COVID19: Some Quick Q&A Part V

by Raywat Deonandan, PhD
Epidemiologist & Associate Professor
University of Ottawa
(I add my credentials to these COVID-19 blog posts in case they get shared. I want readers to know that my opinion is supposedly an educated and informed one)

This is one of those filler blog posts, since once more time has got away from me. This is where I reproduce some of the written comments I’ve given to journalists in the past little while.

Let’s begin.

(1) A journalist asked:  “I know there are big logistical challenges with testing (esp. with kids and PCR/nasopharyngeal swab testing, and delay in results) but I’d be grateful for your thoughts on regular or random testing of kids and teachers. Some US school districts requiring temperature checks before kids get on buses or inside school but again, huge limitations and many kids never develop fever. But how will it be possible for schools to tell quickly who has the virus and whether it’s circulating? Is screening by parents really sufficient for a “safe” return to school?”

My response:

Testing has always been, and continues to be, our best weapon against this disease until an effective vaccine is in our hands.

Yes, there are logistic challenges to testing —getting enough tests, delays in getting results, difficulties in performing them, etc. But it strikes me that more information is always a good thing.

An additional caveat is that if one is in the early stages of infection, a negative test might not indicate that the person is indeed “in the clear”. There just might not have been enough time for the person to develop enough viral load to be detectable. So a negative result doesn’t necessarily put the patient in the clear.

However, if testing is to be deployed at regular intervals, then that will help fill the holes in the net caused by too-early testing.

One potential game changer would be rapid on-site tests, or even easier to conduct lab tests, like saliva tests. Imagine kids spitting into a cup every other day, and public health getting a rolling cross-section of infection status for the entire population of students on a regular basis. That might be sufficient to detect almost all asymptomatic cases and allow us to quarantine them before they case outbreaks.

So yes, I say that if we have the capacity to do so, then testing should be a big part of our strategy to keep schools safe.

 

(2) I was on a Toronto radio show talking about why a COVID vaccine might not be a “silver bullet.” I took the time to write down some of my initial thoughts prior to the interview:

a.  No vaccine is perfectly effective. If it doesn’t work for 1% of the population, and all Canadians get it, that means about 300K still won’t be protected.

b.  There will be those who cannot accept or tolerate a vaccine for any number of medical reasons. These people might also be at great risk of serious COVID complications.

c.  If the vaccine works, it might offer protection for a few months or a few years; we don’t know yet. We might need frequent booster shots.

d.  It’s still unknown whether the leading vaccine will prevent infection or prevent an infection from progressing to serious disease. If the latter, then even with high uptake, a substantial portion of people will still become ill and possibly pass it on to those who are still susceptible to serious illness.

e.  It is unlikely that we will have safety data for children any time soon; so I doubt vaccine will be offered to children in the near future.

f.  A very large proportion of Canadians will refuse to accept the vaccine, requiring public health measures to remain in place to protect those who need protection, but who cannot tolerate a vaccine.

g.  We will have a very hard time as a nation acquiring sufficient doses for most people. If we require booster shots, the task becomes difficult indeed. Distribution and storage will also be a national headache.

h.  Even with mass production and distribution, I don’t see most Canadians getting access until midway through the first quarter of 2021

i.  Once inoculated, it may take several weeks to generate enough antibodies and/or T-cells to garner true immunity, during which time you are still vulnerable

 

(3) A Journalist asked the following questions about Toronto COVID stats. 

a. Is the GTA faring well right now, considering that we seem to be trending behind the rest of the province in cases per day?

The GTA is doing well, all things considered. There are a variety of metrics to consider. One of of them is the reproduction number (R(t)), which is presently 0.66 in Toronto… an excellent number.

b.  When compared to the rest of Canada, is Ontario in much worse shape? Or, are we trending in a similar direction?

