inhalation via Rotahaler device twice a day for 15 days. Rinse mouth and gargle after use. Quantity; 60 rotacaps

4. Rotahaler (Cipla ) Device. Quantity: 1

Dr Suswapna Singh Rawat MBBS(India) MRCGP (UK) CFFP (Canada)

Above is a sample Prescription for mild/early COVID19 Rx in pt's at increased risk (India).

Prescription for mild COVID19 in India- 5 min YT Video

This is a suggestive prescription and it is essential that pt's consult with their care provider for individual advice. This is important because an individual patients risk, clinical disease level , pre-existing conditions and ongoing medications need to be considered when making a recommendation and not doing so would be unsafe and inappropriate.

This treatment can be bought for Rs 3000. As Omicron wave begins there is risk that health infrastructure may be overwhelmed as happened during Delta wave. This would result in a shortage of Oxygen & Hospital beds and is a situation we must avoid. I recommend that pts age 50 & above buy a Rx pack in advance so that you can start Rx in case of a positive COVID19 result straight away.

All treatments have benefits and potential harms. As an example antiviral Molnupiravir can have side effects in pregnant / nursing women and growing children. It's my opinion that using these medications in increased risk patients at or above age fifty achieves a good balance between risk and reward. Using this treatment in low risk patients below age fifty may well result in more harms than benefits and should be considered carefully in a case by case basis.

Definition of increased risk:

For the sake of simplicity I define increased risk patient as anyone either

1. At or above the age of 50 , or

2. Under age 50 with COVID19 symptoms progressing after day 5 of illness

Vaccination booster campaign is yet to begin in earnest in India and the two vaccines used in early 2021 show quite modest effect vs Omicron. We know through immunological studies that naive T cell responses become increasingly slow with age and several studies demonstrate increased risk beyond age 50 for progression of Covid19 to severe disease.

I recommend that these therapeutics should only be used in symptomatic increased risk patients where at least one household member has tested positive for COVID19 (either rapid antigen or rtPCR ) .

Guidance and availability of therapeutics is changing everyday but at this moment I recommend the following medication to be kept at home. I will update this blog as changes take effect so I recommend patient check into the blog regularly rather than taking a screenshot for instance, since advice will change over time.

I was very active in giving advice to Covid19 patients during India's delta surge and advised over 300 patients directly during that time. One of my videos on Instagram received over 250,000 views and it's likely many more patients derived advice indirectly through my social media platforms.

Today we are in a much better situation with evidence based therapies available as early out patients treatment for patients at increased risk. It is important to note that several of the treatments used during the previous Covid19 surge ( e.g Ivermectin ) were subsequently shown to be inffective and removed from AIIMS/ICMR guidance (Sept 2021 update ). It is imperative that clinicians and patients alike keep themselves aware of current evidence based medicine and this is an important purpose of my blogs.

AIIMS / ICMR COVID19 Rx Guidance-5 min YT Video

Treatment of mild COVID19 in Ontario- 5 min YT video

Unlike Canada where healthcare is free at source and public tax payer funded, most of healthcare in India takes place in a private setting. This can lead to wide variations and discrepancies in care. Access to care can also be severely limited during time of surge as we saw with unavailability of oxygen and hospital beds etc during India's Delta surge. Unfortunately this led to a large number of additional unnecessary deaths during India's delta surge, mostly uncounted and considered at the time as inevitable.

In such a situation, I feel it is reasonable for patients at increased risk of Covid19 progression to prepare themselves by keeping therapeutics at home in advance.

Patients under age 50 are at low risk of COVID19 progression, particularly if they have received a primary series of vaccination and do not have risk factors which increase risk. For the first five days such patients would not require any treatment and would be expected to improve by themselves. Patients who wish to consider Ayurveda based immune boosting supplements during this period may refer to the following blog and YT video

Ayurveda derived Immune boosting supplements-Blog

Ayurveda derived Immune boosting supplements-5 min YT video

Patients who appear to be progressing after day five of illness ( e.g. persistent fevers ) may consider using the prescription for increased risk at that time.

