Except for the highly vulnerable in the COVID-19 era, it’s time to immediately end lockdowns and school closures and resume life as normal for everyone else…

The present COVID-inspired lockdowns and business and school closures are counter-productive, not sustainable, and illogical. Worst of all, this is all about a virus with a mortality rate (IFR) roughly similar (or likely lower when all infection data is in) to seasonal influenza. How in the world have we gotten to where we are, and what can we do to stop the harm we are doing by reversing the process? I provide below, my opinion on the lockdowns and school closures and I need to be clear up front, the lockdown and school closure polices (particularly extended or re-closures) were and are a complete catastrophe and have failed! They must be ended now! 

Start with the basic fact that there are tremendous harms to these lockdown and school closure actions, and it is a strategy that has devastated the most vulnerable among us – the poor – and made them worse off. Lockdowns and especially the extended ones have been deeply destructive. Government bureaucrats, who may indeed mean well and depend on the public health and medical experts, are being misled at times, and are ill served by preening ‘camera hungry’ medical experts who have been confusing at best, and inaccurate and damaging at worst. These experts have lost all credibility and have caused a dramatic loss in credibility in our scientific institutions. They often demonstrate by their statements and what they call for that they do not understand what they are talking about. Government bureaucrats seem to have some type of infatuation or strange fetish, with these illogical experts. Bureaucrats are not doing enough to push back and challenge and shut down these experts who seem to be driven by factors other than the science. 

Importantly and sadly for the vast majority of Americans, the elites and those more affluent have enjoyed their stock portfolios escalating in value. They have benefitted and gotten richer and many of these upper crust peoples and professionals have the type of careers and jobs that allows them to maintain their jobs while working remotely in their flannels in the basement sipping their caffe latte. These experts have been making societal policies and demands without them having to experience the effects of their policies. Devastatingly, it remains the nation’s impoverished and working-class households and especially those with children, who have been subjected to a disproportionate share of the burden. The fact is that lower-income Americans and other global citizens are much more likely to be compelled to work in unsafe conditions. These are employees with the least bargaining power, and tend to be female and hourly paid employees. This is horrible and presents a complete catastrophe to their lives! Moreover, there are reports of racialized groups being stigmatized because of the higher burden of severe illness and death among persons already struggling on the fringes of society. Reports of smears and slander on our Arab, Middle-Eastern populations, our West-Asian, Black, Latin-American, South-Asian, Caribbean and Indo-Caribbean, as well as Southeast Asian groups are increasing and are very disturbing. COVID-19 has troublingly revealed it is a disease of disparity and as such, sadly revealed the under-girth racism and sexism that often comes with this and exists in societies, at a time when there should me more social cohesion and compassion in our civil societies as we grapple with this situation. More so because our leaders and their experts have devastated the response. 

The poorer among us have also disproportionately lost their incomes as businesses and schools have closed, as well as the children are unable to optimally learn remotely. In fact, they are dropping out in vast numbers. The fact is that the poorer among us have been at increased risk from deaths of despair (e.g. suicides, opioid-related overdoses etc.) due to the catastrophe lockdowns and school closures visit upon them. There is tremendous mental anguish from the lockdowns and loss of control in one’s life, and the collateral damage from the lockdowns and closures is immense. 

The cost of the lockdowns must not be more than the infection and disease itself and already we are witnessing how future generations may be crippled by these lockdowns. The lockdown policies (especially prolonged) have been poorly thought out and are economically unsustainable and there is a massive cost to it as it is highly destructive. Our younger people are going to be shouldered with the indirect but very real harms and costs of these lockdowns for a generation to come. Poorer underprivileged people pay a much larger economic cost and the devastating burden is unequally distributed onto them. Our impoverished are hit with a double whammy via the unequal impact of COVID-19 which is an illness of disparity, and the nonsensical damaging lockdown and school closure policies. Populations must be adequately informed with the best, highest quality, most trustworthy, robust evidence, so that they can sensibly practice mitigation steps and make decisions. In providing evidence-based information to the public, this will help reduce the polarization and mistrust. 

But the reality is people are suffering. Look around you. Lives are being destroyed for once a business is closed and jobs lost, once someone is laid off, there is long term devastation to all those involved. Business owners are losing everything they worked for and have poured all their investment into. Complete multiple generations of sacrifice being ruined by insane specious medical experts and ‘deer-in-the-headlight’ bureaucrats. People are dying due to the COVID restrictions. Time to turn off the irrational medical experts and actually follow the data and science, for the first time. Time to for the first time, think through these policy decisions and look at what they are doing to the people. You do not just enact a policy and leave it in place if it is destroying the society. You stop it, you revise it! You do not implement policies and force edicts onto the society just to be seen as to be doing something. That is pure insanity and near criminal if it is leading to destruction! We do not need to destroy our societies, the lives of our people, our economies, or our school systems to handle COVID-19. We do not ‘stop COVID at all costs’! At some point this madness must stop and be grounded in sane thinking! 

The truth is that many of these more vocal talking-head “medical experts” do not represent the tremendous numbers of bread-and-butter clinicians and nurses at the forefront of the COVID-19 battle. These are our real heroes. The information these unempirical medical experts feverishly spew at the public 24/7 is relentless, and at times intellectually dishonest, absurd, being untethered from reality and common sense. They have not considered the consequences (even unintended) of their actions/statements and bureaucrats are simply following along, decimating their societies. Their lockdown decisions and input have created policy disasters! With hubris and self-righteousness, these experts run around from media show to media show hurling near vomitus at the public, constantly validating each other, patting each other on the back, praising each other, and seemingly detached from the devastation they are causing. 

These showcased ‘medical experts’ seem unable to read the science and do not seem to understand the data, are blinded to it, and what they say at times is unsubstantiated, conflicting, and makes absolutely no sense. The available data and what we know about COVID-19 often does not match the health policies they advocate for. These ‘vocal experts’ exhibit a kind of groupthink, deceptiveness, academic sloppiness, and cognitive dissonance that ignores data or facts, while driving a sense of hopelessness and helplessness among the public. They act as ideological enforces attacking anyone who disagrees with them and have the media as their attack dogs once you disagree and question the policy. Then attacks and smears begin by the media with no real focus on the data or technical issues, and most importantly, no interest or debate on the crushing harms on societies. They have driven societies now into a blame game, where neighbours and friends and strangers blame each other for infections. Now friends and neighbours attack each other and this is ripping our societies apart. These experts cite research studies that are often very methodologically flawed and junk science. They are apparently driven by craven politics and use fear mongering and it seems at times deliberately, to paralyze the populace and recklessly disregard the problems the protracted lockdowns visit upon the lives of Americans (and really, on any global society). 

There is no logic and these unhinged experts recklessly disregard the fact that the virus has attenuated and death rates are substantially decreased. They have driven populations into turmoil and a fearful frenzy for a virus with an almost 99.9% chance of survival if infected. Let us wrap our minds around this last statement before we read on, “a virus with an over 99% chance of survival and more certainly for persons under 70, especially if reasonably healthy. The vast majority of people who contract SARS-CoV-2 will not get ill or die from it”. 

