The Science of Masks 2: Asymptomatic and Presymptomatic Transmission
Time to start looking at what the intern hath wrought.
For those just joining us, this is one more part in a seemingly endless series of posts in which I discuss (rant about) the actual scientific literature about face masks while simultaneously watching reruns of Dharma & Greg, the last good romantic comedy before the entertainment industry went to hell.
[I’m not going to take this seriously if no one at the CDC will.]
In Part 1, we learned about Covid-19, SARS-CoV-2, and transmission of disease. In this post we move on to the web page that someone at the CDC told the intern to create to justify whatever their story was that day.
[Also, Episode 2: “And the In-Laws Meet”. The two sets of parents meet each other and hi-jinks ensue as everyone argues about the party to announce the marriage. Did I mention that the setup for the show is that the two main characters decide they are soulmates and get married the same day they meet? I may have forgotten to mention that detail.]
Reports on observed cases
Some of the references listed by the CDC are not experimental studies but rather reports on cases - observations made by doctors working with actual patients. It’s common practice for both doctors and medical researchers, when they observe something new or unusual, to sometimes send letters to medical journals describing what they see.
In this case the references are about viral load and potential viral transmission from people who aren’t exhibiting symptoms. The CDC doesn’t explain the reason for each reference but presumably these are included to emphasize the importance of masking even for people who don’t seem sick. These references, however, generally don’t discuss possible interventions (like masks).
This is the most boring part of the whole boring mess so I won’t be insulted if you skim through it very quickly. In fact, if you don’t skim through this part I’m going to start wondering if maybe you should get out of the house more.
1. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany (Rothe et al. 20201)
This is a letter to the editor of the New England Journal of Medicine. The authors are reporting SARS-CoV-2 (which they are calling 2019-nCoV) infection of several people in Germany after meetings in Munich with a Chinese business partner who resides in Shanghai, and who had no symptoms at the time of the meeting.
We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient.
The illness of the index patient (the original patient) was mild. However, the authors point out:
The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak.
They also make a statement about the severity of illness in the four people to whom the the virus was transmitted.
...all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes.
So this first article documents what the authors believe is transmission of SARS-CoV-2 from a person without symptoms, who later developed mild symptoms himself. The other four cases were also mild.
Nothing exciting here. Five people were slightly ill, and four of them may have gotten the illness from someone who didn’t look sick when they met him.
2. Viral Load in Upper Respiratory Specimens of Infected Patients (Zou et al. 20202)
Another letter to the New England Journal of Medicine (they must be the “belle of the ball” in the world of medicine, everybody writes to them), this describes the results of nasal and throat swabs of infected patients, some with symptoms (symptomatic) and some without (asymptomatic).
Based on the amount of virus found in the samples (which indicates the amount of virus in the patients, called their viral load) the authors conclude that it is possible for asymptomatic people to transmit the virus. They also state the shedding* pattern resembles influenza more than it resemble the original SARS coronavirus. The SARS outbreak was brief (2002-2004) so there are no randomized controlled trials on the use of NPI (non-pharmaceutical interventions) to mitigate SARS, but some trials have been done with influenza.
(*Shedding is the release of virus particles from the host. Flint et al., Principles of Virology 20153)
Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza and appears different from that seen in patients infected with SARS-CoV. The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients.
They conclude that more data is needed to learn how the disease is transmitted:
Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
Based on viral load and shedding asymptomatic people can potentially transmit the virus, although the shedding pattern is more similar to influenza than the original SARS-CoV virus.
So more data on asymptomatic shedding, nothing yet on masks. Yawn.
[Show update: Dharma and Greg have just dragged their mattress onto the roof to sleep. Apparently one sleeps on the roof in San Francisco - but only during a full moon. Of course it immediately starts to rain.
G: “Dharma, we’re not gonna sleep in the rain are we?”
D: “No silly, you don’t sleep in the rain. You make love in the rain.”
G: “Ah. What if there’s lightning?”
D: “You get to be on top!”
“We’re in this together but you get all the risk” was a joke in a 90s sitcom, but for the CDC’s vaccination program it seems to be official government policy. Sorry, that was a bit off-topic. We’ll save vaccines for another time.]
