Asymptomatic Transmission: The Achilles’ Heel 1


Research from a Washington State skilled nursing facility confirms over half did not show symptoms but are infecting others with SARS-CoV-2

In early March, this report in JAMA (Journal of the American Medical Association) was the first outside-of-China, peer-reviewed publication that documents asymptomatic spread.

In brief: an otherwise healthy Shanghai businesswoman visited Germany for company meetings from 19 to 22 January, and during her flight back she developed symptoms of COVID-19 disease; she tested positive for SARS-CoV-2 on 26 January. On 24 January, a few days after his business meeting with the Shanghai visitor, a 33-year old developed a sore throat, chills and body aches and a high fever (39.1C); on 27 January he returned to work.

Thanks to careful contact tracing, on the 28 January three additional employees test positive for SARS-CoV-2; at the time of publication (5 March) none of the affected individuals developed severe COVID-19 disease.

Washington State nursing home study

Now a NEJM (New England Journal of Medicine) study comes out with additional details on the asymptomatic spread that I wrote about two weeks ago (13 April) here. Titled “Presymptomatic SARS-CoV2 Infections and Transmission in a Skilled Nursing Facility“, the article details the methods of testing and prevalence among the 76 residents of a facility who were serially tested, both for rRT-PCR molecular testing as well as live virus testing and even Oxford Nanopore sequencing.

63% of the 76 residents (48/76) were tested positive, and of these 48 positives by rRT-PCR, a full 56% of them (27/48) did not show any symptoms. However, 24 of the 27 developed symptoms within a median of four days, and the Ct values indicate all groups (symptomatic, atypical symptomatic, presymptomatic and asymptomatic) all had similarly high viral loads.

Of the 24 individuals who were presymptomatic, 71% (17/24) had viable virus via cell culture, a full 1 to 6 days before onset of symptoms.

The seriousness of this outbreak in a nursing care facility setting cannot be overstated: of the 57 original positive patients (the study followed up on 48 of them in the statistics above), 26% of them died (15/57).

This is not SARS or MERS

SARS-CoV (the original Severe Acute Respiratory Syndrome of 2003) affected 8,096 and killed 774 over a course of eight months. In five months, SARS-CoV-2 affects over 2.8 million and killed over 200,000 over a course as of this writing (25 April 2020). SARS affected the lower lung, and spread once symptoms appeared (high fever) allowing public screening. SARS2 affects both lower and upper lung, and has a high asymptomatic spread, in this case over 50%.

Despite social distancing, PPE measures and limitation of visitors, the current situation in nursing homes is dire, and getting worse. One estimate is that more than 10% of the nursing care facilities (>1300 facilities) have infectious spread.

A call for widespread molecular testing and mask usage

In an editorial, JAMA calls asymptomatic transmission the ‘Achilles’ Heel of current strategies to control COVID-19‘, and recommends testing everyone in skilled nursing facilities, and then expanding to other situations, such as prisons, jails, mental health facilities and homeless shelters.

Importantly they also conclude “these factors also support the case for the general public to use face masks when in crowded outdoor or indoor spaces.”

Outdoors is safe, indoors not so much

Evidence is accumulating that being outside is very safe, and that indoor transmission is a problem.

One study from China (disclaimer: it is a preprint and thus not peer-reviewed) looked at 1,245 cases of COVID-19 disease in China, and classified them as ‘clusters’ and ‘outbreaks’ to divide the individuals into groups.

Their findings (the preprint paper can be found here) was of 318 outbreaks, only one was outdoors, involving two cases (i.e. two individuals infected with SARS-CoV-2). The other striking conclusion was all outbreaks of three or more cases were in indoor environments; the authors conclude:

The transmission of respiratory infections such as SARS-CoV-2 from the infected to the susceptible is an indoor phenomenon.

From Qiu et al Preprint “Indoor transmission of SARS-CoV-2”

In another interesting analysis from Guangzhou China (N.B. an area relatively unaffected by SARS-CoV-2 infection), this report in the CDC Journal of Emerging and Infectious Disease demonstrated 10 people from three families being infected by a single individual after 53 and 73 minutes of time. The single individual was asymptomatic when visiting the restaurant, developing symptoms later that afternoon, and had just arrived in Guangzhou from Wuhan.

A1 = the index patient, A / B / C are the different families sitting at different tables. Figure from J Emerg Inf Dis July 2020.

The new normal

While better diagnostics are rapidly scaling up (nice to see additional serology tests from Ortho, Chembio and Mount Sinai, for the full list see the FDA EUA Diagnostics list here), there are no clearly effective treatments on the horizon, although over a hundred clinical trials are still underway. You may remember the saying, there is no cure for the common cold; and it is four different coronaviruses that are endemic in the human population.

And as far as vaccine goes, there is plenty of reason for skepticism, however work is forging ahead. A fourth clinical trial started in the UK this past week, this remarkable feat went from DNA sequence to cGMP vaccine in only 65 days. (Here’s a twitter thread giving credit to the Wellcome Trust team, by the head of chromosome dynamics of all things.) For the record, the first clinical trial for vaccines is in China from a company called CanSino, and Moderna Therapeutics and the NIH have started the second. The third is from a US company Inovio, that started their Phase I trial earlier in April. These Phase I trials are primarily for safety and take months to evaluate; next up is to test efficacy in Phases II and III. This effort is going to take many, many months of a lot of hard work.

The new normal at the end of our current lock-down status given the evidence of abundant asymptomatic spread is a large emphasis on the nursing home and other institutional environments where widespread testing is urgently needed. For the rest of us, we can expect mandatory mask-wearing, common-sense distancing especially indoors, and a sensitivity to the vulnerable people we may have regular contact with.


About Dale Yuzuki

A sales and marketing professional in the life sciences research-tools area, Dale currently is employed by Sysmex-Inostics USA as the Director of Marketing. He will help Sysmex-Inostics build out their liquid biopsy franchise (OncoBEAM and Plasma SafeSEQ) with market planning, positioning and branding as well as thought leadership, opinion-leader management, and sensing of market trends. He also represents Sysmex at tradeshows and other events. For additional biographical information, please see my LinkedIn profile here: http://www.linkedin.com/in/daleyuzuki and also find me on Twitter @DaleYuzuki.

Leave a comment

Your email address will not be published. Required fields are marked *

One thought on “Asymptomatic Transmission: The Achilles’ Heel

  • AMac78

    Journalist Jonathan Kay assembled COVID-19 Superspreader Events in 28 Countries: Critical Patterns and Lessons on 4/23/20; his list and analysis of common factors is consistent with this post.

    Boris Johnson famously did a volte-face on March 16th, abandoning plans to develop herd immunity in the UK in favor of the “flatten the curve” approach that most of the developed world had adopted. The clincher was the prediction by Neil Ferguson’s Covid-19 Response Team at Imperial College — BoJo’s strategy would have led to 250,000 deaths.

    But it has since turned out that societies around the world are unwittingly and unwillingly undertaking that approach. Not out of choice, and not because Ferguson’s 250,000 estimate erred on the high side. But because the transmission of the virus by asymptomatics means that lockdowns are only partly effective. The Kinsa thermometer data show that social distancing slows transmission (lowers R), but only to a point.

    Fortunately, SARS-CoV-2 is not as bad (in most geographies… for most people…) as it seemed it would be. Unfortunately, its contagiousness is much harder to corral. Now that PCR and serology tests are (belatedly) becoming widely available, perhaps it’s time for a second look at Johnson’s original idea.