COVID-19 virus SARS-CoV-2

world pandemic overview


Introduction

After more than a year of the COVID-19 pandemic much confusion about the disease still exist. This is leaving most people frightened, some indifferent, but also many angry and desperate. There is no person in this world who would not be touched by the pandemic one way or the other. In addition, it has become a common practice by many governments and mainstream media placing much emphasis on dangers and mortality stemming from a disease, which in reality seriously affects only a small segment of human population. On one hand, in most cases this results in unnecessary anxiety and irrational fears of much of the general public. On the other hand, many people subconsciously aware of this artificial exaggeration adopted lax, at times irresponsible attitude towards necessary precautions to be taken in order to mitigate the spread of the disease. In any case, after a year of a full blown pandemic we know that an exposure of a human population to the SARS-CoV-2 virus leads to hospitalization in only about 0.5% of cases and may lead to death in 0.25% of exposed individuals. This seemingly insignificant proportion of severely affected individuals was shown to overwhelm medical system in many countries, fill ICUs rather quickly and can impose potentially costly hardships and complications, in the US for example, for 1655000 Americans of which 827500 might face a premature death.

This brief summary is intended to provide up to date overview of the virus biology and its epidemiology, thus placing things in proper perspective. It is based solely on scientifically supported findings to date and partly on my modeling analyses using the WHO published epidemiological data.

The Virus Biology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus belonging to the family of embedded coronaviruses such as those causing SARS (Severe acute respiratory syndrome) and MERS (Middle eastern respiratory syndrome). It is responsible for a coronaviral disease known as COVID-19. Since December 2019, thanks to its predominantly asymptomatic, or delayed mild symptomatic expression in majority of the population, the disease have spread very quickly throughout the world. The SARS-CoV-2 virus is spread predominantly via inhalation of virus laden particles, through respiratory droplets exhaled by an infectious individual in close proximity, or particles being mixed within an aerosol cloud dispersed within a closed area (public transit, aircraft cabin, shopping malls, etc). Normally transmission through contact with inanimate objects (fomites) is less likely, but it may become important in closed settings like hospitals, hotels, airports, railway stations or cruise ships. Unlike the world famous deadly 1918 Strain A, Influenza (Spanish flu) pandemic, SARS-CoV-2 virus caused disease possesses some peculiarities which are radically different from any more deadly diseases. SARS-CoV-2 virus is more virulent (spreads quickly) on one hand, yet it produces relatively mild disease symptoms in vast majority of the infected population. However, it is exhibited in a broad clinical spectrum of courses, ranging from totally asymptomatic, very light to severe and even fatal outcomes. In majority of younger persons and persons with healthy immune response it usually produces asymptomatic form of the disease or mild unnoticeable flu like symptoms. In such cases the disease remains restricted to upper respiratory tract of a diseased individual and is successfully neutralized by healthy person's cell mediated immune response. 

Our nasal mucosa of the upper respiratory tract is a niche immune site in which all antiviral responses are modulated by external factors such as temperature and humidity in addition to being the first site of the host's innate immune response to infection. Delayed or reduced host antiviral immune response is closely linked to COVID-19 severity and this includes suppressed interferon-induced cytokine expression, which is linked to viral disease symptoms32. Hence, in older persons with weaker immune response and in persons with underlying comorbidities such as lung disease, diabetes, cardiovascular disease, asthma, HIV, morbid obesity, liver or kidney disease1,3 the disease might take a much more severe course. In those cases the infection proceeds to lower respiratory tract and to the epithelial lining of alveolar spaces of patient's lungs. There it may become responsible for severe pulmonary infection and pneumonia, which frequently in combination with excessive innate immune response such as hyperinflammation can promote pronounced T cell activation further amplifying inflammation and disease severity28. This might lead to death especially in older persons (>67 years of age). In clinical practice many instances were encountered where in weakened individuals the virus entered patient's blood circulation. In that case this coronavirus may attack virtually any organ in a body whose cells possess ACE2 receptor. 

The virus exploits Angiotensin-Converting Enzyme 2 (ACE2) receptor in conjunction with the Transmembrane Serine Protease 2 (TMPRSS2) found primarily on epithelial cells in many organs. Both enzymes activate viral Spike protein on its surface cleaving the cell's ACE2 receptor permitting viral internalization within the host's tissue cells and begins to reproduce. Once inside the host cell this virus is characterized by very high rates of replication. The original wild type strain, which began the pandemic was shown to reproduce as much as 270 times faster than comparable coronaviruses responsible for seasonal flu. This is possible in part by the fact that the viral RNA polymerase lacks proofreading capability devoting all its time to continuous replication. As a result the viral RNA polymerase also makes many mistakes in its replication transcript leading to high viral mutability.

