Heinrich Wilhelm Gottfried von Waldeyer-Hartz, eponym of Waldeyer's tonsillar ring in the pharynx, considered “the first line of defense against exogenous aggressors”. Photograph: Wikipedia
Heinrich Wilhelm Gottfried von Waldeyer-Hartz, eponym of Waldeyer’s tonsillar ring in the pharynx, considered “the first line of defense against exogenous aggressors”. Photograph: Wikipedia

Additional thoughts regarding the benefit of throat disinfection during COVID-19-like epidemics

Discussing our sug­ges­tion for pre­ven­tive throat dis­in­fec­tion to counter the Coronavirus pan­dem­ic1 with col­leagues in the med­ical com­mu­ni­ty as well as in acad­e­mia has yield­ed pos­i­tive feed­back as well as objec­tions, and has led to addi­tion­al thoughts. And while in recent weeks we have been, and still are, focused on estab­lish­ing and com­pre­hend­ing as deeply as pos­si­ble the immuno­log­i­cal “big pic­ture” in viral epi­demics and beyond from so far only part­ly inter­con­nect­ed evi­dence in the spe­cial­ist lit­er­a­ture, in order to derive action­able rec­om­men­da­tions, we briefly sum­ma­rize below what has emerged with regard to our first arti­cle since it appeared.

Viral load and disease severity

There are strong indi­ca­tions that viral load in the throat cor­re­lates with dis­ease sever­i­ty in COVID-19.2 In addi­tion, it has been hypoth­e­sized for influen­za3 that dis­ease sever­i­ty cor­re­lates pos­i­tive­ly with the num­ber of con­tacts an infect­ed per­son has with oth­er infect­ed per­sons, put the oth­er way around, that sep­a­ra­tion from virus spread­ers helps in heal­ing. This seems to indi­cate that min­i­miz­ing viral load in gen­er­al should help in safe­ly con­quer­ing viral infec­tions of the res­pi­ra­to­ry tract. Viral load specif­i­cal­ly in the throat is set to mean virus that is still or again (after secre­tion from, or death and sub­se­quent dis­in­te­gra­tion of, infect­ed cells) out­side of body cells in which it can repli­cate and adverse­ly reg­u­late body functions.

Yet, as hypoth­e­sized by Professor Drosten of Charité Berlin, the ini­tial mas­sive repli­ca­tion of the nov­el Coronavirus in the throat, ensur­ing ear­ly sig­nif­i­cant expo­sure of the virus to Waldeyer’s4 ton­sil­lar ring – con­sid­ered “the first line of defense against exoge­nous aggres­sors”5 -, primes the immune sys­tem ear­ly in the course of the infec­tion such that it is bet­ter pre­pared should the infec­tion affect the lungs in a mean­ing­ful way. This may explain why, on a rel­a­tive basis, COVID-19 is far less dead­ly than was SARS 2003, where the virus was detectable in the throat only in about 30 % of cas­es dur­ing the first few days and in about 60 % of cas­es by the time the lungs were already mean­ing­ful­ly affect­ed,6 the lat­ter most pre­sum­ably because virus was trans­port­ed up to the throat with­in lung sputum.

These two points, tak­en togeth­er, should suf­fi­cient­ly explain why an objec­tion we have encoun­tered, also among col­leagues in the med­ical com­mu­ni­ty, along the lines that “once the virus has struck, and entered body cells, the dam­age is done, and employ­ing antivi­ral dis­in­fec­tants in the throat won’t help any­more,” appears mis­placed. If an infec­tion can­not be pre­vent­ed alto­geth­er, it can be ben­e­fi­cial that the virus is present to some extent in cells of a body area that is par­tic­u­lar­ly immuno­com­pe­tent, in order to intro­duce the immune sys­tem to the ene­my in a sig­nif­i­cant way as ear­ly as pos­si­ble and thus expe­dite devel­op­ment of the immune response, while at the same time destroy­ing most virus copies out­side of cells so that those copies can­not infect addi­tion­al cells in the throat and – most­ly via night­ly aspi­ra­tion of infect­ed mucus from the throat dur­ing sleep – even­tu­al­ly the lung.

