For a month it is very fashionable to talk about viral charge of SARSCoV2, often associating it with concepts that are not quite correct.
Let's try to make some clarity by analyzing the various works published by the Scientific Literature.
First of all, what is viral upload? How to measure?
Viral load refers to the concentration of virus present or in the blood or, as in the case of SARSCoV2, on mucous.
In clinical practice, through the now famous tampons, you go to look for some fragments of genetic material of the virus and the examination can give us 3 Results: Negative, weakly positive, Positive.
To calculate the viral load, you have to use more complex methods that, For now, are reserved exclusively for research.
The genetic material is amplified until the machine can detect certain viral genes, more amplification cycles are needed to detect them and fewer viruses were present at the start.
From a scientific point of view it is very important to study the viral load present on mucous, also to get an idea of the contagiousness of the subjects: the more viruses there is on the mucous it's more easily you are contagious
Viral charge is indicative of contagiousness?
This is a reasonable intake valid for other infectious diseases but difficult to prove.
Canadian researchers tried it by publishing their work in May on Clinical Infectious Diseases(1).
Their idea was: if I can grow the virus in vitro from the tampon it means that the virus is vital, potentially infecting.
Viral culture, unlike bacterial culture, is much more complex and failures are expected even in the presence of abundant and vital viruses.
Starting with 90 positive swabs have managed to grow the virus in 26 cases. Interestingly, a significant correlation has been noted between viral load and the likelihood of having a positive culture.
“Multivariate logistic regression using positive culture as a predictor variable (binary result) and STT, age and gender as independent variables showed Ct as being significant (OR 0.64 95% CI 0.49-0.84, p<0.001). This implies that for every one unit increase in Ct, the odds of a positive culture decreased by 32%.>< 0.001) This implies that for every one unit increase in Ct, the odds of a positive culture decreased by 32%.” (per cicli di replicazioni più bassi ci si aspetta una carica virale più alta)
Qual è la carica virale degli asintomatici?
The 19 febbraio, almeno 2 days before any Italian could boast of being an expert on COVID, a letter was published to the publishers in the New England Journal of Medicine(2), in which a group of Chinese researchers described the viral load of 17 infected subjects and concluded:
"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"
Yes, you got it right, The 19 In February, Chinese doctors warned the world that patients with asymptomatic or few symptoms could have a viral charge on symptomatic mucous and could therefore be just as contagious.
Very clear message, published for free on 19 February in one of the most prestigious scientific journals.
It was a letter to the publishers, not a real study. To be considered but always with a reasonable doubt.
In early April, the results of the studies of Prof Crisanti's group on the management of the Vo' Euganeo outbreak are disclosed..
In their work, they are identified 42,5% asymptomatics.
Viral charge of 23 asymptomatic subjects, 3 pre-symptomatic subjects (incubation) and 30 symptomatic subjects.
Their conclusions were:
"We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections".
Another confirmation last to digest. In April this was "just" a pre-print article, not screened by the scientific community, potentially full of errors. Unfortunately for the epidemic, fortunately for science, errors have not found them and after 2 months of review was published today, 30 June, about another very important magazine: Nature, New Year'(3).
It's not enough, The 18 June is published in Nature Medicine(4) another article written by Chinese colleagues in which they were evaluated 37 asymptomatic patients 37 Symptomatic.
Their results confirm what we have seen previously:
"The initial Ct values for 37 asymptomatic individuals and 37 symptomatic patients appeared similar"
It also describes a longer time of elimination of the virus in asymptomatics than symptomatic. Another nice blow for those trying to control this epidemic.
It seems that asymptomatics have the same viral load as symptomatic but that it lasts longer.
Until now, symptomatic but non-serious patients have been assessed.
What is the viral load in severe forms?
Here the discourse changes. The 19/3 a letter is published to the publishers of Lancet Infectious Disease(5) Describes the viral load of 46 symptomatic patients with mild and mild forms 30 with severe forms.
"Patients with severe COVID-19 tend to have a high viral load and a long virus shedding period."
So severe forms have a larger viral load and that lasts longer.
A study on 92 Patients(6) described a greater viral load in severe forms than moderate ones:
"severe patients had significantly lower Ct values than mild-moderate cases at admission" (a low number of replication cycles, Ct, suggests a high viral charge)
Another more systematic study, conducted on 308 hospitalized patients(7) experienced significantly higher viral load in critical patients than other patients:
"Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads"
How viral charge changes over time?
On this point there seems to be a similar pattern between the various forms of the disease (Symptomatic, Asymptomatic, intermediate and severe forms): Viral charge is maximum all’start and decays with time (3,5,7).
"We find that the viral load tends to peak around the day of symptom onset and for most of the subjects tends to decline after symptom onset (Vo)” (3)
Another interesting data can be obtained by assessing the progress of viral load in patients who have or have not developed immunoglobulines(8).
Immunoglobulines are produced after 7-10 days after contagion and represent a response of our immune system.
Researchers have shown that there is a gradual decline in viral load in non-serious patients who have immunoglobulines while in patients who have not yet developed immunoglobuline, viral load continues to grow.
