Working Paper Hypothesis Version 1 This version is not peer-reviewed

The First, Comprehensive Immunological Model of COVID-19: Implications for Prevention, Diagnosis, and Public Health Measures

Version 1 : Received: 22 April 2020 / Approved: 24 April 2020 / Online: 24 April 2020 (10:25:27 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Pediatric Allergy and Immunology 2020
DOI: 10.1111/pai.13271


The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19.


antibodies; COVID-19; glycans; immunoglobulin M; SARS-CoV-2; pneumonia; prediction; protection



Comments (4)

Comment 1
Received: 28 April 2020
Commenter: Stefano corato
The commenter has declared there is no conflict of interests.
Comment: Thanks so much for this helpful document.
Sorry if I dare such question below.
Once admtitted that the DOSE is a basic factor, I cannot refrain from wondering whether there is a kind of minimum dose under which someone might be contacted by the virus without any symptom.
In very much simple words, I'm thinking that there might a certain minimum dose could acting itself as a kind of vaccine.
In other words, all the people defined as healthy carrier must have contacted before the virus.
Maybe a very small dose leave enough time to the body to react.
Therefore my question would be: "how long does the virus take to duplicate itself inside the mouth and nose and throat?".
Question: "what is the duplication time constant of the virus?"
Thank you very much for your kind attention.
Best Regards.
Stefano Corato.
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Comment 2
Received: 2 May 2020
Commenter: SANTO ARENA
The commenter has declared there is no conflict of interests.
Comment: buongiorno
finalmente un articolo con delle osservazioni a tutto campo, che non si aggrappa alle restrittive teoriedella "storia clinica del paziente", " patologie pregresse" , "familiarita' alle patologie polmonari" ecc.
spero di offrirle (offrirvi) uno spunto per un diverso angolo di visuale
perche' francia e germania (nazioni mitteleuropee) hanno percentuali cosi' diverse?
perche' italia e grecia? (penisole mediterranee)
perche' spagna e portogallo? (la stessa penisola)
perche' belgio e olanda?

la ringrazio per il lavoro che state facendo per tutti noi (e quindi anche per me)
spero di averla incuriosita

buona giornata

santo arena

good morning
finally an article with observations in all fields, which does not cling to the restrictive theorem "clinical history of the patient", "previous pathologies", "familiarity' to lung diseases" etc.
I hope to offer you an idea for a different angle of view
Why do France and Germany (Central European nations) have such different percentages?
Why Italy and Greece? (Mediterranean peninsulas)
Why Spain and Portugal? (the same peninsula)
Why Belgium and the Netherlands?

thank you for the work you are doing for all of us (and therefore also for me) :-)
I hope I’ve intrigued you

good day

santo arena
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Comment 3
Received: 2 May 2020
Commenter: santo arena
The commenter has declared there is no conflict of interests.
Comment: Is it possible that the newborns who developed the infection, cried a lot?
santo arena

e' possibile che i neonati che hanno sviluppato l'infezione, piangessero molto?
santo arena
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Comment 4
Received: 27 May 2020
Commenter: Alhussein El-Shennawy
The commenter has declared there is no conflict of interests.
Comment: My input would be the following:
-Can the ingestion of glutathione rich food with/without whey protein improve outcome of covid-19 high risk population? Even when used as a protective and preventive measure?
-Increasing/modifying glutathione intake should stop or minimize cytokine storm, beside the antioxidant properties of glutathione!
I guess it is worth a try! We have nothing to loose!
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