Even otherwise healthy individuals exposed to very high infectious viral loads, as for example in case of some front line health care workers, during their infection may encounter severe course of the disease as their healthy immune system may become overwhelmed with excessive concentration of viral particles. Such situations are exceptional however, and normally about 80-91% of infections have been shown to exhibit only mild to moderate symptoms including sore throat, dry cough and fever2,9. According to 2021 Canadian numbers published by the Public Health Agency of Canada only about 5.3% of SARS-CoV-2 virus testing positive individuals required hospitalization. The remaining 94.7% of virus tested positive cases pass through asymptomatic, mild to moderate disease from which they successfully recover at home. We know however, that in most countries due to passive public reporting the official incidence statistic is underestimating the true number of exposures. Many more people get exposed to the virus than is officially reported. from an early very important German cross-sectional randomized design study it was estimated that the total number of individuals actually exposed to SARS-CoV-2 virus might be as much as 10 times higher than the number of officially reported cases3. This value became generally accepted throughout the scientific literature. This reporting disparity primarily depends on the methodology of nation's sampling strategy. For example during a WHO sponsored "Solidarity II" global serologic study for COVID-19 in Kenya about 5-10% of Kenyans were found with SARS-CoV-2 virus specific antibodies while only 0.2% were confirmed to be testing positive by PCR methodology27. The 10x more exposures to PCR confirmations so far was accepted to be valid for majority of nations' health authorities relying on voluntary passive public reporting. In other words, if a person experiences only mild flu symptoms, and that is mostly the case, he does not bother presenting himself for COVID-19 testing, yet unknowingly he actually did contract the disease and already began mounting his immune response to it, however authorities do not know about him. This has extremely important implications for the estimates of every nation's epidemiological situation, which are largely underestimated and inaccurate. 

Because of this underreporting it implies that in Canada, for example, only 0.5% of the coronavirus exposed population might develop symptoms severe enough to require hospitalization of which about half (0.25%) might succumb to the disease. This 0.25% represents the true Canadian fatality rate of total exposed persons to the SARS-CoV-2 coronavirus and is termed the 'Infection Fatality Rate' (IFR). The IFR is expected to be somewhat variable however, fluctuating together with the pathogen prevalent reproductive rate Rt (see below). In German population at the beginning of the pandemic the IFR for the SARS-CoV-2 virus infected individuals was documented to be around 0.28-0.4%3.

Mounting evidence suggests that the severity of COVID-19 outcomes and the number of symptoms might be directly proportional to the initial load of inhaled viral particles. For example, in the Heinsberg study Streeck et al, 20203 have observed that 36% of infections were asymptomatic in subjects not participating in local festivities, as opposed to only 16% in those attending carnival. In this study many infections were acquired during local carnival festivities where large numbers of persons gathered together speaking loud and singing. The resulting infectious aerosol formation contained large concentrations (titer) of SARS-CoV-2 particles producing in infected individuals infection courses with more symptoms. This compares with approximately 40% of asymptomatic disease courses normally observed elsewhere. The majority of asymptomatic cases appear to be infected during day to day interactions in public, in which the viral titer of infectious inoculum logically is much lower than during super spreading events of large gatherings of persons speaking loud and singing. In the same study the German investigators also observed that the frequency of SARS-CoV-2 virus infection did not differ significantly between age groups (persons of all ages may equally get infected) and sex. However, they also reported an interesting fact that the estimated risk of being infected by another person (secondary infection by a relative coronavirus carrier) in a multi-person household was much lower than expected 100%. It was observed to be 71% when living in two-person household, 53% in three-person household and 38% in four-person household. This observation confirmed similar findings of Li, W. et al. in China4.

