Coming out of lockdown unprepared

Widespread distribution of masks of the N95 standard are a precondition for reopening, but no preparation has been made. The masks are necessary, because the dominant mode of transmission of Covid-129 is by aerosol. The recommended social distancing is ineffective for viruses that are spread by aerosol. Unless special steps are taken, office building ventilation spreads the virus throughout the building.

We hear much about collective or herd immunity. It cannot be relied on. A significant percentage of recovered patients have little or no antibodies. The lack of immunity leads to reinfection.

Reopening runs the serious risk of setting off a second and larger wave of infections as the virus is carried into new areas. For example, the Florida panhandle has few cases as the beaches and vacation rentals were closed, and people from outside were kept from entering. As the panhandle is set for a May 1 reopening, people from impacted areas, such as Atlanta, will bring the virus with them. Keep in mind that half or more of the infections occur from asymptomatic transmission. As people can spread the virus for days and weeks before themselves showing any symptoms, areas that have so far escaped can find themselves overwhelmed. With no experience in treating the virus, they can suddenly find themselves confronted with large numbers of infected people. This is especially the case for parts of the Florida panhandle where medical services have not fully recovered from Hurricane Michael. Moreover, it is highly unlikely that the cleaning services available for weekly and nightly rentals have any way of sanitizing vacation rentals.

This is not to dramatize Florida vacation rentals, but to provide one example of unpreparedness.

I have been able to provide my readers with good information concerning the virus and its threat, because I am in communication with knowledgeable experts whose reputations are secure and who are not dependent on Big Pharma or pubic agencies. Marc Wathelet, an immunologist and virologist who has spent his entire career studying viruses and the immune response, shares with you “A Rational Plan to Come Out of Lockdown,” which follows below. I suggest you read the entire 12 pages as he explains in words you can understand the meaning of aerosol transmission and why the presence of antibodies is not indicative of a functional immunity status. In other words, those including health officials who recommend social distancing, no masks, and are banking on herd immunity have no idea what they are talking about. Indeed, their ignorance will get many people killed.

If you don’t value the knowledge that the 12 pages will give you, there is a 2 page summary at the end.

A rational plan to come out of lockdown by Marc Wathelet

1. The immune response and COVID-19 vs. coming out of lockdown.

The immunity potentially acquired against SARS-CoV-2, the new coronavirus responsible for the COVID-19 disease that taxes our hospital systems, is an absolutely essential factor that must be carefully considered when measures are formulated to come out of lockdown. Individual and collective immunity are extremely complex phenomena, which depend on the innate immunity and the adaptive immunity of individuals vis-à-vis the infectious agent considered.

What we can read in the press today about deconfinement and collective immunity suggests that neither this complexity nor all the implications of the presence of antibodies in the population are sufficiently appreciated by experts who are pronounced, with the exception of Pr. Gala. As I have spent my entire career studying the innate immune response, I qualify more as an immunologist than a virologist in fact, I have prepared a primer in order to help you better understand this complexity as it is expressed in the context of SARS-CoV-2 and the pathophysiology associated with COVID-19. Plus some remarks on the implications of this complexity on deconfinement.

1.1 The innate and adaptive immune response, what everyone knows.

The first immune response to a viral infection is the innate response, it is very fast, powerful and generic, and it is not specific to the virus responsible for the infection. This antiviral response depends on cytokines, such as interferons, and immune cells, such as cytotoxic cells and macrophages, which reside in tissues and monitor the environment to detect and attack foreign bodies. Slower, but specific to the virus responsible for the infection, the adaptive immune response leads to the production of antibodies and cells that specifically attack infected cells to eliminate them, and thus reduce the production of viruses.

1.2 The adaptive immune response, not always what you may wish.

Antibodies, when they have the required qualities, help the body to get rid of the infectious agent, and their maintenance in the blood circulation and on the mucous membranes allows a faster and more effective response if the individual were to be infected again by this same virus. The presence of antibodies is not indicative of a functional immunity status, it is an essential point. For viral infections, the innate immune response must do most of the work since antibodies do not appear until several days have passed. For some viruses, such as HIV, these antibodies do not control either viral replication or the progression of the disease. For other viruses, such as RSV and Dengue virus, the presence of antibodies can worsen the disease and lead to death.