We are trending in a similar direction. Really, the epidemic is a feature of Alberta, BC, Quebec and Ontario. While there are some newsworthy outbreaks in Saskatchewan, for example, those do not drive our national numbers. Among the big 4 provinces, Ontario and BC are the better current performers, in my opinion.

c. How long can we expect before we start to see the effect of Stage 3 on the GTA?

The mantra is always 2 weeks. This is because this is how long it typically takes for symptoms to start showing. And when symptoms start, people will get tested; then it takes a couple of days for those test results to make it into the data stream.

d.  Are we in any better shape in Toronto at this point? In my view, we’ve hit a bit of a lull, but I’m not expecting it to last. Do you think we’ve beat our first wave?

Tough question! I do believer that the first wave is largely over in Canada. It’s a qualitative judgement of whether to “call” the first wave over, when there are still new cases in the community. But I view it as if the number of new cases is low (under 50 or so for a large city) consistently for several days, then we have reached a low-end, and the only likely way up is the explosive growth of a next wave. So yes, we now are in a holding pattern, waiting to see if our efforts and vigilance are sufficient to prevent a second wave in the Fall.

 

(4) I was the guest speaker at a recent event called “Dave’s Digital Cafe”, which is a virtual symposium hosted by a consulting firm. It features a speaker followed by moderated group discussion, and is attended by some fairly well educated and senior members of industry. Anyway, here is the official summary of the discussion following the event I spoke at, posted here because I need to keep it somewhere:

1. What Will We Have Learned from this Pandemic? A year or two years from now, when we look back at this pandemic, we should ask ourselves what did we learn as a society?

Transparency is the best policy. Epidemiologists complain about how non-transparent the data and the process of decision-making has been. We don’t know what indicators the government uses to make decisions about opening up the economy.

2. What do we do to control this epidemic? Low-tech, nineteenth century techniques – staying at home and wearing masks – have been proven to be the most effective for rapid control of an epidemic. The anti-mask demonstrations are denying centuries-old experiences.

Twenty-first century technologies have advantages, among them new technologies to develop vaccines. The internet has facilitated conversations at safe, comfortable distances, which would not have been possible during SARS. The rate of exchange of information between scientists, experts and the public is unparalleled.

3. Animal husbandry might be innately incompatible with long-term human health. Almost every great pandemic of a respiratory nature originates as zoonosis – a disease which moves from animals to humans. This disease probably came from a pangolin and a bat. Our close association with animals is causing us to experience these endless pandemics. These pandemics are a threat to our global economy and our sustained way of being. We’re going to have to revisit our relationship with animals in terms of our agricultural industries.

4. Messaging is key. This has been a pandemic not just of disease, but of misinformation. The only playbook for how we communicate risk in emergencies has been thrown out the window. In this era, people are now dismissive and distrustful of authority and eager to embrace anti-authoritarian identity. Somehow in our culture, we’ve inculcated an anti-authoritarian, anti-expert, anti-education principle, so that is complicating the messaging.

5. Ideology is a big driver, especially in the United States. Whether you’re pro or anti-COVID science seems to be driven by whichever political stance you gravitate towards. Tribalism is so deeply ingrained and cannot be combated by information alone.

6. Chronic disease and infectious disease are entangled. Another way to look at this disease is to see it as a rapid acceleration of what is otherwise a slow-moving train wreck of chronic disease. When you look at who is more affected by this disease, especially in the U.S., it is largely minorities, those who are obese, have hypertension, diabetes, or are low-income.

7. Those kinds of people in correlated factors are more likely to have jobs in which you cannot socially distance, jobs in which you cannot take time off work, no health insurance, no vehicles so they have to take public transit, no opportunities for child care, live in a food desert – and so they are more likely to have these underlying health conditions. These layered effects from a long-term societal approach of disinterest is manifesting in the way of making them more vulnerable in the short-term. A disease like this takes a long-term timeline and compresses it into a couple of weeks, so people who are going to suffer over decades are dying now. So, chronic disease is now shortened.