We also know that documented re-infections of individuals who once passed through the COVID-19 disease are rare. If they do occur the course of the second disease outcome is either very mild or asymptomatic (therefore rarely reported). This suggests that previously infected individuals do mount immune response despite relatively low observed seropositivity (presence of antibodies) within a population. Neutralizing antibodies (NAb), memory B-lymphocytes, and CD4+ and CD8+ memory T cells to SARS-CoV-2 virus generated by infection, reexposure or vaccination are key to acquisition of one's immunity. However, the magnitude of the antibody and T-cell response was observed to be discordant among individuals and is influenced by the disease severity23. Fan Wu et al. (2020)9 found titers of SARS-COV-2–specific NAbs in their study subjects varying substantially and included ~6% of patients who recovered successfully from mild COVID-19 with NAbs below detectable limit. The NAb titers in patients appeared to be associated with age. Older patients had significantly higher titers of NAbs than younger patients in their study. They also note that age has been reported to be an important predictor of adverse disease outcomes after infection with coronavirus. The reasons for this apparent variation in humoral response are currently hotly debated in scientific literature, however it appears that in mild COVID-19 cases no permanent humoral immunity is necessary for convalescence to take place as person's immune protection is afforded by his innate and activated cell mediated immunity response. In COVID-19 patients this is observed primarily in asymptomatic and mild courses of the disease. It follows that the strength of patient's humoral response, hence his antibody titer within his blood stream proportionately increases with the disease severity and the number of symptoms displayed. Since vast majority of COVID-19 disease courses is asymptomatic or mild (80-91%) the level of seropositivity within a population is expected to reflect this low number of severe outcomes accordingly.

In addition, after a year of raging pandemic population seropositivity in many severely affected countries like Spain and Italy remained low and generally below 20%24,25. For most US states it remained below 10% and in a number of states below 1%. In the US it was rarely observed to reach over 20%, only later dropping again back to below 20% level (New York)26. A Kenyan "Solidarity II" global serologic study for COVID-19 carried out during the first pandemic wave in that country (May-September 2020) provides a further insight into serologic dynamics elicited by the SARS-CoV-2 virus during this pandemic. During this study the seropositivity in Kenyan population was found to be between 5 to 10% and varied between 9 to 50% in different population groups. It was shown to be lowest in general population increasing substantially in health care workers and truck drivers in large cities. Not surprisingly it was highest in large urban centers like Nairobi and Mombasa dropping down at the end of the incidence wave27. Second explanation for varying and low population seropositivities observed in many countries is the timing of resulting humoral response dynamics tied to prevalent epidemiological picture within the population in question. The emergence of adaptive immunity in response to SARS-CoV-2 virus exposure occurs within the first 7 to 10 days of infection29,30,31 with secretion of serum IgM and IgA antibodies by day 5 to 7 and IgG by day 7 to 10 from the onset of symptoms. In general, serum IgM and IgA titers decline after approximately 28 days, and IgG titers peak at 49 days slowly waning to below detection limits subsequently, as the short-lived antibody producing plasmablasts (B-cells) die following the viral clearance23. It follows that in the absence of second re-infection the NAb titer normally drops with time within the population thus the observed low seropositivity merely reflects the instantaneous rate of infection incidence rather than population's immuno protection potential.

R0

One measure we often encounter in connection with SARS-CoV-2 virus is R0. It stands for basic reproduction number. It refers to the infectious potential of a disease and reflects a hypothetical number of individuals an infected individual is likely to infect (secondary infection rate). This measure is highly variable however, and reflects not only the infectious potential of a disease, but also the prevalent mode of transmission, genetic factors inherent to a particular target population and population's immunologic history. In connection with SARS-CoV-2 its initial R0 value at the beginning of the world pandemic was estimated to be between 2-3 (i.e. one infectious individual is expected to infect additional 2 to 3 persons)5,10. Please note that R0 is a measure applicable to a communicable disease only at the beginning of epidemic when all other individuals are infection prone, having no immune defense what so ever. Several weeks, months into the epidemic when many individuals have already achieved their natural herd immunity R0 is no longer applicable and is replaced by Rt (reproduction number at time t, or effective reproduction number), which is always lower than R0. Once due to either acquisition of natural immunity by the population or non-pharmacologic intervention such as social distancing for example the Rt becomes suppressed to values < 1 the disease epidemic is in remission and the epidemic might extinguish, since more individuals will recover from the disease than become infected (more on R in reference 5). Canadian modeling data6 reveal that Canadian Rt started off between 2-3 at the beginning of the epidemic, later by May 2020 dropping down to close to 1 and then remained fluctuating between 0.7 and 1.2 for the remainder of the epidemic in Canada regardless of non-pharmaceutical interventions implemented in that country.