3. Asymptomatic cases in a family cluster with SARS-CoV-2 infection (Pan et al. 20204)
This reference is a correspondence (letter) to the journal The Lancet, describing a family of three people with positive test results for the virus, but only one of the three was symptomatic. This correspondence was published 19 February 2020, and the family being described were diagnosed in late January.
Importantly, asymptomatic patients (such as patients 2 and 3) might be unaware of their disease and therefore not isolate themselves or seek treatment, or they might be overlooked by health-care professionals and thus unknowingly transmit the virus to others.
So this letter warns that there are asymptomatic cases; in this case two out of the three patients had no symptoms. The authors believe it is likely that one family member was the source of the infection of the other two.
I am literally gripping my chair with excitement at this point. And by literally I mean figuratively.
4. Presumed Asymptomatic Carrier Transmission of COVID-19 (Bai et al. 20205)
Published in The Journal of the American Medical Association (JAMA), the authors of this study lay out their purpose clearly:
This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.
They explain the reason for publishing the study is because asymptomatic transmission had not yet been reported.
Person-to-person transmission has been demonstrated, to our knowledge, transmission of the novel coronavirus that causes coronavirus disease 2019 (COVID-19) from an asymptomatic carrier with normal chest computed tomography (CT) findings has not been reported.
The authors do not make any conclusions about the mechanism of transmission, but do point out that more study of this subject is needed.
The mechanism by which asymptomatic carriers could acquire and transmit the coronavirus that causes COVID-19 requires further study.
We’re about halfway through these cases and I’m already bored to tears.
5. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington (Kimball et al. 20206)
This discusses the progression of SARS-CoV-2 infections in a long term care facility. The authors infer asymptomatic spread based on their observations.
Approximately half of all residents with positive test results did not have any symptoms at the time of testing, suggesting that transmission from asymptomatic and presymptomatic residents, who were not recognized as having SARS-CoV-2 infection and therefore not isolated, might have contributed to further spread.
The authors point out that asymptomatic transmission warrants considering the use of different strategies for testing and cohorting (grouping) the residents of the facility.
If asymptomatic or presymptomatic residents play an important role in transmission in this population at high risk, additional prevention measures merit consideration, including using testing to guide cohorting strategies or using transmission-based precautions for all residents of a facility after introduction of SARS-CoV-2. Limitations in availability of tests might necessitate taking the latter approach at this time.
When taking care of people infected with the virus they recommend the use of face masks for all health care personnel while in the facility, and if possible, the use of CDC-recommended PPE (personal protective equipment) for the care of all residents.
Once a facility has a case of COVID-19, broad strategies should be implemented to prevent transmission, including restriction of resident-to-resident interactions, universal use of facemasks for all health care personnel while in the facility, and if possible, use of CDC-recommended PPE for the care of all residents (i.e., gown, gloves, eye protection, N95 respirator, or, if not available, a face mask).
There is no mention of mask use in the community outside the facility, or of the health care workers in the facility continuing mask usage once they leave the facility.
[Meanwhile, on the screen to my right, Dharma’s dad Larry is on a rant about the party being planned:
“Gimme one good reason I’d attend a wedding reception at some fascist country club run by a bunch of morally bankrupt fat cat Republicans who care more about capital gains than starving children.”
“Free valet parking?”
Wow, change a few words here and there and Larry has a valid complaint about today’s pharmaceutical industry. But that’s a rant for another day, so let’s just continue.]
6. Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020 (Wei et al. 20207)
This report is documenting occurrences of presymptomatic (prior to symptoms) transmission based on analysis of all cases in Singapore and was published in the Morbidity and Mortality Weekly Report of the CDC. The authors also mention that this presymptomatic transmission is not an unknown phenomenon.
Investigation of all 243 cases of COVID-19 reported in Singapore during January 23–March 16 identified seven clusters of cases in which presymptomatic transmission is the most likely explanation for the occurrence of secondary cases.
Such transmission has also been observed in other respiratory viruses such as influenza.
That’s another reference to the viral transmission being similar to influenza. And they make a recommendation based on their data:
These findings also suggest that to control the pandemic it might not be enough for only persons with symptoms to limit their contact with others because persons without symptoms might transmit infection. Finally, these findings underscore the importance of social distancing in the public health response to the COVID-19 pandemic, including the avoidance of congregate settings.
So the authors of this article recommend social distancing to limit the spread of the virus, but do not discuss other types of NPI.