8. We’re suffering the dividends of decades of poor investment in education. Somehow, we’ve failed at making science education a core aspect of our curriculum.

9. The single biggest barrier to combating this disease is the public. The public must be complicit and compliant in the effort to stop this transmission. Their inability to be partners is why we fail. A big part of that is the failure of compelled science education over the last few decades.

10. How do we move forward? A greater focus on science education, a greater focus on disentangling the ideological quagmire in which we find ourselves, and a greater focus on data transparency and empowering people to take control of their public health.

11. In terms of what have we learned, what is the broad public going to take away from this? The polling data suggests that most Canadians are behind the public health narrative and willing to go along with what experts say. There is still a minority that is more iconoclastic. Going forward, Canadians are a bit more invested in infrastructure. There is a lot more desire to repatriate the manufacturing capacity, especially when it comes to masks, syringes, more biotech-focused endeavours, and a desire to better inculcate educational sectors. In the short-term, there seems to be a desire to be better.

12. What can we do differently to aim public messaging to reach young people? Current public health messaging has a problem as it is one-size-fits-all. What does ‘young person’ mean? We tailor our message to a specific demographic. It’s not just one message, but many. We also use the old-fashioned technique of a ‘carrot and a stick’. The ‘carrot’ is to inspire people and make young people realize there is heroism in protecting others.
They might resonate with the message, if you eschew your desire and right to go and socialize en masse, you might save a life.

13. Can we encourage young people to embrace an ethic of delayed gratification? If you can wait a few weeks or months to socialize, then the payoff will be everything will be open, and you can do whatever you want.

14. Is there cooperation or competition in vaccine development? Is there any use of artificial intelligence and data sharing? It is thought there is more competition than cooperation. There are certain trade secrets not being shared, but there is a push for greater openness because this should be a species-level endeavor, though there are IP constraints.

15. A year from now, we might ask, ‘Should there have been a better international framework for rapidity of vaccine development, balancing the need for IP protection to encourage and incentivize private companies to take these risks, while at the same time encouraging data sharing to accelerate the process?” Altruism alone often does not compel the private sector, who is naturally profit-motivated.

16. What is the zoonosis of this virus, what do we know about it, and where is it going? Even from early on, it was affecting cat and cat-like animals. Viruses tend to affect multiple species. The question is will they learn and steal DNA or RNA from these species that accelerates their evolution such that they can be more infectious. That hasn’t happened yet.

17. The ability for the virus to jump from a bat to a pangolin to a human is a sign of antigenic shift, which is when it makes a sudden mutation and allows it to gain the ability to infect humans from animal populations. It doesn’t appear to be shifting again to other species yet, but it might. In general, they shift in such a way that they become less lethal.

18. We should never allow universities to teach entirely STEM classes. Instead, STEAM courses should be prevalent. It is important that we get back to teaching people not just to have a good job, but to have a good life and be a good citizen.
Everyone has become so fragile; they cannot tolerate views that don’t fit their own.

19. There are two layers of cooperation. One is the scientific layer in fighting the disease. The level of cooperation worldwide is phenomenal and there is a huge amount of data being exchanged in real-time about COVID-19. That is cooperation we need to nurture and build upon. It is the most likely path to finding a vaccine.

20. The other level of cooperation, which is troublesome because it is basically breaking down, is policy-driven cooperation and government-to-government cooperation, notably in the economic and geopolitical space. There is every reason to be concerned about the current picture. The current international system is failing us, and we knew it was happening before the pandemic. There is a critical urgency to reset international institutions.

21. Pandemics, and natural disasters in general, have a way of revealing strengths and fragilities of the people.
It is easy to identify the fragilities in the United States – cracks in the political structure, distrust of authority, tribalistic nature of the population – all exacerbated by this crisis.

22. In Canada, we have this as well, but we have a more reassuring sense that people do seem to care about each other in a larger sense than they do down south. We need not just science education but arts education as well.

