Our son is working mightily to keep his HVAC enterprise alive during the contagion.  Last week a key employee after visiting a pharmacy where a person tested positive was told to go home and get tested (took two days), and then stay home to wait for results (3 more days).  So a work week was lost and the business hobbled during that time.  So I wondered what happened to all those rapid covid tests that were purchased back in September.

The story came out in the Montreal Gazette January 14, 2021 Scientists publish open letter calling for Quebec to use rapid testing.  Excerpts in italics with my bolds.

“We have 1.2 million of those tests just sitting in a warehouse in Farnham,” Université de Montréal professor Roxane Borgès Da Silva says.

A group of 213 scientists, professors, health-care workers and patients published an open letter to the Legault government Thursday calling on Quebec to roll out rapid COVID-19 tests to curb outbreaks more quickly and to step up its communications strategy.

“We have 1.2 million of those tests just sitting in a warehouse in Farnham,” Roxane Borgès Da Silva, a professor with the Université de Montréal’s school of public health, said in an interview Wednesday night. “We have reached a point in the evolution of the pandemic where the health system is at the breaking point. It is time that we use every tool at our disposal.”

In the letter, the signatories from institutions including the Université de Montréal, McGill, Laval, UQAM and the Institut national de santé publique du Québec (INSPQ), note the partial closure of businesses and restrictions on gatherings have failed to stem the increase in coronavirus cases, hospitalizations and deaths.

With a month-long curfew instituted Saturday, officials must take advantage of the expected decline in cases to counter the spread through better screening, which is “all the more important in a context where possible variants of the SARS-CoV-2 virus, which are more infectious, could spread in Quebec,” the letter reads.

Using rapid tests could help to identify positive cases more quickly, particularly those among asymptomatic patients and those who have been at so-called “super-spreader” events, the letter states

“In this regard, we believe that the simple and widely available access throughout the territory to rapid tests … allowing a result to be obtained in a few minutes could be a game-changer, especially in places of propagation.”

Quebec has been hesitant to use the tests widely because it fears their lack of sensitivity could clear people for COVID-19 when they actually have the virus. But Da Silva said the tests are close to 90-per-cent accurate when used on patients who are in an extremely contagious phase, which is crucial to stopping the most dangerous transmitters. The tests could be used at workplaces, high schools and CHSLDs, or be made available at pharmacies and doctors’ offices to allow the public to get tested quickly, Da Silva said.

As well, the signatories argue the government needs to do a better job of transmitting data and information to the public to improve citizens’ confidence in the science and improve compliance with regulations. They suggest using improved communication campaigns that appeal to the general public and using new strategies that incorporate humour and music.

More from CBC (here): 

The tests, which return a result in as little as 15 minutes, have variously been called a “game-changer” (Ontario Premier Doug Ford) and “less safe” as the gold-standard PCR lab test (Quebec Health Minister Christian Dubé, to Le Devoir).

The chair of McGill University’s bioengineering department, Dr. David Juncker, leans to the Ford end of the spectrum —provided the tests are used effectively. Right now they are not, he said, and it’s to the detriment of the broader testing effort.

“The current testing system isn’t very effective in terms of contact, trace and isolate … it’s too slow, it’s too cumbersome, it has too many delays. That’s one of the reasons we’re failing in containing the spread of the pandemic,” said Juncker, an expert on diagnostic testing.

The main area of concern for the provincial government — also voiced by federal officials — is the the rapid test’s lower accuracy, or sensitivity, and the risk of false negatives.

Those fears are overblown, in Juncker’s view, because the rapid tests can still help ferret out highly infectious people.

“If we just speak about diagnostic performance … the PCR test is the most effective one,” he said. “But if we think about what we want to use this for, as a public health tool that we want to use to contain and detect infectious individuals very quickly and isolate them very fast, that’s where rapid tests can be very helpful.”

Comment:  The need is to quickly identify people with enough viral load to infect others, and to become sick themselves.  Rapid tests excel at this when applied to people with symptoms that might or might not be Covid19.  Officials have been obsessed with PCR tests which are hyper-sensitive and show people as positive with too little load or even from a trace of dead virus.  Those false positives generate lots of fear and clog the system with people unnecessarily.