These prescriptions can be obtained online via Netmeds

MOLULOW 200 Capsule 10's * 4

https://www.netmeds.com/prescriptions/molulow-200-capsule-10s

Fluvoxin 100mg Tablet 10'S *3

https://www.netmeds.com/prescriptions/fluvoxin-100mg-tablet-10-s

Budecort 400 Rotacap 30'S * 2

https://www.netmeds.com/prescriptions/budecort-400-rotacap-30-s

Rotahaler (Cipla) Device 1's * 1

https://www.netmeds.com/prescriptions/rotahaler-cipla-device

Trial Evidence:

Molnupiravir

A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo

Molnupiravir reduced the risk of hospitalization or death from 9.7% in the placebo group (68/699) to 6.8% (48/709) in the molnupiravir group, for a relative risk reduction of 30% . Nine deaths were reported in the placebo group, and one in the molnupiravir group.

MERC news release-MOVEOUT Trial

Fluvoxamine

In a murine sepsis model, fluvoxamine was found to bind to the sigma-1 receptor on immune cells, resulting in reduced production of inflammatory cytokines. In an in vitro study of human endothelial cells and macrophages, fluvoxamine reduced the expression of inflammatory genes. Ongoing studies are establishing whether the anti-inflammatory effects of fluvoxamine observed in nonclinical studies also occur in humans and are clinically relevant in the setting of COVID-19.

TOGETHER trial: Aged ≥50 years or aged ≥18 years with comorbidities and ≤7 days of symptoms 741 pts Rx arm & 756 pts in placebo arm

Dosage: Fluvoxamine 100 mg PO twice daily for 10 days

Hospitalizations: 10% in fluvoxamine arm vs. 13% in placebo arm ( not significant statistically )

Mortality (ITT): 2% in fluvoxamine arm vs. 3% in placebo arm

STOP COVID Trial: Aged ≥18 years & ≤7 days of symptoms: 80 pts in Rx arm and 72 pts in placebo arm

Dosage: Fluvoxamine 50 mg PO for 1 dose, then fluvoxamine 100 mg twice daily, then fluvoxamine 100 mg 3 times daily through Day 15

Clinical deterioration: 0% in fluvoxamine arm vs. 8.3% in placebo arm

Hospitalization: 0 patients in fluvoxamine arm and 4 patients in placebo arm

NIH Fluvoxamine Evidence Appraisal

Budesonide may be considered for symptomatic high-risk outpatients

Inhaled corticosteroids have been identified as potential COVID-19 therapeutic agents because of their targeted anti-inflammatory effects on the lungs. In addition, certain inhaled corticosteroids have been shown to impair viral replication of SARS-CoV-2 and downregulate expression of the receptors used for cell entry. Two open-label randomized controlled trials and 2 double-blind placebo-controlled trials provide additional insights regarding the role of inhaled corticosteroids in outpatients with COVID-19, as described below

Inhaled budesonide was studied in 2 open-label randomized controlled trials in outpatients with mild symptoms of COVID-19.

The small STOIC trial suggested that initiation of inhaled budesonide in adult outpatients with mild COVID-19 may reduce the need for urgent care or emergency department assessment or hospitalization.

STOIC Trial: Aged ≥18 years & ≤7 days of symptoms: 73 pts in each arm

Percentage of patients with COVID-19-related urgent care visit or hospitalization: 1% in budesonide arm vs.14% in usual care arm (relative risk reduction 91%).

PRINCIPLE, a larger, open-label trial in nonhospitalized patients with COVID-19 at high risk of disease progression, found that use of inhaled budesonide did not affect the rate of hospitalization or death significantly but did reduce the time to self-reported recovery. The findings from these trials should be interpreted with caution given the open-label design of the studies and other limitations.

Principle Trial: Aged ≥65 years or aged ≥50 years with comorbidities : 1069 pts in treatment arm and 787 pts in placebo arm

Percentage of patients who were hospitalized or died due to COVID-19 within 28 days: 6.8% in budesonide arm vs. 8.8% in usual care arm
Median time to reported recovery: 11.8 days in budesonide arm vs. 14.7 days in usual care arm

NIH Budesonide Evidence Appraisal

The most scientific method of treating Covid19 is through

-antibodies derived through vaccination. By several orders of magnitude, the single intervention which has the greatest impact on Covid19 outcomes is vaccination. Benefits outweigh any potential rare side effects and Covid19 vaccines spearhead humanities charge against this novel virus.