We are also left to question, did governments and their ‘experts’ do this to drive deep fear initially so as to coerce people to readily accept the lockdowns and closures? Do they need more lockdowns now to justify the initial catastrophic lockdown mistakes (or extensions)? These are the type of questions we cannot discount given what we have now seen play out. It is way past time to end the lockdowns and we got life back to normal for everyone but the higher-risk and the elderly among us. It is way past time we target efforts to where they are beneficial. Such age-targeted measures can protect the most vulnerable from COVID-19, while not adversely impacting those not at risk. Why? Because we can actually target the higher-risk based on age and risk. We know how to do this. We know better who is at risk and should take sensible reasonable steps to protect them. We know better what to do now and how to treat COVID-19 patients. We have hospital systems geared up now. We need to stop grabbing our pearls and the never-ending convulsions and vapours each time an irrational expert spews partial or inaccurate information to get us fearful. We need to stop the hang wringing and go on with life. There are far more devastating pathogen out there and which will emerge at some point in time. What will we do then? 

Governments had nine to ten months to secure the elderly and higher-risk persons, so why are they locking down each time there is a new case or cases rise? Logically, the elderly would be secured by now, so are they really acknowledging tacitly as a government and medical experts that the reason they are rushing to lock down again is because the elderly are not optimally secured? And hospitals are not geared up. So, what did they do as a high paid and privileged government with their ‘experts’ over the last nine months while society was under perennial house arrest and being hollowed out? Being devastated. Is this more a failure of governments and public health systems and not the general population that did their part? 

There is absolutely no reason to lock down and constrain an ordinarily healthy “well” society, a younger society, in the first place. Never in human history have we done this, constraining an entire society. We always lockdown/quarantine the cases and vulnerable, not the well. It has never been done. Why do this here then, especially prolonging now, when we know the at-risk sub-population clearly, and can gear and target our response to them? What is the underlying corroborating science to do this? Initially, it was understandable to gain an understanding in the first few weeks of what we were dealing with. But why would we continue this way for so long? Are we going to kill off the entire country or world to stop every case of COVID-19? Is this the goal or policy now, to “stop COVID-19 at all costs?” This is destructive, illogical, and unsound policy if this is the new policy. 

Moreover, we have never asked the experts like Dr. Fauci to provide us their underpinning data. Show us the evidence, do not just stand there and spew nonsense that you cannot back up. You are destroying lives, whole communities, whole nations. Populations must demand this now from the camera-hungry preening medical experts: “where is that evidence for what you just said” and “at what cost to society are we going to implement that public policy?” The issue is what is the trade-off and we must take those trade-offs into account when making policy and make evidence-informed decisions. Has any expert completed a cost-benefit analysis of lockdowns using data we have now? The answer is ‘no’. Our governments are being informed by ‘experts’ seemingly driven by ideology/politics, and thus we are being subjected to ideological policy and not science-based policy, yet they are telling us they are following the science, and we as the public, are realizing they often talk nonsense and drivel. None of this makes sense anymore, even if it initially made some sense. Still running after a ridiculous Imperial College Ferguson modelling that has been discredited. Utter junk science by a researcher (s) that has been proven wrong time and again. They have been flat wrong and these inept experts keep pointing to these models and assumptions when we have actual data now. Who would refer to models when there is data to inform us? What has been the impact and has our response been proportionate and scientific based on confirmable data? ‘The answer is an emphatic ‘no’. Have we matched COVID-19 public policy to data? The answer is ‘no’. 

My thinking many months now is that we must end lockdowns and school closures because of the devastating consequences and the fact that this benefits the well-off and upper class in our societies. Immunity from ‘natural’ exposure (once the elderly and at-risk and those with co-morbidities are fully secured) is a secondary effect of opening up. This is a good thing. Look, I get it. Theoretically, if we quarantined (locked down) any society 100 percent completely in a prolonged manner, and just kept it closed, there is a chance it may stop spread. Cases will go down. However, we would then achieve two outcomes: First, no economy or life to emerge to, and, second, we would not have moved any closer to population-level immunity (often known as herd immunity), which should be the ultimate goal. Importantly, susceptible persons would remain ready and ripe for a virus that is laying in wait. We would be delaying the problem, even as we also cause a host of devastating lockdown consequences. We are witnessing these now. We can never eliminate COVID-19 with a lockdown in any nation! This can never be done and the experts know this. We absolutely need the “low-risk of illness” portions of the populations to be exposed to the virus so as to build immunity and stop the spread. 

Population immunity will come via natural exposure, taking a vaccine, or a combination of both (usually the case). Moreover, we are seeing evidence now that there is some level of cross-reactivity immunity that may also confer some immunity (exposure to other corona viruses, common cold corona virus etc). It is important to also understand that we are not referring to allowing a society to ‘run free’ and everyone get infected. This would be disastrous and has never been the call. Rather, as we await a vaccine that may or may not be entirely effective or may have limited immunity (remember the yearly influenza vaccine has not been entirely effective) or may be delayed or even may have adverse effects that need to be studied, the optimal approach is to secure the at-risk (elderly etc.) fully in their private homes, the society, and in nursing/care homes (this is a necessary component), as well as prepare hospitals to prevent overcrowding and also to allow other medical illness to be dealt with. This will allow the ‘low risk of illness’ portion of the population, this being the healthier, the well, the younger without comorbid conditions, to face the pathogen ‘naturally’ and to develop some level of immunity. Face it naturally via normal day-to-day living. This can be regarded as an age-targeted approach, where constraints increase with age, with the youngest (e.g. children, young people at very low risk etc.) being allowed to live lives pretty much freely and as such, the elderly with medical conditions being at the other end of the spectrum, being fully secured. Younger persons/adults and middle-aged adults who are healthy in the society could thus go on to live reasonably normal lives with reasonable common-sense precautions. It is destructive to employ a ‘one size fits all’ strategy to a society. 

In addition, the key metric is not the number of new active cases being reported and misrepresented by the vocal corrupted experts, but rather what are the hospitalizations that result, the ICU bed use, the ventilation use, and the deaths. What is the severe illness as a result? This is the issue. Not case counts for this is driving needless fear when the risk of illness often is near zero and this causes people to rush to the hospital and this creates the blockage and overcrowding. We test and you may have immunity from prior colds or even prior COVID yet the diagnostic test used often has high false-positive rates. We admit you under suspicion when in fact the test was too sensitive and picks up old or non-viable, non-culturable virus, fragments or viral dust, and inconsequential COVID. See the problem with the fear driven by the cases. The real issue is what is the excess mortality beyond regular baseline? Incident case data, while an important piece of the puzzle, is not the key piece of the puzzle at this time. Specifically, it is not the number of hospitalizations or ICU visits, but it is understanding these numbers so that we can plan and make sure we have the capacity to handle hospitalization and ICU needs. When we flattened curves, it was to prevent overcrowding, as this was to slow hospitalizations to the point where we could have handled the cases and administer important care to others too. Not just COVID-19 patients. All this to say we cannot rush to a lockdown or a school closure every time there are new cases, not now, not based on how far we have come in preparation and what we know now about who COVID-19 targets and how to treat it. This is an insane policy. Not when we know that the tests generate a high number of false positives. 

Look at the utter catastrophic mess our leaders and experts have made. For example, do we shut a school down for one new case? Is this fair to the rest of the students – especially when we know children are at very low risk of spread to other children, to their teachers, or to the home, and are at very low risk of severe illness or death? Influenza is more lethal to children than COVID-19 is, and children take it home, yet there were never any school closures or masking of children to prevent transmission of influenza. When has there been? Additionally, the less advantaged among us cannot work from home, as they often have low paying in-person jobs. Who will take care of the children being sent home? Should the working parent have to quit his or her job, and the family go without income? The less advantaged among us cannot afford tutors, pod schools, or private schools. Lockdowns are essentially a boon, favoring the rich and well off who do not feel the effects in the same manner as the poorer and underprivileged. This is a catastrophe and result of the lockdowns! 

