* van Haren “Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.” Critical Care (2020) 24:454
UFH: Unfractionated Heparin
“UFH prevents SARSCoV-2 from binding to ACE-2 and infecting cells and has relevant anti-coagulant, anti-inflammatory and mucolytic effects. Because of these multiple modes of action, inhaled UFH may offer clinical benefit across the time course of the disease.”
* Kim et al., Rapid generation of circulating and mucosal decoy ACE2 using mRNA nanotherapeutics for the potential treatment of SARS-CoV-2, bioRxiv, July 25, 2020.
— human soluble ACE2, produced in vivo by mRNA (delivered by lipid nanoparticles) was effective in preventing infection of cells.
* Hoffman, T. et al. “Soap versus sanitiser for preventing the transmission of acute respiratory infections: a systematic review with meta-analysis and dose-response analysis.” medRxiv July 24, 2020. — Conclusion: “Adequately performed hand hygiene, with either soap or sanitiser, reduces the risk of ARI virus transmission, however direct and indirect evidence suggest sanitiser might be more effective in practice.”
* Comer, S. et al., “COVID-19 induces a hyperactive phenotype in circulating platelets.” medRxiv (2020). — This hyperactive state in platelets may explain, at least partially, the hypercoagulability of the blood in Covid patients.
* Ooi, Say Tat, et al. “Adjunctive Corticosteroids for COVID-19: A Retrospective Cohort Study.” medRxiv (2020). — Patients given steroids were compared to patients given the same treatment but without steroids. In Covid-19 patients with pneumonia: steroid group was 85% less likely to have clinical progression, and 70% less likely to need mechanical ventilation (MV); and only 11.35 of steroid pneumonia patients had MV or death compared to 41.2% of non-steroid pneumonia patients.
24 July 2020
* Weisblum, Y. et al., “Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.” bioRxiv (2020). — A study which proved that SARS-CoV-2 can make new versions of itself that escape from specific antibodies, mutating into a new version that is immune to the antibody.
22 July 2020
* Lam, Su Datt, et al. “SARS-CoV-2 spike protein predicted to form stable complexes with host receptor protein orthologues from mammals.” BioRxiv (2020). PDF file
~ The Coronavirus can infect a wide range of mammals, but not fish, birds, or reptiles.
21 July 2020
* Zhang, Zhilan, et al. “Pan-Cancer Analysis Reveals that the SARS-CoV-2 Receptor ACE2 is a Protective Factor for Cancer Progression.” (2020). PDF file
Conclusion: “ACE2 upregulation was associated with increased anti-tumor immunity and immunotherapy response, reduced tumor malignancy, and favorable survival in cancer, suggesting that ACE2 is a protective factor for cancer progression. ”
* Acosta-Elias, Jesus, and Ricardo Espinosa-Tanguma. “The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection.” Frontiers in Pharmacology 11 (2020): 1062.
“This evidence shows that FA [Folic Acid] supplementation may protect against SARS-CoV-2.”
* Partridge, Lynda J., et al. “ACE2-independent interaction of SARS-CoV-2 spike protein to human epithelial cells can be inhibited by unfractionated heparin.” bioRxiv (2020).
“Unfractionated heparin inhibited spike protein interaction with an IC50 value of <0.05U/ml whereas two low molecular weight heparins were much less effective."
20 July 2020
* Monreal, Enric, et al. "High Versus Standard Doses Of Corticosteroids In Covid-19 Patients With An Acute Respiratory Distress Syndrome: a controlled observational comparative study.” medRxiv (2020).
Important: “In patients with severe COVID-19, high doses of corticosteroids are associated with a higher mortality and risk of need for mechanical ventilation or death compared to standard doses. This deleterious effect is mainly observed in the elderly.”
* Song, X., et al. “High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients.” bioRxiv (2020).
“These data indicate that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.”
19 July 2020
* Moutal, A. et al. “SARS-CoV-2 Spike protein hijacks VEGF-A/Neuropilin-1 receptor signaling to induce analgesia.” medRxiv (2020).
