Test prudently

by Amy B. Rosenfeld

I do not advocate testing for any person vaccinated against SARS-CoV-2 unless they display severe symptoms or live with those who for whom vaccines are not yet approved. I understand that testing and isolation are mechanisms to break virus transmission chains and were used at the beginning of the pandemic to control virus spread. To continue to follow this same philosophy today, more than 2 years later, suggests that little or no progress has been made to control or understand the virus and the pandemic. Furthermore, excessive testing inhibits our ability to make the proper ‘risk-benefit’ analysis necessary to generate programs that enable society to move forward with SARS-CoV-2. 

My rationale for not testing vaccinated people is very simple and is based upon the precedents set for other pathogens for which vaccines exist. We do not test people for poliovirus, measles virus, influenza virus, or human papillomavirus after vaccination. If we tested the general public, vaccinated and unvaccinated, for rhinovirus or influenza virus infection/exposure, a significant amount of the population would be found positive. Following the CDC COVID-19 guidelines, those who test positive isolate for 5 days. Economies and society would grind to a screeching halt. 

The measles, mumps, influenza and poliovirus vaccines were developed to prevent severe disease, not infection. These vaccines are some of our most successful biological products against infectious diseases. Many of these vaccines were developed when occurrence of severe disease caused by infection with these viruses was high or to mitigate the economic burden of the associated disease. Studies published investigating the mechanisms by which these vaccines protect us, demonstrated significant differences between the mechanisms of protection. For instance, administration of the oral poliovirus vaccine is via the natural route of infection, and confers immunity to the primary site of infection, the gut. It is gut immunity which is believed to protect the vaccinated from subsequent disease. Furthermore, when vaccination rates are high within a population, the community is protected, and virus transmission is interrupted. However, vaccinated people shed infectious neurovirulent poliovirus 30-90 days after vaccination into the environment, which can then infect those who are immunocompromised or unvaccinated and lead to the development of vaccine associated paralytic poliomyelitis. Approximately 1 in every 1.5 million vaccinees develop vaccine associated paralytic poliomyelitis.

The inactivated poliovirus vaccine functions differently. It is administered via the intramuscular route and prevents entry of the virus into the central nervous system and paralysis. When inactivated properly, no vaccinee will develop vaccine associated paralytic poliomyelitis. However, IPV does not elicit gut immunity; thereby, it does not prevent infection of the vaccinated or promote community protection. Those who are vaccinated will get infected and develop a low-grade fever but will not develop poliomyelitis. Consequently, infected vaccinees do not recognize they are infected. 

To achieve global eradication of poliovirus, administration of both vaccines is required. And while the US and many other countries no longer administer the oral poliovirus vaccine to young children, if there is an outbreak of poliomyelitis, it is resolved first by administering OPV and then IPV. This policy is founded upon years of scientific studies to identify sites of virus infection and biology, to track transmission following vaccination and to understand how each vaccine works. 

While the site of primary infection is mostly understood as the nasal and nasopharyngeal cavities, transmission of SARS-CoV-2 is not well understood. No published study has clearly demonstrated if people shed infectious virus following vaccination, if so for how long and if that is enough to transmit to others. Completion of such studies will take years. However, as a society, we do not want to wait for their completion. We are eager to resume activities that we did before the pandemic. Consequently, the question is what is required to resume these activities and what role does testing have in achieving this goal? Does the risk of resuming ‘daily life’ outweigh the costs of not doing so?

From the lessons of the poliovirus vaccine and others including measles, mumps and influenza a single vaccine will most likely be unable to both prevent infection and prevent transmission. The vaccine against human papillomavirus does prevent infection and transmission; however, this trait was a pleasant surprise. To fully understand how this vaccine is able to prevent infection and transmission much more research is required. However, during a pandemic there is no time for such lengthy studies.

Published work clearly shows that the COVID-19 vaccines protect against the development of severe disease and death. Testing does not change the case management of these individuals. If we want a vaccine that protects against infection, additional research and development is required. 