Following medication can also be considered for symptomatic treatment

Cough Management:

-Bromhexine 8 mg/10 mls syrup every eight hours

-Acetylcysteine 600 mg tab once a day

Bromhexine 4mg/5mls cough syrup

Acetyl-cysteine 600mg-Netmeds

Advice on home monitoring

Low risk patients do not required monitoring as it is expected that the condition will self resolve within a few days. On a case by case basis, clinicians may choose to monitor increased risk patients using the following protocol daily:

Provide the following information and vitals to you monitoring physician regularly:

Name:

Age:

Weight:

Current Medications:

Covid19 Vaccination Status:

Allergies:

Active Symptoms:

Day Number of Illness:

Temperature:

(normal is 37.2 C / 99 F and below)

Blood Pressure :

(normal 100-140 sys/ 60-90 dias)

Pulse rate per minute :

(normal under 90 )

Breathing rate per minute:

(normal under 20 )

O2 Sats at rest:

O2 Sats after six minute walk:

(normal above 94 %)

Questions & Concerns:

Management of Hypoxia ( low Oxygen ) at any stage of illness

Even when started on treatment early, some patients will unfortunately progress rapidly and not respond to treatment. Monitoring will help identify such patients in time.

Patients with persistent SPO2 below 94 % or Respiratory Rate above 24 per minute within first ten days of illness should seek hospital admission immediately. This also applies to patient with chest pain or blood in sputum. Adding steroids and anticoagulants can be considered as a bridging prescription on transit to hospital facility if there is delay in access to healthcare.

I feel it is unreasonable to delay hospital admission in patients with rapidly progressing disease by proning or supplemental Oxygen at home as the resultant time delay could disqualify these patient to certain hospital therapies which are time sensitive.

Treatment Intensification with Steroids and Anticoagulants in the community

In an ideal situation all patients who appear to be deteriorating or becoming hypoxic ( low oxygen ) should be in a hospital. However we witnessed an acute shortage of Oxygen and hospital beds during the Delta Wave in India. I hail from the state of Uttarakhand and am acutely aware that there are a subset of remote rural communities who simply do not have access to hospitals. Oxygen was being sent to the villages of such patients and it would also be reasonable to supply the following life saving medication alongside when such patients are found to have low Oxygen.

Anti-inflammatory steroid:

-Prednisolone 50 mg tablet once a day with food for 5 days . Dose is 0.5-1 mg / kg / day

with,

Oral Anticoagulant blood thinner:

-Rivaroxaban 10 mg tab once a day

Prednisolone 10 mg -NetMeds

Rivaroxaban 10 mg -NetMeds

Optional: Antibiotic

Doxycycline 100 mg twice a day with food for 5 days is an antibiotic which can be added in case of coloured sputum / phlemn ( green or brown ). This is required in less than 10 % of cases.

Doxycycline cannot used during breastfeeding, pregnancy or age below 8. Side effects include stomach and food pipe irritation. In such cases use alternative antibiotic Clavulin / Augmentin / Co-Amoxiclav

Early Rx Options for mild COVID19 in Ontario

The most effective and scientific method of treating Covid19 is through antibodies derived through vaccination. By several orders of magnitude, the single intervention which has the greatest impact on Covid19 outcomes is vaccination. Benefits outweigh any potential rare side effects and Covid19 vaccines spearhead humanities charge against this novel virus.

This Blog should be supplemented with the following Youtube Video

Covid19 Rx in Ontario-3 min YT Video

Most up to date scientific guidance and evidence on therapies can be found on Ontario Science Table and NIH websites. It is highly recommended that advice given on this blog is cross referenced with those websites as evidence and guidance changes dynamically.

Ontario Science Table

NIH Guidance

Check the risk assessment as per Ontario Science Table brief dated January 21st 2022 to check which risk tier you fall under. Patients are divided into three risk categories

Ontario Science Table Update

HIGH RISK

Patients at high risk of progression will be either Tier 1 or 2

Patients diagnosed with Covid19 in this category should arrange a virtual assessment at ER department.