[I’m getting a bit of a creepy vibe from the whole “limit their contact with others” comment, in this and in other contexts. We might be looking at part of the justification for isolation mandates as well.]
7. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) (Li et al. 20208)
This article shows the results of epidemiological* models (computer simulations that show the spread of an infectious disease) applied to data about infections in China. The output is a set of parameters (numbers) that can be input to other epidemiological models.
(*Epidemiology is the study of infections in populations. Flint et al. 2015)
Here, we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model, and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV-2, including the fraction of undocumented infections and their contagiousness.
These findings explain the rapid geographic spread of SARS-CoV-2 and indicate that containment of this virus will be particularly challenging.
They tell us the importance of understanding the fraction of undocumented cases.
The fraction of undocumented but infectious cases is a critical epidemiological characteristic that modulates the pandemic potential of an emergent respiratory virus.
The authors have concluded there were a large number of undocumented infections prior to the travel restrictions, and that these were an important factor.
Overall, our findings indicate that a large proportion of COVID-19 infections were undocumented prior to the implementation of travel restrictions and other heightened control measures in China on 23 January and that a large proportion of the total force of infection was mediated through these undocumented infections.
The only mention of non-pharmaceutical interventions comes in the section labeled “Outlook” at the end of the article. In describing the response of authorities in China the authors mention various measures being used.
Further, general population and government response efforts have increased the use of face masks, restricted travel, delayed school reopening, and isolated suspected persons, all of which could additionally slow the spread of SARS-CoV-2.
While noting the actions taken by Chinese authorities, the authors themselves do not recommend specific actions.
The final two references about transmission are literature reviews.
What is a literature review? Is it anything like when the book club meets to discuss Pride and Prejudice?
Scientific literature reviews are published by people knowledgeable in a field who, for one reason or another, wish to generate a summary of the available studies on something and their opinion of what those studies mean. A review of the applicable literature typically provides an overview of the types of studies that have been done and determines the overall meaning of the results of those studies. The CDC has included three literature reviews about COVID-19 in their list of references, two of which cover asymptomatic transmission. Well, the intern did. Everyone else was out to lunch.
8. Evidence supporting transmission of severe acute respiratory syndrome coronavirus 2 while presymptomatic or asymptomatic (Furukawa, Brooks, & Sobel, 20209)
This review summarizes the results of a search for existing articles and studies documenting transmission of the disease by people who are presymptomatic or asymptomatic. It contains references to 40 different studies and articles, and included in this list are the first seven of the nineteen CDC references (feels like that intern at the CDC is trying to pad his homework).
We describe evidence that supports the concept of transmission while presymptomatic and asymptomatic, which we found during a rapid literature review conducted at the Centers for Disease Control and Prevention (CDC) in early April 2020.
The review mentions masks in the context of describing the CDC recommendations. The authors themselves do not make any recommendations about masks or other NPI, but do state that the effectiveness of these measures is still not known. The authors also note several important questions they feel need to be answered.
First, the incidence of asymptomatic compared with symptomatic SARS-CoV-2 infection needs to be determined.
Second, given that a large proportion of infections probably result from transmission from asymptomatic or presymptomatic persons, the effectiveness of public health interventions aimed at reducing their infectiousness needs to be quantified.
Last, knowledge of SARS-CoV-2 immunity among persons with asymptomatic or mild SARS-CoV-2 infection is needed; specifically, whether full or partial immunity develops in these persons, how long protective immunity lasts, and if it is possible to be immune from reinfection but still asymptomatically transmit SARS-CoV-2 while in a carrier state.
So nothing new here.
9. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review (Oran et al. 202010)
This is a review of PubMed reports on transmission of SARS-CoV-2. PubMed (https://pubmed.ncbi.nlm.nih.gov/) is a government website where articles and studies from journals are cataloged - at this point I’m amazed that they still let ordinary people access all this information. We might start reading it and thinking for ourselves, instead of just blindly doing whatever Tony “McStabby” Fauci tells us.
In addition to PubMed reports, the authors also looked for unpublished manuscripts and news reports (using Google) and anything relevant they found on Twitter (If you read Part 1 you already know my opinion of Twitter as a resource). The authors of this review note the incidence of asymptomatic infection in the reports, and conclude:
The likelihood that approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.
