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There are a lot of people that are testing positive for covid that have no symptoms (ie they are asymptomatic). This raises the question - does the current test have an unacceptably high rate of false positives? From a physiological point of view, doesn't an active viral infection of any sort generate tissue damage and hence some sort of response (immunological, inflamatory, histochemical, etc) that DOES lead to outward symptomology? Viral replication necessarily causes tissue damage (is there a human virus of any sort that does not?). Tissue damage, especially in the upper airway and lungs, would (it seems to me) cause a response (coughing, perhaps fever, etc) yet we are told that covid is capable of causing asymptomatic infection. Is this really plausible? We seem to only have these swab tests as the only indicator telling us these asymptomatic people have the covid infection (or the virus is present in their airways). This is, naturally, a huge public health and social problem if these tests are false-positives.

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  • $\begingroup$ Typhoid is an example of an infection that even when it causes symptoms - the symptoms are not readily visible by a bystander (ie caughing by someone with covid). Is there any other example of an upper respiratory or lung infection that does not cause symptoms ? The covid test was necessarily rushed into production and that leaves a reasonable chance that it may give false positive results. And even if covid is somehow able to replicate in the lungs and upper respiratory tract without eliciting an inflamatory response, then how can that person be contageous IF THEY ARE NOT COUGHING? $\endgroup$ – Peggy Schafer Apr 19 '20 at 19:09
  • $\begingroup$ Pine Street Inn homeless shelter in Boston - Of the 397 people tested, 146 people tested positive. Not a single one had any symptoms. Testing of the entire crew of the aircraft carrier Theodore Roosevelt - at least 655 Roosevelt sailors have now tested positive - the majority have displayed no symptoms. $\endgroup$ – Peggy Schafer Apr 19 '20 at 19:40
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    $\begingroup$ As far as asymptomatic caries of other respiratory diseases: in one study Asymptomatic rhinovirus infection outnumbers symptomatic infection four to one among university students $\endgroup$ – Charles E. Grant Apr 19 '20 at 20:29
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    $\begingroup$ @Bryan Krause: what you consider "bad" about the question could be implying that tests should indicate "symptomatic infections" only - at the same time, it's been said that there are asymptomatic infections that are "infectious". So, the question seem unclear about "infectious infections" that are not symptomatic. Am I allowed to set up some "draft answer" based on definitions? To me, Stackexchange has got all the forms and frames needed to discuss - peers should be more tolerant towards "draft" questions. e.g. answers her to me "do not answer the question", however, they are (answers). $\endgroup$ – Peter Bernhard Dec 9 '20 at 12:14
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    $\begingroup$ There are many examples of asymptomatic virus infections. For instance, person can be infected with HIV for years before noticable symptoms appear. Then there's the varicella-zoster virus that gave you chicken pox when you were a kid, only to lie dormant for half a century before reappearing as shingles. $\endgroup$ – jamesqf Dec 23 '20 at 17:52
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It isn't just Sars-Cov-2. Many diseases and medical conditions are known to be asymptomatic in some people. The most famous asymptomatic carrier of a bacterial disease was Mary Mallon ("Typhoid Mary"), a woman who was permanently infected by the Salmonella typhi bacteria. She had no ill effects from the infection but spread it to many other people until she was forced into quarantine.

The underlying issue is that our immune systems are highly variable from person to person.

Tissue damage, especially in the upper airway and lungs, would (it seems to me) cause a response (coughing, perhaps fever, etc)

It isn't that binary. Your respiratory system is constantly being damaged by pathogens and pollutants, but your body is constantly repairing the damage.. As long as the rate of repairs can keep up with the rate of damage, you may not notice anything. When you feel sick from something like Sars-Cov-2, it's an indication that the pathogen is causing damage faster then it can be repaired. The balance between these depends both on how fast your immune system responds, and how efficiently your repair mechanisms work. Both of these can vary widely between individuals, depending on both genetics and the environment.

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First, the 60% asymptomatic numbers for the Roosevelt are fairly consistent (adjusting for age) with those from the Diamond Princess: about 50% at the peak of the infection, but in a much older population. (Also you can be pretty sure the Japanese were using a different test kit [in February] than the US.)