In Ontario, Canada a virtual consult with Emergency Room Doctor can be arranged using following links

Toronto Virtual Emergency Department Central Website

Sunnybrook Hospital

https://sunnybrook.ca/content/?page=tecc-emergency-virtual-appointment

University Health Network

https://www.uhn.ca/PatientsFamilies/Visit_UHN/Emergency/Pages/ED_Virtual_Visit_Pilot_Program_Consent_Form.aspx

Unity Health

https://unityhealth.to/areas-of-care/programs-and-clinics/emergency/virtual-emergency-department/

Currently options they will be offered include

-Monoclonal Antibody infusion of Sotrovimab

-Oral Antiviral Paxlovid

-Infusion of Remdesivir on three consequent days

MODERATE RISK

Patients at moderate risk of progression will be in either Tier 3 or 4

Patients diagnosed with Covid19 in this category should a virtual assessment with a primary care provider as soon as possible for considerable of prescription of repurposed medications to reduce risk of progression to severe disease in the second week. These include

-Fluvoxamine tablet

-Budesonide inhaler

LOW RISK

Patients at low risk of progression do not require any treatment. Antibodies derived from vaccination will be sufficient to clear the infection

OPTIONAL SUPPLEMENTS, DIET & LIFESTYLE TO BOOST IMMUNITY:

I feel that it's reasonable for patients to consider supplements and consider certain diet and lifestyle changes to boost their immunity as long as this does not pose any risk of harm to their health or mix adversely with pre-existing medications.

Ayurveda derived supplements, dietary & lifestyle modifications to boost immunity during illness-Blog

Ayurveda derived Immune Boosting Supplements-5 min YT Video

Supplements for Acute Viral Illness-3 min YT Video

In the blog above I discuss naturally occurring substances with immune boosting properties. Supplements do not go through a FDA approval process like medication do, hence while there may be a scientific hypothesis suggesting how they may help, gold standard scientific evidence ( randomized controlled trials ) is not available.

It's important to stress that supplements are ‘supplementary'. This means that they must not replace any kind of vaccination, testing, assessment or treatment of any given viral illness. Just like lifestyle interventions such as exercising, maintaining ideal weight, sleeping well, reducing stress, consuming an anti-inflammatory and balanced diet, they should all be considered as an extra 'add on'…not as a ‘treatment' or 'cure'.

While these are available without prescription and are generally safe, one must check with the pharmacist / allied health professional with regards to any potential side effects or interactions. WebMD has a good interaction checker which also includes supplements.

WEBMD Interaction Checker

Immune boosting of children in household with Covid19

Covid19 is a mild illness for vast majority of children. I actively recommend vaccination in order to reduce risk further. Nursing mothers with Covid19 should continue to breast feed ( wear a mask and sanitize hands ) during their infection as protective antibodies are passed to the baby via breast milk. During a period of viral illness, children may be given an age appropriate Multivitamin with extra Vitamin C, Vitamin D and Omega 3 supplement as per age and weight.

Monitor closely for symptoms such as skin rash , Covid toes, breathing difficulty, disturbed mentation ie excessive irritability or drowsiness and seek urgent hospital assessment for those.

Childrens MVT-Walmart

Childrens MVT-Healthy Planet

Omega 3- Healthy Planet

Omega 3- Walmart

Supplements for Acute Viral Illness-3 min YT Video

It's also very important to keep children upto date with their usual scheduled vaccinations during Pandemic times and not neglect this.

Childhood Immunization in Ontario-Blog

COVID19 Vaccination in children- 3 min YT Video

Childhood Immunization in Ontario-3 min YT Video

Other actions you can consider to improve outcomes

Continue Long term medication for chronic diseases Studies have demonstrated that medications are associated with reduced in hospital mortality vs controls include

-Statins to reduce cholesterol

-Fibrates to reduce cholesterol

-ACE inhibitors and ARB's to reduce blood pressure

-Metformin to reduce sugar

-Aspirin and blood thinners

It is important to sleep well, keep an ideal weight, stay active, keep stress down and follow a healthy and varied diet.

There is limited evidence that non-COVID vaccinations, in particular MMR, Influenza and Pneumonia vaccines are associated with reduced incidence of severe Covid19.