We would again like to empha­size that evi­dence shows that the deep­er the sleep, the big­ger the risk of aspi­ra­tion of pha­ryn­geal mucus to the lungs.7 Since sleep in the first part of the night, the slow wave (“deep”) sleep phase, is deep­est, this is the most “dan­ger­ous” part of the night, so that much should be helped if the viral pop­u­la­tion present in the throat is destroyed imme­di­ate­ly before going to sleep.

And may we allow our­selves the com­ment that if a viral infec­tion is con­sid­ered, in response to our sug­ges­tion, as sim­ply an “intra­cel­lu­lar” prob­lem, then why try to devel­op vac­cines against COVID-19, when the result­ing anti­bod­ies bind to the virus (if, of course, not only in the throat) just as much exclu­sive­ly out­side of cells as the dis­in­fec­tant destroys it?

One for­mer fel­low stu­dent and now depart­ment head at Charité Berlin told us our sug­ges­tion would not work because the destroyed viral load would “be recre­at­ed with­in 20 min­utes”. Sifting through the lit­er­a­ture, we found no evi­dence sup­port­ing this claim yet sev­er­al indi­ca­tions from indus­tri­al virus pro­duc­tion set­tings that it should def­i­nite­ly take more than the time the slow wave sleep phase lasts to rebuild what the dis­in­fec­tant destroyed. The dis­tinct after­taste of gar­gling with hydro­gen per­ox­ide, even after rins­ing, may even sug­gest that some poten­tial­ly effec­tive rest of the gar­gling solu­tion will be present in the throat for some time dur­ing the ini­tial phase of the night.

While watch­ing the press con­fer­ence pre­sent­ing the Gangelt study by Professor Streeck and oth­ers8 we could not help but notice the log­i­cal incon­sis­ten­cy in the stance of pub­lic health offi­cials stat­ing that their pri­ma­ry aim was “to min­i­mize viral load” in order to reduce dis­ease sever­i­ty and addi­tion­al dead­ly out­comes from COVID-19, but then focus­ing entire­ly on advo­cat­ing sur­face dis­in­fec­tion, all the while Professor Streeck had already clear­ly stat­ed pub­licly9 (essen­tial­ly affirmed by essen­tial­ly every virol­o­gist we have read or heard) that even in very heav­i­ly infect­ed house­holds his team had nev­er been able to iso­late “liv­ing”, infec­tious virus from any sur­face they had tak­en swabs from. While at the same time the virus is clear­ly “liv­ing” in the throat as its ini­tial pri­ma­ry “dis­tri­b­u­tion cen­ter” from which it should be removed as much as fea­si­ble, in our view.

Countering pneumonia progression

Possibly the most impor­tant expan­sion to our thoughts (for which we thank Bruce L. Davidson MD, MPH, Seattle) regards the scope of the like­ly ben­e­fit from reg­u­lar throat dis­in­fec­tion dur­ing a viral epi­dem­ic. We sug­gest­ed doing this to min­i­mize lung involve­ment from an infec­tion, by pre­vent­ing that the virus enter the lungs in large quan­ti­ties via even­tu­al aspi­ra­tion of pha­ryn­geal mucus from the throat to the lungs.10

If one con­tem­plates the high­ly branched macro- (see the sketch above) as well as the micro-anato­my of the lungs, geared towards trans­port­ing every­thing for­eign back up towards the throat to then be either spit out or swal­lowed, and the radi­o­log­i­cal evi­dence of how pneu­mo­nia devel­ops in SARS-COV-like dis­ease, one can­not help but con­sid­er it high­ly like­ly that the ini­tial lung foci mul­ti­ply, at least in part and in ear­li­er stages, when virus present in those foci is trans­port­ed back up to the throat in lung spu­tum and then re-aspi­rat­ed to oth­er, pre­vi­ous­ly unaf­fect­ed parts of the lungs, poten­tial­ly depen­dent on sleep­ing posi­tion dur­ing the time of aspiration.

Normally aspi­ra­tion of small amounts of infect­ed mucus dur­ing pneu­mo­nia does not mat­ter much because the patient is receiv­ing sys­temic antimi­cro­bial ther­a­py. But a pathogen spe­cif­ic for alve­o­lar cells (alve­o­lar type II11) and some low­er air­way cells with no effec­tive antimi­cro­bial ther­a­py (such as the nov­el Coronavirus) can, in the way described above, infect new areas and thus reduce the lungs’ oxy­gena­tion capac­i­ty in pre­vi­ous­ly unaf­fect­ed lung regions.

