COVID-19’s seasonal cycle to be estimated at Lawrence Berkeley National Laboratory (Berkeley Lab) by Artificial Intelligence and Machine Learning Algorithms: Will A Fall and Winter resurgence be Likely??

Reporter: Aviva Lev-Ari, PhD, RN

Using machine learning to estimate COVID-19’s seasonal cycle

Woman walks down empty city street wearing a mask

Credit: Ivan Marc/Shutterstock

Berkeley Lab researchers have launched a project to determine if the novel coronavirus might be seasonal, waning in summer months and resurging in fall and winter.

One of the many unanswered scientific questions about COVID-19 is whether it is seasonal like the flu — waning in warm summer months then resurging in the fall and winter.

Now scientists at Lawrence Berkeley National Laboratory (Berkeley Lab) are launching a project to apply machine-learning methods to a plethora of health and environmental datasets, combined with high-resolution climate models and seasonal forecasts, to tease out the answer.

“Environmental variables, such as temperature, humidity, and UV [ultraviolet radiation] exposure, can have an effect on the virus directly, in terms of its viability. They can also affect the transmission of the virus and the formation of aerosols,” said Berkeley Lab scientist Eoin Brodie, the project lead. “We will use state-of-the-art machine-learning methods to separate the contributions of social factors from the environmental factors to attempt to identify those environmental variables to which disease dynamics are most sensitive.

The research team will take advantage of an abundance of health data available at the county level — such as the severity, distribution and duration of the COVID-19 outbreak, as well as what public health interventions were implemented when — along with demographics, climate and weather factors, and, thanks to smartphone data, population mobility dynamics. The initial goal of the research is to predict — for each county in the United States — how environmental factors influence the transmission of the SARS-CoV-2 virus, which causes COVID-19.

Multidisciplinary team for a complex problem

Untangling environmental factors from social and health factors is a knotty problem with a large number of variables, all interacting in different ways. On top of that, climate and weather affect not only the virus but also human physiology and behavior. For example, people may spend more or less time indoors, depending on the weather; and their immune systems may also change with the seasons.

It’s a complex data problem similar to others tackled by Berkeley Lab’s researchers studying systems like watersheds and agriculture; the challenge involves integrating data across scales to make predictions at the local level. “Downscaling of climate information is something that we routinely do to understand how climate impacts ecosystem processes,” Brodie said. “It involves the same types of variables — temperature, humidity, solar radiation.”

Brodie, deputy director of Berkeley Lab’s Climate and Ecosystem Sciences Division, is leading a cross-disciplinary team of Lab scientists with expertise in climate modeling, data analytics, machine learning, and geospatial analytics. Ben Brown, a computational biologist in Berkeley Lab’s Biosciences Area, is leading the machine-learning analysis. One of their main aims is to understand how climate and weather interact with societal factors.

“We don’t necessarily expect climate to be a massive or dominant effect in and of itself. It’s not going to trump which city shut down when,” Brown said. “But there may be some really important interactions [between the variables]. Looking at New York and California for example, even accounting for the differences between the timing of state-instituted interventions, the death rate in New York may be four times higher than in California — though additional testing on random samples of the population is needed to know for sure. Understanding the environmental interactions may help explain why these patterns appear to be emerging. This is a quintessential problem for machine learning and AI [artificial intelligence].”

The computing work will be conducted at the National Energy Research Scientific Computing Center (NERSC), a DOE Office of Science user facility located at Berkeley Lab.

Signs of climatic influences

map of the worldwide incidence rate of COVID-19
The worldwide incidence rate of COVID-19.
Credit: Center for Systems Science and Engineering at Johns Hopkins University

Already, geographical differences in how the disease behaves have been reported, the researchers point out. Temperature, humidity, and the UV Index have all been statistically associated with rates of COVID-19 transmission — although contact rates are still the dominant influence on the spread of disease. In the southern hemisphere, for example, where it’s currently fall, disease spread has been slower than in the northern hemisphere. “There’s potentially other factors associated with that,” Brodie said. “The question is, when the southern hemisphere moves into winter, will there be an increase in transmission rate, or will fall and winter 2020 lead to a resurgence across the U.S. in the absence of interventions?”

India is another place where COVID-19 does not yet appear to be as virulent. “There are cities where it behaves as if it’s the most infectious disease in recorded history. Then there are cities where it behaves more like influenza,” Brown said. “It is really critical to understand why we see those massive differences.”

Brown notes other experiments suggesting the SARS-CoV-2 virus could be seasonal. In particular, the National Biodefense Analysis and Countermeasures Center (NBACC) assessed the longevity of the virus on various surfaces. “Under sunlight and humidity, they found that the virus loses viability in under 60 minutes,” Brown said. “But in darkness and low temperatures it’s stable for eight days. There’s some really serious differences that need investigating.”

The Berkeley Lab team believes that enough data may now be available to determine what environmental factors may influence the virulence of the virus. “Now we should have enough data from around the world to really make an assessment,” Brown said.

The team hopes to have the first phase of their analysis available by late summer or early fall. The next phase will be to make projections under different scenarios, which could aid in public health decisions.

“We would use models to project forward, with different weather scenarios, different health intervention scenarios — such as continued social distancing or whether there are vaccines or some level of herd immunity — in different parts of the country. For example, we hope to be able to say, if you have kids going back to school under this type of environment, the climate and weather in this zone will influence the potential transmission by this amount,” Brodie explained. “That will be a longer-term task for us to accomplish.”

This research is supported by Berkeley Lab’s Laboratory Directed Research and Development (LDRD) program. Other team members include Dan Feldman, Zhao Hao, Chaincy Kuo, Haruko Wainwright, and Nicola Falco. Berkeley Lab mobilized quickly to provide LDRD funding for several research projects to address the COVID-19 pandemic, including one on text mining scientific literature and another on indoor transmission of the virus.

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Reporter: Aviva Lev-Ari, PhD, RN – Bold face and colors are my addition


Mandeep Mehra, MD, medical director of the Brigham and Women’s Hospital Heart and Vascular Center.

“All these Covid-associated complications were a mystery. We see blood clotting, we see kidney damage, we see inflammation of the heart, we see stroke, we see encephalitis [swelling of the brain],” says William Li, MD, president of the Angiogenesis Foundation. “A whole myriad of seemingly unconnected phenomena that you do not normally see with SARS or H1N1 or, frankly, most infectious diseases.”

“If you start to put all of the data together that’s emerging, it turns out that this virus is probably a vasculotropic virus, meaning that it affects the [blood vessels],”

Mehra explains. “Then it starts to infect endothelial cell after endothelial cell, creates a local immune response, and inflames the endothelium.”

Benhur Lee, MD, a professor of microbiology at the Icahn School of Medicine at Mount Sinai:

“In SARS1, the protein that’s required to cleave it is likely present only in the lung environment, so that’s where it can replicate. To my knowledge, it doesn’t really go systemic,” Lee says. “[SARS-CoV-2] is cleaved by a protein called furin, and that’s a big danger because furin is present in all our cells, it’s ubiquitous.”

Sanjum Sethi, MD, MPH, an interventional cardiologist at Columbia University Irving Medical Center:

“The endothelial cell layer is in part responsible for [clot] regulation, it inhibits clot formation through a variety of ways, If that’s disrupted, you could see why that may potentially promote clot formation.” Damage to endothelial cells causes inflammation in the blood vessels, and that can cause any plaque that’s accumulated to rupture, causing a heart attack. “Inflammation and endothelial dysfunction promote plaque rupture. Endothelial dysfunction is linked towards worse heart outcomes, in particular myocardial infarction or heart attack.”