The devastating consequences resulting from lockdowns and school closures are far more detrimental than the COVID-19 virus itself. So, is the choice death from the disease versus devastation and death from the lockdowns? Businesses have closed as destroyed forever and many are never to return, jobs have been lost, and lives ruined and more of this is on the way; meanwhile, we have seen an increase in anxiety, depression, hopelessness, dependency, suicidal ideation, and deaths of despair across societies. Can you grasp the devastation to the business owner and all involved? Preventive care has been delayed and has catastrophic consequences. Life-saving surgeries and tests/biopsies were stopped. All types of deaths escalate and loss of life years increased. Over half of Americans on chemotherapy (650-700,000) stopped getting chemotherapy due to being scared and the hospitals ceased non-essential procedures. Hip replacements and knee replacements were stopped. Children vaccinations for vaccine-preventable illness declined by half with a risk of re-emergence. How many people may have died, by the thousands likely, who may have survived an injury or heart ailment or even acute stroke but were too scared to access the clinic or hospital system (did not call the ambulance)? Or procedures pushed off. 

Sadly, the very elderly we seek to protect the most are being decimated by the lockdowns and restrictions imposed at the nursing/care homes they reside in. Reports are that the restrictions from visitations and normal routines have accelerated the aging process, with many reports of increased falls due to declining strength and loss of ability to adequately ambulate. Dementia is escalating as the rhyme and rhythm of daily life is lost for our precious elderly and there is a sense of hopelessness and depression with the isolation from restricting loved ones. We are making the final time for our elderly very painful and anguishing by all of this insanity. 

There is a reported one percent (1%) increase in suicides for each 1 percent increase in the unemployment rate. One in four Americans between the ages of 18 and 24 had suicidal ideations in the last months due to the lockdown, not COVID-19. These include College and University aged students across the US, the strongest among us. Reports from England indicate that deaths by suicide in persons under 18 years old markedly increased during lockdown. Children are being locked out of school when they are at incredibly low risk. Our children are failing in remote learning, and being irreparably damaged in many regards, dropping out and not getting the chance to meet their social and maturational milestones when outside of the school setting. 

Many children – and particularly those less advantaged – get their main needs met at school, including nutrition (often their only daily meal), eye tests and glasses, and hearing tests. Importantly, schools often function as a protective system or watchguard for children who are sexually or physically abused and the visibility of it declines. Due to the lockdowns and the lost jobs, adult parents are so angry and bitter, the stress and pressure in the home escalates due to no income and loss of independence and control over their lives as well as the dysfunctional remote schooling that they often cannot help with, and some sadly are reacting by lashing out at each other and abusing their children. There are reports by experts that children are being taken to the ER with parents thinking they may have killed their child who is unresponsive with multiple broken bones. This is real. This is happening because of lockdowns and extended ones. The mental health impacts are staggering. 

In early October, among tens of thousands of students (18-24 years old) on approximately 30 university campuses who tested positive, not one student was hospitalized – yet students were sent home. These are among the most-healthy among us, with very low risk of severe illness if infected. By sending them home (which is an incredibly flawed policy), they could spread the virus to their communities. Is this not placing the ones you sought to protect (elderly) at high risk? See the nonsense and how these ‘experts’ misguide the government bureaucrats? The real question now is are we anywhere ahead today? The answer is no. In no way are we better off! In fact, we are much worse off, so why not allow people to make common sense sensible decisions and take precautions, and go on with their lives? The US data shows that around 95 percent of those over 70 years survive COVID-19. We know that persons 0-19 years have an approximate 99.997 percent risk or likelihood of survival, those 20-49 have a 99.98 percent risk of survival, and those 50-69/70 years an approximate 99.5 percent risk of survival. Nearly all persons under 70 years recover. This virus is less deadly for younger people (far less deadly in children) than the annual flu and more deadly for older people than the flu. We must not downplay this virus and it is different to the flu and can be catastrophic for the elderly. But the ‘good news’ data is never reported by the “experts.” The vast majority of people do not have any substantial risk of dying from COVID-19. The fact is that most COVID-19 positive persons have no or very mild symptoms and do not develop severe illness. What does this all mean? It means the risk of severe illness and death under 60 to 69 years or so is vanishingly small. It means that we do not lock a nation down for such a low death rate for persons under 70 years of age, especially if they are reasonably healthy peoples. 

We must take common-sense mitigation precautions as we go on with life. This does not mean we stop life altogether! This does not mean we destroy the society to stop each case of COVID! We now know how to treat COVID-19 much better, and we have therapeutics that, while each on its own is not a silver bullet, we seem to be able to treat with a cocktail approach that is apparently working. We can target and double and triple down protection of the elderly in our private homes and in old aged/care/nursing homes, while at the same time ensure the hospital system is not overwhelmed and can respond. This includes proactive responding to our higher-risk populations (at home or in nursing homes) who test positive by intervening much earlier (offering early outpatient ambulatory treatment to prevent decline to severe illness while the illness is self-limiting with mild flu-like illness) with available inexpensive treatments (off-target antivirals, corticosteroids, and antiplatelet/antithrombotic-early oral multidrug therapy in an attempt to avoid hospitalization and death). The aim of early treatment before hospitalization is to prevent hospitalization and severe illness, and as such, to save lives. Early home treatment has been shown to drop hospitalization by 85% and death by 50%. 

The reality is that we did not protect our nursing home populations early on as well as we might have (while we did an excellent job with the hospitals), and this has to be acutely focused on. We must fix the nursing home situation immediately and we have learnt that the core breach is the nursing staff who bring infection into the homes. Why has it been 10 months and this has not been solved? We have to immediately cauterize that breach! We also know more now that COVID-19 strikes in an age-specific manner and as such, we should gear resources and efforts in an age-specific manner. 

From where we started 9-10 months ago in the US, between the therapeutics, a potential vaccine (s), an early outpatient treatment approach in COVID positive symptomatic persons, replenishing empty stockpiles, and revived US supply chains, this is very good news societally. What has been learnt from COVID-19 will help dramatically for coming respiratory epidemics and pandemics as this back-and-forth with pathogen will rage on. Our battle and co-existence with pathogen will continue as long as there is life. We also cannot discount the potential damage to normally healthy immune systems that have not been sheltered in place or locked down like this before. We are effectively isolating ourselves and this is potentially dangerous to our immune systems. Immune systems especially of our children function optimally daily by being taxed and ‘tuned’ up We are engaging in a policy that we have no idea how healthy immune systems will react long term and be downregulated so much so that typically benign opportunistic pathogen will be a challenge once persons emerge from lockdowns. This is potentially very dangerous as we have no experience with it and we may set healthy, well populations onto a path of vulnerability to existing and new pathogens. 

Certainly, no effectiveness evidence that children should be masked exists and in fact, masks can be very harmful to children as per evidence, and particularly in terms of potentially weakening their immune systems against usually benign opportunistic pathogen. Children drive seasonal influenza into the home yearly and suffer devastatingly from influenza, including death. Children do not drive COVID-19 home and COVID-19 has largely spared our children from severe illness or death (the risk if very small), unlike the flu. But there has never been a school closure for influenza or masking of children during the influenza season. Why? Why the different children mask policy (and even school closures) with COVID-19 that is less lethal to children and children are at much lower risk of spreading it as well as getting severely ill or dying? Why, when nursing homes have been secured over the 9-10 months since COVID-19 inception. Why? This is the key question and medical experts have so far failed to provide any explanation for this. 