Masks

The use of masks is just as misunderstood by the general public, as it is by most politicians and governmental agencies. Therefore I will spend more time on it, as it will lead me to my next topic on herd immunity. Our success in eliminating COVID-19, and returning back to normality depends on masks. Masks do work. Not only that WHO finally acknowledged it last November, I already documented it in August, 2020. Figure 1 depicts a comparison of COVID-19 epidemiological profile during the first wave between March 1st and August 16th, 2020 in two separate jurisdictions - 8.5 million province of Quebec, Canada and a 10.7 million Czech Republic. Both populations were subject to similar government-induced non-pharmaceutical interventions (lockdowns, school closures, closure of non-essential businesses, travel restrictions etc.) with one key exception. Czech Republic implemented mandatory mask-wearing directive right from the start of the pandemic on March 1st. Quebec, Canada did that four and half months later on July 13, 2020. The results are obvious (Fig.1). Wearing a mask will not prevent infection by any means, as the most common simple facial mask filtering efficiencies were estimated to fall between 25-80%. However, as I have mentioned above, the severity of COVID-19 disease is proportional to the initial inhaled viral load therefore wearing a mask will not prevent an infection, it will prevent severe outcome. Thus while wearing a mask minimizes the severity of the disease, it still permits mild infection to proceed so that an infected individual, either asymptomatic or with a mild course of the disease will start mounting his immune response hence facilitate the formation of national herd immunity. It could be thought of wearing of a mask as subjecting oneself to a free natural vaccination. It is free, and effective. An indiscriminate compulsory mask-wearing anywhere in public, as sadly it was enforced in Czech Republic for example, is unnecessary (emphasis added) and likely would result in public aversion and incompliance. Masks need to be worn only in areas with increased probability of infection through inhalation of viral particles, particularly in crowded closed settings such as hospitals, public transit, office buildings, large stores and shopping malls.

Natural Herd Immunity

Natural collective immunity, also known as herd immunity refers to the protection of susceptible individuals against an infection when a sufficiently large proportion of immune individuals exists in a population. It is the inability of infected individuals to propagate the epidemic outbreak due to lack of sufficient number of susceptible individuals around them. It stems from an individual immunity acquired through natural exposure to infection7,8. From the well known deadly pandemic of H1N1 Influenza (Spanish Flu) of the 1918 humanity recovered only thanks to the natural global immunity acquired by the exposed individuals during the course of the epidemic. There was no governmental vaccination program employed in 1918.

Herd immunity threshold is defined as the proportion of individuals in a population who, having acquired natural immunity, can no longer participate in the chain of transmission. If the proportion of immunized individuals within a population surpassed this threshold, the transmission of the pathogen would be interrupted and the current outbreak would begin to extinguish. For SARS-CoV-2 virus the herd immunity threshold was estimated to be about 60% of the population5. Number of countries reached their 60% herd immunity threshold at the end of 2020 and the beginning of 2021 (Table 1).
 

Country Date of achieved 60% herd immunity Start of wave 2 fluctuations
Czech Republic December 20, 2020 November 1, 2020
USA December 27, 2020 January 10, 2021
Spain February 2, 2021 November 8, 2020
Sweden February 9, 2021 December 20, 2020
UK February 16, 2021 January 10, 2021
Slovakia March 9, 2021 November 1, 2020
France March 9, 2021 November 8, 2020
Italy March 28, 2021 November 15, 2020
Brazil March 28, 2021 March 28, 2021 (?)
Canada still short by ~ 10 million individuals (on May 9, 21) January 10, 2021
Data: WHO weekly epidemiology reports

Table 1 - Selected countries reaching their 60% global immunity threshold and the start of their corresponding Wave 2 epidemiological oscillations. Please refer to the updated graphical representation of epidemiological situation in each country on the upper left side bar.
 

At the onset of the COVID-19 pandemic a number of countries contemplated relying on the development of natural herd immunity in their populations to fight the pandemic rather than introducing strict social distancing measures. UK initially mulled this approach. In the sequel of escalating deaths however, UK abandoned this strategy. Sweden avoided the use of severe social distancing measures altogether. It severely strained its health care system in the process, nevertheless eventually managed to minimize severe social and economic impacts stemming from harsh social distancing measures. Today, Sweden is not in any worse position than other countries which relied on drastic restrictions and lockdowns (Fig.2). 

