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COVID19: when you are contagious?

This is a very important question whose answer would allow efficient isolation of asymptomatic cases and subjects with mild symptoms and an easier approach to symptomatic subjects.
Unfortunately we don't have a certain answer, to try to clarify our ideas a little bit let's try to retrace the knowledge that we have acquired since the beginning of the epidemic.
A positive swab is an indication of contagiousness?
At the beginning of the epidemic we had a certainty: a positive swab corresponds to the presence of viruses and therefore the patient should be considered as contagious potential.
It is a reasonable and partly correct assumption but as often happens in Medicine certainties are few and the first doubts came when we saw people with positive swab for a few weeks even in the absence of symptoms.
Many patients continued to have viruses on the mucous membranes and so we feared in a very long contagious phase, even after the symptoms have been resolved.

Doubts increased when the first cases of repositioning were described, i.e. people who, after being infected and having symptoms, they were healed (with the "guarantee" of two negative swabs) but later a positive swab was again found.
Positive patients with symptoms, then negative and then again positive in the absence of symptoms. Situation not easy to interpret that has raised fears of reactivation of the virus or second infections.
Thankfully the Korean CDC (Center for Disease Control and Prevention) did an excellent job of trying to clarify the situation and in May they were published(1) their results (later updated): in South Korea have been identified 447 repositivizations (so positive after healing both clinical and laboratory), the researchers
they were able to study it thoroughly 285 (63,8%), were buffered all their 790 contacts finding only 3 positive who however had had other contacts at risk.
In 108 repositioned cases an attempt was made to grow the virus from tampons without succeeding in a single case.
So the cases of repositioning, with a high probability, even with positive buffer, they don't have on the mucous membranes live virus (crops are negative) and almost certainly aren't contagious.
The hypothesis is that there may remain viral fragments or very few viruses on the mucous membranes even for a few weeks, still detectable by tampons but no longer able to trigger infection in other subjects.
A pillar has therefore fallen: a positive swab doesn't necessarily mean you're contagious.
How long you are contagious?
If the swab is definitely not a sign of contagiousness as we can understand when an infected person is contagious?
To evaluate the contagious period we can see when the virus on the mucous membranes is vital: if in the laboratory on a viral culture we see the effects of a replicating virus then it means that the virus is alive and therefore the patient is potentially contagious.
Unfortunately, viral culture is a complex technique, reserved almost exclusively for research and you can have failures in the culture even in the presence of vital virus.
At the beginning of April an interesting work was published in Nature(2): the virus has been cultivated by 43 positive swabs, without ever being able to proliferate the virus from patients who had symptoms from more than 8 days, unfortunately in the same work you also see many negative crops even after a few days from the beginning of the symptoms and therefore their results, definitely interesting, are not conclusive.
"To understand infectivity, we attempted live virus isolation on multiple occasions from clinical samples (Fig. 1d). Whereas the virus was readily isolated during the first week of symptoms from a considerable fraction of samples (16.66% of swabs and 83.33% of sputum samples), no isolates were obtained from samples taken after day 8 in spite of ongoing high viral loads."
In May comes another important scientific contribution (3) published in Clinical Infectious Disease: the researchers tried to grow the virus from 90 patients succeeding in 26 cases, nobody after the eighth days of symptoms.
"positive cultures were only observed up to day 8 post symptom onset".
This work has also provided valuable data: the viral load on the swabs was related to the probability of having a positive culture, a higher viral load corresponded to a greater probability of being able to grow the virus.
So we can take advantage of our knowledge about viral load and assume that a high viral load is matched by a greater probability of cultivating the virus and therefore that the subject is contagious.
We know that the viral load can be found by 2-3 days before symptoms, maximum in the first days of symptoms and then decreases.
So it's possible that contagiousness follows the same pattern.
The 16 June the World Health Organization(4), also in light of these studies, amended the criteria to consider the isolation of the infected to be concluded, as they are probably no longer contagious.
It is recommended to stop isolating 3 days after the end of the symptoms (and never less than 13 total days) for symptomatic and 10 days from the tampon for asymptomatics.
"-For symptomatic patients: 10 days after symptom onset, plus at least 3 additional days without symptoms (including without fever and without respiratory symptoms)
-For asymptomatic cases: 10 days after positive test for SARS-CoV-2"
After this period you are no longer contagious?
By who's own admission there is a low residual probability and more caution is advised in those who need to come back into contact with frail people (such as healthcare professionals).
"There is a minimal residual risk that transmission could occur with these non-test-based criteria. There can be situations in which a minimal residual risk is unacceptable, for example, in individuals at high risk of transmitting the virus to vulnerable groups or those in high-risk situations or environments."
So we have an idea of the contagious period that might be about 8 days from the onset of symptoms (to which it is reasonable to add a few days out of prudence).
Now another question should arise spontaneously ...
You can be contagious in the absence of symptoms?