23. As we move this pandemic from its acute phase to its chronic phase, increasingly the role of humanities experts comes to bear. As a vaccine arrives, how do we have equitable distribution? How do we manage the expectations around it? If the goal of a challenge trial is to expose people to infection to test the efficacy of this vaccine, how does the ethics of this challenge trial unroll? This is where the arts and the humanities bring to bear their skill sets.

24. In moving from an acute infection to a chronic infection, the larger the number of ideologues who complain, the more difficult this is going to be to solve and this is going to pile up with other problems.

25. In terms of planning for the future, how much of our planning needs to include a plan to make Canadians healthy? There doesn’t seem to be any public health talk in terms of what you can do to reduce risk factors.

26. That is the challenge of managing public health in liberal democracies. Any effort we’ve made to encourage people to be healthy has been met with extreme resistance. This is the price we pay for maybe being a bit too lenient on the libertarian side of the democracy, of celebrating the right of the individual to be unwell. The price is, when a pandemic hits, we must all act to protect a fragile but large subset of the population. It’s a question that is a social science, civil liberties, civics-minded question.

27. Where is the line between authoritarian reach of public health to compel you and encourage you to be healthy, versus the line of the individual citizen in a liberal democracy to celebrate the right to be unwell and therefore to be vulnerable.
People smoke too much, drink too much, and don’t exercise. If you solve those three issues, you can begin to reduce expenditures in health care and focus much more on public health.

28. As the pressures are focused on provincial governments to increase health care expenditures for long-term care and revitalizing the system once the weaknesses are revealed, it’s going to be at the cost of a new generation. You’re going to have an inter-generational conflict in terms of where you make investments. These are going to be difficult challenges we are going to face.

29. It’s up to high schools to make sure that graduates are good citizens and know about the world, their country, philosophy and literature. At universities you specialize in the field you wish to study.

30. The reason that international institutions are failing us is because the people who have graduated to positions of authority are poorly educated. This gradual moving away from quality education has been going on since the 1980s and 90s. The solution is going to be long-term as well.

31. We keep teaching things on the surface, as opposed to teaching people the components that make it work. The two greatest inventions the human species has produced are science and law. They’re similar and based on experience. As you get more experienced with the world, you have nuances that are added to it. Science and law are never fixed.

32. The most fundamental concept of law is the reasonable man. What would a reasonable person do in any situation?
The key to success is cooperation and caring for each other. All the technical gains we’ve made since then has made civilization possible, but none of that would have happened if we hadn’t figured out how to cooperate.

33. Cooperation is very difficult to get going with everyone. If people cared about each other and really wanted to save each other from the pandemic, the dicta of policies and the core values of basic governance would be much better. The ideals of being on your own isn’t the kind of future that is going to allow us to sustain ourselves.

 

(5) On July 31, I just lost my cool on a radio interview. The topic was mandatory masking in schools in Manitoba. Their officials refuse to mandate it because they claim: (1) there isn’t enough evidence that masks work; and (2) they are concerned that improper mask use might spread the disease.

No no no no no. Arrrgh. I wish some of my colleagues would get out of their clinical paradigm.

First, masks are not vectors for COVID transmission, neither is fidgeting with a mask or touching your face, if you’re NOT in a clinical environment or other high-prevalence environment. This is the way infectious disease doctors think, and it’s not appropriate for population health dynamics in the greater community.

Second, what level of evidence will be sufficient to compel action? Again, so many clinicians, like those at WHO, are stuck in the “evidence based medicine” (EBM) way of thinking, where you don’t act until you’ve twenty high quality randomized clinical trials. This is not an EBM situation; it’s a public health emergency.

In a public health emergency, the threshold for action is lower than in an EBM scenario, especially when the risk-vs-reward metric is obvious. The risk of wearing a mask is negligible, as it does *not* contribute to infection. The potential reward, if it works, is that the disease is kept at bay in the community.

Can you sense my frustration?