This pandemic ends when more of us get vaccinated and when society accepts the fact that we will all get exposed or infected by SARS-CoV-2 at some point in time. Prudent use of these tools we have can prevent the development of severe disease, not burden our healthcare system. Working all together will prevent our economy from grinding to halt and enable us to resume the activities we participated in prior to the pandemic. A better use of our energy is finding ways to encourage vaccination of the vaccination-hesitant, and facilitate acceptance of the fact that unlike smallpox and poliovirus, eradication of SARS-CoV-2 is impossible. As populations become more and more immune to disease, the way our tools are used change. How testing vaccinated individuals promotes these changes is unclear. 

Society accepts the risk of spreading rhinovirus, influenza virus and other respiratory pathogens to others including the unvaccinated and immunocompromised. The definition of a pandemic is not the number of the deaths, economic burden but the number of infections. Consequently, it is not correct to state that rhinoviruses are not etiologic agents of global pandemics. Rhinoviruses/enteroviruses are the most common human pathogens, and do cause pandemics, but we rarely die. Instead, they economically overwhelm society and we do not test for their presence. 

Dr. Rosenfeld is a virologist at Columbia University.

17 thoughts on “Test prudently”

  1. Pingback: Test prudently | News I Can

  2. I’m unclear, what is the purpose of testing unvaccinated people? Why test anyone?

    Also, wouldn’t a good way of encouraging the unvaccinated to be vaccinated be offering a different sort of vaccine -https://www.bmj.com/content/376/bmj.o48? (What’s that saying about insanity?) I understand that it’s thought that offering a whole inactivated virus vaccine could increase uptake vaccine uptake by several percentage points. (https://www.reuters.com/business/healthcare-pharmaceuticals/valneva-talks-with-several-countries-over-further-vaccine-supply-contracts-2021-12-16/) Is that being done/considered in the US?

  3. Thank you Dr Rosenfeld. You have encapsulated my layman’s thoughts perfectly I think about COVID. I was not aware of what you said about other vaccines but I wish our policy makers in UK had been. In this country the phrase “breakthrough infection” appears to be used synonymously with a positive COVID test.

  4. Jennnifer Fallon

    Dr. Rosenfeld,
    Thank You for being a voice of reason in this age of media over saturation with misinformation!
    If only our leaders had brains that worked as well as yours! What an amazing place this world would be.
    I will dream about that utopia while I go to work today and swab my millionth baby nostril for Sars- Cov2.
    Thank you for the Science!
    Jen Fallon

  5. Don’t ask the question if you don’t want to hear, or don’t know what to do with, the answer.

    An answer may be useful or inform a decision sometimes, and sometimes not.

    In this case it may be useful for epidemiologist to track spread, or for an individual to decide on a treatment (as with monoclonals, antivirals, or other drugs), to refrain from visiting someone who is vulnerable, or use extra protective measures to limit exposure for others, such as unvaccinated children. It’s a waste of resources if testing for idle curiosity, without clear purpose.

  6. Brian P. Hanley, PhD

    Yes, Dr. Rosenfeld, except that the order of vaccination is backwards for the developed world with order cold chain storage.

    Here, the order should be IPV followed by OPV, or administration of both simultaneously. Otherwise, you will guarantee serious disease in some people.

  7. I think there are two missing factors that need to added to consideration.

    1) As common as the other pathogens you list are, they do not cause the disease burden seen in the current wave. By my rough calculations, influenza probably hits around 100,000 new cases per day at the peak of flu season. RSV much less. Numbers are obviously hard to come by for “generic” rhino- and enteroviruses, but I am skeptical that they get much higher than peak flu. Given that the US has been recording (much) more than 200,000 new cases per day for three solid weeks (and counting), I think there’s a strong case to be made for (temporary) testing to try and break the wave. Indeed, if we were seeing sustained influenza infection rates at this level, I think we *would* be testing, quarantining, etc.