In part I already anticipated the answer when I told you that crops are positive when we have a higher viral load. From some works we know (5–7) that asymptomatics have a viral load similar to non-serious symptomatic.
From this consideration we can already assume that it is contagious even in the absence of the symptoms.
In Science, assumptions have a limited weight, let's see if research has led to stronger knowledge.
First of all we have to make a distinction, a person infected with SARSCoV2 may not have symptoms in 2 Situations:
-in the incubation period, that is, in the period between the contagion and the onsus of the symptoms (From 2 in 14 days, on average 5 (8)) Subjects who have been infected and will subsequently develop symptoms are referred to as presintomatic.
– asymptomatic proper: infected subjects but who will never show any symptoms, nothing at all.
Many studies have been carried out to evaluate the contagiousness of the presintomatic and asymptomatic subjects and in the Scientific Literature there is a good agreement: the presintomatic cases (incubation) and asymptomatics can be contagious.
The CDC (9) analysed scientific publications and in July published a review that collects about forty scientific articles highlighting the contagiousness of presymptomatic and asymptomatic cases.
The contagiousness of asymptomatics and presintomatics has been supported by:
1-epidemiological evidence: that is, studying the infections triggered by contact with subjects without symptoms but with subsequent feedback of positive swab.
2-virological evidence: i.e. the detection in presintomatics and asymptomatics of positive swabs, of viral load comparable to symptomatic or positive cultures even in asymptomatics.
3-mathematical models: simulations showed that the epidemic would not have had the same course if asymptomatics and presintomatics were not contagious.
Agatha Christie said: "A clue is a clue, two clues are a coincidence, but three clues give a try"
In Science this is not the case but let's say that we have a lot of evidence to support the contagiousness of both presintomatics and asymptomatics.
Some object that having no symptoms do not cough and do not snee at but everyone talks, Cry, touch the nose and mouth and above all, having no symptoms, they definitely have more contact with other people than those, having symptoms, should stay at home or in the hospital.
The duration of the contagious period in asymptomatics is unclear.
Since the trend of viral load is similar between asymptomatics and symptomatic, we can assume (only this unfortunately for now) that contagiousness follows the same pattern as symptomatic.
Let's see the “Path” of a symptomatic: contagion -> incubation time (2-14 Gg, on average 5 Gg) -> Symptoms.
The contagious phase could begin 2-3 before the symptoms and 8 days after the onset of symptoms, 10-11 days in all.
It is reasonable to think that even asymptomatics can be contagious to 10-11 days but if we don't have the symptoms since we count them?
If we have a positive swab we can count them from that swab assuming it's the first time viruses are present on its mucous membranes.
If we know the moment of contagion we could hypothesize that an asymptomatic subject is contagious up to a maximum of 22 days from the contagion (equivalent of the maximum incubation period, 14 Gg + 8 Gg).
Summarizing, medical literature suggests that:
-the contagious phase may begin before the symptoms (presintomatics), is maximum in the first days of symptoms and decreases significantly after the eighth day.
-asymptomatics are most likely contagious, maybe for 2-3 weeks from the contagion, maximum.
-the data in our possession are not conclusive and therefore you must be cautious especially when in contact with serious patients and with respect to those who are in contact with fragile people (e.g. healthcare personnel).
Bibliography
1. KCDC. Findings from investigation and analysis of re-positive cases [Internet]. 2020. Available from: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030&act=view property&list_no=367267&nPage=8&fbclid=IwAR1mtqQvegCiH_T2Eya5NaNtSeVZ2OtUBkUpRbtBs_q57oC-8lNZZkjCMNE #
2. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature, New Year' [Internet]. 2020 May, New10 1;581(7809):465–9. Available from: http://www.nature.com/articles/s41586-020-2196-x
3. Bullard J, Dust K, Funk D, Strong JE, Alexander D, Garnett L, et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis [Internet]. 2020 May, New10 22; Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa638/5842165
4. Who. Criteria for releasing COVID-19 patients from isolation [Internet]. 2020. Available from: https://www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolation
5. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients [Internet]. Vol. 382, New England Journal of Medicine. Massachussetts Medical Society; 2020 [cited 2020 Apr 22]. p. 1177–9. Available from: http://www.nejm.org/doi/10.1056/NEJMc2001737
6. Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Del Vecchio C, et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature, New Year' [Internet]. 2020 Jun 30; Available from: http://www.nature.com/articles/s41586-020-2488-1
7. Long Q-X, Tang X-J, Shi Q-L, Li Q, Deng H-J, Yuan J, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med [Internet]. 2020 Jun 18; Available from: http://www.nature.com/articles/s41591-020-0965-6
8. Cdc. Coronavirus symptoms [Internet]. 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html?CDC_AA_refVal=https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html
9. Cdc. Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic [Internet]. 2020. Available from: https://wwwnc.cdc.gov/eid/article/26/7/20-1595_article?fbclid=IwAR01oG1F_E09ob0ugebOtLHHNL25gaalqsACpo7gBe-8p7nyqmuF5q5h2gA