1.3 The adaptive immune response and endemic human coronaviruses.

The “benign” human coronaviruses which are endemic throughout the world (229E, NL63, OC43 and HKU1) induce very little natural immunity in humans! As infected individuals develop antibodies against these coronaviruses, the immunity conferred by these antibodies is weak and unstable. Result? These human coronaviruses infect and reinfect the human population in the absence of an animal reservoir. The low effectiveness of natural immunity is not explained by a very rapid evolution of the facets of the coronavirus recognized by our immune system, because these viruses evolve more slowly than other respiratory viruses, such as the flu.

1.4 The adaptive immune response and the human coronaviruses SARS and MERS.

The human coronaviruses responsible for the SARS and MERS epidemics, which have emerged more recently, also induce antibodies, but a large fraction of individuals had little or no antibody and their ability to protect the individual is not resolved. Tests of treatment of SARS patients in 2003 using the serum of convalescent patients rich in antibodies did not lead to any clear conclusion.

1.5 The adaptive immune response and SARS-CoV-2 (COVID-19).

A first indication of low natural immunity against COVID-19 is the large number of infected individuals in China, Japan and South Korea, and now in Europe, apparently cured but who after a few weeks fall ill again. Whether it is re-infection or the virus that is silently held in the body and then reactivated is not clearly established, but it is a phenomenon that does not occur when natural immunity is robust. Symptomatic individuals are contagious on average for around twenty days without treatment, which is much longer than for the majority of viruses, the only one which is comparable is the hepatitis B virus. In a COVID-19 case , an individual remained contagious for 49 days, and these long periods of contagiousness are also indicative of low natural immunity. These observations suggest that the new coronavirus too may induce ineffective natural immunity.

1.6 The presence of antibodies to SARS-CoV-2 (COVID-19).

Early reports suggest that natural immunity to COVID-19 is not robust either. Indeed, among people positive for the virus by PCR and tested after their cure, 6% have an undetectable level of antibody, 24% have a low level of antibody and 17% a moderately low level, results confirmed semi-quantitatively at the University of Mons. In this regard, it is quite incomprehensible that the government prohibits tests that would quantify these antibodies, no rational justification comes to mind and this is a provision which must be changed without further delay to allow Belgian researchers to work on this topic.

1.7 Antibodies to COVID-19, protection or exacerbation of the disease?

An antibody a priori can have a protective effect, a deleterious effect, or no effect. The deleterious effect occurs for example when the antibody instead of neutralizing the virus by binding to it, promotes the introduction of the virus into the sentinel cells of the lungs, the macrophages, and this attack leads to an exacerbation of the disease. . This is the case for the human respiratory syncytial virus against which a vaccine had been produced but which had led to deaths when the vaccinated children were then infected with this virus; this is also the case for Dengue viruses. There are no vaccines for human coronaviruses, but for coronaviruses that infect economically important animals, some of these vaccines protect, others worsen the disease or have no effect. Any vaccine candidate against COVID-19 should therefore be thoroughly tested to ensure that they are not dangerous but effective.

1.8 The amount of antibodies against SARS-CoV-2 (COVID-19) is correlated with the severity of the disease, not with protection against the disease.

Anti-SARS-CoV-2 antibodies appear between 10 and 15 days after the onset of symptoms, which corresponds to the critical period in the progression of the disease, where the condition of some patients worsens rapidly. There is an association between a high titer of anti-SARS-CoV-2 antibodies and a more serious clinical condition (p = 0.006), and this increase in titer is not always accompanied by a decrease in viral load. These observations suggest that not only are the antibodies insufficient to clear the virus, but more importantly that they may be involved in an exacerbation of the disease, as observed for SARS patients in 2003. In different strains of mutant mice, the absence of NK, T and B cells does not lead to more severe disease, indicating that the cellular innate response and the adaptive response play only a minor role in controlling SARS-CoV . In a mouse infection model with SARS-CoV, the presence of antibody induced by vaccination reduces viral replication but leads to Th2 type immunopathology. Similarly in a model of macaque infection with SARS-CoV, the presence of anti-Spike antibodies leads to very severe inflammation of the lungs linked to the pro-inflammatory polarization of alveolar macrophages. In conclusion, we absolutely cannot rely on natural immunity to control the spread of COVID-19.