Adult Vaccination in Ontario-Blog

Adult Vaccination in Ontario-3 min YT video

Non-Covid Vaccinations as a method to train the immune system

This study demonstrated that low Mumps antibody titres were associated with more severe Covid19 disease

https://mbio.asm.org/content/11/6/e02628-20

This study from Netherlands demonstrated lower incidence of Covid19 in hospital staff who had received Flu vaccine compared to those who had not

https://www.medrxiv.org/content/10.1101/2020.10.14.20212498v1.full-text

These observational studies from Italy showed less prevalence and less severity of Covid19 in populations which had received Influenza vaccination

https://www.mdpi.com/2076-393X/8/3/535/htm

https://onlinelibrary.wiley.com/doi/10.1002/jmv.26120

This observational analysis from Mayo clinic found that uptake of multiple vaccinations were associated with lesser odds of contracting Covid19

https://onlinelibrary.wiley.com/doi/10.1002/jmv.26120

Advice on home monitoring

Provide the following information and vitals to you monitoring physician daily

Name:

Age:

Weight:

Current Medications:

Covid19 Vaccination Status:

Allergies:

Questions & Concerns:

Management of Hypoxia ( low Oxygen ) at any stage of illness

Even when started on treatment early, some patients will unfortunately progress rapidly and not respond to treatment. Monitoring will help identify such patients in time.

Patients with persistent SPO2 below 94 % or Respiratory Rate above 24 per minute at any stage of illness should seek hospital admission immediately.

Differences between Covid19 management in Ontario & India

Therapies available in Canada and India differ. Notable differences are annoted below. Therapies can be divided into three categories according to mechanism of action:

INHALED ANTI-INFLAMMATORY

-Inhaled Budesonide features on both Ontario as well as Indian guidance for consideration for patients with moderate risk. This can now be considered as inhaled anti-inflammatory of choice. ACTIV-6 trial is currently testing another inhaled steroid Flucitasone.

SYSTEMIC ANTI-INFLAMMATORY

-Oral Fluvoxamine can be considered for moderate risk patients as per Ontario Science Table guidance. This does not feature on ICMR/AIIMS guidance however. The two main trials of Fluvoxamine were done in USA and Canada/Brazil and have been detailed below. This can now be considered as oral systemic anti-inflammatory of choice.

ANTIVIRAL AGENTS:

-Oral antiviral Molnupiravir is available in India while the oral antiviral available in Canada and USA is Paxlovid. It is anticipated that supply of Paxlovid will be limited until March 2022 and Molnupiravir will be more widely available in USA ( although less effective than Paxlovid ) .

-Monoclonal antibody Sotronimab is available in North America but not in India. However even in North America this is in short supply and limited for those patients with highest risk. It is administered as single i.v infusion.

-Three days of i.v Remdesivir now features on Ontario Science table guidance and is being considered in USA. This is not part of Indian guidance at present but may be considered.

TRIAL EVIDENCE FOR RECOMMENDED THERAPIES

Paxlovid

EPIC-HR study: 389 pts received Paxlovid and 385 pts received placebo. Patients were in increased risk category of progression to severe disease

3 hospitalizations and no deaths in Paxlovid arm

27 hospitalizations and 7 deaths in Placebo arm

89 % relative risk reduction of hospitalization or death

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

https://clinicaltrials.gov/ct2/show/NCT04960202

Budesonide 800 mcg inhaled twice daily for 14 days may be considered for symptomatic high-risk outpatients (as described under sotrovimab recommendation)

Inhaled budesonide was studied in 2 open-label randomized controlled trials in outpatients with mild symptoms of COVID-19.

STOIC Trial: Aged ≥18 years & ≤7 days of symptoms: 73 pts in each arm

Percentage of patients with COVID-19-related urgent care visit or hospitalization: 1% in budesonide arm vs.14% in usual care arm (relative risk reduction 91%).

Principle Trial: Aged ≥65 years or aged ≥50 years with comorbidities : 1069 pts in treatment arm and 787 pts in placebo arm

Percentage of patients who were hospitalized or died due to COVID-19 within 28 days: 6.8% in budesonide arm vs. 8.8% in usual care arm
Median time to reported recovery: 11.8 days in budesonide arm vs. 14.7 days in usual care arm

NIH Budesonide Evidence Appraisal

Fluvoxamine 50 mg PO daily titrated up to 100 mg PO TID for 15 days may be considered for mildly ill patients presenting within 7 days of symptom onset.