    2) Even with the common viruses mentioned, we still expect (or should) that people stay home while they are infectious. My kids have been sent home from daycare/school for pink eye, strep throat, and plenty of rhino- and enteroviruses. I think it should be uncontroversial to expect people who are infectious with SARS-CoV-2 to stay home, as well, regardless of vaccination status. And that’s exactly the value of testing, due to asymptomatic/pre-symptomatic transmission. I agree that we’re long past the point of routine PCR tests making much sense, but rapid antigen testing, especially home testing and test-to-stay in schools makes a ton of sense to me.
    One caveat to this second point: I could well imagine that many other respiratory viruses turn out spread primarily through pre-symptomatic transmission and that we haven’t realized this because it was never important enough to look before. If so, my logic results in a rather impractical requirement for home antigen testing of the full respiratory panel. At that point, we’d have to decide as a society which, if any, are worth the effort to keep transmission down, again, just as a practical matter. But even if that is the case, I think the justification for temporary testing as per my first point is still strong.

  8. Yes but what are the consequences of not testing? Specifically how will this reduce the burden on our health care system which is overwhelmed right now?

    Crisis care is being activated in multiple states, and in mine I can be denied an ambulance now or refused a hospital bed and redirected elsewhere. We even have the military sending in healthcare workers.

    I wish I could understand how doing less, being less vigilant, being less proactive, is going to help.

  9. Here in England, we are currently under the government’s “plan B” restrictions, which make testing legally required in a number of situations, and it is government guidance (but not a legal requirement) for testing to be carried out in a much wider range of situations (e.g. vaccinated asymptomatic individuals who are going to be indoors in a crowded place).

    England’s “Plan B” is expected to be very temporary, just during the height of the winter peak of infections, and so we expect it to be gone soon. The Scottish and Welsh governments have announced lifting of some of their restrictions towards the end of January. The current guidance for mass testing of asymptomatic individuals in England could be gone by February.

    The government’s stated goal is to keep the number of hospitalisations within the capacity of our hospital system (so, for example, it doesn’t matter how many people have mild cold-like symptoms).

    The government greatly extended the availability of Pfizer and Moderna booster shots just before Christmas, which given the early effectiveness data on booster shots, ought to have had a substantial effect on achieving the government’s goal. (Preventing hospitalisation, but not infection, is sufficient to meet the goal of reducing the number of hospitalisations).

    The mass asymptomatic testing is presumably an attempt to slow the speed of the pandemic during the winter peak, such that even if it doesn’t much change the number of people who are hospitalised in total, it at least means they aren’t all in hospital at the same time over Christmas.(peak rate matters for the government’s success metric). As such, it doesn’t make much sense to keep on doing it when the hospitalisation rate is slowing due to the virus running out of new people to infect/warmer weather reducing transmission). You could reasonably justify mass testing being ended by the end of January.

  10. As other people have noticed in the comments, this argument against testing asymptomatic vaccinated individuals would seem to apply equally well to asymptomatic unvaccinated individuals.

    =====

    England has fewer covid restrictions than many other countries.

    If I’ve understood the current rules correctly, Wales is currently in “alert level 2” which means that going to a nightclub or an organized indoor event of more than 30 people is currently illegal, regardless of your vaccination status or LFT result. In England, on the other hand, these are roughly the types of event for which a test is recommended by government guidance but not required by law (unless you’re unvaccinated and going to a nightclub, in which case it’s required by law).

    So in England the government guidance is mostly to use the LFT’s for people who are going to events that, across the border in Wales, would just be illegal no matter what.

    So one could argue that the tests are being used to enable opening up faster: rather than making big indoor events illegal, the position is you can go to them but you are recommended (but not legally required) to take a LFT first.