1.9 From the absence of symptoms in intensive care, the spectrum of COVID-19 manifestations.

SARS-CoV-2 can infect all ages, and for the resulting disease, COVID-19, the severity of symptoms increases with age and with the presence of co-morbidities, as is the case with most infections, with the notable exception of the respiratory pandemic of 1918-1919. The virus initiates its replication in the sinuses, throat, airways (bronchi and bronchioles), or in the respiratory parenchyma where gas exchanges between blood and air take place. The first week is typical of respiratory infections with one or more flu-like symptoms, and it may progress to atypical pneumonia that requires hospitalization. In atypical pneumonia, it is the respiratory epithelium that is affected, and if it is compromised the gas exchange suffers and the level of oxygen transported by the blood decreases, which puts the life of the patient in danger. The virus also affects blood capillaries, which further decreases gas exchange, increases the risk of pulmonary thromboembolism, which the presence of antibodies can worsen by activation of the complement, and leads the virus to other organs, especially the intestines, kidneys, heart and nervous system. It is too much inflammation of the lungs that may require intubation, and even lead to respiratory arrest and death. Even for patients who survive without the need for intubation, respiratory, cardiac, hepatic and neurological sequelae can be serious, and impose significant individual and collective costs.

1.10 Collective immunity requires good individual immunity.

One of the implications of the high basic reproduction rate R0 of COVID-19 is that a large proportion of the population must be well immunized individually to ensure collective immunity, namely 85% for an R0 ~ 7. As natural immunity depends on the quantity of antibodies present, it seems unlikely that the 85% of effective individual immunity necessary for collective immunity can be reached when 30% of the population has little or no anti-COVID-19 antibody. An R0 ~ 7 is the largest estimate in the literature, chosen according to the precautionary principle. Even with a value of only 4 for R0, 75% effective individual immunity would be required. It seems clear that collective immunity cannot be relied on to stop the spread of COVID-19 when the individual level of antibody is often low and when a high level of antibody is associated with an exacerbation of the disease.

1.11 It is not always possible to make an effective and safe vaccine.

In the absence of sufficiently robust natural immunity against COVID-19, vaccination is an option, but not a guarantee. Thus, natural immunity against the human immunodeficiency virus is almost nonexistent, and no vaccine has been developed against this virus which is sufficiently effective. Indeed, it is not enough to have enough antibodies against a virus, they must also be of good quality and that they can follow the evolution of the virus. While it is possible that in the natural course of the disease, anti-SARS-CoV-2 antibodies would be an aggravating factor, it is also possible that protective immunity would be induced by a vaccine, if and only if the antibodies can prevent progression to the second phase of the disease where they would be toxic.

Any vaccine candidate against COVID-19 should therefore be thoroughly tested to ensure that they are not dangerous but effective.

2. Transmission of COVID-19, implication for deconfinement

2.1 Aerosol transmission of COVID-19: the world must face reality.

I have a dispute with WHO and Sciensano (NdT an official Belgian Institute) about the mode of transmission of SARS-CoV-2 and this must be resolved because this question completely conditions the deconfinement strategy.

An article published in the scientific journal Environment International has just been published and its title is very unusual for a scientific article: “the airborne transmission of SARS-CoV-2: the world must face reality”. When the authors speak of the world, they specify the WHO and governments around the world, and they underline the extreme importance of the recognition by national authorities of the reality of aerosol transmission: it is necessary that they put in place adequate control measures to prevent the transmission of COVID-19 by aerosol.

2.2 What is an aerosol? And why is this mode so important?

The internal surface of the lungs, the alveoli where gas exchange takes place, corresponds to that of a tennis court. This surface is moist so that with each breath the exhaled air has microdroplets coming from this surface, it is the Venturi effect as for a carburetor. These micro droplets remain suspended in the air, and their existence can be easily verified by blowing on a cold window: the fogging that forms is the result of the condensation of these microdroplets; if you pass your finger over this fogging, drops become visible. As with a carburetor, the greater the air movement, the more the liquid is entrained, and therefore speaking, singing, shouting, coughing, sneezing gradually increases the production of this aerosol, of these microdroplets, independently of the production of droplets which can accompany speech and that accompany sneezing.