 

At the end of the first wave of the pandemic vast majority of the world's populations was still immunologically vulnerable having no defenses against SARS-CoV-2 coronavirus what so ever. Passing through this second wave we are finding ourselves with majority of human populations around the globe, but especially in North America and Europe already exposed and immune as populations in many countries through exposure have already reached their immunity. Table 1 summarizes several selected countries by the end of March 2021 reaching their COVID-19 60% global (herd) immunity threshold. In European and North American nations nearing the population's herd immunity threshold can be well visualized from the difference in epidemiological profiles of the first and second pandemic waves. The earlier, wave 1 is exhibited by shallow profile easily flattened by the implementation non-pharmaceutical public health measures (Fig.1). The latter, wave 2 entered wild oscillations characterized by accompanying steep rises, sharp peaks, and steep falls in incidence fluctuating in relatively short succession. This can be explained by the virus hitting more and more individuals who have already previously been exposed to the virus and acquired natural immune defenses to it. It likely indicates the progress of herd immunity within the countries presented here. This progress would also be expected to be accompanied with a gradual shift from community transmission to isolated clusters of cases. In Canada then, the advancement of population herd immunity can further be seen in consistent decrease in COVID-19 hospitalizations throughout the epidemic (Table 2).
 

Date Total +ve cases 
to date
Total hospitalized to date %
Aug. 30, 2020 127940 11477 9.0
Sep. 11, 2020  135626 11703 8.6
Nov. 28, 2020 365560 21828 6.0
Jan. 02, 2021 596364 32091 5.4
Jan. 23, 2021 743058 39819 5.4
Feb. 13, 2021 823805 45330 5.5
Feb. 20, 2021 843805 46188 5.5
Mar. 06, 2021 884630 48309 5.5
Mar. 27, 2021  962019 51402 5.3
Apr. 24, 2021 1172885 60293 5.1
Source: Public Health Agency of Canada

Table 2 - Consistently dropping hospitalizations in Canada on selected dates of the pandemic further provides the evidence of the progress of herd immunity through Canadian population.
 

Synthesis and Discussion

One commonly recurring theme throughout the scientific literature about COVID-19 is the inconsistent and unreliable reporting of crucial epidemiological data carried out by different countries and their public health authorities. Unfortunately, many Canadian provinces like Québec are not an exception. In most Canadian provinces official reporting of epidemic statistics appears to be based primarily on non-systematic testing carried out on voluntary basis. This results in biased, often incomplete picture of the true epidemiological situation in the provinces. This is especially true for COVID-19 - a disease with such a large spectrum of clinical outcomes ranging from unnoticeable asymptomatic course (in 40% of individuals) to fatality due to multiple organ failure (in 14% of seriously ill hospitalized Chinese patients9). Table 3 reports COVID-19 epidemic in Canada as of November 28, 2020. Total of 365560 individuals tested +ve for SARS-CoV-2 virus. Of those, 276611 were followed up because they actually developed some symptoms of the disease. In other words, in Canada by November 28, 2020 88949 tested positive individuals were asymptomatic; this is 24% of all confirmed cases - clearly an underestimation of true situation. Where are the remaining 16%? The answer to this question may lie in the way testing in Canadian provinces is performed, accessibility to test centers and distances that have to be covered in order to reach them in addition to meeting artificial conditions and criteria put forward in order to qualify for testing. If you are really sick, having COVID-19 symptoms, the chances that you would be accepted for testing are good. If you just wanted to be tested to be "on safe side" but have no symptoms even if you actually were exposed to the virus and would test positive, the chances of being tested are reduced.
 
Total Cases Followed up cases Hospitalized
Total
Deaths
Total
Immunized
Total *
CFR % IFR %
365560 276611 21828 11991 3241000 3.3 0.33

Table 3 - summary of COVID-19 pandemic in Canada as of November 28, 2020 listing total cumulative number of cases to date as reported in ref.6. CFR-Case Fatality Rate is a number of deaths related to COVID-19 confirmed cases. IFR-Infection Fatality Rate stands for total number of death in relation to total number of infected individuals. *Total infected and therefore immunized (see discussion below for explanation).

Note: The definition of a "case" is rather subjective. It is any individual testing +ve for the presence of SARS-CoV-2 virus RNA using RT-PCR methodology regardless whether the individual develops any symptoms of illness or not. RT-PCR is a rather sensitive methodology. It can detect the presence of live SARS-CoV-2 viral genome (RNA) and its non-viable fragments in the swab sample, or in any tissue.
 