Background from Previous Post On Non-Infectious Covid Positives

Daniel Payne writes at Just the News Growing research indicates many COVID-19 cases might not be infectious at all. Excerpts in italics with my bolds.

Elevated ‘cycle thresholds’ may be detecting virus long after it is past the point of infection.

A growing body of research suggests that a significant number of confirmed COVID-19 infections in the U.S. — perhaps as many as 9 out of every 10 — may not be infectious at all, with much of the country’s testing equipment possibly picking up mere fragments of the disease rather than full-blown infections.

Yet a burgeoning line of scientific inquiry suggests that many confirmed infections of COVID-19 may actually be just residual traces of the virus itself, a contention that — if true — may suggest both that current high levels of positive viruses are clinically insignificant and that the mitigation measures used to suppress them may be excessive.

Background from previous post: New Better and Faster Covid Test

Kevin Pham reports on a breakthrough in coronavirus testing. Excerpts in italics with my bolds.

Another new test for COVID-19 was recently authorized — and this one could be a game-changer.

The Abbot Diagnostics BinaxNOW antigen test is a new point-of-care test that reportedly costs only $5 to administer, delivers results in as little as 15 minutes, and requires no laboratory equipment to perform. That means it can be used in clinics far from commercial labs or without relying on a nearby hospital lab.

That last factor is key. There are other quick COVID-19 tests on the market, but they have all required lab equipment that can be expensive to maintain and operate, and costs can be prohibitive in places that need tests most.

This kind of test is reminiscent of rapid flu tests that are ubiquitous in clinics. They’ll give providers tremendous flexibility in testing for the disease in not just clinics, but with trained and licensed medical professionals, in schools, workplaces, camps, or any other number of places.

So what’s new about this test? Most of the current tests detect viral RNA, the genetic material of SARS-CoV-2. This is a very accurate way of detecting the virus, but it requires lab equipment to break apart the virus and amplify the amount of genetic material to high enough levels for detection.

The BinaxNOW test detects antigens — proteins unique to the virus that are usually detectable whenever there is an active infection.

Abbott says it intends to produce 50 million tests per month starting in October. That’s far more than the number tested in July, when we were breaking new testing records on a daily basis with approximately 23 million tests recorded.

There’s a more important reason to be encouraged by this test coming available.  The viral load is not amplified by the test, so a positive is actually a person needing isolation and treatment.  As explained in a previous post below,  the PCR tests used up to now clutter up the record by showing as positive people with viral loads too low to be sick or to infect others.

Background from Previous Post The Truth About CV Tests

The peoples’ instincts are right, though they have been kept in the dark about this “pandemic” that isn’t.  Responsible citizens are starting to act out their outrage from being victimized by a medical-industrial complex (to update Eisenhower’s warning decades ago).  The truth is, governments are not justified to take away inalienable rights to life, liberty and the pursuit of happiness.  There are several layers of disinformation involved in scaring the public.  This post digs into the CV tests, and why the results don’t mean what the media and officials claim.

For months now, I have been updating the progress in Canada of the CV outbreak.  A previous post later on goes into the details of extracting data on tests, persons testing positive (termed “cases” without regard for illness symptoms) and deaths after testing positive.  Currently, the contagion looks like this.

The graph shows that deaths are less than 5 a day, compared to a daily death rate of 906 in Canada from all causes.  Also significant is the positivity ratio:  the % of persons testing positive out of all persons tested each day.  That % has been fairly steady for months now:  1% positive means 99% of people are not infected. And this is despite more than doubling the rate of testing.

But what does testing positive actually mean?  Herein lies more truth that has been hidden from the public for the sake of an agenda to control free movement and activity.  Background context comes from  Could Rapid Coronavirus Testing Help Life Return To Normal?, an interview at On Point with Dr. Michael Mina.  Excerpts in italics with my bolds. H/T Kip Hansen

Dr. Michael Mina:

COVID tests can actually be put onto a piece of paper, very much like a pregnancy test. In fact, it’s almost exactly like a pregnancy test. But instead of looking for the hormones that tell if somebody is pregnant, it looks for the virus proteins that are part of SA’s code to virus. And it would be very simple: You’d either swab the front of your nose or you’d take some saliva from under your tongue, for example, and put it onto one of these paper strips, essentially. And if you see a line, it means you’re positive. And if you see no line, it means you are negative, at least for having a high viral load that could be transmissible to other people.