Endothelial cell dysfunction: pre-existing conditions like high blood pressure, high cholesterol, diabetes, and heart disease are at a higher risk for severe complications from a virus that’s supposed to just infect the lungs. Why ventilation often isn’t enough to help many Covid-19 patients breathe better. Moving air into the lungs, which ventilators help with, is only one part of the equation. The exchange of oxygen and carbon dioxide in the blood is just as important to provide the rest of the body with oxygen, and that process relies on functioning blood vessels in the lungs.

William Li, MD, president of the Angiogenesis Foundation:

“If you have blood clots within the blood vessels that are required for complete oxygen exchange, even if you’re moving air in and out of the airways, [if] the circulation is blocked, the full benefits of mechanical ventilatory support are somewhat thwarted,” “We were observing virus particles filling up the endothelial cell like filling up a gumball machine. The endothelial cell swells and the cell membrane starts to break down, and now you have a layer of injured endothelium.” “Endothelial cells connect the entire circulation [system], 60,000 miles worth of blood vessels throughout our body,” says Li. “Is this one way that Covid-19 can impact the brain, the heart, the Covid toe? Does SARS-CoV-2 traffic itself through the endothelial cells or get into the bloodstream this way? We don’t know the answer to that.”


If Covid-19 is a vascular disease, the best antiviral therapy might not be antiviral therapy

“I suspect from what we see and what our preliminary data show is that this virus has an additional risk factor for blood clots, but I can’t prove that yet,” Sethi says. An alternative theory is that the blood clotting and symptoms in other organs are caused by inflammation in the body due to an over-reactive immune response — the so-called cytokine storm

SARS-CoV-2 virus can infect the endothelial cells that line the inside of blood vessels. Endothelial cells protect the cardiovascular system, and they release proteins that influence everything from blood clotting to the immune response. In the paper, the scientists showed damage to endothelial cells in the lungs, heart, kidneys, liver, and intestines in people with Covid-19.

Treatment Protocol for COVID-19

The good news is that if Covid-19 is a vascular disease, there are existing drugs that can help protect against endothelial cell damage. In another New England Journal of Medicine paper that looked at nearly 9,000 people with Covid-19, Mehra showed that the use of statins and ACE inhibitors were linked to higher rates of survival. Statins reduce the risk of heart attacks not only by lowering cholesterol or preventing plaque, they also stabilize existing plaque, meaning they’re less likely to rupture if someone is on the drugs.

“It turns out that both statins and ACE inhibitors are extremely protective on vascular dysfunction,” Mehra says. “Most of their benefit in the continuum of cardiovascular illness — be it high blood pressure, be it stroke, be it heart attack, be it arrhythmia, be it heart failure — in any situation the mechanism by which they protect the cardiovascular system starts with their ability to stabilize the endothelial cells.”

  • The best therapy might actually be a drug that stabilizes the vascular endothelial.

Endothelial cell infection and endotheliitis in COVID-19

Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.
SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells.
Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Intriguingly, SARS-CoV-2 can directly infect engineered human blood vessel organoids in vitro.
Here we demonstrate endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19 (further case details are provided in the appendix).
Patient 1 was a male renal transplant recipient, aged 71 years, with coronary artery disease and arterial hypertension. The patient’s condition deteriorated following COVID-19 diagnosis, and he required mechanical ventilation. Multisystem organ failure occurred, and the patient died on day 8.

Post-mortem analysis of the transplanted kidney by electron microscopy revealed viral inclusion structures in endothelial cells (figure A, B). In histological analyses, we found an accumulation of inflammatory cells associated with endothelium, as well as apoptotic bodies, in the heart, the small bowel (figure C) and lung (figure D). An accumulation of mononuclear cells was found in the lung, and most small lung vessels appeared congested.

See Figures in https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext


We found evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation. Although the virus uses ACE2 receptor expressed by pneumocytes in the epithelial alveolar lining to infect the host, thereby causing lung injury, the ACE2 receptor is also widely expressed on endothelial cells, which traverse multiple organs.
Recruitment of immune cells, either by direct viral infection of the endothelium or immune-mediated, can result in widespread endothelial dysfunction associated with apoptosis (figure D).
The vascular endothelium is an active paracrine, endocrine, and autocrine organ that is indispensable for the regulation of vascular tone and the maintenance of vascular homoeostasis.
Endothelial dysfunction is a principal determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischaemia, inflammation with associated tissue oedema, and a pro-coagulant state.
Our findings show the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. These findings suggest that SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral involvement (as noted with presence of viral bodies) and of the host inflammatory response. In addition, induction of apoptosis and pyroptosis might have an important role in endothelial cell injury in patients with COVID-19.
COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. This hypothesis provides a rationale for therapies to stabilise the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins., , , ,
This strategy could be particularly relevant for vulnerable patients with pre-existing endothelial dysfunction, which is associated with male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease, all of which are associated with adverse outcomes in COVID-19.


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Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

List of authors.

  • Mandeep R. Mehra, M.D.,
  • Sapan S. Desai, M.D., Ph.D.,
  • SreyRam Kuy, M.D., M.H.S.,
  • Timothy D. Henry, M.D.,
  • and Amit N. Patel, M.D.




Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.


Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.


Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)

As the coronavirus disease 2019 (Covid-19) pandemic has spread around the globe, there has been growing recognition that persons with underlying increased cardiovascular risk may be disproportionately affected.1-3 Several studies of case series have noted cardiac arrhythmias, cardiomyopathy, and cardiac arrest as terminal events in patients with Covid-19.1-4 Higher incidences of cardiac arrhythmias, acute coronary syndromes, and heart failure–related events have also been reported during seasonal influenza outbreaks, which suggests that acute respiratory infections may result in activation of coagulation pathways, proinflammatory effects, and endothelial cell dysfunction.5 In addition, however, concern has been expressed that medical therapy for cardiovascular disease might specifically contribute to the severity of illness in patients with Covid-19.6,7

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Covid-19, has been shown to establish itself in the host through the use of angiotensin-converting enzyme 2 (ACE2) as its cellular receptor.8 ACE2 is a membrane-bound monocarboxypeptidase found ubiquitously in humans and expressed predominantly in heart, intestine, kidney, and pulmonary alveolar (type II) cells.7,9 Entry of SARS-CoV-2 into human cells is facilitated by the interaction of a receptor-binding domain in its viral spike glycoprotein ectodomain with the ACE2 receptor.10

ACE2 is counterregulatory to the activity of angiotensin II generated through ACE1 and is protective against detrimental activation of the renin–angiotensin–aldosterone system. Angiotensin II is catalyzed by ACE2 to angiotensin-(1–7), which exerts vasodilatory, antiinflammatory, antifibrotic, and antigrowth effects.11 It has been suggested that ACE inhibitors and angiotensin-receptor blockers (ARBs) may increase the expression of ACE2, which has been shown in the heart in rats,12 and thereby may confer a predisposition to more severe infection and adverse outcomes during Covid-19.6,7 Others have suggested that ACE inhibitors may counter the antiinflammatory effects of ACE2. However, in vitro studies have not shown direct inhibitory activity of ACE inhibitors against ACE2 function.9,13

Despite these uncertainties, some have recommended cessation of treatment with ACE inhibitors and ARBs in patients with Covid-19.6 However, several scientific societies, including the American Heart Association, the American College of Cardiology, the Heart Failure Society of America, and the Council on Hypertension of the European Society of Cardiology, have urged that these important medications should not be discontinued in the absence of clear clinical evidence of harm.14,15 We therefore undertook a study to investigate the relationship between underlying cardiovascular disease and Covid-19 outcomes and to evaluate the association between cardiovascular drug therapy and mortality in this illness.


Our investigation confirms previous reports of the independent relationship of older age, underlying cardiovascular disease (coronary artery disease, heart failure, and cardiac arrhythmias), current smoking, and COPD with death in Covid-19. Our results also suggest that women are proportionately more likely than men to survive the infection. Neither harmful nor beneficial associations were noted for antiplatelet therapy, beta-blockers, or hypoglycemic therapy. It is important to note that we were not able to confirm previous concerns regarding a potential harmful association of either ACE inhibitors or ARBs with in-hospital mortality in this clinical context.