According to Canadian breakdown of the incidence of COVID-19 outbreaks in different settings of our society, it is reported that out of total of nine settings, the long term care facilities (senior residences) such as Québec CHSLDs and schools experienced the highest proportions of outbreaks6. They did, however, it is predominantly institutions like CHSLDs and schools that are subject to extensive scrutiny by public health officials and to periodic monitoring through testing, therefore they are likely to be over represented in the total sampling effort. It is therefore necessary interpreting daily numbers and publicized updates on the pandemic with caution. In addition, relying on the frequently reported numbers obtained from clinical setting (number of hospitalized cases, number of patients in ICUs) is an underestimation of the extent of the pandemic on one hand, and an overestimation of the seriousness of the disease on the other since only the very ill individuals requiring hospitalization are recorded by the system. Many of the 80-91% of asymptomatic and mild COVID-19 cases fall out of the picture. 

Unfortunately relevant and reliable COVID-19 epidemiological studies are rare. One objective and an extremely important cross-sectional epidemiological study carried out at the beginning of the first wave was the German study of Streeck et al, 20203. It used a simple randomized design eliminating many sources of bias. From the empirically determined Infection Fatality Rate (IFR) (see definition in Table 3) it estimated that the actual number of individuals exposed to SARS-CoV-2 virus in any population might be approximately 10x higher than the officially reported number of positive cases. The COVID-19 infection fatality rate of 0.37% is an empirically derived value determined in this study from the German population. It reflects the number of expected fatalities as a proportion of all exposed individuals to SARS-CoV-2 virus (i.e. even of those who were not officially reported). Applying this value to Canadian population we assume genetic similarity and a comparable quality of medical care offered to both, German and Canadian populations. Assuming the applicability of the German IFR data in Canada we can now estimate the total number of Canadians that were already exposed to the SARS-CoV-2 virus and who have consequently attained their immunity against the COVID-19 disease. In Canada at the end of November it would be about 3241000 individuals. This is about 8.5% of the 38 million population. 

Children and COVID-19

In the German study Streeck et al, (2020)3 observed that the frequency of infection did not differ significantly between age groups. Note however, that this notion may still be equivocal but it appears at present that children might get infected with SARS-CoV-2 as often as adults do. Studies directly addressing the issue of children being vectors to the disease spread are few however. One Australian school contact tracing study suggests that at population level children and adolescents might play only a limited role in the transmission of the virus18. This is consistent with data on susceptibility in many other studies leading us to believe that lower rates of secondary infection mean that children and adolescents have less opportunity to become important vectors for the disease19. In the Gangelt study Streeck et al, (2020)3 noted that presence of a child in a family did raise the probability of a family member being infected by about 20%. Due to small sample size the variance was large and the increase in this study may have been statistically insignificant. There is however evidence of transmission by children to others in households and in schools from other studies as well19 and school outbreaks have been reported6,19. The US CDC (Center for Disease Control) noted that in children and youth < 18 years of age, which represent 22% of the US population, only 1.7% of young patients actually required hospitalization due to COVID-1911. A Milan study comparing asymptomatic adults with asymptomatic children concluded that very few asymptomatic children carried live coronavirus16. This suggests that unlike in case of Influenza to which children become prone and the primary vectors for the disease, in case of COVID-19 children and young people handle the disease remarkably well. This sentiment was echoed in a number of other publications12,13,14,15 just to mention a few. Overall, the few available studies suggest children and adolescents play a lesser role in transmission of SARS-CoV-2 virus, which is in marked contrast to Influenza epidemics20. Generally it is felt that children are not significant vectors for COVID-1912,13,14 and in my review I did not find one publication claiming to the contrary. 

In the USA racial/ethnic disparities in the effect of SARS-CoV-2 virus on clinical outcomes of children of black, hispanic and asian descent were noted. Currently it is believed that these disparities are primarily of cultural and socioeconomic nature rather than genetic, therefore they will not be discussed here.

With the reference to the recognition that children are unlikely vectors to SARS-CoV-2 virus and that their infection burden is relatively light, many authors have openly questioned the value of school closures, which have been massively implemented throughout the globe during the first wave of the pandemic. They point out that the limited benefits of school closures to the disease transmission control do not outweigh the long term impacts and adversities such measures might have on lost education opportunities, physical and psychological health and well-being of children in addition to imposing increased stress burden on working parents12,13,14,17,18. There appears to be some acknowledgment of this fact on the part of the Québec Government as Premier Legault permitted our schools to remain open during the second wave of Québec epidemic.

From the above discussion a few important points stand out:

  • First, school closures are unnecessary and contribute little to controlling the spread of the disease.