Disinfecting the throat dai­ly and pre­ven­tive­ly (because in rare cas­es lung involve­ment may occur even before the onset of rec­og­niz­able symp­toms) dur­ing viral epi­demics in the way we have sug­gest­ed may thus help not only in pneu­mo­nia pre­ven­tion, but also in coun­ter­ing its pro­gres­sion should one have devel­oped already. 

Implication of other organs as an argument against the usefulness of throat disinfection

Finally, we encoun­tered the argu­ment that phe­nom­e­na such as loss of taste and smell, affec­tion of the gas­tro-intesti­nal tract, of the kid­neys and the heart have been report­ed, so that dis­in­fect­ing the throat would be essen­tial­ly useless.

Loss of taste and smell hap­pen in the mouth and nose where the virus ini­tial­ly resides, and where our sug­ges­tion seeks to counter viral spread. The phe­nom­e­non is report­ed to be tran­sient, and no one dies of it.

The gas­tro-intesti­nal tract is affect­ed through swal­low­ing mucus, and low­er­ing the viral load this mucus car­ries is what our sug­ges­tion is about. In addi­tion, no one has been report­ed to have died of COVID-19-induced nau­sea or diar­rhea, and avoid­ing death from the infec­tion is all that is need­ed to con­quer COVID-19.

The kid­neys and the heart are affect­ed as a con­se­quence of sys­temic inflam­ma­tion result­ing from pneu­mo­nia, exact­ly the con­di­tion we want to pre­vent or at least ren­der less severe and non-lethal.

In sum­ma­ry, we believe it would be a good idea, also with a view to poten­tial future viral epi- and pan­demics, if the CDC and the WHO endorsed our sug­ges­tion so as to make it effec­tive on a glob­al scale.

The one objec­tion we could imag­ine is that the CDC and the WHO only dare endorse mea­sures that have been suc­cess­ful­ly test­ed in a clin­i­cal set­ting, even if com­mon sense and decades of expe­ri­ence in the den­tal are­na say that no risk worth men­tion­ing is asso­ci­at­ed with throat dis­in­fec­tion in the way we have described. Surprisingly, a clin­i­cal tri­al as to the effec­tive­ness of our sug­ges­tion has nev­er been con­duct­ed,12 despite a num­ber of cur­rent and espe­cial­ly retired med­ical prac­ti­tion­ers call­ing it “a good idea” and an “old-fash­ioned method”, imply­ing it has been prac­ticed before. We there­fore sug­gest it be clin­i­cal­ly test­ed in a large-scale clin­i­cal tri­al in dif­fer­ent age cohorts as soon as possible.

_____
  1. https://loico.com/the-logic-of-surviving-the-coronavirus-pandemic/[]
  2. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30232-2/fulltext[]
  3. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011655[]
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723023/[]
  5. https://www.ncbi.nlm.nih.gov/pubmed/11082757[]
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/[]
  7. https://www.amjmed.com/article/0002-9343(78)90574-0/pdf[]
  8. https://www.youtube.com/watch?v=VnrHamW8OXQ[]
  9. https://www.youtube.com/watch?v=VP7La2bkOMo[]
  10. Some addi­tion­al evi­dence as to the extent such aspi­ra­tion hap­pens dur­ing sleep: https://pubmed.ncbi.nlm.nih.gov/9149581/; https://pubmed.ncbi.nlm.nih.gov/15179196/[]
  11. https://www.britannica.com/science/type-II-pneumocyte[]
  12. The study in Guangdong, PRC, that we have pre­vi­ous­ly referred to appears to have a dif­fer­ent objec­tive and to not even be active­ly recruit­ing at this time: http://www.chictr.org.cn/showprojen.aspx?proj=50660[]
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This Post Has 8 Comments