In closing, these ‘experts’ are costing futures and lives by their insane and baseless advice and guidance to bureaucrats who appear to have no idea what they are doing. This is an economic disaster, that is causing more harm to physical and mental health. It is time to end these lockdowns, they have a very limited benefit! There is no basis for prolonging the lockdowns, and people must be allowed to live their normal lives once again, making common sense decisions. Lockdowns (particularly extended or re-lockdowns) cause irreparable damage and bureaucrats have been often misled by illogical and often unscientific experts. “One-size” does not fit all, and responses must be targeted to those at greatest risk. 

Turn off these politicized biased experts with their pseudoscience nonsense, only spewing what we do not know, wringing their hands, and failing to showcase the good news and what we do know already about what works. We must demand that they showcase the good news, there is lots around us! There is so much hope nationally and globally for we can beat COVID-19 and similar pathogen to come. We have before and can again. Inform the populace with both the benefits and the costs (harms) of these kinds of societal lockdowns and school closure polices, so that they can make the trade-offs. Nothing is risk free. Consider what the population will optimally want. Polices must be based on a consideration of the implications of the policy societally, traded off and balanced accordingly whereby the population does not face more harms than benefits. 

A vast lot of information and data has accumulated now and we know lots more on COVID-19 and thus we can take these into account in our decisions. All we seek as societies are the facts, the data, the science as they exist, with pure honesty as to the risk so that we can be informed and empowered to make our own personal decisions and choices. We want this fear mongering and near terrorizing of us to end, at the hands of our governments and insane medical establishment. We want to be informed always of the risks versus benefits and allow us to make decisions with our personal clinicians. We have the pandemic management tools, allow us to use them optimally. Inform populations properly, and allow populations to exercise their personal responsibility and to live free once again, as they take all the necessary risk-reduction steps (following relevant guidance) as a cohesive people to safeguard the vulnerable among! 


Dr. Paul Alexander, PhD (University of Oxford, University of Toronto, York University, and McMaster University) graduate and postdoc educated in a combination of epidemiology, research methodology, biostatistics, and evidence-based medicine/EBM)

Of masks and men: no clear evidence masks are effective in COVID-19

The question on whether to wear a mask or not during the COVID-19 pandemic in terms of effectiveness in stopping viral spread remains contentious and unresolved. On balance, the evidence is severely conflicted and leans toward masks having no significant effect in stopping spread of respiratory virus. This question is now overwrought with steep politicization. Arguments against the use of masks in the current COVID-19 pandemic emerged when a recent CDC case-control study (a weaker design due to an inability to control for all key confounding factors, though employing sub-optimal adjustment) reported that 84.4% of cases always or often wore masks. This raised many questions as to the utility of masks in the COVID-19 emergency.

Moreover, accumulating evidence in toto suggests a lack of evidence to support mask use (in adults or children) including as a broad mask mandate e.g. CDCOxford’s CEBMCIDRAP and policyKlompas and universal maskingJefferson et al., CDC 2, Brainard et al. (Norwich School of Medicine), and Hunter et al. My overall conclusion Based on the body of evidence, is that there is no conclusive evidence to support the use of masks for COVID-19 (except N-95 type masks in a hospital setting and when appropriately utilized) and in fact masking appears to carry substantial risks to the user. 

Urgent well-designed clinical research is needed to definitively address the question about the utility of face masks in curtailing or stopping spread of COVID-19. It is surprising that researchers have not commissioned adequate face mask studies or social distancing studies since the onset of COVID-19 in February 2020. This was not Herculean. We are way past the time in research whereby we can make illogical or irrational, often intellectually dishonest statements not backed with evidence and data. It appears that the face mask issue is now fraught with politics and agendas by medical experts and the media. The cognitive dissonance by experts must end as well as the politicization of this mask question. Populations are being hurt by the academic sloppiness and reckless behavior of these camera-hungry experts and ill-informed media. COVID-19 conclusions are often baseless and I suspect the research community has not studied the mask issue appropriately and have viewed it as Damoclean, because they are afraid of what the findings may reveal. 

Evidence of effectiveness? 

What does the best body of evidence show at this time? To answer this, we are left to debate this using research principally on respiratory influenza viruses or similar, this being considered indirect evidence, albeit very applicable to COVID-19. Overall, the available research is of very poor methodological quality using largely indirect unadjusted evidence, and not the optimal clinical research that is needed. A major limitation is the use of the same evidence base by all reviews and thus arrival at similar findings. However, this low-quality evidence is useful enough to guide us. 

Dr. Anthony Fauci of the NIH/NIAID stated in March 2020as part of his COVID-19 role, “wearing a mask might make people feel a little bit better” but “it’s not providing the perfect protection that people think it is.” Then and now, he actually echoed scientific agreement, and this was in line with the World Health Organization’s guidance. 

Specifically, the World Health Organization (WHO) states that “the widespread use of masks by healthy people in the community setting is not yet supported by high quality or direct scientific evidence and there are potential benefits and harms to consider”. 

More specifically, research by CDC (May 2020) published in Emerging Infectious Diseases (EID) examined personal protective measures and environmental hygiene measures for the effectiveness of such measures in reducing transmission of laboratory-confirmed influenza in the community. Researchers focused on disposable surgical or medical (typical blue coloured) face masks and identified 7 studies involving influenza and influenza-like illness (ILI) and reported no significant reduction in influenza transmission with the use of face masks. Overall, there was no significant effect of face masks in the transmission of laboratory-confirmed influenza and these findings could potentially be extrapolated to SARS-CoV-2 virus. 

Researchers from the University of Oxford’s Center for Evidence-Based Medicine (CEBM) examined the evidence on mask effectiveness within the current highly charged backdrop of politics. They concluded that after nearly 20 years of preparedness for coming pandemics, the evidence on face mask use remains very conflicted and raised tremendous uncertainty today. They are asking why has the right applicable research not been conducted. They also speculate on the elevated rates of harms (infection) when using cloth face masks. They specifically looked at 6 RCTs in 2010 that examined face masks in respiratory viruses whereby 2 were in healthcare employees and 4 were in family and student groups. The trials for ILI showed very poor mask wearing compliance and seldom reported the harms of use. 

In 2013, CADTH which is the Canadian Agency for Drugs and Technologies in Health, stated: “No evidence was found on the effectiveness of wearing surgical face masks to protect staff from infectious material in the operating room, no evidence was found to support the use of surgical face masks to reduce the frequency of surgical site infections, and guidelines recommend the use of surgical face masks by staff in the operating room to protect both operating room staff and patients (despite the lack of evidence)”. 

Jefferson et al. studied physical interventions to interrupt or reduce the spread of respiratory viruses (updating a prior Cochrane review (2011) to now include 15 RCTs (n=13,259 persons) exploring the impact of masks (14 trials) in healthcare workers, the general population and those in quarantine (1 trial)). When compared to no masks, researchers found no significant reduction of ILI cases or influenza for masks in the general population and in healthcare workers. There was also no difference between surgical masks and N95 respirators for ILI or for influenza. The body of evidence was considered to be of ‘low’ quality based on included study limitation, for even though RCTs, they were plagued with serious methodological concerns. 