These expired microdroplets form a cloud that is normally invisible, unless it is cold enough for the microdroplets to condense into fog. When a person is contagious, these microdroplets are infectious and can remain infectious for a long time (hours), floating in the air and being able to move over long distances, very much greater than the separation distance recommended today in Belgium (in the in the case of foot-and-mouth disease in England, aerosol transmissions over tens of kilometers have been observed).

One might think that these clouds of infectious particles disperse quickly, but in the absence of turbulence, the fluid mechanics tells us that they do not, and the observation of clouds in the sky confirms to us that if they can deform, the clouds are not quickly diluted in the air by wind but move with the wind (the clouds in the sky being aerosols, too). Likewise the smell of cooking, someone who is barbecueing in his garden for example, can be perceived over long distances if the observer is downwind. And of course aerosol transmission is much more problematic in confined spaces.

2.3 Asymptomatic transmission involves aerosol transmission.

A study indicates that 79% of cases of COVID-19 transmission are not documented (people who are asymptomatic or whose symptom is so minor that it is not recognized) https://tinyurl.com/tpx4css. A Belgian study indicates that 50% of transmissions are asymptomatic https://tinyurl.com/yc3r3592.

The implication is undeniable: asymptomatic transmission, where, by definition, the contagious individual has no symptoms, and therefore in particular has no runny nose, no sneezing, no cough, and therefore no possibility of producing droplets capable of contaminating a physically close individual or a surface, the only modes of transmission recognized by the WHO and Sciensano, can only occur by aerosol!

And since even symptomatic transmission also involves aerosol transmission, it is undeniable that the dominant mode of transmission of COVID-19 is by aerosol.

2.4 The consequences on public health measures of aerosol transmission.

WHO and Sciensano continue to recommend social distancing and personal protection measures that are not suited to the reality of the transmission of COVID-19 by aerosol. I do not criticize Sciensano for pleasure, and I defend their point of view when they are right, for example on the question of mortality in Belgium https://tinyurl.com/yb8tj6qq. But on the aerosol question they are mistaken. For specialists in the biology of infectious aerosols, there is no doubt that COVID-19 is transmitted by aerosol: “it is a no-brainer” https://tinyurl.com/w2tt7rx. For Professor Gala, “The distance of 1m50 is rubbish. We know that it is a distance which is absolutely minimal and which does not correspond to anything.

Social distancing is simply ineffective for viruses that are transmitted by aerosol. Only the masks allow a crowd density compatible with an almost normal economic activity.

2.5 Consequences on ventilation systems of aerosol transmission.

Air confinement promotes aerosol transmission. The ventilation systems are complex and specific to each building, and they must be reconsidered individually in all public or corporate access buildings to prevent them from promoting and amplifying aerosol transmission. If the air is circulated in the building, it is imperative that it goes through decontamination (UV, HEPA filters) before being redistributed, and that the distribution sequence does not transport the air from room to room .

2.6 The contagiousness of COVID-19 is measured by its basic reproduction rate, R0, and the speed of its propagation by the doubling time.

The WHO tells us in its first report that the basic reproduction rate R0 of COVID-19 is

2.5 as during the SARS epidemic in 2003, and a doubling time of 6.7 days; this information is included in the scientific literature. The first independent publication estimates the R0 to be between 4.4 and 6.7 with a doubling every 2.4 days, the second estimates an R0 of 7.05, and the third of 6.22. The first implication is that the virus is much more contagious than announced by the WHO and observations in Europe confirm it, with doubling times before confinement of 3.3 days for Italy and 3.2 days for Belgium for example. While I criticize the WHO for many aspects of its response to COVID-19, I note that a virus mutates and that different strains will each have a certain R0 and that in vitro we can observe marked differences in the replication speed of the virus.