  1. Elaine Camilleri

    AMEN . All that you have so intel­li­gent­ly and thought­ful­ly writ­ten makes so much sense. I can see the con­nec­tion very well because I am a speech pathol­o­gist and work with dys­pha­gia patients who are aspi­rat­ing espe­cial­ly post extu­ba­tion and we so reg­u­lar­ly stress oral care and hygiene with these patients. In fact we have a pro­gram called Frazier Water pro­to­col which requires thor­ough oral care every 2 hours for NPO patients before pt can have water or water and ice only in order to pre­vent aspi­ra­tion of oral micro organ­isms. So I can see how the high viral load of COVID in the oral cav­i­ty which is aspi­rat­ed when we sleep would be dis­as­trous. Since noth­ing is real­ly proven any­way at this time with this nov­el virus, why can­not you (as a doc­tor and sci­en­tist) reach out to pub­lic com­men­ta­tors in Europe and/or in the US? Tucker Carlson and Steve Hilton (Fox News) are two such good exam­ples here in the US. They are try­ing to help the coun­try but are offer­ing con­flict­ing and con­fused info about social dis­tanc­ing which is not fea­si­ble and incom­pat­i­ble with get­ting back to work and com­mu­ni­ty; sad­ly they offer no tan­gi­ble pre­ven­ta­tives except hand wash­ing and more test­ing. The only way to tack­le this is to reduce the sever­i­ty of it and reduce the trag­ic deaths it caus­es as you said. What can we do to get your valu­able info out there?

    1. loico

      Thank you very much for shar­ing your insight and your expe­ri­ence from an impor­tant front­line! As regards “get­ting the word out”, most of our enlarged per­son­al envi­ron­ment, and beyond that – judg­ing by the inter­est we see show­ing up in our pageview sta­tis­tics – pre­sum­ably at least sev­er­al thou­sand peo­ple world­wide are doing what we have sug­gest­ed. Family and friends are also pre­ven­tive­ly tak­ing a potent immune mod­u­la­tor, FDA approved for anoth­er indi­ca­tion, which we will very like­ly include in the planned arti­cle on the immuno­log­i­cal side of COVID-19-like crises. That said, it seems the WHO with its appar­ent­ly pop­u­lar and pow­er­ful yet part­ly mis­lead­ing “myth busters” has unnec­es­sar­i­ly cre­at­ed an envi­ron­ment of fear ver­sus non-WHO endorsed rec­om­men­da­tions. No one wants to “get caught” spread­ing “myths”, of course. As per your request, we have retweet­ed our arti­cle announce­ment to the two news anchors you named with the fol­low­ing text: “As request­ed by a read­er form­ing part of the med­ical com­mu­ni­ty, we com­mend this arti­cle and the one it expands upon to your val­ued atten­tion; what we have sug­gest­ed may help to save lung func­tions, lives and liveli­hoods. Thanks for shar­ing as you see fit.” We pro­mote our arti­cles to the lim­it­ed extent time cur­rent­ly per­mits, and we must at this point most­ly rely on our read­ers to spread the word via social media or oth­er con­tacts they may have. We can tell you that a promi­nent entre­pre­neur and reg­u­lar author with a well-known online pub­li­ca­tion, who him­self does, togeth­er with his fam­i­ly, what we have sug­gest­ed, has not been able to con­vince the med­ical doc­tor respon­si­ble for med­ical con­tent at said pub­li­ca­tion to pick up our sug­ges­tion, sim­ply because this col­league would not trust his own log­i­cal judge­ment over WHO “author­i­ty”. All the while he express­ly acknowl­edged that what we say was “plau­si­ble”. – What loico is fun­da­men­tal­ly about is a new (and at the same time actu­al­ly very old) par­a­digm in sci­ence, for­mu­lat­ed, among oth­ers, by Albert Einstein: “It is your the­o­ry that deter­mines what you can observe, not the oth­er way around.” People are con­di­tioned to rely on “facts”, not log­ic. It will take time for minds to open up to log­ic being a legit­i­mate extrac­tor of knowl­edge from dis­persed pieces of infor­ma­tion once again. So again, in case you have a minute left of your day, shar­ing your views as a med­ical pro­fes­sion­al – and poten­tial­ly our arti­cles – might help.

  2. Steffen

    It sounds plau­si­ble — would be great to test this in ani­mal models…!?
    I am not sure if you can make ani­mals gar­gle for a minute however.