The New England Journal of Medicine (NEJM)  recently published an article on COVID-19 and masks which appeared to suggest that masks have become no more than a psychological crutch, and stated that “We know that wearing a mask outside health care facilities offers little, if any, protection from infection…It is also clear that masks serve symbolic roles. Masks are not only tools, they are also talismans that may help increase health care workers’ ‘perceived’ sense of safety, well-being, and trust in their hospitals. Although such reactions may not be strictly logical, we are all subject to fear and anxiety, especially during times of crisis. One might argue that fear and anxiety are better countered with data and education than with a marginally beneficial mask”. 

A recent WHO sponsored systematic review and meta-analysis included 39 nonrandomized observational studies (weaker study designs) that were not always fully adjusted and reported that face masks could be effective. These studies were small sampled sized with small event numbers, and plagued with potential selection bias and residual confounding bias. The body of evidence was judged to be at low quality (low certainty) and were at risk of recall bias and measurement bias. Researchers principally assessed mask use in households or contacts of cases that reported on SARS and MERS epidemics (limited for COVID-19), but researchers argue that this indirect evidence can be regarded as the most direct information for COVID-19. Moreover, the Newcastle-Ottawa scale was used to rate risk of bias and this is presently regarded as outdated and lacks the coverage to adequately assess risk of bias in nonrandomized studies. The ROBINS-I tool is the more applicable risk of bias tool for nonrandomized studies and has been recently designed by Cochrane to address the limitations of prior tools such as the Newcastle-Ottawa scale. 

Researchers led by University of Toronto epidemiology professor Peter Jueni, have now come forward asking LANCET to retract the study, citing numerous serious methodological flaws such as (but not limited to): 

i) 7 studies are unpublished and non-peer-reviewed observational studies 

ii) the review failed to consider the randomized evidence 

iii) 25 included studies are about the SARS-1 virus or the MERS virus, both of which have very different transmission characteristics: they were transmitted almost exclusively by severely ill hospitalized patients and not by community transmission 

iv) of the 4 studies relating to the SARS-CoV-2 virus, 2 were misinterpreted by the Lancet meta-study authors, 1 is inconclusive, and 1 is about N95 (FFP2) respirators and not about medical masks or cloth masks and 

v) this review is used to guide global facemask policy for the general population whereby one included study was judged to be misclassified (relating to masks in a hospital environment), one showed no benefit of facemasks, and one is a poorly designed retrospective study about SARS-1 in Beijing based on telephone interviews. None of these studies refer to SARS-CoV-2.

Similarly, a recent study published in PNAS surrounding airborne transmission and facemasks has also provoked substantial consternation and argued to be a political study more than a scientific one. It has led to over 40 leading scientists to call for its withdrawal due to it being very flawed due to very sub-optimal statistical analyses. 

A review by the Norwich School of Medicine (preprint) looked at the effectiveness of wearing facemasks and examined 31 published studies of all research designs. They reported that “the evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations”.

A recent Danish Study  published in the Annals of Internal Medicine sought to assess whether recommending surgical mask utilization outside of the home works to reduce the wearers’ risk of SARS-CoV-2 virus infection in a setting where masks were uncommon and not among recommended public health measures. They included a total of 3030 participants being randomly assigned to the recommendation to wear masks, and 2994 being assigned to the control arm; 4862 persons completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was −0.3 percentage point (95% CI, −1.2 to 0.4 percentage point; P = 0.38). Researchers concluded that the studied recommendation to wear a surgical mask when outside the home among others did not reduce new or incident SARS-CoV-2 infection when compared with a no mask recommendation. These results emerged in a setting where social distancing and other public health measures were in effect, mask recommendations were not among those measures, and community use of masks was uncommon. No doubt this study findings has serious implications for the drive for mandatory masking of populations.

Additionally, in regards to cloth face masks, recent reports suggest that they should never be used as a protective barrier as they offer no transmission protection (as PPE or as source control) e.g. a Tokyo report and BMJ study

In the BMJ cluster randomized study, researchers sought to compare the efficacy of cloth masks to medical masks in hospital workers (in 14 Vietnamese hospitals utilizing 1607 workers over 18 years if age). Wards were randomized to medical masks, cloth masks or to a control group of usual practice which did include wearing masks (masks used on every shift for 4 consecutive weeks). The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Researchers found that penetration of the cloth masks by particles were near 97% and for medical masks, it was 44%. This being the first RCT of cloth masks, the researchers cautioned against the use of cloth masks. There is extensive moisture retention and poor filtration with reuse results in increased risk of infection. Cloth masks should not be recommended for healthcare workers and especially in high-risk settings. 

The Norwegian Institute of public health (NIPH) conducted a recent rapid review to assess if individuals in the community without respiratory symptoms should wear facemasks to reduce the spread of COVID-19. They modelled that, assuming 20% are asymptomatic and with a risk reduction of 40% when wearing masks, that approximately 200,000 persons would need to wear a mask to prevent one new infection per week. Researchers concluded that based on the existing epidemic/pandemic in Norway, that “wearing facemasks to reduce the spread of COVID-19 is not recommended for individuals in the community without respiratory symptoms who are not in near contact with people who are known to be infected”.  They went on to report that only if the epidemiological situation worsens significantly in a geographical area, then the use of facemasks as a precautionary measure should be reconsidered.

In a May 2020 communication report in Nature (Medicine), Leung et al. examined the importance of respiratory droplet as well as aerosol routes of spread with a specific focus on coronaviruses, influenza viruses, and rhinoviruses. They quantified the quantity of respiratory virus in exhaled breath of participants with acute respiratory infections (ARIs) and determined the possible efficacy of surgical face masks to prevent respiratory virus transmission. As part of the study, they screened 3,363 persons in two study phases, eventually enrolling 246 participants who provided exhaled breath samples, with 122 (50%) of the participants being randomized to either not wearing a face mask during the first exhaled breath collection or randomized to wearing a face mask (n=124 (50%)). They identified seasonal human coronaviruses, influenza viruses and rhinoviruses within exhaled breath and coughs of children as well as adults with ARI. In this study, they found that surgical face masks can significantly reduce detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, and with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Overall, researchers concluded that aerosol transmission is a likely mode of transmission for coronaviruses as well as influenza viruses and rhinoviruses, their results suggestive that surgical masks can effectively reduce the release of influenza virus particles into the environment in respiratory droplets, but not in aerosols. 

In a recent NEJM publication (CHARM study), researchers looked at SARS-CoV-2 transmission among marine recruits during quarantine. Recruits (n=1848 of 3143 eligible recruits) who volunteered underwent a 2-week quarantine at home that was followed by a 2nd 2-week quarantine in a closed college campus setting. As part of the study, participants wore masks and socially distanced, and symptoms were monitored with daily checks of temperature. RT-PCR testing was used to assess the effectiveness of these strategies and nasal swab samples were collected between arrival and the 2nd day of supervised quarantine and on days 7 and 14 (the 2nd quarantine used to mitigate infection among recruits). All recruits were required to have a negative RT-PCR result prior to entering Parris Island. Researchers reported that within 2 days from arrival on the closed campus, 16 tested positive for SARS-CoV-2 (15 being asymptomatic) and 35 more tested positive on day 7 or on day 14 (n=51 in total). In addition, 5 (9.8%) of the 51 positive volunteers had symptoms in the week prior to a positive PCR test. Phylogenetic analysis was conducted whereby 6 independent monophyletic transmission clusters (independent viral strains) indicative of local transmission were uncovered, occurring during the supervised quarantine. The majority of clusters principally included members of the same platoon, and numerous infected recruits had an infected roommate. 