In viral infections such as influenza, older age is associated with an increased risk of cardiovascular events and death.5 In the 2003 epidemic of severe acute respiratory syndrome (SARS, caused by SARS-CoV-1 infection), sex differences in the risk of death similar to those we observed were noted.17 Women have stronger innate and adaptive immunity and greater resistance to viral infections than men.18 In animal models of SARS-CoV-1 infection, higher susceptibility of male mice to SARS-CoV-1 and greater accumulation of macrophages and neutrophils in the lungs have been described.19 Ovariectomy or the use of estrogen-receptor antagonists increased mortality from SARS-CoV-1 infection in female animals. Furthermore, the difference in risk between the sexes increased with advancing age.19 These findings may support the observation in our investigation that suggested an association between survival and female sex, independent of older age.

Infection with SARS-CoV-2 is a mild disease in most people, but in some the disease progresses to a severe respiratory illness characterized by a hyperinflammatory syndrome, multiorgan dysfunction, and death.20 In the lung, the viral spike glycoprotein of SARS-CoV-2 interacts with cell-surface ACE2, and the virus is internalized by endocytosis. The endocytic event up-regulates the activity of ADAM metallopeptidase domain 17 (ADAM17), which cleaves ACE2 from the cell membrane, resulting in a loss of ACE2-mediated protection against the effects of activation of the tissue renin–angiotensin–aldosterone system while mediating the release of proinflammatory cytokines into the circulation.21 The stress of critical illness and inflammation may unite in destabilizing preexisting cardiovascular illness. Vascular endothelial cell dysfunction, inflammation-associated myocardial depression, stress cardiomyopathy, direct viral infection of the heart and its vessels, or the host response may cause or worsen heart failure, demand-related ischemia, and arrhythmias.22 These factors may underlie the observed associations between cardiovascular disease and death in Covid-19.

In our analyses, use of either ACE inhibitors or statins was associated with better survival among patients with Covid-19. However, these associations should be considered with extreme caution. Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data also offer no information concerning the potential effect of initiation of ACE inhibitor or statin therapy in patients with Covid-19 who do not have an appropriate indication for these medications. Randomized clinical trials evaluating the role of ACE inhibitors and statins will be necessary before any conclusion can be reached regarding a potential benefit of these agents in patients with Covid-19.

In this multinational observational study involving patients hospitalized with Covid-19, we confirmed previous observations suggesting that underlying cardiovascular disease is independently associated with an increased risk of in-hospital death. We were not able to confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital mortality in this clinical context.

Supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital. The development and maintenance of the Surgical Outcomes Collaborative database was funded by Surgisphere.

This article was published on May 1, 2020, and updated on May 8, 2020, at NEJM.org.

Author Affiliations

From Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston (M.R.M.); Surgisphere, Chicago (S.S.D.); Baylor College of Medicine and Department of Veterans Affairs, Houston (S.K.); Christ Hospital, Cincinnati (T.D.H.); the Department of Biomedical Engineering, University of Utah, Salt Lake City (A.N.P.); and HCA Research Institute, Nashville (A.N.P.).


1. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020 March 3 (Epub ahead of print).

2. Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020 March 25 (Epub ahead of print).

3. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020 March 27 (Epub ahead of print).

4. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020 March 19 (Epub ahead of print).

5. Nguyen JL, Yang W, Ito K, Matte TD, Shaman J, Kinney PL. Seasonal influenza infections and cardiovascular disease mortality. JAMA Cardiol 2016;1:274-81.

6. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8(4): e21.

7. Nicin L, Abplanalp WT, Mellentin H, et al. Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Eur Heart J 2020 April 15 (Epub ahead of print).

8. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2):271.e8-280.e8.

9. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J 2004;383: 45-51.

10. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARSCoV-2 spike glycoprotein. Cell 2020; 181(2):281.e6-292.e6.

11. Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res 2017;125:21-38.

12. Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111: 2605-10.

13. Patel AB, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA 2020 March 24 (Epub ahead of print).

14. American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. March 17, 2020 (https://www .acc.org/latest-in-cardiology/articles/ 2020/03/17/08/59/hfsa-acc-aha-statement -addresses-concerns-re-using-raas -antagonists-in-covid-19).

15. European Society of Cardiology. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. March 13, 2020 (https://www.escardio.org/Councils/ Council-on-Hypertension-(CHT)/News/ position-statement-of-the-esc-council-on -hypertension-on-ace-inhibitors-and-ang).

16. World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance. March 13, 2020 (https://www.who.int/docs/default -source/coronaviruse/clinical -management-of-novel-cov.pdf).

17. Karlberg J, Chong DSY, Lai WYY. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol 2004;159:229- 31. The New England Journal of Medicine Downloaded from nejm.org on June 1, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. 8 n engl j med nejm.org The new england journal o f medicine

18. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626-38.

19. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J Immunol 2017;198: 4046-53.

20. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant 2020;39:405-7.

21. Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double edged sword. Circulation 2020 March 26 (Epub ahead of print).

22. Mehra MR, Ruschitzka F. COVID-19 illness and heart failure: a missing link? JACC Heart Fail (in press). Copyright © 2020 Massachusetts Medical Society

SARS-CoV-2 is pre-adapted to Human Transmission, branches of evolution stemming from a less well-adapted human SARS-CoV-2-like virus have been found: The Role of SARS-CoV-2 Virus Progenitors for Future Virus Disease Transmission and Pandemic Re-Emergence

Reporter and Curator: Aviva Lev-Ari, PhD, RN – all bold face and colors are my additions


LPBI Position Statement

A.  SARS-CoV-2 is pre-adapted to Human Transmission

B.  Branches of evolution stemming from a less well-adapted human SARS-CoV-2-like virus have been found

C.  The Role of SARS-CoV-2 Virus Progenitors – ARE CLEAR

D. Virus Progenitors will potentiate Future Virus Disease Transmission

E.  Pandemic Re-Emergence – Is  InEVITABLE and Virus Progenitors will be the subject for 2nd generation of virus genetic engineering technologies for human infectivity


  • Top vaccine scientist says coronavirus is ‘almost perfectly human adapted’

The coronavirus that causes COVID-19 is “almost perfectly human adapted” — lending credence to the possibility it was man-made in a Chinese lab, a top Australian vaccine researcher says.

Nikolai Petrovsky was shocked when research found that the virus was more virulent in humans than any other animal, the Daily Mail reported.

He said it was like the new strain of coronavirus, called SARS-CoV-2, was “completely optimized from day one without the need to evolve” like other viruses.

“This is a new virus that has never been in humans before, but it has an extraordinarily high binding to human receptors, which is very surprising,” Petrovsky told the Mail. “It is almost perfectly human adapted, it couldn’t do any better.”

He said it is possible the virus was created in a lab in China — deepening suspicions that the global pandemic originated in Wuhan.

“We have to ask how that happened. Was it a complete fluke? It can be as nature has many shots at goal and you only see the ones that land,” Petrovsky said.