    This could bridge the gap between in-vit­ro tests and humans. There might be reser­va­tions to test it in humans (argu­ment could be, e.g. by gar­gling you active­ly pro­mote virus pro­gres­sion to oth­er body areas – not that it would make too much sense, but, you know, test it but then you might have for­got­ten some­thing, and make things worse)

    I guess this would be anoth­er ani­mal test­ing set, mean­ing pro­fes­sion­al set­ting + fund­ings needed

    1. loico

      We agree: ” … not that it would make too much sense … ” 😉

      Since what we have pro­posed is known to be essen­tial­ly harm­less, there appears to be lit­tle need for ani­mal mod­els, and indeed a clin­i­cal tri­al test­ing it in humans is now under­way (see today’s “Update”).

  3. Given the effec­tive­ness of cata­lase [https://en.wikipedia.org/wiki/Catalase] in our mouths wouldn’t you sug­gest anoth­er type of laryn­geal antiseptic?

    1. loico

      Thank you for your ques­tion. We apol­o­gize on behalf of our com­ment man­age­ment sys­tem for the mis­deed of clas­si­fy­ing your ques­tion as “spam”, pre­vent­ing it from com­ing to our atten­tion earlier.

      1. The “effec­tive­ness of cata­lase in our mouths” depends on what you under­stand by “in”. Catalase is present pre­dom­i­nant­ly inside of (in this case mucos­al) cells while we pre­dom­i­nant­ly tar­get virus already secret­ed from cells and ready to infect neigh­bor­ing cells and / or to be aspi­rat­ed (most­ly at night dur­ing sleep) to the lungs. Is is well doc­u­ment­ed that too high a con­cen­tra­tion of hydro­gen per­ox­ide used in a mouth­wash or gar­gle solu­tion caus­es (even severe) mucos­al dam­age, log­i­cal­ly imply­ing that “effec­tive­ness of cata­lase in our mouths [yet espe­cial­ly on the pri­mar­i­ly pro­tec­tive out­side of cell mem­branes]” is lim­it­ed. Therefore, con­cen­tra­tions of hydro­gen per­ox­ide of only between 0.5 and 3 % are com­mon­ly rec­om­mend­ed. As almost always, the log­i­cal cat­e­go­ry of “mea­sure” is king here.
      2. In “The log­ic of sur­viv­ing the Coronavirus pan­dem­ic” (https://loico.com/the-logic-of-surviving-the-coronavirus-pandemic/), we have dis­cussed sev­er­al alter­na­tives to hydro­gen per­ox­ide. To a large extent, select­ing between the three top choic­es is effec­tive­ly a mat­ter of per­son­al preference.

      1. Elaine Camilleri

        Thank you so much for con­tin­u­ing this dis­cus­sion of oral care in rela­tion to low­er­ing viral load for COVID , not nec­es­sar­i­ly elim­i­nat­ing it but reduc­ing the sever­i­ty of it. If we lived in an ide­al world we would all have been advised to wear a mask from the begin­ning and gar­gle with var­i­ous solu­tions ie hydro­gen per­ox­ide as you not­ed and that is avail­able in dilut­ed form otc. But also we would be giv­en nasal sprays such as beta­dine car­rageenan and or oral sprays such as coldzyme for those who can­not gar­gle. All these could be used togeth­er to effec­tive­ly reduce covid. See also Dr Bale and his info regard­ing a sim­ple cheap salt saline rinse for mouth and nose . But the world is not ide­al. This has become a bat­tle of the egos and polit­i­cal gains. Creativity is reduced due to legal con­straints and noth­ing “proven”. No cre­ativ­i­ty to just try it any­way if it is fair­ly harm­less. No funds being put into giv­ing each fam­i­ly some of these items to use as a pos­si­ble effec­tive pro­phy­lac­tic rather than spend­ing bil­lions on shut­ting down the econ­o­my. Very sad. Some peo­ple lis­ten and some just dis­miss this advice. Has any­one ever won­dered if The Japanese and oth­er Asian coun­tries’ rel­a­tive­ly low death rate from Covid due to their metic­u­lous gar­gling also advised by their health ministry???

      2. loico

        Great points again, Elaine, thank you, also for men­tion­ing the sprays that we were always going to say some­thing about but some­how nev­er got to doing so.
        Creativity, right­ly under­stood, is indeed what log­ic and sci­ence is all about as we will even­tu­al­ly show. We have actu­al­ly thought about the Japanese expe­ri­ence, yet, cau­tious as we try to be, we were not entire­ly com­fort­able writ­ing about this giv­en the data avail­able to us at the time.

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