 

(6) A journalist asked me to answer the following questions:

a. What sort of failures make up new surges of the virus? Especially in places once succeeding in containment?

I’m thinking of Hong Kong. Their surges seem to be due to outbreaks in bars, gyms, and beauty parlours. In other words, those aspects of the economy that encourage intimate gathering without much distancing seem to have triggered the resurgences.

b. Where did the U.S. go wrong? Does the tiered policy making – federal, state, local health regulations – play a part? Does travel within the country play a part?

Wow. Where to begin? The tiered policy making is not that different from Canada’s. And frankly, it might have saved some parts of the USA. The failure of strong science-based leadership of the federal government was buffered by more sane responses from some state governors.

The USA struggles with some almost intractable problems that were always going to make them a hotbed of cases. First, the heavy burden of chronic illnesses (obesity, diabetes, hypertension, etc) makes them vulnerable.

Second, the lack of health insurance for many is a factor preventing early and proper care. Insecure employment means that many people cannot work from home, take sick days at home, or physically distance while at work or at home.

Third, infrastructural issues played a role. Food deserts mean that many people are chronically poorly nourished. Poor urban transit compels crowding.

Fourth, decades of ignoring science education now manifests as susceptibility to misinformation.

All of the above are correlated with race and income, such that existing inequities in the USA are exacerbated by the diabolical forces of this disease.

Fifth, ideological divisions are now hard baked into the American system, causing tribal lines to be drawn between science-supporters and science-deniers. Thisis exacerbated by the aforementioned educational crisis.

Sixth is a duplicitous and, dare I say it, criminal central leadership stoked these divisions and did not prioritize a science-based response that put the reduction of human suffering above political posturing.

This manifested in such ways as early opening of the economy, slowness to adopt masks, refusal to enforce distancing, and either an encouragement or lack of dissuading of the COVID-denial messaging in some states.

I could go on, but you get the point.

c. Spain had one of the strictest lockdowns in Europe. Public health authorities say there was pressure to resume tourism, which nurtured a surge. Is it possible countries can balance resuming things like tourism with keeping cases low?

That is yet to be seen. It depends entirely on three factors: (1) initial case load; (2) the case loads in the tourism origin countries; and (3) the public heath measures taken once tourists arrive.

d. Australia was once one of the success stories in containment. It even had its remote location on its side. The government acknowledged errors in state-run quarantine policies for international travelers. But is that the failure? Or is it opening borders and travel, overall? Why?

Frankly, I feel it is too early for any amount of global tourism. The economic impacts are another matter, and economists can best comment on that. But from a public health standpoint, it is clear that new seeding events are often introduced by travellers. Repatriation and business travel is necessary. But tourism is a source of infection that is too great right now, in my mind, if the goal is a clean reopening of schools in the Fall.

e. Is opening travel and borders the biggest risk factor at this point in the pandemic?

It depends on the border. I would feel better accepting travellers from New Zealand or Singapore, for example. But the US border must remain closed. The threat of new seeding events from American travellers is too great right now.

f. What can Canada learn from some of this?

We can learn a lot:

(1) listen to scientists
(2) have a consistent public health approach across all provinces
(3) be prepared to close some sectors if the data suggests it: bars, gyms, luxury services
(4) beware of unnecessary international travel

My tired mantra is that right now 100% of our focus should be on safely opening schools in the Fall. Everything hinges on that: the mental health of our children, the ability of employees to go to work without having to compromise for child care, and the equitable treatment of different socioeconomic levels, some of whom cannot keep their kids at home.

The best way to keep schools safe is to drive the case load in the community as low as possible. And to that, we need to compromise on some aspects of the economy that threaten that possibility: travel, bars, entertainment, etc.