In conclusion, authors reported that about 2% who had earlier negative tests for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits who had unknown prior status, tested positive by day 14. Positive volunteers were mainly asymptomatic and transmission clusters occurred within platoons. The predominant finding is that despite the very strict and enforced quarantine (including 2 full weeks of supervised confinement and then forced social distancing and masking protocols), the result was a higher transmission rate and not a lower one. Masks not only did not work, but it appears it made things worse. Despite quarantines, social distancing, and masking, in this cohort of mainly young male recruits, roughly 2% still went on to become infected and tested positive for SARS-CoV-2. Sharing of rooms and platoon membership were reported risk factors for viral transmission. The study raises questions about the utility of quarantines as it appears they do not work even when supervised for 2 weeks in a closed college etc., and it seems that quarantines are ineffective. Masks do not work for even when under full time military supervision in a boot camp environment and the masking is enforced, it emerges as ineffective. Moreover, social distancing in very strict military boot camp conditions appear to be ineffective also in preventing infections. In this study when compliance was monitored and enforced, and the conditions are favourable enough to support a rigorous study, we find that the so called ‘mitigation’ strategies do not work. This study stands as one of the higher-quality more robust studies on the question of masking. 

What about possible harms from wearing masks? Is there any evidence of this? 

But what about harms from mask use? The harms and negative effects are accumulating, extensive, and very troubling especially as they pertain to risk to children. This given that evidence suggests that children do not readily acquire the COVID virus or spread it to other children or take the virus home or get seriously ill or die from it (which is opposite to children being the drivers of seasonal influenza and do go on to suffer morbidity and mortality from influenza far above what is visited upon them by COVID-19). The reports are even more directly applicable to COVID-19. The evidence is not optimal clinical comparative research and is principally media reporting. However, this in itself is evidence and credible direct evidence at that. What is accumulating involves mask wearers within a COVID-19 environment and raises many concerns. It suggests that masks can impair breathing, can cause inhalation of toxic substances such as microplastics and chlorine compounds located in the masks (serious risks), can potentially cause CO2 intoxication or sudden cardiac arrest seen in children, can cause psychological damage, can cause (N95 masks) a reduction in the PaO2 level, increased the respiratory rate, and increased the occurrence of chest discomfort and respiratory distress with prolonged use, and can cause dizziness and light-headednessheadaches. There appears to be a risk of toxic carbon-dioxide buildup as well as some deprivation of oxygen. Mask use can potentially lead to bacterial and mould buildup in children, can cause decaying teeth, receding gum lines and inflammation in gums, can lead to anxiety and sleep problems, behavioral disorders and fear of contamination in children, can cause mask mouth, and can even lead to car accidents. In addition, Stanford engineers report that masks can make it much more difficult to breathe, estimating that N95 masks as an example, reduce oxygen intake from 5% to 20% and if worn for a prolonged period, can damage the lungs and for a person in respiratory distress, it is life threatening. 

Predominant finding? 

The predominant conclusion by global nations is that face masks have a very important role in places such as hospitals, but there exists very little evidence of widespread benefit for members of the public (adults or children). Masks are basically better than nothing, not sealed properly to the face and do not effectively stop the virus. Policy must be undergirded by sound data, and the reality is that widespread use of masks is not supported by science. This mask hysteria is driving unnecessary fear in the population and must end. These people make relentless statements on the use of masks that have no credible basis. However, it is important to understand that as we await definitive research, given the situation and the desire to prevent spread to higher-risk persons (e.g. elderly), when consistent social distancing is not possible, and out of an abundance of caution, face coverings may reduce the spread of droplets from individuals with SARS-CoV-2 infection to others. This must also be considered when a setting is experiencing elevated transmission. 

It is very sensible that one would use a face mask when visiting an elderly person who is high-risk or even if the setting is controlled such as a healthcare one of nursing home. I stand by this and practice and advocate for this. Thus personally, if a situation is judged by me as a high-risk one and I cannot socially distance, I would wear a mask for the wellness of all involved, despite no evidence of its effectiveness as described above. It is reasonable to be cautions, even in the light of limited or non-existent evidence of effectiveness and strong evidence of harms. Situation-by-situation decisions pending on the risk at hand. The full context must be considered but if you are adequately socially distanced, there is no reason to wear a mask. There is no evidence for this. 

Very alarming is Danish reporting of a higher-quality mask study on COVID and masks being rejected by the top journals Lancet, New England Journal of Medicine, and the American Association’s JAMA. If this is proven true, it continues a pattern of politicization of the research and medical community more concerned in advancing their political ideologies, and potential bias by journal editors and the peer-review process. 

In closing, perhaps Yinon Weiss who is a U.S. military veteran, and who holds a degree in bioengineering from U.C. Berkeley, captures our current face-mask calamity by reminding us how masks constrain our return to a more normal life, which seems to be the aim of those using the pandemic for political ideology and election aims. It is potentially being used to medicalize us, to make us believe we are perennially very ill as a society and as such, drives fear. He eloquently states “Our universal use of unscientific face coverings is therefore closer to medieval superstition than it is to science, but many powerful institutions have too much political capital invested in the mask narrative at this point, so the dogma is perpetuated”.

To conclude this overview, this represents my look at the complete and most updated mask-related evidence and my personal opinion and decision. I am all for masks in high- risk settings when no other mitigation is possible and also for individual responsibility but there is no more effective substitute for this virus or any virus for that matter, than hand-washing hygiene. This is especially so given accumulating evidence out of Oxford (CEBM) of a fecal-oral route of COVID-19 transmission (taken together with fomite spread). Handwashing is one of the most effective actions we each can take to minimize spread of such respiratory viruses (common cold, influenza, COVID-19 virus etc.) that use the droplet and contact route to spread. One can even speculate that COVID-19 hand-washing will likely contribute to marked declines in influenza and other respiratory type illnesses globally this upcoming season. In sum, when we look at the science, there is emerging and troubling evidence of harms from mask use e.g. there is incorrect use, a complacency that emerges due to mask use and thus the relaxation of other mitigation steps, as well as mask contamination. Importantly, there are problems breathing when wearing masks.  There is no strong definitive evidence of benefits. There is no scientific basis for a broad mask mandate, anywhere. The evidence to support mask use is not available. We urge individual common-sense decisions and evidence-informed decisions by policy makers that take the data and science into account.


Dr. Paul Alexander, PhD (Oxford, McMaster, York University, and University of Toronto graduate and postdoc educated in a combination of epidemiology, research methodology, biostatistics, and evidence-based medicine/EBM)

Pre-existing immune system memory T-cells recognizing past common-cold coronaviruses: a reason why some children and adults have milder COVID symptoms or do not get severely ill or are immune?

Based on reports, the COVID-19 pandemic respiratory disease emerged from Wuhan, China and is caused by the SARS-CoV-2 betacoronavirus. SARS-CoV-2 virus is believed to have zoonotic origins with genetic similarities to bat coronaviruses.  The spread of SARS-CoV-2 globally has led to millions of infections and the majority of persons infected with SARS-CoV-2 have no or very mild symptoms (a mild self-limiting illness). However, an atypical pneumonia can often result in a small sub-set of higher-risk patients with infection (typically elderly persons (65 years and older) with underlying medical conditions (one or more) or morbidly obese persons or younger persons with serious co-morbid conditions, leading to moderate to severe pulmonary distress/failure (acute respiratory distress syndrome (ARDS)). The pulmonary failure can be linked to a hyperinflammatory immune response (cytokine or bradykinin storm) and can result in multiple organ failure. At-risk persons who develop ARDS require more invasive oxygenation via mechanical ventilation or even extra-corporeal membrane oxygenation (ECMO). 