  • No known animal host and ‘almost perfect’ human adaption: Top Australian vaccine scientist reveals how COVID-19’s unique structure means it’s either man-made – or a ‘complete fluke’ of nature
  • Professor Nikolai Petrovsky said virus was better at attaching itself to human cells than to any other animal
  • It is so ‘perfectly adapted’ to infect humans that the possibility it was made in a Chinese lab can’t be ignored
  • Wuhan Institute of Virology studied bat coronaviruses and is theorised to have accidentally leaked COVID-19
  • Virus could have been formed naturally by mixing bat and pangolin versions, but this is statistically unlikely
  • Professor Petrovsky said the inquiry into virus origins needed urgently and should have started months ago

“This, plus the fact that no corresponding virus has been found to exist in nature, leads to the possibility that COVID-19 is a human-created virus. It is therefore entirely plausible that the virus was created in the biosecurity facility in Wuhan [WIV] by selection on cells expressing human ACE2 [receptor], a laboratory that was known to be cultivating exotic bat coronaviruses at the time.” https://www.washingtontimes.com/news/2020/may/21/australian-researchers-see-virus-design-manipulati/

Scientist in protective overall

“We can’t exclude the possibility that this came from a laboratory experiment rather than from an animal” – Prof Nikolai Petrovsky

Genetic engineering the quicker way to human infectivity

Commenting on Prof Petrovsky’s conclusion that SARS-CoV-2 could have originated from culture of a wild virus and selection in human cells, the London-based molecular geneticist Dr Michael Antoniou agreed that this scenario was plausible: “You can certainly develop a human-infective virus like SARS-CoV-2 by repeatedly passing a wild bat virus through human cells, in the way that Prof Petrovsky describes. You culture human cells with the virus, allowing the virus to replicate, and harvest the resulting viruses. This selects for the most human-infective viruses, which you use to re-infect more cells. By going through successive rounds of this process, you are gradually selecting for viruses that have acquired mutations leading to enhancement of human infectivity. Eventually you end up with a virus that is optimized for human infectivity.”

However, Dr Antoniou added that there are far quicker and more efficient ways to achieve this aim.

For example, if you start with little information about what your human-infective virus looks like, you can genetically engineer a large number of SARS-CoV spike protein variants within phages. Phages are viruses that can infect bacteria. Phages can be genetically engineered to express on their exterior coat the CoV spike protein with a different variant of the receptor binding domain (RBD) – the part of the spike protein that allows the virus to bind to the ACE2 protein on human cell surfaces and thus enables infection to take place. This collection of phage variants with different RBDs is called a “phage display library”. The “library” of variants is then cultured with human cells in order to select for those phages with spike protein variants that bind to the ACE2 receptor.

Then the DNA is extracted from the phage with the best-binding spike protein and sequenced. Based on the sequence, a whole virus optimized for human infectivity can be synthesized.

Alternatively, Dr Antoniou explained, if you start with some information, as is likely with a group of researchers experienced in coronavirus gain-of-function research, there is an even quicker way to create a human-infective virus. Given that past research indicates that the nature of the spike protein alone doesn’t determine infectivity, it seems sensible to generate a library of spike mutant proteins directly within a whole coronavirus, which would also contain any other components necessary for infectivity.

In this case, you would take a DNA clone of a coronavirus that you know to be close to human infectivity, based on the sequence of its RBD. (Manipulation of DNA clones of coronaviruses is the standard procedure used to generate mutant viruses, including chimeras, in gain-of-function experiments, such as those carried out by scientists at the University of North Carolina and the Wuhan Institute of Virology.) You would then use the genetic engineering technique of DNA synthesis to generate a large number of randomly mutated versions of the spike protein RBD. The RBD mutations that you engineer could be more narrowly targeted by focusing on those regions encoding the amino acids whose nature and positions you know to be most critical for docking onto the human ACE2 receptor. The mutant versions of the RBD would then be selected for strong binding to the ACE2 receptor and consequently high infectivity of human cells.

Both methods described above would not leave any “signature” of genetic engineering. That’s an important consideration, given that Prof Petrovsky believes that genetic engineering was not involved in the development of SARS-CoV-2 due to the absence of such a signature.

Genetic engineering likely

In GMWatch’s view, to bypass the efficient genetic engineering-based methods described by Dr Antoniou in favour of the more laborious culture and selection-only method suggested by Prof Petrovsky would seem a curious decision for any laboratory committed to investigating coronavirus gain-of-function, such as the WIV.

The conclusions that we draw from these two new papers and Dr Antoniou’s input are that the “zoonosis” theory of SARS-CoV-2’s origin looks increasingly open to question, that the lab escape theory appears to be a solidly based scenario and, if that is what happened, genetic engineering is highly likely to have played a part in the development of the virus.

Report by Claire Robinson



  • Why Was Wuhan Lab Locked Down When Outbreak Began?
Analysis by Dr. Joseph Mercola Fact Checked

GAs reported in “Bioweapon Labs Must Be Shut Down and Scientists Prosecuted,” there’s mounting evidence suggesting SARS-CoV-2 may have been leaked (whether inadvertently or not) from the biosafety level (BSL) 4 laboratory in Wuhan, China.1,2I’ve also interviewed bioweapons expert Francis Boyle and molecular biologist Judy Mikovits, both of whom have cited evidence that strongly points toward SARS-CoV-2 being an escaped laboratory creation.

Why Was Wuhan Lab Shut Down?

Fueling suspicions that SARS-CoV-2 escaped from the lab in Wuhan — and that it began far earlier than admitted — is an analysis3 of commercial telemetry (i.e., cellphone) data showing a significant and unusual reduction in device activity in and around the Wuhan Institute of Virology’s (WIV) National Biosafety Laboratory during October 2019.4,5,6According to the open source telemetry report,7 “Beginning on October 11, there was a substantial decrease in activity,” and “the last time a device is active prior to October 11 is October 6.”Between October 14 and October 19, there was no device activity in the area around the laboratory at all. “During this time, it is believed that roadblocks were put in place to prevent traffic from coming near the facility,” the report states. What’s more, between October 7 and October 24, there was no activity within the facility itself.While not concrete proof of a biohazard leak, the absence of cellphone traffic in and around the laboratory in October 2019 suggests the lab may have been shut down for a period, and the roads around it blocked off. The question is why?Amid accusations that the World Health Organization helped suppress information about the pandemic on behalf of China, a review of its handling of the COVID-19 pandemic will be conducted,8 although it is still unclear which body will conduct the review and when. Many are also asking just how independent such a review will or can be.According to Martenson, the fact that SARS-CoV-2’s spike protein has a furin cleavage site is “the smoking gun” that proves it was created in a lab. I invite you to review his easy-to-follow analysis in “The Smoking Gun Proving SARS-CoV-2 Is an Engineered Virus.”If the Nerd Has Power blogger is correct, and the bat virus RaTG13 was in fact fabricated in order to give the natural evolution theory of SARS-CoV-2 some credence, then the evidence for a man-made pandemic becomes all the more compelling. There’s also other evidence that raise serious questions about the origin of this pandemic virus. Other Evidence of ManipulationIn an earlier blog post, dated March 15, 2020, Nerd Has Power explains the importance of the S1 and S2 spikes of a given virus.38 In that post, the blogger also details significant changes found in the S1 portion of the SARS-CoV-2 spike protein, “which dictates which host a coronavirus targets,” whereas much of the rest of the spike is very similar to the bat coronaviruses ZC45 and ZXC21. According to the blogger:39

“… the details of these differences and the way the human and the bat viruses differ from each other here in S1, in my and many other people’s eyes, practically spell out the origin of the Wuhan coronavirus — it is created by people, not by nature.”