Asymptomatic persons can transmit SARS-CoV-2 to others for an extended period, perhaps longer than 14 days.
Interestingly, they note a possible reason for some people having preexisting immunity to the disease. One of the reports they review shows a 96% asymptomatic rate among inmates in four state prison systems. The authors suggest this may be an error (for example, this could be due to false positive tests) but may also indicate preexisting immunity. Per the CDC, another human coronavirus was active shortly before SARS-CoV-2 was first detected in the U.S.
According to the U.S. Centers for Disease Control and Prevention, HCoV-HKU1 was active across the United States from late November 2019 through mid-February 2020.
Recall from the earlier section that HCoV-HKU1 is one of the four human coronaviruses that are endemic in the population and believed responsible for many common colds.
Summary: The short version (for government officials and other non-intelligent life forms)
SARS-CoV-2 is transmissible between humans, even when asymptomatic, but the exact mechanism of transmission is unknown. Some reports indicate it may be transmitted by droplets, some indicate that the transmission may be similar to influenza, which can be spread by contact or by aerosols. All of these are also characteristics of other known respiratory diseases. Some people also speculate about the mechanism of transmission even when no transmission occurs.
We also learned there was an outbreak of another, endemic human coronavirus (HCoV-HKU1) in late 2019. This outbreak may may have resulted in some false positives for COVID-19, and it may also mean some people already had natural immunity to COVID-19 based on previous infection with a different coronavirus.
Note that previous infection with one coronavirus might convey immunity to another coronavirus. So you could gain natural immunity to SARS-CoV-2 after infection with another virus that causes a lot of common colds.
Beyond that we’ve learned very little besides “it maybe spreads like the flu.”
In the meantime, Episode 2 has finished. Here’s something interesting: at the end of each episode a there is a paragraph of text displayed for a about a second - back in the 90s if you wanted to read this you would have to record the episode on something called a “VCR” and pause it at this point.
Apparently this is creator Chuck Lorre’s “vanity card” where he shares his personal thoughts. One of those is “I believe that the Laws of Karma do not apply to show business, where good things happen to bad people on a fairly regular basis.”
Who wants to tell him this applies to government bureaucracies as well?
Next up: Part 3: “What’s a Literature Review?” and Episode 3: “Shower the People You Love With Love”.
Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020;382(10):970-971. doi:10.1056/NEJMc2001468
https://pubmed.ncbi.nlm.nih.gov/32003551/
Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020;382(12):1177-1179. doi:10.1056/NEJMc2001737
https://pubmed.ncbi.nlm.nih.gov/32074444/
J. Flint, V.R. Racaniello, G.F. Rall, A.M. Skalka. Principles of Virology, Fourth Edition, Bundle. American Society of Microbiology (2015). doi:10.1128/9781555819521. ISBN 978-1-55581-952-1.
Pan X, Chen D, Xia Y, et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020;20(4):410-411. doi:10.1016/S1473-3099(20)30114-6
https://pubmed.ncbi.nlm.nih.gov/32087116/
Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19 [published online ahead of print, 2020 Feb 21]. JAMA. 2020;323(14):1406-1407. doi:10.1001/jama.2020.2565
https://pubmed.ncbi.nlm.nih.gov/32083643/
Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69(13):377-381. Published 2020 Apr 3. doi:10.15585/mmwr.mm6913e1
https://pubmed.ncbi.nlm.nih.gov/32240128/
Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):411-415. Published 2020 Apr 10. doi:10.15585/mmwr.mm6914e1
https://pubmed.ncbi.nlm.nih.gov/32271722/
Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science. 2020;368(6490):489-493. doi:10.1126/science.abb3221
https://pubmed.ncbi.nlm.nih.gov/32179701/
Furukawa NW, Brooks JT, Sobel J. Evidence supporting transmission of severe acute respiratory syndrome coronavirus 2 while presymptomatic or asymptomatic. Emerg Infect Dis. 2020 Jul [cited 20 August 2020]. DOI: 10.3201/eid2607.201595https://wwwnc.cdc.gov/eid/article/26/7/20-1595_article
Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review [published online ahead of print, 2020 Jun 3]. Ann Intern Med. 2020;M20-3012. doi:10.7326/M20-3012https://pubmed.ncbi.nlm.nih.gov/32491919/