2.7 Differences in the presentation of SARS and COVID-19.

While all of the WHO recommendations are essentially a copy and paste of those for SARS in 2003, SARS and COVID-19 are two very different diseases. In one study, the first swabs returned positive for SARS-CoV-2 were the day after the first symptoms that were mild or predictive of the disease. All the diagnostic tests were positive between D1 and D5. This is a notable difference from what is observed in SARS where the peak of the viral load is observed between D7 and D10. This study also shows that the viral load in COVID-19 disease can reach a peak before D5 and that, moreover, it is more than 1000 times higher. These observations are in agreement with the epidemiology, which indicates that for SARS transmission was observed only from D5, while for COVID-19, transmission occurs mainly before the onset of symptoms. Also, the observation that the majority of transmission of SARS was to relatives and medical staff, while the majority of transmission of COVID-19 is undocumented and in the community, can only be explained by very different modes of transmission. With a much higher viral load for COVID-19, these observations explain the huge difference in the spread of SARS-CoV-1, some 8,000 cases in 6 months, vs. more than two million for SARS-CoV-2 in the same time frame.

2.8 Differences in the transmission of SARS and COVID-19 in children.

The fact that for SARS transmission in schools was not a significant phenomenon is very well explained by the differences in transmission of this disease. A child who is contagious only 5 days after the onset of symptoms will simply not be present at school! On the other hand for influenza, which is transmitted like COVID-19 in an asymptomatic way, the accumulated evidence indicates that transmission in schools is a phenomenon which is very important quantitatively when the transmission of the virus can be done in an asymptomatic and aerosol manner. Scientific evidence indicates that the utmost caution should be exercised before schools reopen, and that the lack of a means to prevent aerosol transmission can only lead to a second wave.

In terms of government communication, after insisting that children were at great risk of infecting their grandparents, the message is now no worries about it? Besides the fact that this is a misreading of science, the answer on social networks is that it is a repetition of “masks are useless for the public”, who does the government take us for?

3. Masks and others to limit aerosol transmission.

The distance of 1 to 2 m according to the countries would be suitable for a virus which is transmitted little or not by aerosol, like SARS in 2003 and MERS in 2012, but not at all for the viruses that are transmitted by aerosol and asymptomatically, especially when this mode of transmission is responsible for the majority of cases, as for COVID-19. For Professor Gala, it is necessary to impose the wearing of a mask, “because the wearing of a mask is the second essential pillar to avoid increased transmission in the population and a rebound effect”. Because, for him, the social distancing of 1.5 m it does not work. The Royal Belgian Academy of Medicine recommends wearing a mask for the population during this period of COVID-19 and while coming out of lockdown.

3.1 What masks for the Belgian citizen, fabrics vs. surgical?

It seems that the GEES (NdT a Belgian government task force) is going to recommend the wearing of a fabric mask for the population, as a complement to hygiene and social distancing, and this recommendation is completely insufficient. At a time when many less wealthy countries than Belgium distribute surgical masks for free or at very low cost to their population, why should we be satisfied with fabric masks, when surgical masks are 4 times more effective, and therefore reduce transmission between those who wear them by a factor of 16 (4 x 4) compared to cloth masks? We will inevitably have a second wave, and surgical masks for the entire population can only contribute massively to the flattening of the curve.

3.2 What masks for the Belgian citizen, surgical vs. FFP2 (N95)?

It seems to me that the government would be particularly inspired to recommend the wearing of masks capable of limiting aerosol transmission for everyone, so not only could we flatten the curve but actually squash it. Indeed, surgical masks are of limited effectiveness in stopping aerosol transmission. They are the ones who equipped the medical staff in Wuhan and 3,000 of them were infected. On the other hand, the 42,000 personnel sent in reinforcements but equipped with FFP2 did not have to deplore any contamination. Wearing the FFP2 mask is particularly beneficial for people at risk, but everyone can help protect these people by not becoming a link in the transmission chain and the best way is that everyone is equipped with FFP2. Let’s not impose the wearing of FFP2, but let’s explain that everyone would benefit, directly and indirectly.

Another considerable advantage of the generalized wearing of FFP2 masks is protection against pollution by fine particles, which has a significant socio-economic cost. The standard is 35 to 70 µg / m3 depending on their size and it is exceeded in Belgian agglomerations where concentrations above 50 to 100 µg / m3 are regularly observed. The impact of fine particles on health is considerable in Europe, and consequently the impact on health budgets. The widespread use of FFP2 masks when people are moving around the city is a measure that will reduce these costs and improve the health of the public.