While the underpinning mechanisms of the spectrum of underlying disease is uncertain, evidence suggests that the hyper-inflammatory ‘dysregulated’ immune response (cytokine storm) characterized by elevated levels of cytokines (IL-1, IL-6, IL-10 etc.) can result in morbidity and mortality. Major improvements have been made since March 2020 in terms of how to manage severely ill patients in hospitals/ICUs but no treatment has yet been shown entirely effective. However, the good news is that what therapeutic options currently exists (potentially as combination treatments optimally given at varying stages of the disease sequelae) and the ramped-up healthcare capacities and personal protective equipment (PPEs) as well as the acute ‘exposure risk reduction’ focus on nursing homes for the aged populations, have resulted in steep declines in ICU use, need for aggressive mechanical ventilations, and severe illness or death. Since much is still unknown about the virus and given the limited therapeutic options and the ongoing quest for an effective vaccine to drive immunity, the focus has been on population mitigation strategies to reduce the risk of transmission to high-risk subpopulations. 

Global nations have experienced lockdowns and mitigation strategies such as social distancing that sought to reduce the contacts we may have and as such, work to constrain the COVID-19 pandemic.1 Evidence also suggests that UV light, temperature, humidity and pressure may also confer reduced risk of transmission and could be important in the mitigation efforts.2  At the same time, after six to seven months of spread and infection suppression strategies, the epidemic’s course is seemingly changing and leaving us to speculate on what is contributing to what appears to be a flattening and decline in incident active cases as well as less severe cases. Is it the mitigation alone that is bending the epidemic curve or is there some form of population immunity that is playing a beneficial role? Are there emerging SARS-CoV-2 mutations contributing to less virulence and pathogenicity? 

Recent research suggests that individual variation in susceptibility or exposure to SARS-CoV-2 lowers the herd immunity threshold (pre-print publication, not yet peer-reviewed).3 This suggests that persons in a population who are more susceptible or are more exposed, will tend to be infected much earlier, resulting in a depletion of the susceptible subpopulation of those who are at greater risk of infection. This type of selective depletion of susceptible persons can cause an increased slowing in incidence, leading researchers to argue that the susceptible numbers then become low enough to prevent epidemic growth and the herd immunity threshold (HIT) is arrived at.3 If so, this can have a significant impact on herd immunity considerations and vaccine design and development.

So why would some people get infected or severely ill and others do not? For example, why would children be less at risk of infection, or transmit less infection, as well as suffer less severe illness or death from COVID? 4-8 Evidence does seem to suggests that children are at very low risk of severe illness or death if infected (essentially near zero risk), but importantly, there is very limited spread to other children, or to adults, or even into the home. It appears that children typically get infected from home clusters, while recognizing that the risk of infection (and severity of illness) will increase with age. As an example, a recent review of 31 studies found that children are not a major source of transmission of COVID-19 and that transmission could be traced directly to the community or home settings with adults.8 Can it also be that children are unable to acquire the infection in the first place and as such, unable to spread it readily? Is this why they are not at higher risk? Or is there some form of prior immunity? Some tantalizing novel evidence seems to suggest that expression of the ACE2 receptor enzyme and TMPRSS2 serine protease enzyme (enzymes needed to bind to the virus’s surface glycoprotein S (spike) as part of invasion human host cells) in the nasal and bronchial airways is significantly lower in the upper and lower airways (nasal and bronchial) of children.9,10  Could this explain the low risk in children? This is very appealing and warrants urgent study and as we study this further, we also must consider that the pathway to infection was interrupted in April/May 2020 due to nationwide (and global) school closures and with re-openings, we will be better able to assess the impact on transmission dynamics. 

Adding to this speculation, provocative and hypothetical evidence relating to our human immune system’s memory is also accumulating, and appears to shed some more light on why some become infected with SARS-CoV-2 COVID virus (or develop severe illness) and others do not. While putative and not yet definitive and while we know little about pre-existing immune memory’s role in recognizing SARS-CoV-2 virus (and protecting against it), the nascent evidence seems to indicate that prior exposure to ‘old’ coronaviruses (e.g. exposure to common-cold coronavirus), may indeed influence population immunity against the SARS-CoV-2 COVID virus. Our hypothesis is that perhaps a prior exposure or multiple rounds of exposures to one (or several) coronavirus(s) could potentially confer at least partial ‘acquired’ immunity to another (or all). This no doubt warrants further study but indeed is a very intriguing possibility. 

 In this regard, researchers have been taking a closer look at memory T-cells that are part of the immune system and which recognize other viruses and common-cold coronaviruses.11-19 Preliminary evidence (Table 1) suggests that these memory T-cells (potentially in some adults and children) can also cross-recognize or ‘cross-react’ with fragments of SARS-CoV-2 COVID virus in terms of specific molecular structures.15-17, 18,19 This is very encouraging and exciting for it suggests a recognition of COVID virus structures the T-cells had never encountered before. Persons never infected with SARS-CoV-2 possessing these cellular defenses can have profound implications for a vaccine search as it may uncover that T-cell immunity not only recognizes the SARS-CoV-2 spike protein, but potentially other sites on the virus. Understanding this role of pre-existing SARS-CoV-2 cross-reactive T-cells can impact the dynamics of spread in the pandemic, and also help us in vaccine research and in tailoring and more acutely gearing epidemic and pandemic control strategies. 

T-cell immunity (adaptive immunity) operates a bit differently within the immune response than antibodies (adaptive immunity) which we are more familiar with, the latter latching onto and neutralizing viruses and other invading substances. In the case of SARS-CoV-2 infection, antibodies latch onto the SARS-CoV-2 spike protein and neutralizes it, working to prevent the virus from entering host cells. At the same time, researchers suggest that antibodies offer only short-term immunity against reinfection from SARS-CoV-2 virus, based on existing findings.11   If this is so, then what is the role of memory T-cells? How can it help? Is it a helpful role or is it toxic? Is it of no significance in terms of SARS-CoV-2? 

T-cells function to attack invading pathogen like viruses, and plays an executive type immune system ‘enhancer’ role (synchronizing other immune systems molecules), also ramping up and driving immune B cells to manufacture antibodies as part of the overall defense (via helper T-cells). Killer T-cells on the other hand work to seek out, target, and destroy cells that are infected. Memory T-cells remain following the initial infection and are thus primed and ready for subsequent exposures, and this may be what is underpinning the emerging evidence of cross-reactivity and interest in memory T-cells’ ability to cross-recognize other ‘prior’ coronaviruses, in so doing conferring protection across a range of coronaviruses. There are indications that this occurs for influenza A with broad CD8+ and CD4 T cell cross-reactivity of distinct influenza A strains in humans,12,13 as well as for dengue and Zika viruses.14   

The focus in this report has been on persons who have not been exposed to SARS-CoV-2 virus but have memory T-cells from prior common-colds which show reactivity to the SARS-CoV-2 virus. How do the memory T-cells react? What does the emerging T-cell cross-reactivity evidence show? The emerging findings are very interesting and positive15-19 (Table 1).  