~ Note that another research study found that the virus releases some Spikes apart from the virus itself, many lone Spikes floating around in the bloodstream.
18 July 2020
* Liu, W., & Li, H. (2020). “COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism.” Preprint revised on, 10(04).
* Segovia-Juarez, Jose, Jesús M. Castagnetto, and Gustavo F. Gonzales. “High altitude reduces infection rate of COVID-19 but not case-fatality rate.” Respiratory Physiology & Neurobiology (2020): 103494.
* Gatti, Milo, et al. “Serious adverse events with tocilizumab: pharmacovigilance as an aid to prioritize monitoring in COVID‐19.” British Journal of Clinical Pharmacology.
15 July 2020
* Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors – Taking proton pump inhibitors, but not H2 blockers, increased risk of infection with Covid-19 by 2.15 times for once daily use, and by 3.67 times for twice daily use. Famotidine and ranitidine (and others) are H2 blockers (also called H2 antagonists).
* Ramachandran, P. et al., “Prehospitalization Proton Pump Inhibitor (PPI) use and Clinical Outcomes in COVID-19.” medRxiv (2020). Results: “Mortality among PPI-users was 2.3 times higher than non-users, along with 2.5 times higher risk of mechanical ventilation.”
14 July 2020
* Ding, Jun, et al. “A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19.” medRxiv (2020).
Theory: the release of Neutrophils Extracellular Traps (NETs) “in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation.”
* Rapkiewicz, Amy V., et al. “Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series.” EClinicalMedicine (2020): 100434.
13 July 2020
* Hogan, Reed B., et al. “Dual-Histamine Blockade with Cetirizine-Famotidine Reduces Pulmonary Symptoms in COVID-19 Patients.” medRxiv (2020).
The study used a combination of Histamine-1 and Histamine-2 receptor antagonists to treat Covid-19. Rates of intubation and mortality were low. Note thta cetirizine is an inhibitor of RdRp, and famotidine inhibits PLpro and RdRp.
11 July 2020
10 July 2020
* Zhang, Q., et al. “Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity.” Nano Letters 20:7, 5570–5574, June 17, 2020.
Important New Treatment:
* Schettig, Robert, et al. “COVID-19 Patient with Multifocal Pneumonia and Respiratory Difficulty Resolved Quickly: Possible Antiviral and Anti-Inflammatory Benefits of Quercinex (Nebulized Quercetin-NAC) as Adjuvant.” Advances in Infectious Diseases 10.3 (2020): 45-55.
Study authors: “Following 30 minutes after each nebulization treatment, the patient experienced immediate deep breathing relief that lasted for multiple hours. Within the following 48 hours after the first treatment, respiratory symptoms continued to diminish and resolve quickly. Finally, post-treatment follow-up chest X-rays revealed no pulmonary fibrosis (scarring) and clear lung fields.”
My comments: The article states that the formula can be ordered by prescription via compounding pharmacies. So this is not a company promoting its own product, but a medical center sharing what works for them.
* Palayakotai raghavan, Nanorx Inc., “Metadichol®, a novel nano lipid formulation that inhibits SARS-COV-2 and a multitude of pathological viruses in vitro.” SSRN (2020). A company study of its own product, but interesting nontheless. Metadichol appears to be an inhibitor of TMPRSS2.
9 July 2020
* Chang, Timothy S., et al. “Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System.” medRxiv (2020). Risk factors for Covid-19 included: Hispanic or Latinx, other non-white ethnicities, pre-existing dementia, depression, anxiety, being male, being over 65 years, and vitamin D deficiency.
8 July 2020
* Panagiotou, Grigorios et al., “Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.” medRxiv (2020). Conclusion: “we found that patients requiring ITU admission [in the ICU] were more frequently vitamin D deficient than those managed on medical wards [on the floor], despite being significantly younger.”
* Moghaddam, Arash, et al. “Selenium Deficiency is Associated with Mortality Risk from COVID-19.” preprints.org (2020). Approximately 40% of Covid-19 patients had selenium levels below the 2.5th percentile for the population. “Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors”. A negative correlation was found between selenium status and Covid-19 disease (infection and mortality).