3.3 What masks for the Belgian citizen, Belgian innovation?

FFP2 (N95) masks may seem too expensive for the average person if they have to be replaced daily. This is not necessary, one needs masks with good elastic bands like certain models, of course, but they can be reused without danger and sterilization is not even essential for the individual (in experiments, it is very difficult to isolate infectious virus from FFP2 exposed to an aerosol of enveloped virus, because the virus will stick on the filter fibers and only the nucleic acid can be recovered). These FFP2 masks are an intermediate solution, like the fabric masks before them.

Two Belgian companies consulted me for the design of masks that would be more effective than FFP2, NanOx masks: two models for medical personnel and one for the general public, in all sizes. They are based on silicone and a filter cartridge, and fit the face much better than FFP2, not only on inspiration, but also on exhalation. NanOx tells me about a production capacity of 50,000 masks per day which could be increased to 200,000 days. My consultation was free and I have no financial interest. I think this is a very good approach and certainly they will not be the only ones on this market, many comfortable and reusable masks to protect from FFP2 / 3 dust already exist. It seems to me that the government would be inspired to pursue the path of NanOx and other manufacturers capable of producing comfortable masks that protect from aerosols and fine particles.

In general, the masks allow return to work, taking public transport, safe access to shops, and the resumption of public education. The more effective the quality of these masks is in controlling aerosols, the less transmission of the virus will occur and therefore the less risk of a second wave requiring the confinement of part of the population.

3.4 Screening and tracing.

The benefits of rapid detection of cases presenting a single flu symptom and the identification and screening of those with whom they have been in contact recently seem to me to be well understood by the government when I hear minister Philippe De Backer’s statements on this topic. The mobilization of 2,000 people for the tracing is necessary and it remains to be seen whether it is sufficient according to the intensity of the second wave, but I trust that we will adapt. However, I would like to make two practical suggestions. The first concerns the collection of samples for PCR in patients with flu-like symptoms, who suffer from a significant proportion of false negatives (30-50%), a situation which seriously limits the effectiveness of the screening / tracing approach.

In addition to nose or throat sampling, I also propose to collect a respiratory sample by the individual blowing into a tube terminated by a filter to collect the aerosol, a filter which is then transferred to Trizol or another nucleic acid stabilizer for later extraction. The time it takes to blow into the tube and collect enough material to detect the virus can be determined in preliminary tests with COVID-19 positive patients. It is a method used at the Lovelace Respiratory Research Institute where I worked for seven years; we used a common PCR technique to increase sensitivity (nested PCR).

I also propose, in addition to the lifting of the ban on serological tests for research laboratories, systematic serological screening of the population when individuals have a blood test for another reason, because then the cost is minimum and this information is important for the health of the individual in view of the possible sequelae to COVID-19.

3.5 Large-scale decontamination of public places.

The use of snow cannons has been suggested to disinfect public places, but the choice of agent to use is important. Chlorine dioxide gas (ClO2) is the disinfectant for public places that I recommend, it is very well understood and leaves no pollution after use. It must be produced on site due to the instability of this gas, and the cleanest reaction to obtain it is a mixture of sodium chlorite and hydrochloric acid: 5NaClO2 + 4HCl → 4ClO2↑ + 5NaCl + 2H2O. (we can also start from sodium chlorate which is cheaper: 5NaClO3 + 6HCl → 6ClO2↑ + 5NaCl + 3H2O).

4. Medical interventions and exit strategy.

COVID-19 is a new disease and new information is emerging every day about the most promising approaches to treat it. Many clinical trials are underway and their results are being analyzed. The pandemic situation seriously complicates these clinical studies, but it is probable that effective antiviral molecules will eventually be identified among the candidates studied: hydroxychloroquine, remdesivir, ivermectin, interferons, macrolides, zinc (cation), and vitamin C in high doses intravenously, for example.

The pandemic situation led to an antiviral intervention that was too late for most patients, only severe cases were admitted to hospital, a time when antivirals no longer made a difference. However, a number of general practitioners have developed approaches that appear to be beneficial to their suspected COVID-19 patients, even if it is under conditions that do not meet the demands of a medicine based on strict evidence, given the urgency of the situation.