Second, asymptomatic when tested, doesn't mean you won't develop symptoms later, as the damage accumulates. (In fact, accumulated lung damage is the main problem with Covid-19; see q on Skeptics on the death of Rooselvelt sailor.) Nonetheless, the presymptomatic people can shed enough virus to infect others:

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector–infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

And yeah, this asymptomatic presentation is not unique to Covid-19 among respiratory diseases. Influenzas cause this too:

We identified 235 virologically confirmed secondary cases of influenza virus infection in the household setting, including 31 (13%) paucisymptomatic and 25 (11%) asymptomatic cases. The duration of viral RNA shedding was shorter and declined more rapidly in paucisymptomatic and asymptomatic than in symptomatic cases. The mean levels of influenza viral RNA shedding in asymptomatic and paucisymptomatic cases were approximately 1–2 log10 copies lower than in symptomatic cases.

It does seem to be that case that the less "sick"/symptomatic shed less virus, in influenza at least, and probably by analogy in Covid-19 as well.

The degree of asymptomatic presentation can vary between strains (and likewise by age group) even for viruses that are pretty similar, like the "common cold" CoVs:

enter image description here

(If you want to know more about the specificity of Covid-19 tests, ask on med SE. Your question was pretty broad, and I can't touch all the angles here. I've only shown you that asymptomatic cases in other viral respiratory illnesses are not uncommon.)

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To answer your question it is necessary to distinguish the concepts of:

  • infection
  • symptom
  • test set up

The term infection might even denote the swallowing of a "dose from a nose", without any replication of virus. On the other side of the ladder, "infection" might refer to a symptomatic disease. However, "to explain infection without symptoms" implies that there does exist some stage in between - and "replication of virus within individual cells of the body" might "explain infection without symptoms" in the sense of the question.

Moreover, defining infection by "infection of single cells" is the basis for test set ups: "take" a "dose of the nose": a test would not run the risk of false positive results just to include that rare case of an infection that has not reached the stage of viral replication. (And a test should not run the risk of false negative by setting the minimum that high that viral replication surely leads to symptoms).

Most important, the key concept "viral replication" explains why there may be contagiousness (there is no such term as "infectiousness", but a contagious person "always" is considered "infected", of course) without symptoms: viral replication does not imply symptoms of the disease.

The above should explain why there is infection=disease without symptoms, in principle.

Cp. https://www.verywellhealth.com/how-do-you-define-asymptomatic-2721956 where they talk of "over-diagnosis" which might be the opposite to "symptomless spread", as you might get treated not because of being sick "just a little bit" (without being infectious). For Diseases that do not exhibit symptoms cp. https://en.wikipedia.org/wiki/Asymptomatic. Maybe you speak of "asymptomatic disease" if there are some persons that do not show symptoms compared to persons that do exhibit symptoms, both groups refering to a common denominator, "viral load" for instance.

To answer the question which refers to Covid-19 one must look at the symptoms of covid. How can it be that viral replication in the case of CoV-19 does not INSTANTANEOUSLY lead to symptoms - if AT ALL?

A common concept is to differentiate symptoms that result from the activity of immune cells from those symptoms that result from the destruction of the infected individual body cells, which is a common differentiation.

It seems difficult to find reputable sources googling as with Covid it is mostly "explaining asymptomatic spreading" that is the main issue. Your question pertains to that as well, but focuses on "explain asymptomatic disease" - which might be considered a self-contradictory concepts as it denotes some "hidden disease" that should have certain symptoms that are just not being unveiled.

To "explain asymptomatic infectiousness", compare for instance https://www.nejm.org/doi/full/10.1056/NEJMe2009758 "A key factor in the transmissibility of Covid-19 is the high level of SARS-CoV-2 shedding in the upper respiratory tract,1 even among presymptomatic patients, which distinguishes it from SARS-CoV-1, where replication occurs mainly in the lower respiratory tract."

One more link: https://www.nejm.org/doi/full/10.1056/NEJMe2009758 refering to influenza (the more viral load in the upper tract the more symptoms - which should not explain asymptomatic transmission)

Some reputable source on "asymptomatic disease" (i.e. not on asymptomatic spread): "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections" https://www.nature.com/articles/s41591-020-0965-6

There are attempts at explaining "asymptomatic covid-disease" specifically. However, for instance, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30460-6/fulltext specifically names "Lactate dehydrogenase" which seems to refer to the immune system in a corona-unspecific way, i.e. seems to refer to individuals' being different in strength of their immune systems.

