9 April 2020 Blog Post: COVID-19 Update

In what has become a shelter-in-place quarantine ritual, my family gathers around CNN ostensibly to follow Chris Cuomo’s progress (who is looking better day by day) and as a group repeat back “together, as ever, as one” at the end of his show. After Chris’ show comes Don Lemon CNN and as we watched Don’s show, a segment on New Zealand cited a truly astonishing statistic which I had not heard before. Out of 1239 cases in New Zealand there has been only 1 death. This is a mortality rate of: 0.08% (worldwide the mortality rate is 5.9%). Now the report itself largely focused on mitigation efforts including physical distancing (which I will argue below may be why there is only one death) but I found this statistic to be compelling and worth further discussion.

To highlight just how astonishing New Zealand’s mortality rate has been, let’s contextualize it. Rather than percentages, I’m going to use COVID-19 deaths per million population:
 
San Marino: 1002 deaths per million population
Spain: 326
Andorra: 324
Italy: 302
Belgium: 218
France: 167
USA: 48
Australia: 2
New Zealand: 0.2 deaths per million population
 
Well wait a second I can hear my biostatistical colleagues already muttering about ‘ascertainment bias.’ And, in fact, the lack of widespread, systematic testing in most countries is the main source of discrepancies in death rates internationally. This is because, to get an accurate figure across a population, it is necessary to test not just symptomatic cases, but asymptomatic people too. But, OK, lets see if that is true by looking at testing rates per million population.
 
San Marino: 21,278 tests per million population
Spain: 7,593
Andorra: 21,653
Italy: 14,114
Belgium: 7,269
France: 3,436
USA: 6,864
Australia: 12,946
New Zealand: 10,610 tests per million population
 
So looking at these, I think we would all agree that New Zealand is not testing at a disproportionately greater rate than other countries (what’s going on in France by the way?). In fact San Marino and Andorra who have two of the three highest mortality rates have tested their population in far greater frequency than other countries.
 
More rumbling from the statisticians – but what about the problem of hidden deaths from Covid-19: those people who die from the disease who are never tested? This comes into play when health services are overwhelmed and even those patients who have severe symptoms of the virus are not taken into the hospital to be tested and treated, simply because there isn’t capacity.
 
However, I would argue that the issue of ‘hidden deaths’ would artificially lower the mortality rates in countries with a high caseload (Italy, Spain, and epicenters in the US). With 1239 cases in New Zealand, I would think that they could identify deaths due to COVID-19 accurately as well.
 
So how does New Zealand end up with a mortality rate that is 10 times lower than Australia and 5000 times lower than San Marino? (5000 times lower – just think that for each death in New Zealand, San Marino grapples with 5000).
 
There are a number of other predictors that may account for an excess in mortality rate country by country. Not to become overly granular, but many of these have been extensively covered. Age being the most consistent risk predictor as well as the overall health of the population – particularly given that people who have underlying health problems are more vulnerable
 
The age of those acquiring the infection in New Zealand may indeed be part of the explanation for their low mortality rate. People aged 20 to 29 make up the largest group of people in New Zealand with the virus (300 of the 1239 cases; 24.2%). The age group with the second-highest number of cases is those aged 50 to 59 (206 of 1239 cases; 16.6%). But I don’t think that alone would account for such an astonishing low mortality rate.
 
So what do I think? I thought you’d never ask. We are beginning to accumulate evidence that severity of disease may also be related to dose of inoculum. In English? What I mean is that a COVID-19 carrier who transmits a low viral load to their contacts could then lead to lower severity of disease and a lower likelihood of mortality. I believe that COVID-19 cases in New Zealand transmit fewer infectious particles to their susceptible contacts (by a combination of physical distancing measures and low population density), leading to this low death rate.
 
New Zealand saw its first confirmed case on February 28th. On March 19th, the country fully closed its borders to international visitors. Prime Minister Ardern pushed a “stay home” message and implemented a strong social distancing order as of March 23. Further, the population density in New Zealand is very low – 46 people per square mile.
 
Dr. Raoult, a researcher in Marseille, France, has suggested that after infection by COVID-19, “a sort of race decides the course of the events” (see figure below). Either a immune response rapidly clears the infection without any (or mild) disease (best-case-scenario). Or, the virus causes a state of immunosuppression that “debilitates and sometimes overwhelms the host’s defense.”
 
In this context, the initial dose of the virus leading to infection may have a decisive impact on all subsequent events. It is overly simplistic to believe that population density alone will influence disease severity, but as a point of reference there are 26,403 people per square mile in New York City – 573 times that of New Zealand. The COVID-19 mortality rate of COVID-19 in NYC is currently 1800 times that of New Zealand.
 
Remember also early in the epidemic that mortality rates among younger healthcare workers in Wuhan City were quite high. Could it be that they were exposed to a high particulate dose of virus as they, say, intubated a patient? Perhaps they saw multiple patients in a day and thus exposed to a high cumulative dose of COVID-19? In either event, continued physical distancing at the population level as well as the use of masks (even if only partially effective), would further decrease the number of transmitted viral particles with each cough or sneeze. Perhaps this leads to milder disease if one has the bad luck to breathe in one of these infectious particles.
 
That said, current evidence suggests that the most solid predictors of disease severity after infection with SARS-COV-2 are the patient’s age and the concurrence of specific co-morbidities. There is no proof that infection with a low dose of contagion would result in a milder clinical course of immunocompetent newly infected person. But it is possible. Stay tuned…
 
(Source: Raoult, D et al. Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses. Cell Stress. 2020 Mar 2).

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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