I propose that instead of prohibiting any treatment of COVID-19 cases by general practitioners, such as for example the prohibition of hydroxychloroquine outside the hospital context at the start of the pandemic, we allow these doctors the freedom to prescribe what their experience and conscience dictate and in informed consent with the patient, with a monitoring framework at the national level so that the results are usable. The side effects of these drugs are well understood and controlled. This approach will reduce the pressure on the hospital system and thus facilitate coming out of the lockdown.

4.1 Medical interventions: hydroxychloroquine + azithromycin + Zinc.

Dr. Raoult proposed a controversial treatment. Studies that use this treatment too late can only conclude that it is ineffective, and the others lack control. However, a study in Brazil on 636 symptomatic outpatients tested the combination of hydroxychloroquine and azithromycin: 412 started treatment and the 224 who refused it were used as a control group. The need for hospitalization was 1.9% for the treated and 5.4% for the control group; for those who started treatment before, instead of after, 7 days since the onset of symptoms, these figures were 1.17 and 3.2% (p <0.001. Similarly, a study on 699 patients concluded that the combination of hydroxychloroquine + azithromycin + Zinc was effective.

4.2 Medical procedures: azithromycin or other macrolide + Zinc.

Doctors in northern France have used azithromycin, or another macrolide, + Zinc due to the unavailability of hydroxychloroquine, with good results that have yet to be validated more rigorously. Zinc interferes with viral replication and azithromycin, an antibiotic, has intrinsic antiviral activity that may be linked to its mitochondrial toxicity. Indeed, viral replication depends on the inhibition of apoptosis and the stress of the mitochondria can promote this apoptosis, and therefore the elimination of infected cells. It is also possible that the effect of the replication of the virus in the lungs influences the flora, the microbiome, present in the lungs and that antibiotics prevent the emergence of harmful strains. Whatever the mechanism, the effect of macrolides and Zinc led to a clear clinical improvement, the main limitation of these studies is that the cases were presumed COVID-19, unconfirmed.

4.3 Medical procedures: ivermectin.

Ivermectin causes an influx of chlorine ion and thus exerts a broad anti-parasitic action. Ivermectin treats onchocerciasis (river blindness), a public health problem in Africa, as well as lymphatic filariasis. In vitro, ivermectin very effectively suppresses the replication of SARS-CoV-2 with a single dose.

The Malagasy government has announced very good results based on plants, artemisia and ravensara, (one of which contains arteminisin, which, like hydroxychloroquine, is an antimalarial treatment).

5. Conclusions

5.1 We cannot count on collective immunity

It seems clear that collective immunity cannot be relied upon to counter the spread of COVID-19 when the individual level of antibody is often low and when a high level of antibody is associated with an exacerbation of the disease .

5.2 The dominant mode of transmission of COVID-19 is by aerosol.

One cannot conceive of a serious lockdown exit strategy that does not accept this reality.

5.3 Social distancing is simply ineffective for viruses that are transmitted by aerosol.

Only effective masks allow a crowd density compatible with an almost normal economic activity.

5.4 The properties of SARS-CoV-1 and SARS-CoV-2 are very different.

These epidemiological and mode of transmission differences explain the huge difference in the spread of SARS-CoV-1, only some 8,000 cases in 6 months, vs. more than two million for SARS-CoV-2 in the same time frame.

5.5 The transmission of SARS-CoV-1 and SARS-CoV-2 is very different – schools.

Scientific evidence indicates that the utmost caution should be exercised before schools reopen, and that the lack of means to prevent aerosol transmission can only lead to a second wave. We need masks to take the bus and go back to school.

5.6 The cost of a second wave can be very significant, in the short and long term.

In addition to the significant cost associated with hospitalization, patients do not always emerge free from COVID-19. In addition to a long and costly rehabilitation for those who have survived an intubation in intensive care, hospitalized patients can have respiratory, cardiac, hepatic and neurological sequelae. These consequences can be serious, and impose a significant individual and collective cost.

5.7 Give doctors the freedom to exercise their profession without interference.

Physicians should be given the freedom to prescribe what their experience and conscience dictate and in informed consent with the patient, which should reduce hospitalizations, deaths and costs.