TOGETHER trial: Aged ≥50 years or aged ≥18 years with comorbidities and ≤7 days of symptoms 741 pts Rx arm & 756 pts in placebo arm

Dosage: Fluvoxamine 100 mg PO twice daily for 10 days

Hospitalizations: 10% in fluvoxamine arm vs. 13% in placebo arm ( not significant statistically )

Mortality (ITT): 2% in fluvoxamine arm vs. 3% in placebo arm

STOP COVID Trial: Aged ≥18 years & ≤7 days of symptoms: 80 pts in Rx arm and 72 pts in placebo arm

Dosage: Fluvoxamine 50 mg PO for 1 dose, then fluvoxamine 100 mg twice daily, then fluvoxamine 100 mg 3 times daily through Day 15

Clinical deterioration: 0% in fluvoxamine arm vs. 8.3% in placebo arm

Hospitalization: 0 patients in fluvoxamine arm and 4 patients in placebo arm

NIH Fluvoxamine Evidence Appraisal

Monoclonal Antibody Sotrovimab 500 mg IV x 1 dose is recommended for mildly ill patients who present within 7 days of symptom onset and meet any one of the following criteria:

-Un-Vaccinated: Age 50 plus with one or more risk factors or age 60 plus

-Vaccinated but immune compromised, so not expected to mount an adequate immune response. Priority will be given to patients who have not received a booster, ie they are more than six months past their previous vaccine dose.

Immune compromising conditions include:

-receiving active cancer treatment or immune suppressive therapy

-solid organ or stem cell transplant recipients

-HIV / AIDS, etc

The data that support EUA for sotrovimab are from the Phase 3 COMET-ICE trial, which included outpatients with mild to moderate COVID-19 who were at high risk for progression to severe COVID-19 within 5 days of symptom onset.

Endpoint events of hospitalizations or death measured on day 29 occurred in 3 of 291 participants (1%) in the sotrovimab arm and 21 of 292 participants (7%) in the placebo arm (P = 0.002), resulting in a 6% absolute reduction and an 85% relative reduction

Early Covid19 Rx-Ontario Science Table-Jan 8th 2022 Update

NIH Statement on Omicron vs Monoclonal Antibodies

Remdesivir ( early use )

Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo.

279 patients in the remdesivir group and 283 in the placebo group.

Covid-19–related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group

Early Remdesivir for mild COVID19-NEJM

Molnupiravir ( currently FDA approved but not by Health Canada )

A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo

MERC news release-MOVEOUT Trial

It's my personal opinion that COVID19 patients who display signs of persistent inflammation can also be considered for Budesonide and Fluvoxamine. In my experience this would present as persistent fevers and systemic symptoms beyond day five of illness, occasionally associated with a downward trend in Oxygen Saturations after a six minute walk test. Secondary bacterial pneumonia and thromboembolic disease may also have to be considered in such cases depending upon history and clinical picture.

INFORMATION & DISCLAIMER:

I obtained my primary medical education from India and post graduate MD in Family Medicine from the United Kingdom. After working in National Health Service, England for 15 years, I moved to Canada five years ago. As a Family Physician, I consider my speciality as engaging patients, interpreting medical information for them, guiding them through their health journey, promoting wise health choices and encouraging early detection and management of disease.

The information on this blog is accurate as per time of publishing. Scientific information and evidence changes dynamically and my opinions would change accordingly.

The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique situation.

Physician websites I commonly use for reference include

https://www.medscape.com/familymedicine

https://gpnotebook.com/homepage.cfm

https://www.guidelinesinpractice.co.uk/

Patient reference websites I commonly recommend to patients include

https://www.aboutkidshealth.ca/

https://www.mayoclinic.org/patient-care-and-health-information

https://www.webmd.com/a-to-z-guides/common-topics

https://patient.info/

Patient confidentiality must be upheld at all times and any patients wishing to discuss specific medical scenarios on social media are requested to do so anonymously in 'third party' sense.

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