7 July 2020
* Yamamoto, Naoki, et al. “SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.” Gene (2020): 144944. — Persons with a certain type of ACE1 (the companion cell-surface receptor to ACE2) are less likely to be infected with Covid and less likely to die.
6 July 2020
* Moozhipurath, Rahul Kalippurayil, and Lennart Kraft. “Does Lockdown Decrease the Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths? Manuscript 15. June. 2020.” (2020). — the authors concluded that the lockdown saved lives, but also would have reduced the death rate by an additional 21% if people had been advised to get out in the sun (which increases vitamin D levels): “we estimate that there would be 21% fewer deaths on average with sufficient UVB exposure while people were recommended not to leave their house.”
5 July 2020
* Gao, Zhaobing, et al. “SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damage and constitutes an antiviral target.” bioRxiv (2020). — The E-protein or E-channel of the Corornavirus by itself can cause the cytokine storm and it therefore an important target for inhibitors.
3 July 2020
* Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis. “Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents.”
* Merzon, Eugene, et al. “Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study.” medRxiv (2020). — Low vitamin D increased risk (adjusted OR) of infection with Covid-19 by 45% and of hospitalization for Covid by 95%. This is the 14th study showing benefits of vitamin D versus Covid.
* HIV and risk of COVID-19 death: a population cohort study from the Western Cape Province, South Africa. HIV doubles risk of death from Covid; current or previous tuberculosis also increases risk, somewhat less.
1 July 2020
* Zhu, Yun, et al. “Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials.” medRxiv (2020). — Remdesivir patients were 36% less likely to die, and 23% less likely to experience serious adverse events.
* Pugach, Isaac Z. and Pugach, Sofya “Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe.” medRxiv (2020). Death rate from Covid per million of the population is strongly correlated to vitamin D deficiency.
* Patrikar, Seema, et al. “Incubation Period and Reproduction Number for novel coronavirus (COVID-19) infections in India.” medRxiv (2020). Reproduction number pre-lockdown was 2.6, and during lockdown was 1.57; herd immunity threshold for the former is 61% and for the latter is 36%.
30 June 2020
* Platelet Gene Expression and Function in COVID-19 Patients – SARS-CoV-2 infects platelets, even though they don’t have ACE2, and causes the platelets to go into a state of hyperactivity.
29 June 2020
* Song, Eric, et al. “Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model.” bioRxiv (2020). The study provide evidence for “direct infection of neurons by SARS-CoV2.”
* Turoňová, Beata, et al. “In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.” bioRxiv (2020). “We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat.”
* SARS-CoV-2 has been circulating in northern Italy since December 2019: evidence from environmental monitoring – The Covid virus found in Italy as early as December 18th, 2019.
27 June 2020
* Chowdhury, Abu Taiub Mohammed Mohiuddin, et al. “A comparative observational study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients.” In summary, Ivermectin with Doxy works better than HCQ/AZ, but both work quite well in moderate to mild cases. This was not a study of severe cases.
* Association between regional selenium status and reported outcome of COVID-19 cases in China – higher selenium status (as measured by hair samples) correlated with lower death rates of Covid-19.
25 June 2020
* SARS-CoV-2 E protein is a potential ion channel that can Be inhibited by Gliclazide and Memantine — dementia drug Namenda, also called Memantine, may inhibit the coronavirus by blocking the E-protein of the virus (which is a calcium ion channel).
* Famotidine is an inhibitor of a dozen different viral targets of SARS-CoV-2. “Molecular Mechanism of Clinically Oriented Drug Famotidine with the Identified Potential Target of SARS-CoV-2.” PDF file
* SARS‐CoV‐2 coinfections: Could influenza and the common cold be beneficial? — hypothesis: having a cold or the flu about the same time as Covid could reduce the severity of the disease.
24 June 2020
22 June 2020
* Arul, Murugan Natarajan, et al. “Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach.” (2020). — New study finds that tadalafil (Cialis) inhibits 3CLpro, PLpro, and RdRp with binding affinities of -8.6, -9.2, and -9.1, respectively.