An antigen is one of the proteins in the virus. And so unlike the PCR test, which is what most people who have received a test today have generally received a PCR test. And looking those types of tests look for the genome of the virus to RNA and you could think of RNA the same way that humans have DNA. This virus has RNA. But instead of looking for RNA like the PCR test, these antigen tests look for pieces of the protein. It would be like if I wanted a test to tell me, you know, that somebody was an individual, it would actually look for features like their eyes or their nose. And in this case, it is looking for different parts of the virus. In general, the spike protein or the nuclear capsid, these are two parts of the virus.

The reason that these antigen tests are going to be a little bit less sensitive to detect the virus molecules is because there’s no step that we call an amplification step. One of the things that makes the PCR test that looks for the virus RNA so powerful is that it can take just one molecule, which the sensor on the machine might not be able to detect readily, but then it amplifies that molecule millions and millions of times so that the sensor can see it. These antigen tests, because they’re so simple and so easy to use and just happen on a piece of paper, they don’t have that amplification step right now. And so they require a larger amount of virus in order to be able to detect it. And that’s why I like to think of these types of tests having their primary advantage to detect people with enough virus that they might be transmitting or transmissible to other people.”

The PCR test, provides a simple yes/no answer to the question of whether a patient is infected.
Source: Covid Confusion On PCR Testing: Maybe Most Of Those Positives Are Negatives.

Similar PCR tests for other viruses nearly always offer some measure of the amount of virus. But yes/no isn’t good enough, Mina added. “It’s the amount of virus that should dictate the infected patient’s next steps. “It’s really irresponsible, I think, to [ignore this]” Dr. Mina said, of how contagious an infected patient may be.

“We’ve been using one type of data for everything,” Mina said. “for [diagnosing patients], for public health, and for policy decision-making.”

The PCR test amplifies genetic matter from the virus in cycles; the fewer cycles required, the greater the amount of virus, or viral load, in the sample. The greater the viral load, the more likely the patient is to be contagious.

This number of amplification cycles needed to find the virus, called the cycle threshold, is never included in the results sent to doctors and coronavirus patients, although if it was, it could give them an idea of how infectious the patients are.

One solution would be to adjust the cycle threshold used now to decide that a patient is infected. Most tests set the limit at 40, a few at 37. This means that you are positive for the coronavirus if the test process required up to 40 cycles, or 37, to detect the virus.

Any test with a cycle threshold above 35 is too sensitive, Juliet Morrison, a virologist at the University of California, Riverside told the New York Times. “I’m shocked that people would think that 40 could represent a positive,” she said.

A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he would set the figure at 30, or even less.

Another solution, researchers agree, is to use even more widespread use of Rapid Diagnostic Tests (RDTs) which are much less sensitive and more likely to identify only patients with high levels of virus who are a transmission risk.

Comment:  In other words, when they analyzed the tests that also reported cycle threshold (CT), they found that 85 to 90 percent were above 30. According to Dr. Mina a CT of 37 is 100 times too sensitive (7 cycles too much, 2^7 = 128) and a CT of 40 is 1,000 times too sensitive (10 cycles too much, 2^10 = 1024). Based on their sample of tests that also reported CT, as few as 10 percent of people with positive PCR tests actually have an active COVID-19 infection. Which is a lot less than reported.

Here is a graph showing how this applies to Canada.

It is evident that increased testing has resulted in more positives, while the positivity rate is unchanged. Doubling the tests has doubled the positives, up from 300 a day to nearly 600 a day presently.  Note these are PCR results. And the discussion above suggests that the number of persons with an active infectious viral load is likely 10% of those reported positive: IOW up from 30 a day to 60 a day.  And in the graph below, the total of actual cases in Canada is likely on the order of 13,000 total from the last 7 months, an average of 62 cases a day.

 

Fig. 1. The four pillars of pandemic response to COVID-19. The four pillars of pandemic response to COVID-19 are:
1) contagion control or efforts to reduce spread of SARS-CoV-2,
2) early ambulatory or home treatment of COVID-19 syndrome to reduce hospitalization and death,
3) hospitalization as a safety net to prevent death in cases that require respiratory support or other invasive therapies,
4) natural and vaccination mediated immunity that converge to provide herd immunity and ultimate cessation of the viral pandemic.