In my opinion, the strongest pieces of evidence so far all point toward SARS-CoV-2 being a laboratory creation. How it got released, however, and why, remains to be determined.The fact that the people responsible would want to cover it up is obvious, however, when you consider that the punishment in such an event could include life in prison for violating the Biological Weapons Anti-Terrorism Act of 1989.40

Sources & References

wuhan bio lab shut down


  • Fueling suspicions that SARS-CoV-2 escaped from the Wuhan lab is an analysis of commercial telemetry (i.e., cellphone) data showing a significant and unusual reduction in device activity in and around the Wuhan Institute of Virology’s National Biosafety Laboratory during October 2019
  • Between October 14 and October 19, there was no device activity in the area around the laboratory at all, and between October 7 and October 24, there was no activity within the facility itself
  • While not concrete proof of a biohazard leak, the absence of cellphone traffic in and around the laboratory in October 2019 suggests the lab may have been shut down for a period, and the roads around it blocked off
  • A crucial piece of the lab release hypothesis that is missing from media reports and scientific opinion is a clear description of the experiments being conducted at the Wuhan Institute of Virology
  • Researchers have engineered chimeric viruses where the gene for the cell entry protein (S protein receptor-binding domain) from one virus is replaced by that of another virus
  • Bioweapon Labs Must Be Shut Down and Scientists Prosecuted
Analysis by Dr. Joseph Mercola Fact Checked
  • Gain of Function Research at NIH



  • A pneumonia outbreak associated with a new coronavirus of probable bat origin

Nature volume 579, pages270–273(2020)Cite this article



  • A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7


Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1,2,3,4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5,6,7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.


  1. Li, W. et al. Bats are natural reservoirs of SARS-like coronaviruses. Science310, 676–679 (2005).
  2. Ge, X.-Y. et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature503, 535–538 (2013).
  3. Yang, L. et al. Novel SARS-like betacoronaviruses in bats, China, 2011. Emerg. Infect. Dis19, 989–991 (2013).
  4. Hu, B. et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog13, e1006698 (2017).


  • A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Menachery, V., Yount, B., Debbink, K. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 21, 1508–1513 (2015). https://doi.org/10.1038/nm.3985


The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations1. Using the SARS-CoV reverse genetics system2, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.



Donato Gemmati, Barbara Bramanti, […] & Veronica Tisato

International Journal of Molecular Sciences (2020)


  • Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes

Hua Guo, Bing-Jie Hu, Xing-Lou Yang, Lei-Ping Zeng, Bei Li, Song-Ying Ouyang, Zheng-Li Shi

doi: https://doi.org/10.1101/2020.05.13.093658



LPBI Position 

A.  SARS-CoV-2 is pre-adapted to Human Transmission

B.  Branches of evolution stemming from a less well-adapted human SARS-CoV-2-like virus have been found

C.  The Role of SARS-CoV-2 Virus Progenitors – ARE CLEAR

D. Virus Progenitors will potentiate Future Virus Disease Transmission

E.  Pandemic Re-Emergence – Is  InEVITABLE and Virus Progenitors will be the subject for 2nd generation of genetic engineering technologies

COVID-19: Novel Treatment Protocols using Approved drugs vs Standard of Care vs Vaccine and Antiviral new drug discovery and development – An LPBI Group Response and An LPBI Group & Affiliates Response

Curator: Aviva Lev-Ari, PhD, RN


On 5/26/2020 LPBI organized a Symposium on New Therapeutics for COVID-19

AGENDA included presentations by:

  • Dr. Raphael Nir, PhD, CSO, SBH, Sciences, Inc. – Drug Concept to mitigate Cytokine Storm in COVID-19 – ATTACHMENT
  • Dr. Ajay Gupta, MD, Professor & Entrepreneur – Rhinitis drug approved in Japan – REPURPOSED for COVID-19 and Application for FDA Approval
  • Dr. Yigal Blum, PhD, ex-SRI Int’l VP and Entrepreneur –  AMORPHOUS CALCIUM CARBONATE (ACC) TREATMENT FOR COVID-19
  • Dr. Orna Harel, PhD, Managing Partner, Agbiopro – Representation for – Prof. Saul Yedgar on the concept and state of preclinical efforts for COVID-19 drug development 
  • Aviva Lev-Ari, PhD, RN – The Potential of REVIVAL of Drug Discovery Initiative and Explorations of Joint Ventures with Biotech companies – An Interim Phase toward POST Coronavirus Pandemic Exit

DISCUSSION – Where and What is the INTERFACE between what our External Relations attempt to accomplish and the Capabilities of LPBI Group’s Team

In the concluding remarks, Dr. Lev-Ari discussed the importance of TREATMENT PROTOCOLS vs. one Therapeutics at a time vs. Combination Drug therapies.

Dr. Lev-Ari pointed the Symposium attendees to the following two points:

1.  The State of Science been endorsed by LPBI Group

RNA from the SARS-CoV-2 virus taking over the cells it infects: Virulence – Pathogen’s ability to infect a Resistant Host: The Imbalance between Controlling Virus Replication versus Activation of the Adaptive Immune Response
Curator: Aviva Lev-Ari, PhD, RN – I added colors and bold face

2.  LPBI Group’s Position for Treatment Protocol(s)

In continuation to 5/26/2020 Symposium on New Therapeutics for COVID-19, we will follow up with an AGENDA for 6/16/2020 

Part I: Therapeutics for COVID-19

  • Prof. Saul Yedgar – Holder of US Patents on Rhinitis, anti-inflatation and other indications – 40 minutes
  • Dr. Ajay Gupta, MD – Rhinitis drug approved in Japan – FDA Application for Approval of Repurpusing to COVID-19 in the US – 40 minutes
  • Discussion – 20 minutes


On 5/29/2020 Dr. Lev-Ari read the article, COVID-19 Critical Care

Analysis by Dr. Joseph Mercola


  • Despite the fact that many critical care specialists are using treatment protocols that differ from standard of care, information about natural therapeutics in particular are still being suppressed by the media and is not received by critical care physicians
  • Five critical care physicians have formed the Front Line COVID-19 Critical Care Working Group (FLCCC). The group has developed a highly effective treatment protocol known as MATH+
  • Of the more than 100 hospitalized COVID-19 patients treated with the MATH+ protocol as of mid-April, only two died. Both were in their 80s and had advanced chronic medical conditions
  • The protocols call for the use of intravenous methylprednisolone, vitamin C and subcutaneous heparin within six hours of admission into the hospital, along with high-flow nasal oxygen. Optional additions include thiamine, zinc and vitamin D
  • COVID-19 kills by triggering hyperinflammation, hypercoagulation and hypoxia. The MATH+ protocol addresses these three core pathological processes

COVID-19 Early Intervention Protocol

According to Kory, the FLCCCs MATH+ protocol has been delivered to the White House on four occasions, yet no interest has been shown. Worse, he says they continue to be stonewalled by the U.S. Centers for Disease Control and the National Institute for Health. Why?

Isn’t saving lives, right now, and by any means possible, more important than pushing for a vaccine? If the MATH+ protocol works with near-100% effectiveness, a vaccine may not even be necessary. The MATH+ protocol gets its name from:

Intravenous Methylprednisolone

High-dose intravenous Ascorbic acid

Plus optional treatments Thiamine, zinc and vitamin D

Full dose low molecular weight Heparin

Kory’s testimony transcript reviews and summarizes the MATH+ protocol, and explains why the timing of the treatment is so important. As explained by Kory, there are two distinct yet overlapping phases of COVID-19 infection.

  1. Phase 1 is the viral replication phase. Typically, patients will only experience mild symptoms, if any, during this phase. At this time, it’s important to focus on antiviral therapies.
  2. In Phase 2, the hyperinflammatory immune response sets in, which can result in organ failures (lungs, brain, heart and kidneys). The MATH+ protocol is designed to treat this active phase, but it needs to be administered early enough.

The MATH+ Protocol

The MATH+ protocol7 calls for the use of three medicines, all of which need to be started within six hours of hospital admission:

  • Intravenous methylprednisolone, to suppress the immune system and prevent organ damage from cytokine storms — For mild hypoxia, 40 milligrams (mg) daily until off oxygen; moderate to severe illness, 80 mg bolus followed by 20 mg per day for seven days. On Day 8, switch to oral prednisone and taper down over the next six days.
  • Intravenous ascorbic acid (vitamin C), to control inflammation and prevent the development of leaky blood vessels in the lungs — 3 grams/100 ml every six hours for up to seven days.
  • Subcutaneous heparin (enoxaparin), to thin the blood and prevent blood clots — For mild to moderate illness, 40 mg to 60 mg daily until discharged.