5.8 At the level of the general population, it is necessary to make a transition from the masks in tissues, to surgical masks, then to FFP2 or better.

The easiest and cheapest way to crush the second wave is to provide progressively more effective masks, depending on their availability, to the general public. The more the second wave is crushed, the more the human and economic costs will be reduced.

2-page Summary:

An alternative: a rational lockdown exit strategy

Belgium, like the rest of the world, is working on a lockdown exit strategy. This is a very difficult question: we hope to be able to resume economic activity without causing a new wave of cases that would require re-imposing containment.

The GEES (NdT a Belgian Government Task Force) proposes a plan which will of course have the ear of the government, but which suffers from a disconnection of certain realities concerning COVID-19, in particular the nature of this disease, the properties of the virus which causes it, its mode of transmission, and the individual and collective immune response to this virus, SARS-CoV-2.

As an alternative to the government’s plan, I am proposing a serious lockdown exit strategy, which is based on the reality principle, on understanding the differences between SARS and COVID-19, on understanding the public health measures required, and on the precautionary principle. In addition, this plan would restart the Belgian economy as quickly as possible and at the lowest cost, if adopted. And it involves the participation of Belgian private companies in addition to government actions.

This plan is long and detailed, and the full text can be found here. I first consider the question of immunity, a complex subject apparently misunderstood by experts who have spoken out publicly on the subject, and the implications for a return to school and work.

I explain the essential differences between SARS and COVID-19. An official Belgian Institute, Sciensano, and the government continue to deny these differences. The government is therefore proposing a strategy that is not suited to the situation. Yet these differences must inform our lockdown exit strategy.

I also explain the asymptomatic and aerosol transmission to reach the conclusion that masks for everyone will be essential. Here I deliver some key conclusions from my plan.

1 We cannot count on individual or collective immunity

It seems clear that collective immunity cannot be relied on to counter the spread of COVID-19 for two reasons: the individual level of antibody induced during infection is often too low and unstable; and a high level of antibodies is associated in COVID-19 patients with a severe exacerbation of the disease: antibodies are not always beneficial, they can have deleterious effects, this is a phenomenon observed with some viruses.

2 The dominant mode of transmission of COVID-19 is by aerosol.

One cannot conceive of a serious lockdown exit plan that does not accept this reality. I explain how we produce aerosols just by breathing and how infectious aerosols contribute to the spread of the disease. A plan that does not take this reality into account can only lead to a second wave larger than necessary.

3 Social distancing is simply ineffective for viruses that are transmitted by aerosol.

With a sneeze that can throw infectious droplets 8 m away, and with an aerosol transmission that can send microdroplets over even greater distances, it is not a social distance of 1.5 m that will contain the virus. Only effective masks allow a crowd density compatible with an almost normal economic activity.

4 The properties of SARS-CoV-1 and SARS-CoV-2 are very different.

These epidemiological and mode of transmission differences explain the huge difference in the spread of SARS-CoV-1, only some 8,000 cases in 6 months, vs. more than two million for SARS-CoV-2 in the same time frame.

5 The transmission of SARS-CoV-1 and SARS-CoV-2 is very different – schools.

Scientific evidence indicates that the utmost caution should be exercised before schools are reopened, since the idea that children will contribute little to the spread of the virus is based on an erroneous analysis. The lack of means to prevent aerosol transmission can only lead to a second wave. Masks will be required to take the bus and return to school without endangering the community.

6 The cost of a second wave can be very significant, in the short and long term.

In addition to the significant cost associated with hospitalization, patients do not always emerge unscathed from COVID-19. In addition to a long and costly rehabilitation for those who have survived an intubation in intensive care, hospitalized patients can have respiratory, cardiac, hepatic and neurological sequelae. These consequences can be serious, and impose a significant individual and collective cost.

7 Give doctors the freedom to exercise their profession without interference.

Physicians should be free to prescribe what their experience and conscience dictate and in informed consent with the patient, which should reduce hospitalizations, deaths and costs.

8 At the level of the general population, it is necessary to make a transition from masks in tissues, to surgical masks, then to FFP2 or better.

The easiest and cheapest way to crush the second wave is to provide progressively more effective masks, depending on their availability, to the general public. The more the second wave is crushed, the more the human and economic costs will be reduced.