* Gautret, Philippe, et al. “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.” International journal of antimicrobial agents (2020): 105949. — no effect on viral load from HCQ.
* Sbidian, Emilie, et al. “Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France.” medRxiv (2020). — a large study from 39 hospitals combined found no excess risk of death from HCQ alone, no benefit to mortality, but a benefit to early discharge from the hospital home.
* Klemm, Theresa, et al. “Mechanism and inhibition of SARS-CoV-2 PLpro.” bioRxiv (2020). PLpro attacks the immune system and causes inflammation by cleaving proteins involved in the immune system.
* Dittmar, Mark, et al. “Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2.” bioRxiv (2020). This is important: SARS-CoV-2 “Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH….” So the claims that hydroxychloroquine works by lower pH might not be true. Also, it means TMPRSS2 is more important than we realized.
18 June 2020
* Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19 — risk of death from any cause was significantly higher in the HC group. Hydroxychloroquine is the the Covid-19 medication we are seeking.
17 June 2020
* Jehi, Lara, et al. “Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients.” Chest (2020).
16 June 2020
* RRM Prediction of Erythrocyte Band3 Protein as Alternative Receptor for SARS-CoV-2 Virus — SARS-CoV-2 may infect Red Blood Cells via the Band3 protein
* Casalino, Lorenzo, et al. “Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein.” bioRxiv (2020). The SARS-CoV-2 spike proteins are shielded from the immune system (and from vaccines) by a coating of sugar groups (glycans). This study examines the multiple roles of the glycans.
* Woolcott, Orison O., and Richard N. Bergman. “Mortality Attributed to COVID-19 in High-Altitude Populations.” medRxiv (2020). — Men under 65 years and living at altitudes above 2000 meters (6500 feet) are at increased risk of death from Covid-19.
15 June 2020
* The Effects of Steroids in Severe Hospitalized Patients with COVID-19: A Retrospective Cohort Study – “Our findings indicated the short-term corticosteroid at a low to moderate dose did not improve the clinical outcomes for patients with severe COVID-19.”
* Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States – More evidence in favor of vitamin D from sunlight or supplements. “When the states were classified into high latitude (>N 370) and low latitude (<N 370) groups, both the cases (702 vs 255 cases/100k population) and deaths (43 vs 11 deaths/100k population) were significantly different (p < 0.001) between the two categories. The results suggested that sunlight and vitamin D, with latitude as an indicator, might be associated with decreased risks for both COVID-19 cases and deaths."
* Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) — This disease is probably seasonal, which means summer and fall will see a moderate decline in severity, but December through next May will be worse, potentially much worse.
* Dr. Mobeen Syed (“Drbeen Medical Lectures”) – reviews a study on vitamin K and clotting. He asserts that maintaining normal vitamin K levels may help fend off thrombosis as happens in some Covid-19 patients. Drbeen lecture is here and the study is here.
14 June 2020
* A new study found that untreated vitamin D deficiency was associated with a 77% increase in likelihood of Covid-19 infection. Persons with sufficient vitamin D were 56% less likely to become infected with Covid-19.
Meltzer, David O., et al. “Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence.” medRxiv (2020).
13 June 2020
* la Cour Freiesleben, Nina, et al. “SARS-CoV-2 in first trimester pregnancy-does it affect the fetus?.” medRxiv (2020). — “Conclusion Maternal SARS-CoV-2 infection did not seem harmful in first trimester pregnancies.”
* “A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care.” Patel, Tejas K., et al. “Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review.” Journal of Neuroimmune Pharmacology: 1.
12 June 2020
* Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19 — “especially in patients who required higher inspired oxygen or ventilatory support”. Controls were not randomized. Patients treated with ivermectin were 48% less likely to die; patients with severe pulmonary disease were 85% less likely to die.
~ Compare this result to a recent trial in which “13.9% of the remdesivir patients had died compared to 12.8% of patients in the control arm.”