"Among IgM positive patients, viral loads showed different trends among cases with different severity, while viral loads of IgM-negative patients tended to increase along with the time after onset."
Viral load is an indicator of the severity of the disease?
We have seen that the most severe forms have a greater viral load, it is also reasonable to wonder whether a higher viral load on debut corresponds to a worse course.
As early as April, Chinese colleagues(6) described that patients with higher viral loads onset developed a more serious disease.
"patients with a higher baseline viral load are more likely to become severe".
A very comprehensive study has just been published, conducted by colleagues in New York(9): viral load was verified on the debut of well 678 patients hospitalized 2 big hospitals in the Big Apple.
They divided the tampons into 3 groups based on viral load and assessed the probability of being intubated and mortality.
"In a multivariate model [...], having a high viral load was independently associated with increased risk of in-hospital mortality (adjusted odds ratio [aOR] 6.05; 95% CI: 2.92-12.52; P<0.001) compared to having a low viral load”
“Compared to those with a low viral load, having a high viral load was also independently associated with increased risk of intubation (aOR 2.73; 95% CI: 1.68-4.44; P<0.001)”
Quindi chi ha una bassa carica virale ha minore probabilità di essere intubato e di morire.
Ho trovato questo articolo molto interessato e mi sembra corretto spendere qualche parola in più su alcuni dati che emergono.
“Of the 49 patients who had a positive SARS-CoV-2 test but were discharged from the ED and not admitted, the median Ct value was 29.1" (And: emergency department)
The 49 patients discharged from the emergency room (so probably with mild forms) they had an average viral load that fell into the middle class.
Another important consideration: Of 727 (678 + 49) patients who have swab in the emergency room only on 7% he was discharged.
New York has experienced the same drama as so many great hospitals in Lombardy: who could get to the hospital is because he needed a bed.
Overall mortality also had data similar to our:
"19.2% of patients had died during their admission"
Excuse the excursus, let's go back to the topic.
So let's come to the fateful question: the viral load in Italy has changed?
The 29/5 was sent to the journal Clinical Chemistry and Laboratory Medicine the work of the san Raffaele group in Milan(10), not yet published but already peer-reviewed and accepted 4/6 (available on Reserchgate)
In this work, they were assessed 100 swabs made between 7 and 10 April and 100 swabs made between 12 and 19 May.
The groups were homogeneous with regard to sex, age and percentage of hospitalized patients (12 Vs 14%).
Tampons carried out in May had a significantly lower viral charge than those carried out in April.
From the other articles we have seen that the main factors influencing the average viral load of a group of subjects are the share of severe patients and the distance between symptoms/contagion and the tampon.
Unfortunately, these data were not explained in the study and, in my opinion, does not allow a full analysis, especially considering how the use of tampons in Italy has changed in the epidemic: in March in Lombardy swabs were made almost exclusively to patients who were considering hospitalization, now extensive use of tampons is made and a lot of asymptomatics emerge. In addition, since May, massive use of serological products has been made, starting with quarantined subjects and health professionals., highlighting so many positives studied with tampon, whose positivity was indicative of an infection of at least 7-10 days.
-viral charge is an index of contagiousness
-asymptomatics have a viral load similar to non-serious symptoms.
-in severe forms, a significantly higher viral load is observed
-the viral charge is maximum in the first days and decays with time, especially in patients with Ig
-high viral loads onset are characterized by a worse prognosis
-In medical terms asymptomatics are the infected people who never have any symptoms.
-Viral load and infecting charge are 2 different concepts: viral load is the amount of virus present on mucous, I talked about in this post; the infecting charge is the amount of virus with which a subject is infected. It has not yet been clarified whether a low infecting charge really corresponds to a minor condition, it's possible but it hasn't been proven yet and anyway it's not certain.
1. 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
2. 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
3. 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
4. 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
5. Liu Y, Yan L-M, Wan L, Xiang T-X, Le A, Liu J-M, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis [Internet]. 2020 Mar 19; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32199493
6. Yu X, Sun S, Shi Y, Wang H, Zhao R, Sheng J. SARS-CoV-2 viral load in sputum correlates with risk of COVID-19 progression. Crit Care [Internet]. 2020 Dec 23;24(1):170. Available from: https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02893-8
7. Huang J-T, Ran R-X, Lv Z-H, Feng L-N, Ran C-Y, Tong Y-Q, et al. Chronological Changes of Viral Shedding in Adult Inpatients with COVID-19 in Wuhan, China. Clin Infect Dis [Internet]. 2020 May, New10 23; Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa631/5843466
8. Shi F, Wu T, Zhu X, Ge Y, Zeng X, Chi Y, et al. Association of viral load with serum biomakers among COVID-19 cases. Virology [Internet]. 2020 Jul;546:122–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0042682220300787
9. Magleby R, Westblade LF, Trzebucki A, Simon MS, Rajan M, Park J, et al. Impact of SARS-CoV-2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients with Coronavirus Disease 2019. Clin Infect Dis [Internet]. 2020 Jun 30; Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa851/5865363
10. Clementi N, Ferrarese R, Tonelli M, Amato V, Racca S, Locatelli M, et al. Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital. Clin Chem Lab Med. 2020;