Table 1: Evidence of T-cell cross-reactivity between SARS-CoV-2 and prior corona viruses

Author surname, year, reference #Study titleStudy detail and findings Evidence of some level of cross-reactivity immunity?
Weiskopf, 2020, 15Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndromePatients (n=20) were between 49 to 72 years old (average 58.9 ± 7.2 years) (4 female, 6 male). Healthy controls were between 30 and 66 years old (average 43 ± 13.6 years, not statistically different from the patient group) and of mixed gender (4 female, 4 male, no data available for 2 donors).  All patients were positive for SARS-CoV-2 via RT-PCR and ventilated during their stay at the ICU. In ten (10) COVID-19 patients who were admitted to ICU with moderate to severe ARDS (with the duration of self-reported illness varying between 5 to 14 days prior inclusion), researchers detected SARS-CoV-2 specific CD4+ T-cells in 10 of 10 patients and CD8+ T-cells in 8 of 10 patients.15 At the same time, they detected SARS-CoV-2 reactive T-cells in 2 of 10 age-matched controls who had no prior exposure to SARS-CoV-2, leaving them to conclude that there is cross-reactivity based on prior infection with common-cold coronaviruses. Researchers report that the greatest T-cell responses were against the spike surface glycoprotein of the SARS-CoV-2 complex and the T-cells mainly produced effector and Th1, Th2, and Th17 cytokines. Yes
Grifoni, 2020, 16Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed IndividualsPatients (n=40), range of age in exposed group was 20–64 (median = 44, IQR = 9) and in the unexposed, 20–66 (median = 31, IQR = 21); 45% of exposed were males versus 35% males in the unexposed group. Researchers looked at 40 patients,16  20 which were exposed SARS-CoV-2 patients and 20 were unexposed to the SARS-CoV-2 virus. Researchers measured SARS-CoV-2-specific CD4+ and CD8+ T-cells responses in COVID-19 cases using multiple experimental approaches e.g. HLA class I and II predicted peptide ‘mega-pools’. Researchers reported that circulating SARS-CoV-2-specific CD8+ and CD4+ T-cells were uncovered in approximately 70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T-cell responses to spikes were very strong and were associated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M spike, and N proteins accounted for 11%–27% of the total CD4+ response. They reported that for the CD8+ T- cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. They also reported SARS-CoV-2-reactive CD4+ T cells in approximately 40-60% of persons that were unexposed to SARS-CoV-2, suggestive of cross-reactive T-cell recognition between circulating common-cold coronaviruses e.g. HCoV-OC43 and HCoV-229E, to varying degrees and SARS-CoV-2. Researchers reported that 6 different unexposed donors with IgG against common-cold coronaviruses had SARS-CoV-2-reactive CD4+ T cells, leading them to conclude that cross-reactivity may be common. Yes
Braun, 2020, 17Presence of SARS-CoV-2-reactive T cells in COVID-19 patients and healthy donorsPatients (n=18 healthy donors, SARS-CoV-2 unexposed), 13 males (72%), age range 21-81 years. Researchers report on direct detection and characterization of SARS-CoV-2 spike glycoprotein (S)-reactive CD4+ T cells in peripheral blood, finding the presence of S-reactive CD4+ T cells in 83% of COVID-19 patients, as well as in 35% of SARS-CoV-2 seronegative healthy donors (SARS-CoV-2 naïve);  researchers detected SARS-CoV-2 S-reactive CD4+ T cells in 83% of patients with COVID-19 but also in 35% of HD. S-reactive CD4+ T cells in HD reacted primarily to C-terminal S epitopes, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared to N-terminal epitopes. S-reactive T cell lines generated from SARS-CoV-2-naive HD responded similarly to C-terminal S of human endemic coronaviruses 229E and OC43 and SARS-CoV-2, demonstrating the presence of S-cross-reactive T cells, probably generated during past encounters with endemic coronaviruses. Yes
Le Bert, 2020, 18SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controlsPatients (n=96, COVID-19 recovered n=36, SARS recovered, and SARS-CoV 1 and 2 unexposed n=37), median age 42 (27-78) COVID-19 exposed, 49 (21-67) SARS recovered, and 39 (28-63) SARS-CoV 1 and 2 unexposed; males 57.2% (72% COVID-19, 26% SARS recovered, and 62% in SARS-CoV 1 and 2 unexposed.  Researchers studied T cell responses against the structural (nucleo-capsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease. SARS-CoV-2-specific T- cells in uninfected healthy donors (n=37) tended to target NSP7 and NSP13 as well as the N protein. Researchers detected SARS-CoV-2-specific IFNγ responses in 19 out of 37 unexposed donors (51%). They report that while NSP peptides stimulated a dominant response in only 1 out of 59 individuals (1.7%) who had resolved COVID-19 or SARS, the peptides triggered dominant reactivity in 9 out of 19 unexposed donors (47%) with SARS-CoV-2-reactive cells; moreover, the SARS-CoV-2-reactive cells from unexposed donors had the capacity to expand after stimulation with SARS-CoV-2-specific peptides. Yes
Mateus, 2020, 19Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humansReactivity was determined after 17 days of in vitro stimulation of unexposed donor Peripheral blood mononuclear cells (PBMCs) (n=18) with one pool of peptides spanning the entire sequence of the spike protein (CD4-S), or a non-spike mega-pool (CD4-R) of predicted epitopes from the non-spike regions of the SARS-CoV-2 genome.  Using human blood samples derived before the SARS-CoV-2 virus, researchers mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. Researchers demonstrate a range of pre-existing memory CD4+ T-cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. They concluded that T-cell memory to common-cold coronaviruses could possibly underlie at least some of the extensive heterogeneity observed in COVID-19 disease.Yes


Memory T-cells prompted by previous pathogens can shape predisposition to, and the clinical severity of subsequent infections. Our interest was the impact of prior exposure to common-cold coronaviruses such as HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, and what this does to the immune response (T-cell) to SARS-CoV-2. Human coronaviruses represent approximately 20% of common-cold upper respiratory tract infections and are global and omnipresent, operating with a winter seasonality.20 Specifically, we wanted to summarize the preliminary evidence on pre-existing cross-reactive T-cell memory as it relates to SARS-CoV-2 in unexposed persons. We found that in several antigen-specific T-cell studies using varying patient cohorts and conducted in various nations e.g. USA, Germany, Singapore, Netherlands, and the UK etc.), approximately 20 to 50% of persons who had never been exposed to SARS-CoV-2 had appreciable T-cell recognition and reactivity that was trained onto peptides that corresponded to or paralleled SARS-CoV-2 sequences (principally facilitated by CD4+ T-cells). The limitations of these studies included small sample sizes, in some instances a focus on non-hospitalized patients, and limited details on common-cold history. 

What can we conclude from these preliminary cross-reactivity findings? Taken together, these results are indeed exploratory and requires further validation but provides for a very intriguing hypothesis for it shows that persons who are unexposed to SARS-CoV-2 do produce memory T-cells that show some reactivity to both SARS-CoV-2 and various common-cold coronaviruses. The case is indeed building for a possible cross-reactive role in COVID-19 in terms of SARS-CoV-2 and prior common-cold coronaviruses. Larger scale, trustworthy, high-quality, prospective cohort T-cell studies are required to clarify these findings on pre-existing SARS-CoV-2 cross-reactive T cells. These ‘immune memory’ findings while still preliminary, may account for some level of COVID-19 immunity beside antibodies and potentially explain why some people have no illness or milder illness and do not go on to severe illness or death from COVID-19 relative to others. This may shed light onto the limited COVID-19 illness in young children whose tendency to contract routine colds may actually be conferring some protection. We conclude that this is speculative and preliminary at this time given the developing evidence. There is a need for additional urgent study on what exactly is the role of T-cells and prior common-cold coronavirus exposure, as part of the larger immune system response, in fighting back at COVID-19. 


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