The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

Pediatric Allergy and Immunology - Tập 31 Số 5 - Trang 454-470 - 2020
Paolo Maria Matricardi1, Roberto W. Dal Negro2, Roberto Nisini3
1Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
2National Centre of Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy
3Unit of Immunology Dipartimento di Malattie Infettive Istituto Superiore di Sanità Rome Italy

Tóm tắt

AbstractThe natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10‐15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose‐binding lectin). 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. Low‐moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID‐19 facilitates re‐inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies ("viral auto‐inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches 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 at all ages.

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Pediatric Allergy and Immunology

Tập 31 Số 5

454-470

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