Robert Clancy explains in his Quadrant article  COVID-19: A realistic approach to community management The author is Emeritus Professor of Pathology at the University of Newcastle Medical School. He is a member of the Australian Academy of Science’s COVID-19 Expert Database.   Excerpts in italics with my bolds.

Historically pandemics generate suspicion, speculation and emotion, before logic and empiric decisions determine optimal management. The current Covid19 pandemic is no exception. Twelve months on, there is an emerging consensus supporting an integration of a four-pillar plan: public health strategies; vaccination; early pre-hospital treatment; and hospital treatment. This position replaces an early confusion, with supporting data appearing on a near daily basis.

Public Health strategies are well understood and highly effective, forming the bedrock for disease control, while hospital management is a work in progress, but with progressive improvement in outcomes. Typical data for high risk subjects (>50 years with 1 or more co-morbidities) in the USA is currently 18-20% hospitalisation, with mortality around 1%. Less attention has been given to ongoing symptoms, with about 80% of hospitalised patients having profound fatigue and/or breathlessness 3-4 months after discharge. Many are unable to return to full time work 6 months after infection control.

The area of intense disagreement is community management combining prevention by vaccine and reduction of hospital admission, using pre-hospital treatment.

There is a global expectation that vaccines will dramatically change the current face of Covid19 while there is broad based denial that any of the available (unpatented) drugs beneficially alter the natural history of infection. Expectation of a vaccine nirvana alongside therapeutic nihilism are both incorrect, although each is promoted with a vigour rooted in socio-political conviction (& supported by the Pharma industry).

The conclusion based on logic and data, is that vaccines and early treatment strategies are both necessary for optimal disease control. As a result, a community plan has been formulated, aimed at keeping patients out of hospital. Experienced physicians have developed protocols based on evidence, with sequenced multi-drug regimens that support >80% reductions in admissions to hospital and death.

Implementation of this approach would effectively end the US, UK, Canada, and EU hospitalisation crises.

The objective of this brief review is to provide argument in support of these conclusions, based on an untangling of the pathobiology of Covid19 over the last 12 months; review of the available data on the three vaccines used in the western world; and current data supporting significant benefit of pre-hospital drug treatment.

The Vaccine

The idea that a vaccine would induce sterilising immunity and therefore prevent community spread by creating herd immunity, has become the dominant political and medical story. Political, economic and social planning has been based on a sense of certainty that this will happen. This was never a likely outcome, as such success was asking more of the immune apparatus responsible for containment of a respiratory virus, than had been observed. The first principal of vaccinology has always been that a vaccine is unlikely to give better protection than does the disease itself. First cousin Corona viruses cause recurrent airways infections over many years, manifest clinically as “common colds”. Recurrent Covid19 infections have been documented during the first year of the pandemic. Mucosal immunological memory for corona viruses is predictably poor.

The objective of any Covid19 vaccine is to limit virus replication within the mucosal compartment of the airways. This requires specific activation of the mucosal immune system, which differs from systemic immunity, geared to protect the internal spaces of the body. Blood antibody levels characterise the systemic immune response. These antibodies are very effective at neutralising virus that passes through the blood stream in its normal course of infection, such as the measles or mumps virus. These vaccines readily induce sterilising immunity.

The relevance of this immune machinery to Covid19 vaccines can be summarised:

•  the systemic and mucosal immune compartments communicate poorly, with minimal mixing. Some mixing occurs in regions such as the nasal cavity and the alveolar space as demonstrated by injected pneumococcal vaccines where IgG antibody from blood can inhibit pneumocooci in the nose and the gas exchange apparatus of the lungs and thus protect from ear infections and pneumonia. This may explain the high level of “PCR-ve Covid19 infections” (that is, apparent clinical infection by Covid19 virus, but with a negative laboratory test in the mRNA trials, as discussed below. 
• mucosal immune responses to the virus are transient.
• immune senescence at a mucosal level is marked.