10 June 2020
* El-Kurdi, Bara, et al. “Mortality from Covid-19 Increases with Unsaturated Fat, and may be Reduced by Early Calcium and Albumin Supplementation.” Gastroenterology (2020).
8 June 2020
* This is important. A new study has found that the two proteases used by SARS-CoV-2 to make smaller functional proteins out of two long non-functional proteins also have a secondary role: to cut up and thereby deactivate three important human proteins used by the immune system. “Direct cleavage of IRF3 by NSP3 could explain the blunted Type- I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients.” The take-away is that treatment of Covid-19 should include medications that inhibit both viral proteases, so as to spare the immune system from this attack.
* In a new study, discontinuing ACEi/ARB drugs more than doubled mortality for hospitalized Covid-19 patients:
Cannata, Francesco, et al. “Continuation versus discontinuation of ACE inhibitors or angiotensin II receptor blockers in COVID-19: effects on blood pressure control and mortality.” European Heart Journal-Cardiovascular Pharmacotherapy (2020).
* Boulware, David R., et al. “A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.” New England Journal of Medicine (2020). — Hydroxychloroquine did not work as a prophylaxis against Covid-19.
* In a case series, famotidine at high dosage was well-tolerated and was associated with improved symptoms for non-hospitalized patients:
Janowitz, Tobias, et al. “Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series.” Gut (2020).
* Study: “An increase in absolute latitude by one degree is associated with a 2.6% increase in COVID-19 cases per million inhabitants after controlling for several important factors.” COVID-19 and climate: global evidence from 117 countries “The Northern hemisphere may see a decline in new COVID-19 cases during summer and a resurgence during winter.”
6 June 2020
* Huang, Sui, et al. “Mechanical ventilation stimulates expression of ACE2, the receptor for SARS-Cov-2.” (2020). Use of mechanical ventilation may make Covid-19 worse by producing more ACE2 for further infection of lung cells, whereas the use of high-flow oxygen has been called a “game changing Covid-19 alternative to ventilator” — “Of the six earliest Covid-19 patients placed on ventilators at the hospital, all six did not make it. However, high-flow oxygen was administered to seven more patients and, of these, six were able to recover without the use of a ventilator.”
* Cour, Martin, Michel Ovize, and Laurent Argaud. “Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?.” (2020): 1-3.
* Jeong, Han Eol, et al. “Association between NSAIDs use and adverse clinical outcomes among adults hospitalised with COVID-19 in South Korea: A nationwide study.” medRxiv (2020). IMPORTANT: use of NSAIDS in Covid-19 patients increased risk of the primary composite outcome: “death, intensive care unit admission, mechanical ventilation use, and/or sepsis” by 50% (OR 1.56) and more than doubled the risk of “cardiovascular or renal complications” (OR 2.64). Tylenol (paracetamol) did not have the same risk.
5 June 2020
* Tan, Chuen Wen, et al. “A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.” medRxiv (2020).
4 June 2020
* Maximum Daily Temperature, Precipitation, Ultra-Violet Light and Rates of Transmission of SARS-Cov-2 in the United States – The incidence of disease declines with increasing temperature up until 52°F and is lower at warmer versus cooler temperatures. Higher UV light also reduces Covid-19 incidence.
* Azithromycin and hydroxychloroquine accelerate recovery of outpatients with mild/moderate COVID-19 – mean times to clinical recovery for symptomatic treatment, 25.8 days; azithromycin alone, 12.9 days; and azithromycin plus hydroxychloriquine, 9.2 days.
3 June 2020
* Enantiomers of Chloroquine and Hydroxychloroquine Exhibit Different Activities Against SARS-CoV-2 in vitro, Evidencing S-Hydroxychloroquine as a Potentially Superior Drug for COVID-19 — They say the S-enantiomer was 60% more effective than the R-enantiomer. Yes, but it was only 17.6% more effective than the mix of R- and S-HCQ that is used as medicine. This is also one of very few in vitro studies of SARS-CoV-2. They also tested Azithromycin and found its IC50 at 15.75 µM.
