Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome

被引:57
作者
Buonsenso, Danilo [1 ]
Piazza, Michele [2 ]
Boner, Attilio L. [2 ]
Bellanti, Joseph A. [3 ,4 ,5 ]
机构
[1] Ist Ricovero & Cura Carattere Sci, Dept Woman & Child Hlth & Publ Hlth, Fdn Policlin Univ A Gemelli, Rome, Italy
[2] Univ Verona, Dept Surg Dent Paediat & Gynaecol, Pediat Sect, Verona, Italy
[3] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA
[4] Georgetown Univ, Med Ctr, Dept Microbiol Immunol, 3900 Reservoir Rd NW,Room 308 NW, Washington, DC 20057 USA
[5] Georgetown Univ, Med Ctr, Int Ctr Interdisciplinary Studies Immunol, Washington, DC 20057 USA
关键词
EXPRESSION;
D O I
10.2500/aap.2022.43.220018
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor K B (NF-KB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production. Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as ???long COVID??? Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome. (Allergy Asthma Proc 43:187???193, 2022; doi: 10.2500/aap.2022.43.220018)
引用
收藏
页码:187 / 193
页数:7
相关论文
共 54 条
[1]   Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms [J].
Andrade, Bruno Silva ;
Siqueira, Sergio ;
de Assis Soares, Wagner Rodrigues ;
Rangel, Fernanda de Souza ;
Santos, Naiane Oliveira ;
Freitas, Andria dos Santos ;
da Silveira, Priscila Ribeiro ;
Tiwari, Sandeep ;
Alzahrani, Khalid J. ;
Goes-Neto, Aristoteles ;
Azevedo, Vasco ;
Ghosh, Preetam ;
Barh, Debmalya .
VIRUSES-BASEL, 2021, 13 (04)
[2]   Long COVID and kids: more research is urgently needed [J].
不详 .
NATURE, 2022, 602 (7896) :183-183
[3]   Female gender is associated with long COVID syndrome: a prospective cohort study [J].
Bai, Francesca ;
Tomasoni, Daniele ;
Falcinella, Camilla ;
Barbanotti, Diletta ;
Castoldi, Roberto ;
Mule, Giovanni ;
Augello, Matteo ;
Mondatore, Debora ;
Allegrini, Marina ;
Cona, Andrea ;
Tesoro, Daniele ;
Tagliaferri, Gianmarco ;
Vigano, Ottavia ;
Suardi, Elisa ;
Tincati, Camilla ;
Beringheli, Tomaso ;
Varisco, Benedetta ;
Battistini, Chiara Luridiana ;
Piscopo, Kyrie ;
Vegni, Elena ;
Tavelli, Alessandro ;
Terzoni, Stefano ;
Marchetti, Giulia ;
Monforte, Antonella D'Arminio .
CLINICAL MICROBIOLOGY AND INFECTION, 2022, 28 (04) :611.e9-611.e16
[4]   Role of the Microbiota in Immunity and Inflammation [J].
Belkaid, Yasmine ;
Hand, Timothy W. .
CELL, 2014, 157 (01) :121-141
[5]  
BELLANTI JA, 1971, LANCET, V2, P526
[6]  
Bellanti JA., 2012, Immunology IV: Clinical Applications in Health and Disease
[7]   TLR7 Ligands induce higher IFN-α production in females [J].
Berghofer, Beate ;
Frommer, Ture ;
Haley, Gabriela ;
Fink, Ludger ;
Bein, Gregor ;
Hackstein, Holger .
JOURNAL OF IMMUNOLOGY, 2006, 177 (04) :2088-2096
[8]   SARS-CoV2 entry and spread in the lymphatic drainage system of the brain [J].
Bostanciklioglu, Mehmet .
BRAIN BEHAVIOR AND IMMUNITY, 2020, 87 :122-123
[9]   Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19 [J].
Bousquet, Jean ;
Anto, Josep M. ;
Czarlewski, Wienczyslawa ;
Haahtela, Tari ;
Fonseca, Susana C. ;
Iaccarino, Guido ;
Blain, Hubert ;
Vidal, Alain ;
Sheikh, Aziz ;
Akdis, Cezmi A. ;
Zuberbier, Torsten ;
Abdul Latiff, Amir Hamzah ;
Abdullah, Baharudin ;
Aberer, Werner ;
Abusada, Nancy ;
Adcock, Ian ;
Afani, Alejandro ;
Agache, Ioana ;
Aggelidis, Xenofon ;
Agustin, Jenifer ;
Akdis, Cezmi A. ;
Akdis, Mubeccel ;
Al-Ahmad, Mona ;
Al-Zahab Bassam, Abou ;
Alburdan, Hussam ;
Aldrey-Palacios, Oscar ;
Alvarez Cuesta, Emilio ;
Alwan Salman, Hiba ;
Alzaabi, Ashraf ;
Amade, Salma ;
Ambrocio, Gene ;
Angles, Rosana ;
Annesi-Maesano, Isabella ;
Ansotegui, Ignacio J. ;
Anto, Josep M. ;
Ara Bardajo, Paula ;
Arasi, Stefania ;
Arrais, Margarete ;
Arshad, Hasan ;
Artesani, Maria-Cristina ;
Asayag, Estrella ;
Avolio, Francesca ;
Azhari, Khuzama ;
Bachert, Claus ;
Bagnasco, Diego ;
Baiardini, Ilaria ;
Bajrovic, Nissera ;
Bakakos, Petros ;
Bakeyala Mongono, Sergio ;
Balotro-Torres, Christine .
ALLERGY, 2021, 76 (03) :735-750
[10]   Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors [J].
Brigelius-Flohe, Regina ;
Flohe, Leopold .
ANTIOXIDANTS & REDOX SIGNALING, 2011, 15 (08) :2335-2381