Three vaccines have been released in the US and UK after limited observation and review due to the dramatic circumstances of the pandemic. . . The outcome of these reviews suggest that little difference exists between the three vaccines.  To summarise current position with vaccines;

• Little protection against infection occurs, although protection against symptomatic disease is significant, but is likely to be far less than 90%. It remains to be demonstrated whether this translates into protection against admission to hospital, & mortality since this was not the case in 2 months of follow-up with the mRNA vaccines. The duration of protection and level of protection in high risk individuals over time, need to be monitored. The likely outcome is that vaccines push the disease profile towards asymptomatic infection, rather than induce any discrete sterilising immune state. It is unhelpful and risky to attempt to choose between available vaccines until far more data becomes available.
• Re-infection in vaccinated subjects appears to occur at a similar rate as it does for community non-vaccinated controls.
• There is no realistic chance of herd immunity, given the high rate of asymptomatic infections in vaccinated individuals. This becomes more probable should the current intention of about 30% of the population (US figures) to not be vaccinated irrespective of advice given, be accurate. In Australia, every encouragement should support over 90% vaccination, with whatever of the available vaccines are available: dissention and argument over “false news” undermines this endeavour. In other words, though immunity with Covid19 vaccination appears to be neither complete nor durable, any chance of approaching “herd immunity” depends on a near 100% vaccination rate. Time will give answers to the critical questions, and vaccines still in trials, may be a better choice in the longer run. None of the “clever” delivery systems have yet proved to be an advantage over traditional (or 21st century variations) adjuvenated split vaccines (other than for those who own the patent).
• It can be predicted that endemic spread of the virus throughout the population will occur. The observations in the UK trial of high levels of asymptomatic infection, and “Diagnostic Test Negative” infections in the Pfizer study, focus attention on confirming the dynamics of asymptomatic infection post vaccination, and the degree of transmission in the community, from that source. Data on these critical issues is limited.
• There is a potential danger that as vaccination levels increase, but remain short of comprehensive cover, virus could spread with “hotspots” difficult to identify. Such spread could promote the emergence of resistant strains.The worst scenario would be an increase in mortality due to spread from unrecognised vaccinated subjects with asymptomatic infection, to those without vaccination protection. On this, current data is scanty, indicating about 20% of Covid19 infections are asymptomatic, but that the infectivity of these, is reduced, perhaps 3-4 fold. Similar data in the post-vaccine world will be of central importance.

Early Drug Treatment

It could be summarised that in a “Post Truth World’, those with Covid19 disease are denied safe, effective treatment which if given early can reduce admission to hospital and death. The main purpose of the comments to follow, is to show that the data have moved on, and that science-based decisions can and must be made if lives are to be saved. Two drugs are effective: hydroxychloroquine (HCQ), and ivermectin (IVM) with most effective trials including nutraceutical, zinc and intracellular antibiotics. These antivirals have been available as antimicrobial drugs for many years. Their antiviral activity is due to intracellular processes that inhibit virus assemblage – HCQ reduces acidity within cytoplasmic vesicles, and IVM blocks communication between the cytoplasm and the nucleus, while both have many sites of action that impair the inflammatory response.

The basic principal in treating viral infections is to treat early. This is well established for all virus therapy including acyclovir treatment for shingles, herpes simplex infections, and neuraminidase inhibitors in influenza. The same principal applies to treatment of Covid19. Treatment during the first “virus dominant” phase is directed at reducing the viral load within the mucosal compartment, while in the second phase treatment aims at inhibition of the damaging inflammatory response. Patients with significant second phase disease are usually in hospital, and treated with organ support, anticoagulation and anti-inflammatory drugs.

The data base supporting the value of early treatment of Covid19 disease is so strong, that it is hard to understand the current philosophy of “wait until you are sick enough, then go to hospital” (The question I put to naysayers is “would you give or not give HCQ or IVM to your grandparent with early Covid19 disease in an Australian aged care facility?”). Suggested reasons for unscientific denial include: ideological unmovable mind sets; a rapidly evolving pandemic where new data appears on a daily basis making it hard to keep up with the data flow; failure to understand the value of non RCT data sets which from a scientific and ethical viewpoint are appropriate to the circumstances of a pandemic; and a total focus on an anticipated Covid-free world following the release of vaccines.