2 June 2020
* COVID-19 & ABO blood group: another viewpoint – This paper claims that the difference in severity of Covid-19 between blood groups is due to the anti-A antibodies found in types O and B, and in the different kind of anti-A antibodies found in O versus B. The result is that persons with type O blood seem to have a lower risk of contracting Covid-19. More research is needed as this is still in the realm of hypothesis.
1 June 2020
* COVID-19 immunity lasts only six months, reinfection possible — And here is a link to the study; the researchers looked at the types of coronaviruses that cause the common cold, in only 10 persons, from 1985-2020.
30 May 2020
* Huang, Sui, et al. “Mechanical Ventilation Stimulates Expression of ACE2, the Receptor for SARS-Cov-2.” (2020).
* Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review – “Conclusion: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.” Hernandez et al., Annals of Internal Medicine, 27 May 2020.
* Shen, Chenguang, et al. “Treatment of 5 critically ill patients with COVID-19 with convalescent plasma.” Jama 323.16 (2020): 1582-1589. — Basically, this treatment works, but not very well.
29 May 2020
* de Novales, Francisco Javier Membrillo, et al. “Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study.” (2020). — Early use seems to be the key to the effectiveness of HYQ.
26 May 2020
* Brenner, S. R. “The Potential of Memantine and related adamantanes such as amantadine, to reduce the neurotoxic effects of COVID-19, including ARDS and to reduce viral replication through lysosomal effects.” Journal of Medical Virology (2020).
* Cholesterol Metabolism—Impacts on SARS-CoV-2 Infection Prognosis, Entry, and Antiviral Therapies – “SARS-CoV-2 infection was associated with clinically significant lower level of HDL cholesterol (HDL-C), which can be used as indicators of disease severity and poor prognosis…. Antagonists of HDL receptor-Scavenger receptor class B type I (SR-B1), strongly inhibited SARS-CoV-2 infection.”
25 May 2020
* Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone – Zinc supplement reduced risk of death, and increased the likelihood that the patient would be discharged home, rather than to a hospice. Earlier use of zinc gave better results.
21 May 2020
* Letarov, Andrey, and Vladislav Babenko. “Hypothesis: Free SARS-CoV-2 spike protein S1 particles may act as a factor of COVID-19 pathogenesis.” (2020).
~ A stunning hypothesis: that infected cells release free Spike protein fragments, in particular the S1 portion of the Spike, along with whole virions. These fragments bind to ACE2 receptors, inhibiting ACE2 and deregulating the Renin Angiotensin System. So the virus has its own drug-like product that acts as an inhibitor.
* Cao, Yu-chen, et al. “Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence.” Travel Medicine and Infectious Disease (2020): 101647.
“A systematic review was performed using 18 articles and it was concluded that there is strong evidence supporting the link between 2019-nCoV and nervous damage, and that there are at least three means by which it may directly enter the CNS, and three by which it may cause indirect harm to the CNS.”
20 May 2020
* The Effect of Temperature and Humidity May Reduce the Growth Rate of the Coronavirus Disease 2019 Epidemic This study concluded that increased temperature and decreased humidity (hot dry climate) decreased the growth rate of the Covid epidemic. However, the effect was not a straight line relationship. For example, a warmer than usual winter would not really help, and while summer should have a lower growth rate to the epidemic, a heat wave will not improve the situation any further.
~ Note that we are already seeing the results of this effect in the U.S., Canada, and European nations, which are seeing fewer cases and fewer deaths from Covid.
* The Korean CDC released a Findings from Investigations report on patients who recover from Covid, and who soon after re-test as positive (“re-positives”). They found that these patients had zero whole viral genomes, only partial segments of viral RNA. They also found that none of the close contacts of these patients became ill. There were 285 re-positives (Covid patients) and 790 close contacts, with no infections in the contacts attributable to the re-positives. Conclusion: re-positives are no longer infectious and no longer infected, but are merely shedding virus from the past infection. See the explanation by Dr. Roger Seheult of MedCram on YouTube.