  •  
  • Second, 80-91% of general relatively healthy population handles COVID-19 well. Importantly, it is this segment of the population, given the opportunity, plays a key part in formation of nation's natural global (herd) immunity.

  •  
  • Third, it is the elderly and the immunocompromised individuals with comorbidities which are the most vulnerable and which need most of the attention of health authorities.

  •  
  • Fourth, together with the most vulnerable members of the society it is the health care workers and caregivers of elderly requiring special attention (for example vaccination, frequent PCR monitoring etc.) until nation's herd immunity becomes established, as they may be exposed to potentially significant viral loads in the course of their day to day work activities becoming potentially significant viral vectors.

  •  
  • Finally, seropositivity monitoring for COVID-19 antibodies at the individual or population level is not informative and does not lead to definitive conclusions about nations resilience to the disease.

Health Intervention Measures

The implementation of non-pharmaceutical interventions (NPI) was justified at the beginning of the COVID-19 pandemic. A year ago neither the governments nor the scientific community knew what we were dealing with. The initial fears stemmed from previous epidemics caused by SARS and MERS viruses due to their genetic relatedness to SARS-CoV-2 virus and its zoonotic (animal vector) origin. In humans however both these diseases are much more deadly than COVID-19. Nevertheless, in order to prevent a humanitarian catastrophe WHO immediately issued the necessary recommendations resulting in an immediate implementation of drastic non-pharmaceutical interventions and social distancing measures tailored to a severe pathogen. Majority of world governments complied by imposing unprecedented wide-spread lockdowns, severe travel restrictions, stay-at-home orders, limitations of gatherings, curfews, closures of schools, businesses and halt of all non-essential services. Not unexpectedly, during the first wave the implementation of public health interventions at such a grand scale in most countries did work, as they were predicted to work in a number of theoretical modeling studies prepared for other pathogens. When one considers the daily numbers of infected individuals together with the resulting fatalities of the elderly and immunocompromised segment of the population, they were all dropping. In northern and temperate latitudes this positive trend was further facilitated by the arrival of warm weather in the spring of 2020. So far so good, but what's next? Well, as severe and complete, as the interventions in a number of countries were after their relaxation COVID-19 positive cases still continued trickling in throughout the summer (Fig.1). The SARS-CoV-2 virus was never eliminated from the population and eventually seeded very strong second wave in the autumn of 2020. Since the pandemic debut in Wuhan, China has imposed very strict, almost draconian measures on its citizens. Over a year later China is still smoldering, continuously coping with isolated outbreaks averaging around 150-200 cases per week, which will continue for many more years, if not decades to come. In reality little was accomplished.

These drastic social distancing measures come at a cost however, very high cost. They are inevitably linked to economic destruction, enormous stress and psychological traumas imposed on citizens through isolation resulting in many forms of social disharmony, possibly even in increase of suicides in addition to resulting loss of education opportunities for children and youth, and enormous hardships imposed on country's population by reduction of access to, or even complete closure or elimination of essential services. Unlike the obvious and frequently publicized numbers from the hospital ICUs the silent hardships and suffering of vast majority of citizens of countries enforcing such measures have largely gone unnoticed and unreported. The costs, though often undocumented, are heavy. Number of US authors began describing only a proportion of these costs as "excess deaths" in the US, i.e. deaths linked to COVID-19 pandemic and its intervention measures, yet not being a direct result of the disease (Bauchner H and Fontarosa PB, 202021, Woolf SH et al., 202022). These authors however, focus only on easily quantifiable deaths in the United States. They cannot document the shattered lives, relationships, livelihoods and artificially induced starvation of millions around the globe. At the beginning of the pandemic WHO apparently was aware of this, and in its Epidemiology Report #50, appropriately cautioned the governments against taking disproportionate measures as part of their non-pharmaceutical interventions: 

"WHO reiterates that measures that restrict the movement of people during this outbreak should be proportionate to the public health risk, short in duration and reviewed regularly as more information about the virus, the disease epidemiology and clinical characteristics becomes available."