Optional additions include thiamine, zinc and vitamin D. In addition to these medications, the protocol calls for high-flow nasal oxygen to avoid mechanical ventilation, “which itself damages the lungs and is associated with a mortality rate approaching nearly 90% in some centers,” Kory notes.8

Together, this approach addresses the three core pathological processes seen in COVID-19, namely hyperinflammation, hypercoagulability of the blood, and hypoxia (shortness of breath due to low oxygenation).

COVID-19 Should Not Be Treated as ARDS

In the video, Dr. Paul Marik points out that it’s crucial for doctors to treat each patient as an individual case, as COVID-19 is not conventional acute respiratory distress syndrome (ARDS).

If the patient is assumed to have ARDS and placed on a ventilator, you’re likely going to damage their lungs. Indeed, research has now shown that patients placed on mechanical ventilation have far higher mortality rates than patients who are not ventilated. While not discussed here, some doctors are also incorporating hyperbaric oxygen treatment in lieu of ventilation, with great success.

The reason for this is because the primary problem is inflammation, not fluid in the lungs. So, Marik says, they need anti-inflammatory drugs. “It’s not the virus that is hurting the host, it’s the acute inflammatory dysregulated response,” he says. “That’s why you need to use vitamin C and steroids.” He points out that steroids play a crucial role, as it creates synergy with vitamin C.

COVID-19 patients also have a hypercoagulation problem, so they need anticoagulants. In addition to using the proper medication, they must also be treated early. “You have to intervene early and aggressively to prevent them from deteriorating,” Marik says.

Methylprednisolone May Be a Crucial Component

Kory expresses concerns over the fact that health organizations around the world are warning doctors against the use of corticosteroids, calling this a “tragic error”9 as “COVID-19 is a steroid-responsive disease.”10 In his testimony, he points out:11

“Sorin Draghici, CEO of Advaita Bioinformatics, just reported12 that their incredibly sophisticated Artificial Intelligence platform called iPathwayGuide, using cultured human cell lines infected with COVID-19, is able to map all the human genes which are activated by this virus …

Note almost all the activated genes are those that express triggers of inflammation. With this knowledge of the specific COVID inflammatory gene activation combined with knowledge of the gene suppression activity of all known medicines they were able to match the most effective drug for COVID-19 human gene suppression, and that drug is methylprednisolone.

This must be recognized, as the ability of other corticosteroids to control inflammation in COVID-19 was much less impactful. This is, we believe, an absolutely critical and historic finding. Many centers are using similar but less effective agents such as dexamethasone or prednisone.”

As noted by Kory in his senate testimony, Marik, chief of pulmonary and critical care medicine at the Eastern Virginia Medical School in Norfolk, Virginia, is a member of the FLCCC.13 You may recall that Marik was the one who in 2017 announced he had developed an extraordinarily effective treatment against sepsis.

Marik’s sepsis protocol also calls for intravenous vitamin C and a steroid, in this case hydrocortisone, along with thiamine. I for one am not surprised that the two protocols are so similar, seeing how sepsis is also a major cause of death in severe COVID-19 cases.

Safe and Effective Treatments Must Not Be Ignored

As noted by Marik in the video, COVID-19 is not regular ARDS and should not be treated as such. What kills people with COVID-19 is the inflammation, and steroids in combination with vitamin C work synergistically together to control and regulate that inflammation. The heparin, meanwhile, addresses the hypercoagulation that causes blood clots, which is a unique feature of COVID-19. As for the “lack of studies” supporting their protocol, FLCCC notes:14

“A number of official guidelines, such as those of the WHO and several other U.S. agencies, recommend limiting treatment for … critically ill patients to ‘supportive care only’ — and to allow the therapies described here to be studied in randomized controlled trials where half of the patients would receive placebo and where the results would come in months or years.

Our physicians agree that while a randomized controlled trial (RCT), under normal circumstances, might be considered, the early provisions of MATH+, which must be given within hours of critical illness, would inevitably be delayed by such a study design, rendering the validity of the RCT questionable.

Furthermore, while the results of an RCT would not be available for months or more, well-designed observational studies of the protocol could yield timely feedback during this pandemic, to improve the treatment process much more quickly.”

I believe this information needs to be shared far and wide, if we are to prevent more people from dying unnecessarily. More and more, as doctors are starting to speak openly about their clinical findings, we’re seeing that there are quite a few different ways to tackle this illness without novel antivirals or vaccines, using older, inexpensive and readily available medications that are already known to be safe.





A Response by LPBI Group and a Potential Response by LPBI Group and its Affiliates


LPBI Group’s Components in Novel Treatment Protocol Definition


  • Forthcoming by Stephen J. Williams, PhD – Immuno-theraphy boosting Protocol

based on

T cells found in COVID-19 patients ‘bode well’ for long-term immunity | Science | AAAS


  • Forthcoming by Aviva Lev-Ari, PhD, RN and Stephen J. Williams, PhD – Nitric Oxide Inhaler OR Bystolic® (nebivolol) www.bystolicpro.com
  • Two alternatives per stage of COVID-19 infections: Severe or Moderate

based on


  • LPBI Group’s Affiliates:

If you wish your Therapeutic solution to be included in the NEW DEFINITION of Treatment Protocol(s), then propose your component for inclusion in the Novel Treatment Protocol to be discussed on June 16, 2020

LPBI Group’s Affiliates Components in the Novel Treatment Protocol(s) Definition

  • Prof. Saul Yedgar – Holder of US Patents on Rhinitis, anti-inflammation and other indications – 40 minutes
  • Dr. Ajay Gupta, MD – Rhinitis drug approved in Japan – FDA Application for Approval of Repurposing to COVID-19 in the US – 40 minutes
  • Dr. Raphael Nir, PhD, CSO, SBH, Sciences, Inc. – Drug Concept to mitigate Cytokine Storm in COVID-19 
  • Dr. Yigal Blum, PhD, ex-SRI Int’l VP and Entrepreneur –  AMORPHOUS CALCIUM CARBONATE (ACC) TREATMENT FOR COVID-19

References on Nitric Oxide on PharmaceuticalIntellige.com – Open Access Online Scientific Journal include 299 articles


Of note


Included in the 299 articles

  • Transposon-mediated Gene Therapy improves Pulmonary Hemodynamics and attenuates Right Ventricular Hypertrophy: eNOS gene therapy reduces Pulmonary vascular remodeling and Arterial wall hyperplasia

Reporter: Aviva Lev-Ari, PhD, RN



Author and Curator of an Investigator Initiated Study: Aviva Lev-Ari, PhD, RN



  • Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production,  stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

Curator of an Investigator Initiated Study: Aviva Lev-Ari, PhD, RN



  • Cardiovascular Disease (CVD) and the Role of Agent Alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

Curator and Investigator Initiated Study: Aviva Lev-Ari, PhD, RN



RNA from the SARS-CoV-2 virus taking over the cells it infects: Virulence – Pathogen’s ability to infect a Resistant Host: The Imbalance between Controlling Virus Replication versus Activation of the Adaptive Immune Response

Curator: Aviva Lev-Ari, PhD, RN – I added colors and bold face



The Genome Structure of CORONAVIRUS, SARS-CoV-2

Reporter: Aviva Lev-Ari, PhD, RN



Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Open Access Published:May 15, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.026


  • SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response
  • Strong chemokine expression is consistent across in vitroex vivo, and in vivo models
  • Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19


Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

Graphical Abstract



Defining the Transcriptional Response to SARS-CoV-2 Relative to Other Respiratory Viruses

To compare the transcriptional response of SARS-CoV-2 with other respiratory viruses, including MERS-CoV, SARS-CoV-1, human parainfluenza virus 3 (HPIV3), respiratory syncytial virus (RSV), and IAV, we first chose to focus on infection in a variety of respiratory cell lines (Figure 1). To this end, we collected poly(A) RNA from infected cells and performed RNA sequencing (RNA-seq) to estimate viral load. These data show that virus infection levels ranged from 0.1% to more than 50% of total RNA reads (Figure 1A).