* BCG Vaccination Policy and Salmiak Consumption Are Inversely Associated with COVID-19 Death Rates in Europe. Other studies have suggested the same relation between Bacillus Calmette–Guérin (BCG) vaccine (against tuberculosis) and a reduction in Covid-19 severity or mortality.
But this study also found that consumption of foods containing ammonium chloride (primarily a type of licorice coated with ammonium chloride as a type of salt) reduced Covid mortality. The ammonium chloride has similar effects to hydroxychloroquine and chloroquine in changing cell pH to prohibit cell wall fusion and cell infection.
However, licorice itself contains a compound, Glycyrrhizin, which inhibits both Mpro and ACE2 in molecular docking studies [Yan et al. “Discovery of Anti-2019-nCoV Agents from Chinese Patent Drugs via Docking Screening.” (2020)] The study attributes effectiveness to ammonium chloride, which is most often consumed as a salty-coating to licorice candy. Either or both compounds could produce an effect against Covid-19.
* de Novales, Francisco Javier Membrillo, et al. “Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study.” (2020).
— Giving patients Hydroxychloroquine reduced risk of death in all patient groupos; statistical significance was reached only in mild/early disease cases.
* Gomeni, R., et al. “Model Based Approach for Estimating the Dosage Regimen of Indomethacin a Potential Antiviral Treatment of Patients Infected with SARS CoV-2.” (2020).
— Determined dosing for Indomethacin vs. Covid-19; expected to be effective as an anti-viral and anti-inflammatory; may reduce risk of cytokine storm
* Carlucci, Philip, et al. “Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients.” medRxiv (2020).
— Successful test of triple therapy; addition of zinc sulfate increased odds of discharge home by more than 50%, decreased odds of death or hospice more than 50%.
* Vivanti, A., et al. “Transplacental transmission of SARS-CoV-2 infection.” (2020).
— Sars-Cov-2 can be transmitted through the placenta from mother to prenatal.
* Spearow, Jimmy L., and Linda Copeland. “Improving Therapeutics for COVID-19 with Glutathione-boosting Treatments that Improve Immune Responses and Reduce the Severity of Viral Infections.” (2020).
— Proposes N-Acetyl Cysteine and Alpha Lipoic Acid as a prophylaxis for Covid.
* Liu, Hongbo, et al. “Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro.” bioRxiv (2020).
— One of few in vitro tests of SARS-CoV-2; high inhibition at low concentration for Chinese skullcap extract and for bacalein (not bacalin).
* Fantini, Jacques, Henri Chahinian, and Nouara Yahi. “nSynergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: what molecular dynamics studies of virus-host interactions reveal.” International Journal of Antimicrobial Agents (2020): 106020.
— New theory on how hydroxychloroquine and azithromycin inhibit SARS-Cov-2. Azithromycin competitively inhibits ganglioside used by virus to land on cell surface before docking with ACE2. Hydroxychloroquine binds to spike protein to prevent the spike from being able to bind to the ganglioside.
* Mycroft-West, Courtney, et al. “Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin.” bioRxiv (2020).
— “the addition of heparin (100 μg.ml-1) to vero cells inhibits invasion
by SARS-CoV-2 by 70%. We also demonstrate that heparin binds to the Spike (S1) protein receptor binding domain and induces a conformational change….”
* Shaheen, Alaa. “An unorthodox approach to handle SARS-CoV-2: Breaking the virus spikes.”
— Fasting or a keto-genic diet will induce ketosis; the resulting ketones in the blood, especially beta-hydroxybutyrate, may break the spikes on SARS-Cov-2 and reduce infectivity and viral titer.
* Blanc, Frederic, et al. “Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study.” (2020).
— Certain proton pump inhibitors “lowered the risk of development of COVID-19 infection,” especially lansoprazole; 12 elderly patients were on lansoprazole, but only one of them contracted Covid-19. By comparison, 31 were on pantoprazole, while 15 of them contracted Covid-19.
* Freedberg, Daniel E., et al. “Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.” medRxiv (2020).
— Patients on famotidine has a lower risk of intubation or death; other proton pump inhibitors did not show this benefit.