As the COVID-19 pandemic progressed through the first wave, with time it became clear that SARS-CoV-2 virus was not as dangerous as initially feared. Nevertheless despite of the clear recognition by the scientific community that in 80-91% of the population COVID-19 produces only mild or asymptomatic courses, in reality in Canadian provinces like Québec, and possibly others, only numbers of cases, numbers of patients in ICU and numbers of daily deaths continued to be reported through mainstream media and on public transit electronic billboards rooting irrational fears in general public. The harsh measures continued being repeatedly enforced and the above cautionary note of WHO have largely fallen on deaf ears of many misinformed Canadian politicians who apparently sought their own political gain rather than scientific guidance. For over a year now they have repeatedly subjected Canadians to harsh, sometimes, I do not hesitate using the word oppressive restrictions to control a disease, which is mild or asymptomatic for majority of our population. As pointed out earlier, according to the Public Health Agency of Canada, by January 23 Canada recorded 743058 confirmed positive cases of which only 39819 (5.3%), required hospitalization. In other words, total of 94.7% of official COVID-19 cases in Canada were mild or asymptomatic! This however does not include the estimated ten times more individuals (i.e.~7430500 of Canadians) who, like myself, were by January 23 exposed to the virus yet because of mild or asymptomatic course of their COVID-19, or thinking it was just another seasonal flu chose not to be tested. It follows that in Canada only about 0.5% of COVID-19 infected individuals require hospitalization. In other words 99.5% of Canadians exposed to the coronavirus pass through the COVID-19 disease either completely asymptomatic or predominantly with mild symptoms. Canadians showing moderate symptoms still successfully recover from their disease at home. At the same time however, this same large number of coronavirus exposed individuals play an exceedingly important role in formation of nations' global (herd) immunity, as through their exposure to the disease they will start mounting their own immune response to the SARS-CoV-2 virus. This may be thought of as a natural free and safe vaccination program.

Therefore besides the fact that the present observed trend of fluctuating and dropping incidence elsewhere clearly appear to be unrelated to announced and implemented government measures we know that humoral immune response is only one out of three effective body's defenses against invading pathogens. Regrettably, often overlooked and in main stream media rarely mentioned innate and cell-mediated immunity have always played a vital role in the first line of defense against viral pathogens and thus in individual's recovery from any respiratory viral disease such as seasonal Influenza or other seasonal coronaviral flu. In addition, after over a year of fully established world pandemic we know that SARS-CoV-2 virus infections are predominantly mild or asymptomatic in children. In children humoral immunity is weaker than in adults, yet it is adults, not children who predominantly spread COVID-19. It is all three types of natural immunity that play an essential role in formation of acquired natural global (herd) immunity at the population level. In the two mentioned well known pandemics it was this natural herd immunity that broke the infection chain in both pandemics and not any governments' artificial vaccination program.

Conclusion

At the beginning of the world pandemic, which started in Wuhan, China in December of 2019 the novel severe acute respiratory syndrome coronavirus 2 caught the world governments and scientific community unprepared. This resulted in an immediate implementation of drastic non-pharmaceutical measures tailored to severe pathogen. It was not until the results of the first scientific investigations began flowing into our knowledge base when we realized that we are dealing with a virus of completely different etiology. Today we should know that SARS-CoV-2 affects severely only a small proportion of the population and that its effects on 80-91% of the members of our society are relatively mild leading to hospitalizations in only 0.5% of infected individuals. As much as 40% of infections might be completely asymptomatic. Many drastic measures introduced at the onset of wave 1 imposed unnecessary hardships on families and might have had substantial detrimental effects on well-being of children, therefore they should not continue during this ongoing wave 2. Furthermore, at the end of the first wave of the pandemic vast majority of the world's populations was still immunologically vulnerable having no defenses against SARS-CoV-2 coronavirus what so ever. Passing through this second wave it should have been clear to the authorities that we are finding ourselves with majority of human populations around the globe, but especially in North America and Europe already exposed and reaching our natural global immunity rapidly. The progress of this natural herd immunity throughout our societies can be visualized by wild oscillations in epidemiological incidence accompanied by steep rises, sharp peaks, and steep falls fluctuating in relatively short succession. 

The attainment of the populations' herd immunity during the second wave have largely been overlooked and drastic restrictions and draconian social distancing measures are still being enforced despite lack of evidence for their utility. Finally, we know that SARS-CoV-2 virus, which produces wide range of clinical outcomes causes complications in only small segment of immunocompromised members of our society just as any disease, no matter how common, would. One must then ask whether it is ethically acceptable holding the remaining 99.5% of healthy population hostage by imposing draconian oppressive measures and restrictions on the entire society, when the immunocompromised few could be effectively protected by separate focused social distancing measures until the society at large becomes properly immunized through natural herd immunity in conjunction with supporting artificial vaccination programs.

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