The RCT mantra selectively used against HCQ and IVM is cynical, given the experience with Remdesivir. This antiviral agent has been tried in the treatment of Covid19 and was shown in a RCT to reduce time in hospital by 4 days, with no reduction in mortality. On this scanty evidence it was rushed through the regulatory process. Although three additional RCTs failed to confirm this slight benefit, it continues to be used at around A$4,000 a course, with many significant side effects.

Review of clinical studies in early (pre-hospital) disease as at end of November 2020 illustrate the data:

• All 27 trials of HCQ showed protection (OR 0.37 (0.29-0.47)). 10 of these were RCT (OR 0.71 (0.54-0.95)) (the Odds Ratio , or OR of , say, 0.37, means “63% protection”, and 0.71 would be “29% protection”). The figures in ( ) are the 95% confidence levels: if <1.0, this is equivalent to {at least } a P value <0.05) (P value refers to probability of result being by chance. A value of 0.05 means a 1 in 20 chance that it is “by chance”, with that level taken as reflecting a significant observation).
• 26 of 32 prophylaxis studies using HCQ showed protection (OR for 5 post exposure studies: 0.61 (0.4-0.74))
• IVM in 8 studies, half of which were RCT, showed protection in early treatment studies (OR 0.28(0.13-0.59) P=0.004)

As this clinical data continues to accumulate, regions around the world are adopting therapy with HCQ or IVM with dramatic results, when compared to adjoining areas that have not adopted this therapy. This has been marked in regions in Brazil.

The incidence and mortality of Covid19 in the US and Europe is of crushing proportions with no end in sight. . . Planning on the basis that all this will change following introduction of vaccines, needs reassessment, as early review of trial data, while showing short term protection from significant symptomatic disease, must be tempered by evidence that infection is little reduced when asymptomatic and “PCR-ve Covid19” (a negative test for virus on a nasal swab) cases are counted. . . Uncertainties regarding the capacity of current vaccines to attain herd immunity due to continued asymptomatic infection, dictate that additional measures to reduce the impact of the pandemic must be put in place.

Two drugs used early in disease reduce admission into hospital and death, including in those considered high-risk subjects, and they go a significant way to filling this need: HCQ and IVM. Both can be used as prophylactic or therapeutic medications. From uncertain beginnings, an impressive data base has more recently accumulated, that strongly supports the use of HCQ and/or IVM. Their use in concert with vaccines can no longer be denied; indeed this is the only science-based option.

Background from previous post Why Pandemic Responses Fail

As reported in the journal Reviews in Cardiovascular Medicine, Top US medics recommend ‘sequenced multidrug therapy’ including HCQ & Ivermectin, for early high-risk COVID-19 infections (source Palmer Foundation).  Bureaucratic public health officials obsessed with top-down, high-tech solutions have failed to provide citizens with the most important pillar: advice and the means to treat themselves and take charge of their own health care.  Excerpts in italics with my bolds.

The pandemic of SARS-CoV-2 (COVID-19) is advancing unabated across the world with each country and region developing distinct epidemiologic patterns in terms of frequency, hospitalization, and death. There are four pillars to an effective pandemic response:
1) contagion control,
2) early treatment,
3) hospitalization, and
4) vaccination to assist with herd immunity (Fig. 1).

Additionally, when feasible, prophylaxis could be viewed as an additional pillar since it works to reduce the spread as well as the incidence of acute illness.

Many countries have operationalized all four pillars including the second pillar of early home-based treatment with distributed medication kits of generic medications and supplements as shown in Table 1.

In the US, Canada, United Kingdom, Western European Union, Australia, and some South American Countries there have been three major areas of focus for pandemic response:
1) containment of the spread of infection (masking, social distancing, etc.,
2) late hospitalization and delayed treatments (remdesivir, convalescent plasma, antiviral antibodies), and
3) vaccine development (Bhimraj et al., 2020; COVID-19 Treatment Guidelines, 2020).

Thus the missing pillar of pandemic response is early home-based treatment (as seen in Fig. 1).

The current three-pronged approach has missed the predominant opportunity to reduce hospitalization and death given the practice of directing patients to self-isolation at home. Early sequential multidrug therapy (SMDT) is the only currently available method by which hospitalizations and possibly death could be reduced in the short term (McCullough et al., 2020a).

Innovative SMDT regimens forCOVID-19 utilize principles learned from hospitalized patients as well as data from treated ambulatory patients.