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  12. stephen paluszek

    Thank you Dr. Rosenfeld – as usual you are spot on. I wanted to add – the U.S. with an an estimate of vaccinations and/or SARS-CoV-2 infections exceeding over 75% of the population – does it really make good economic policy to spend $100 billion annually for testing for this particular virus? This is not free – taxpayers ultimately have to fund this government expense. This reminds me of the large investment the U.S. government made in manufacturing ventilators in early 2020 when most doctors knew that individuals who are intubated have an extremely high mortality rate.

    Testing vaccinated, previously infected or asymptomatic individuals has minimal benefit and significant societal cost. Stop over-testing now!

  13. Dear Dr Rosenfeld,

    Thank you for your participation here and in the videos and podcasts. I’m a fan.

    I don’t agree with limiting testing of vaccinated persons to only those with severe symptoms. Testing is clinically useful to guide both treatment when called for, and behavior of those with positive tests to help them limit transmission.

    We do actually test vaccinated persons for influenza on patients with flu-like-symptoms when they report for care. The test results guide the clinical treatment.

    Finally, since vaccines are not 100% effective in preventing disease, the sentence “Consequently, infected vaccinees do not recognize they are infected.” would not hold true where a vaccinee begins to experience any degree of paralysis due to inadequate immunity to the polio virus.

    In any case, my observation is that in the USA, over-testing is random. Many persons needing clinical care do not get care and do not get formally tested because of the difficulty getting into the health care system in many times and places. In other cases, anybody who can wait in line can be tested for no particular reason thanks to the total lack of testing management.

    I have very low expectations that the new US program of distributing free home tests to whoever can persevere and ask for them will have any measurable effect on the course of the pandemic. But, within each individuals ecosystem of family, friends, co-workers and random encounters, knowledge is power to help control the spread locally.

  14. I can only comment from my personal experience here in England with friends and family all of whom are fully vaccinated and boosted but who still rush to open their (free NHS supplied) LFD at the least sniffle or sneeze. “Gives me peace of mind”. “makes me feel less anxious” are the typical answers when questioned.

    It perhaps should be put to the test but my impression is that the people with the lower risk of even mild infection are those who are testing unnecessarily. And those with the higher risk, including the unvaccinated, are more likely to spurn testing as they do with other precautions such as distancing and masking.

  15. As expected, England has now lifted the “plan b” restrictions. The guidance (not a legal requirement) for use of lateral flow tests appears to still be in place:

    https://www.nhs.uk/conditions/coronavirus-covid-19/testing/regular-rapid-coronavirus-tests-if-you-do-not-have-symptoms/

    .. which is basically (a) before mixing with people in a crowded indoor space (b) before visiting a vulnerable person (c) if you’ve recently been in contact with someone who had covid19.

    Negative results can be kept private to yourself or optionally reported to the government, along with the reason for the test. On the report to the government, I’ve been ticking the box meaning roughly, “well, I’m going to a Christmas party”, which falls under (a).

  16. The recently published challenge study
    https://www.researchsquare.com/article/rs-1121993/v1
    again confirms viral shedding prior to system onset.

    As a musician occasionally playing in packed clubs full of maskless, alcohol infused revelers yelling and screaming, who likely gained entry with a forged vax cert and feel that the virus is a hoax, I will isolate and test after. I test once per week regardless. This is prudent testing. I encourage all with whom I might gather to do likewise: Wednesday is test day.

    I understand well that the PRC assay, in the absence of symptoms, is not confirmation of infection. It does though confirm the presence of viral protein, replication competent or not. Were I to receive notice of a positive result from an airway sample I would isolate and test again in a day or two. This is prudent testing.

    Frequent testing is prudent. This is not the flu. This is a disease from which a significant number of the infected will not recover. We are likely to reach one million Covid associated deaths in this quarter. China on the other hand claims under 5,000. While China’s Zero Covid policy is considered draconian, China’s reliance on testing is to be applauded.

    Frequent testing in regions of high prevalence is prudent.

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