In the present study, we focus on defining the host response to SARS-CoV-2 and other human respiratory viruses in cell lines, primary cell cultures, ferrets, and COVID-19 patients. In general, our data show that the overall transcriptional footprint of SARS-CoV-2 infection was distinct in comparison with other highly pathogenic coronaviruses and common respiratory viruses such as IAV, HPIV3, and RSV. It is noteworthy that, despite a reduced IFN-I and -III response to SARS-CoV-2, we observed a consistent chemokine signature. One exception to this observation is the response to high-MOI infection in A549-ACE2 and Calu-3 cells, where replication was robust and an IFN-I and -III signature could be observed. In both of these examples, cells were infected at a rate to theoretically deliver two functional virions per cell in addition to any defective interfering particles within the virus stock that were not accounted for by plaque assays. Under these conditions, the threshold for PAMP may be achieved prior to the ability of the virus to evade detection through production of a viral antagonist. Alternatively, addition of multiple genomes to a single cell may disrupt the stoichiometry of viral components, which, in turn, may itself generate PAMPs that would not form otherwise. These ideas are supported by the fact that, at a low-MOI infection in A549-ACE2 cells, high levels of replication could also be achieved, but in the absence of IFN-I and -III induction. Taken together, these data suggest that, at low MOIs, the virus is not a strong inducer of the IFN-I and -III system, as opposed to conditions where the MOI is high.
Taken together, the data presented here suggest that the response to SARS-CoV-2 is imbalanced with regard to controlling virus replication versus activation of the adaptive immune response. Given this dynamic, treatments for COVID-19 have less to do with the IFN response and more to do with controlling inflammation. Because our data suggest that numerous chemokines and ILs are elevated in COVID-19 patients, future efforts should focus on U.S. Food and Drug Administration (FDA)-approved drugs that can be rapidly deployed and have immunomodulating properties.



SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

Yoriyuki KonnoIzumi KimuraKeiya UriuMasaya FukushiTakashi IrieYoshio KoyanagiSo NakagawaKei Sato


One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasi-species with extended ORF3b that may exacerbate COVID-19 symptoms.


  • ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist

  • SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog

  • The anti-IFN activity of ORF3b depends on the length of its C-terminus

  • An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases

Competing Interest Statement

The authors have declared no competing interest.

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv






A deep dive into how the new coronavirus infects cells has found that it orchestrates a hostile takeover of their genes unlike any other known viruses do, producing what one leading scientist calls “unique” and “aberrant” changes.Recent studies show that in seizing control of genes in the human cells it invades, the virus changes how segments of DNA are read, doing so in a way that might explain why the elderly are more likely to die of Covid-19 and why antiviral drugs might not only save sick patients’ lives but also prevent severe disease if taken before infection.“It’s something I have never seen in my 20 years of” studying viruses, said virologist Benjamin tenOever of the Icahn School of Medicine at Mount Sinai, referring to how SARS-CoV-2, the virus that causes Covid-19, hijacks cells’ genomes.

The “something” he and his colleagues saw is how SARS-CoV-2 blocks one virus-fighting set of genes but allows another set to launch, a pattern never seen with other viruses. Influenza and the original SARS virus (in the early 2000s), for instance, interfere with both arms of the body’s immune response — what tenOever dubs “call to arms” genes and “call for reinforcement” genes.

The first group of genes produces interferons. These proteins, which infected cells release, are biological semaphores, signaling to neighboring cells to activate some 500 of their own genes that will slow down the virus’ ability to make millions of copies of itself if it invades them. This lasts seven to 10 days, tenOever said, controlling virus replication and thereby buying time for the second group of genes to act.

This second set of genes produce their own secreted proteins, called chemokines, that emit a biochemical “come here!” alarm. When far-flung antibody-making B cells and virus-killing T cells sense the alarm, they race to its source. If all goes well, the first set of genes holds the virus at bay long enough for the lethal professional killers to arrive and start eradicating viruses.

“Most other viruses interfere with some aspect of both the call to arms and the call for reinforcements,” tenOever said. “If they didn’t, no one would ever get a viral illness”: The one-two punch would pummel any incipient infection into submission.

SARS-CoV-2, however, uniquely blocks one cellular defense but activates the other, he and his colleagues reported in a study published last week in Cell. They studied healthy human lung cells growing in lab dishes, ferrets (which the virus infects easily), and lung cells from Covid-19 patients. In all three, they found that within three days of infection, the virus induces cells’ call-for-reinforcement genes to produce cytokines. But it blocks their call-to-arms genes — the interferons that dampen the virus’ replication.

The result is essentially no brakes on the virus’s replication, but a storm of inflammatory molecules in the lungs, which is what tenOever calls an “unique” and “aberrant” consequence of how SARS-CoV-2 manipulates the genome of its target.

In another new study, scientists in Japan last week identified how SARS-CoV-2 accomplishes that genetic manipulation. Its ORF3b gene produces a protein called a transcription factor that has “strong anti-interferon activity,” Kei Sato of the University of Tokyo and colleagues found — stronger than the original SARS virus or influenza viruses. The protein basically blocks the cell from recognizing that a virus is present, in a way that prevents interferon genes from being expressed.

In fact, the Icahn School team found no interferons in the lung cells of Covid-19 patients. Without interferons, tenOever said, “there is nothing to stop the virus from replicating and festering in the lungs forever.”

That causes lung cells to emit even more “call-for-reinforcement” genes, summoning more and more immune cells. Now the lungs have macrophages and neutrophils and other immune cells “everywhere,” tenOever said, causing such runaway inflammation “that you start having inflammation that induces more inflammation.”

At the same time, unchecked viral replication kills lung cells involved in oxygen exchange. “And suddenly you’re in the hospital in severe respiratory distress,” he said.

In elderly people, as well as those with diabetes, heart disease, and other underlying conditions, the call-to-arms part of the immune system is weaker than in younger, healthier people, even before the coronavirus arrives. That reduces even further the cells’ ability to knock down virus replication with interferons, and imbalances the immune system toward the dangerous inflammatory response.

The discovery that SARS-CoV-2 strongly suppresses infected cells’ production of interferons has raised an intriguing possibility: that taking interferons might prevent severe Covid-19 or even prevent it in the first place, said Vineet Menachery of the University of Texas Medical Branch.

In a study of human cells growing in lab dishes, described in a preprint (not peer-reviewed or published in a journal yet), he and his colleagues also found that SARS-CoV-2 “prevents the vast amount” of interferon genes from turning on. But when cells growing in lab dishes received the interferon IFN-1 before exposure to the coronavirus, “the virus has a difficult time replicating.”

After a few days, the amount of virus in infected but interferon-treated cells was 1,000- to 10,000-fold lower than in infected cells not pre-treated with interferon. (The original SARS virus, in contrast, is insensitive to interferon.)

Ending the pandemic and preventing its return is assumed to require an effective vaccine to prevent infectionand antiviral drugs such as remdesivir to treat the very sick, but the genetic studies suggest a third strategy: preventive drugs.

It’s possible that treatment with so-called type-1 interferon “could stop the virus before it could get established,” Menachery said.

Giving drugs to healthy people is always a dicey proposition, since all drugs have side effects — something considered less acceptable than when a drug is used to treat an illness. “Interferon treatment is rife with complications,” Menachery warned. The various interferons, which are prescribed for hepatitis, cancers, and many other diseases, can cause flu-like symptoms.