For the ambulatory patient with recognized signs and symptoms of COVID-19 on the first day (Fig. 2), often with nasal real-time reverse transcription or oral antigen testing not yet performed, the following three therapeutic principles apply (Centers for Disease Control and Prevention, 2020) :

1) combination anti-infective therapy to attenuate viral replication,
2) corticosteroids to modulate cytokine storm, and
4) antiplatelet agent/antithrombotic therapy to prevent and manage micro- or overt vascular thrombosis.

For patients with cardinal features of the syndrome (fever, viral malaise, nasal congestion, loss of taste and smell, dry cough, etc) with pending or suspected false negative testing, therapy is the same as those with confirmed COVID-19.

Fig. 3. Sequential multidrug treatment algorithm for ambulatory acute COVID-19 like and confirmed COVID-19 illness in patients in self-quarantine. Yr = year, BMI = body mass index, Dz = disease, DM = diabetes mellitus, CVD = cardiovascular disease, chronic kidney disease, HCQ = hydroxychloroquine, IVM = ivermectin, Mgt = management, Ox = oximetry, reproduced with permission from reference.

Summary

The SARS-CoV-2 outbreak is a once in a hundred-year pandemic that has not been addressed by rapid establishment of infrastructure amenable to support the conduct of large, randomized trials in outpatients in the community setting.

The early flu-like stage of viral replication provides a therapeutic window of tremendous opportunity to potentially reduce the risk of more severe sequelae in high risk patients. Precious time is squandered with a “wait and see” approach in which there is no anti-viral treatment as the condition worsens, possibly resulting in unnecessary hospitalisation, morbidity, and death.

Once infected, the only means of preventing a hospitalization in a high-risk patient is to apply treatment before arrival of symptoms that prompt paramedic calls or emergency room visits. Given the current failure of government support for randomized clinical trials evaluating widely available, generic, inexpensive therapeutics, and the lack of instructive out-patient treatment guidelines (U.S., Canada, U.K., Western EU, Australia, some South American Countries), clinicians must act according to clinical judgement and in shared decision making with fully informed patients.

Early SMDT developed empirically based upon pathophysiology and evidence from randomized data and the treated natural history of COVID-19 has demonstrated safety and efficacy.

In newly diagnosed, high-risk, symptomatic patients with COVID-19, SMDT has a reasonable chance of therapeutic gain with an acceptable benefit-to-risk profile.

Until the pandemic closes with population-level herd immunity potentially augmented with vaccination, early ambulatory SMDT should be a standard practice in high risk and severely symptomatic acute COVID-19 patients beginning at the onset of illness.

Authors:

Peter A. McCullough, Paul E. Alexander, Robin Armstrong, Cristian Arvinte, Alan F. Bain, Richard P. Bartlett, Robert L. Berkowitz, Andrew C. Berry, Thomas J. Borody, Joseph H. Brewer, Adam M. Brufsky, Teryn Clarke, Roland Derwand, Alieta Eck, John Eck, Richard A. Eisner, George C. Fareed, Angelina Farella, Silvia N. S. Fonseca, Charles E. Geyer Jr., Russell S. Gonnering, Karladine E. Graves, Kenneth B. V. Gross, Sabine Hazan, Kristin S. Held, H. Thomas Hight, Stella Immanuel, Michael M. Jacobs, Joseph A. Ladapo, Lionel H. Lee, John Littell, Ivette Lozano, Harpal S. Mangat, Ben Marble, John E. McKinnon, Lee D. Merritt, Jane M. Orient, Ramin Oskoui, Donald C. Pompan, Brian C. Procter, Chad Prodromos, Juliana Cepelowicz Rajter, Jean-Jacques Rajter, C. Venkata S. Ram, Salete S. Rios , Harvey A. Risch, Michael J. A. Robb, Molly Rutherford, Martin Scholz, Marilyn M. Singleton, James A. Tumlin, Brian M. Tyson, Richard G. Urso, Kelly Victory, Elizabeth Lee Vliet, Craig M. Wax, Alexandre G. Wolkoff, Vicki Wooll, Vladimir Zelenko. Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19). Reviews in Cardiovascular Medicine, 2020, 21(4): 517-530.