Here is my own personal approach based on the type of target cells of Covid, which are epithelial cells called "pneumocytes II" (target antigen of the spike is ACE2)

  1. As target cells are stem cells their loss of function in replacing dead epithelial cells (whose apoptosis is a regular one and, interestingly, not caused by the virus!) might be felt only very late or not at all

  2. The second function of Covid's target cells, pneumocytes II, besides their function as stem cells renewing epthelium, ist the production of surfactant. Hereby, I tentatively hypthesize that loss of that function of only leads to symptoms of shortage of breath if the muscle activity of breathing in (which is supported by surfactant) does not overcompensate the loss of surfactant when the breathing activity of the patient in general is low.

  3. I had to rule out my idea that the inflammatory reaction, in asymptomatic cases, might even be less in degree than with common cold caused by corona virus because stem cells as such should be lesser in number compared to differentiated epithelial cells - this idea is wrong: counterintuitively, stem cells, i.e. pneumocytes II are much higher in number than pneumocytes type I.

For whom it may concern some explanatory remarks on "infection and symptoms" in abstract terms:

The term symptom according to commmon usage refers to the signs sick person present with when they feel at uneas. However, in a more intricate way, "symptomatic" might be defined as: infection of single body cells causing replication of virus. In that case, there would not exist any "asymptomatic infection" as that would be self-contradictory: if "symptom" does come with "infection" - of one single cell.

To explain asymptomatic infection the underlying concepts of "symptom" and "infection" must clearly be set apart. The replication of the virus (infection) is different from the symptoms as consequences of this event. Viruses only replicate in cells, thus turning a test to a positive result, and only then (not before infection of single cell, "after contact".)

On the other hand, tests are not set up to turn positive before this replication starts, as it is the basis for contagiousness. Your question may seem to blame tests for being "false positive". However, tests are not set up to show negative results when it's only the symptoms that do not show, but the cells have harboured viruses that have replicated, thus causing contagiousness. Test are truly positive when they indicate virus replication only, and, on the other hand, presumably only turn positive if there ,in fact, has been some minimal infection of single cells, thus indicating some more virus than has been inhaled.

If there is "infection without symptoms" this might quite easily be explained by the symptoms being caused be the reaction of the immune system, not by the loss of function of body cells. There may be a common situation where epithelial cells are infected already, implying virus replication, thus contagiousness - without the immune system causing the symptoms, and no defunct epithelial cells either, thus resulting in a test being positive showing "symptomless infection".

For a very up-to-date and surprising alternative answer to your question that refers to insertion of viral RNA as DNA into the genome (retroviral like mechanism ) that is detected by positive testing "without symptoms" see the following reference.

https://www.sciencemag.org/news/2020/12/coronavirus-may-sometimes-slip-its-genetic-material-human-chromosomes-what-does-mean

which is like a review of the reference in some other question at stackexchange Does SARS-CoV-2 kill its host cell or not?

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    $\begingroup$ This is a (not very good) criticism of the question, but by no stretch of the imagination an answer to it. Answers should be answers. If you have $\endgroup$ – David Dec 9 '20 at 19:22
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    $\begingroup$ By adding some "no stretching" to your comment it becomes much more "substantial" (don't know how to say in English) than what I have gotten used to around here - so sad.... $\endgroup$ – Peter Bernhard Dec 11 '20 at 9:37
  • $\begingroup$ @David Please see - I coorected the criticism you criticized as - yes, indeed - it is incoherent to my commenting on "first comment" of question. Let me know if this is being unclear to you. $\endgroup$ – Peter Bernhard Dec 11 '20 at 9:58
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    $\begingroup$ This still doesn't answer the question. Symptoms are defined, for xample see here. It does not mean the infection of the body with a pathogen. $\endgroup$ – Chris Dec 11 '20 at 10:05
  • $\begingroup$ @user1136 All this flagging makes me look important. So I should get along alone very well as soon as you have skipped me out :-) What you're saying suits me fine! You are right. I haven't said anything to the contrary. Your reproach is that I haven not answered what the question is about, and you have? $\endgroup$ – Peter Bernhard Dec 14 '20 at 10:50

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