 

(7) Several people had asked me to comment on the new Detroit study showing a benefit to hydroxychloroquine. I posted a quick and dirty critical appraisal to Facebook, and might write a deeper analysis in a subsequent blog post. Here is the initial Facebook post:

The paper:

“Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19” by Arshad et al. International Journal of Infectious Diseases

Design:

This was a retrospective observational (cohort) study that evaluated the medical records for 2541 COVID19 patients in 6 hospitals in Detroit,

Their findings:

(1) Those treated with azithromycin (AZM) alone or a combination of hydroxychloroquine (HCQ) and AZM were slightly (though statistically significantly) less likely to die than those not treated with the drugs. (22.4% of those treated only with AZM died; 20.1% with a combination of AZM and HCQ died, compared to 26.4% of patients dying who were not treated with either medication.)

(2) They found no effect of steroids, which is at odds with other (better) studies (see the RECOVERY trial out of UK)

Authors’ Conclusions:

(1) HCQ with or without AZM reduces the risk of death in COVID patients

(2) They attribute their findings that differ from other studies to early treatment and dosing changes

My Issues:

(1) authors excluded patients who died in the first 24 hours after admission and another 10% of patients for whom final outcome data were unavailable (e.g., still hospitalized, left against medical advice, or transferred to another facility). Unsure how this biases results.

(2) The co-treatment with steroids is likely to reflect differences in disease severity. This could have biased results favourably toward HCQ/AZM. (More steroids given in the HCQ group (78.9%) and HCQ+AZM group (74.3%) compared to AZM alone (38.8%) and neither med group (35.7%)).

(3) Their regression analysis took into account only factors the authors chose and could not address residual confounding, which is the crux of the issue (see point (4) )

(4) This is an observational study. While I adore observational studies, there’s a reason they are not preferred when assessing the efficacy of drugs. Usually, we rely on only the best double blinded randomized clinical trials (RCTs).

Observational studies can find associations but suck at determining a causal link between exposure and outcome. There are many co-factors that can confound an analysis and make it difficult to assess whether any differences in mortality are actually related to the use of HCQ or AZM. This is why selection of the variables that go into the regression is so important.

Observational studies are rife with bias and are subject to alternative explanations for the observed results. For example, ~25% of patients had missing measures of disease severity and were excluded from the regression model. This can skew results tremendously.

In the gold standard design, the RCT, the known and unknown factors associated with mortality are evenly distributed between the comparison groups, which helps to reduce the chances of biases. This is why, while this study is suggestive, it is not better evidence than the RCTs which have already assessed HCQ+AZM efficacy.

My Conclusion:

Many of the other studies (better ones, RCTs) examined patients who were much sicker than those in this one. The unbalanced use of steroids could have biased the results toward an advantage for HCQ/AZM users. At best, these data support keeping HCQ in the treatment options, at least for early stage patients with relatively mild symptoms. At worst, it’s noise in the system that would need to be rectified with a better prospective study. Certainly not evidence that HCQ is a cure, though; far from it.

 

(8)  A journalist asked: “What’s the latest science about how infectious kids are when they return to school. I read they wouldn’t infect each other and adults under 10 years of age, but above 10, they’d be just as infectious as adults. Is that the case?”

My response:

“The science is still very unclear about the extent to which children catch and transmit COVID-19. The data you are referring to comes from a South Korean contact tracing study, which looked at 65,000 people. They essentially found that those aged 10-19 were just as likely to transmit the disease as were adults, but that those under 10 were about 72% less likely to transmit it.

However, I would take this data with great caution. For one thing, we also know that children under 10 are three times more likely to be asymptomatic, so often are not captured in the data as index cases. Children in general are under-sampled. And most studies only look at symptomatic cases, missing out on the asymptomatic ones, which are more likely to be children. In Epidemiology, we would call this asymptomatic nature a “confounder”, in that it might be creating a false association between being a child and not being a strong transmitter of disease.

I will add that in Ontario, we are seeing that the percent of tests that come back positive is roughly the same among adults as among children. This suggests that here, at least, children are just as likely to become infected.”

 

Whoa, that’s a lot of backlog!  And I have more…. but I will save those for a future post.  Hasta mas tarde mis amigos!

 

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