But the risk-benefit equation might shift, both for individuals and for society, if interferons or antivirals or other medications are shown to reduce the risk of developing serious Covid-19 or even make any infection nearly asymptomatic.

Interferon “would be warning the cells the virus is coming,” Menachery said, so such pretreatment might “allow treated cells to fend off the virus better and limit its spread.” Determining that will of course require clinical trials, which are underway.

Is Remdesivir the miracle cure or a short term cure for COVID-19?

Reporter: Irina Robu, PhD


Updated on 5/23/2020


New England Journal of Medicine




The trial was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases, the NIH, and funded in part by the NIAID and the National Cancer Institute, NIH. The trial has also been funded in part by the governments of Japan, Mexico, Denmark, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council.

Beigel disclosed no conflicts of interest.

Other co-authors disclosed support from NIH/NIAID/DMID, University of Minnesota, Medical Research Council U.K., Novo Nordisk Foundation, Simonsen Foundation, GSK, Pfizer, Boehringer Ingelheim, Gliead, MSD, Lundbeck Foundation, Merck, Sanofi-Pasteur,Cepheid, Ellume, Genentech, Janssen, ViiV Healthcare, Integrum Scientific LLC, UCL, Bristol University, Gilead Sciences Europe, ECDC, EU Social funds and National resources.

One co-author is an employee of the U.S. government.



Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.


We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.


A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).


Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705. opens in new tab.)

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Remdesivir Data from NIAID Trial Published

— “Not a panacea” or a “cure-all,” expert cautions

Peer-reviewed findings were published late Friday from one of the key trials of remdesivir, perhaps the most promising antiviral agent for COVID-19, confirming and extending topline results announced a month ago via press release.

Hospitalized patients with COVID-19 who received remdesivir had a median recovery time of 11 days versus 15 days with placebo (rate ratio for recovery 1.32, 95% CI 1.12-1.55, P<0.001), reported John Beigel, MD, of the National Institute of Allergy and Infectious Diseases (NIAID), and colleagues.

Mortality estimates by 14 days were lower for the remdesivir group compared to placebo, but non-significant (HR for death 0.70, 95% CI 0.47-1.04), the authors wrote in the New England Journal of Medicine.

Interestingly, when researchers examined outcomes on an 8-point ordinal scale, they found patients with a baseline ordinal score of 5 had a rate ratio for recovery of 1.47 (95% CI 1.17-1.84), while patients with a baseline score of 7 had a rate ratio for recovery of 0.95 (95% CI 0.64-1.42).

Some of these data were released by the NIAID on April 29, but without further details such as 95% confidence intervals. On May 1, the FDA agreed to let remdesivir be used clinically under an emergency use authorization. Since then, however, clinicians and other researchers have clamored for a fuller report, to help guide their clinical practice. For example, questions were raised as to whether particular subgroups got more benefit from the drug than others.

David Aronoff, MD, of Vanderbilt University Medical Center in Nashville, who was not involved in the research, noted the drug seemed more effective when given to patients who weren’t as severely ill, earlier in the course of disease. He added this wasn’t surprising, given remdesivir’s mechanism of action as an antiviral, which works by blocking the virus from replicating.

“The drug doesn’t affect the host, it only affects the virus. What seems to cause major problems late in the course of disease is the inflammatory response to the initial damage the virus causes,” he told MedPage Today.

Aronoff likened the virus to an arsonist setting fires, and antivirals like remdesivir as the police trying to catch the arsonist before they set more fires.

“But once the building is on fire, it doesn’t matter where the arsonist is,” he noted.

This is why combining a drug to address the viral response with a drug to address the host response may be critical to treating the virus. Aronoff cited the NIAID’s ACTT-2 trial in progress, which will examine combination therapy with remdesivir and anti-inflammatory drug, baricitinib, versus remdesivir alone.




Is Remdesivir the miracle cure or a short term cure for COVID-19?

Reporter: Irina Robu, PhD


In 1947, amid the “Golden Age” of antibiotic research that yielded many of the medicines used against bacteria such as chloramphenicol, a molecule that could combat a wide array of bacteria from different families. It was among the first FDA-approved broad-spectrum antibiotics used against typhus/meningitis. Now, chloramphenicol’s side effects make it a last-resort drug but it remains invaluable against a host of bacterial infections.
Viruses are more slippery targets than bacteria and they are a hundred times smaller and consist only of bare-bones cellular machinery. There are simply fewer targets at which to aim antivirals, especially for drugs that would shoot for the rare viral components that remain common across diverse types of viruses. Scientists call this virus-pinpointing model the “one drug, one bug” approach. An antiviral’s mechanism can’t be too generic, either.

Even with that, there is no common mechanism to target all viruses but instead researchers hope to expand the existing list of broad-spectrum antivirals and find more medicines that work on all viruses of a certain family. This reality makes the search for treatments for SARS-CoV-2 all the more challenging. Presently, no broad-spectrum antiviral is accepted for the treatment of all coronaviruses of which a new strain has driven the current pandemic.

With no specific antiviral drug for treatment of patients with severe COVID-19, scientists are rushing to find a solution. Yet, remdesivir’s journey from hypothesis to treatment is unparalleled. The drug was originally investigated by Gilead as a treatment for another lethal viral disease, Ebola. Remdesivir, a nucleoside analogue prodrug has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.

However, Gilead was unwilling to give up on its investment in the drug and remained hopeful that the drug might be useful in treating COVID-19. In collaboration with Chinese researchers, the National Institute of Allergy and Infectious Diseases (NIAID) and the pharmaceutical company behind the drug, Gilead, all launched studies of remdesivir’s efficacy in treating COVID-19. Based on those encouraging results in May 1, the FDA issued an emergency-use authorization that permits doctors to treat severely ill COVID-19 patients with remdesivir. Japanese health officials issued a similar clearance days later.

On top of the biological challenge of finding new broad-spectrum antiviral drugs lies an economic one, partly because there is little financial incentive to develop broad-spectrum drugs against emerging diseases. And with all the government backed research, there is no guarantee that pharma companies have enough incentive to continue working on research. Yet, broad-spectrum antivirals are not miracle drugs, but they can be a helpful addition to a toolbox that is currently sparse.

Remdesivir’s potential first drew public attention in October 2015 during an Ebola outbreak in West Africa that claimed more than 11,000 lives. Remdesivir subdues a virus by interfering with replication. First, the body changes remdesivir into an imposter. It becomes what’s called a nucleoside analog, a genetic doppelganger that resembles adenosine. When the virus replicates, it weaves this analog into the new strand of genetic material. Nevertheless, the analog’s molecular makeup differs from real adenosine just enough to grind the copying process to a halt.

As COVID-19 swept the globe, scientists led an international trial of remdesivir as a treatment option. EIDD-2801, another treatment option has demonstrated broad-spectrum antiviral potential, as well as an ability to defend cells from SARS-CoV-2. Yet, the best treatment for COVID-19 can be remdesivir, EIDD-2801 or any single antiviral at all. Even with that, broad spectrum antivirals can be invaluable in the short-term.
The early success of remdesivir suggests that broad-spectrum antivirals will get their moment in the scientific limelight. After a pandemic pass, though, the rush interest about a multipurpose treatment diminishes.






SARS-CoV-2 Testing and Outcomes in the First 30 Days After the First Case of COVID-19 at an Australian Children’s Hospital

Reporter: Gail S. Thornton, M.A.


Objective: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children’s hospital according to the state health department guidelines, which varied over time.

Methods: We conducted a retrospective cohort study at The Royal Children’s Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the Emergency Department (ED) or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21st March 2020, until 19th April 2020. We recorded epidemiological and clinical data.

Results: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 (76%)) or RIC (102 (24%)). There were 4 (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients.

Conclusions: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.

Keywords: Australia; COVID-19; SARS-CoV-2; children; novel coronavirus.