With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.

ALL MED Medical Research Institute Wroclaw Poland

Allergy and Clinical Immunology Transylvania University Brasov Romania

ARADyAL RD16 0006 0015 Thematic Network and Cooperative Research Centers ISCIII Madrid Spain

Center for Allergy and Environment Technical University and Helmholtz Center Munich Munich Germany

Centre for Inflammation Research and Child Life and Health The University of Edinburgh Edinburgh UK

Children's Allergy Service Evelina Children's Hospital Guy's and St Thomas' Hospital NHS Foundation Trust London UK

Christine Kühne Center for Allergy Research and Education Davos Switzerland

Comparative Medicine Interuniversity Messerli Research Institute University of Veterinary Medicine and Medical University Vienna Austria

Department of Allergology and Internal Medicine Medical University of Bialystok Poland

Department of Allergy and Clinical Immunology National Research Institute for Child Health and Development Japan

Department of Biochemistry and Molecular Biology Chemistry School Complutense University of Madrid Madrid Spain

Department of Clinical Immunology Wroclaw Medical University Wrocław Poland

Department of Immunology and Oncology Centro Nacional de Biotecnología Madrid Spain

Department of Immunology Motol University Hospital 2nd Faculty of Medicine Charles University Prague

Department of Immunology University of Toronto Toronto ON Canada

Department of Paediatric Medicine Franciscus Gasthuis and Vlietland Rotterdam the Netherlands

Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada

Department of Pediatric Basic Sciences Institute of Child Health Istanbul University Istanbul Turkey

Department of Pediatric Pneumonology and Allergy Medical University of Warsaw Warsaw Poland

Department of Regenerative Medicine and Immune Regulation Medical University of Bialystok Bialystok Poland

Department of Rheumatology Medical University of Lodz Lodz Poland

Departments of Immunology and Dermatology Allergology University Medical Center Utrecht Utrecht the Netherlands

Departments of Medicine and Microbiology APC Microbiome Ireland University College Cork Cork Ireland

Division of Allergy Immunology and Rheumatology Department of Medicine Stanford University Stanford CA USA

Division of Immunology and Allergy Food Allergy and Anaphylaxis Program The Hospital for Sick Children Toronto ON Canada

Division of Pediatric Allergy and Immunology Department of Pediatrics Istanbul Faculty of Medicine Istanbul University Istanbul Turkey

Division of Pulmonary and Critical Care Medicine Department of Medicine Stanford University Stanford CA USA

Faculty of Science Charles University Prague Czech Republic

Genetics of Cognition laboratory Istituto Italiano di Tecnologia Genova Italy

Immunomodulation and Tolerance Group Allergy and Clinical Immunology Inflammation Repair and Development National Heart and Lung Institute Imperial College London Asthma UK Centre in Allergic Mechanisms of Asthma London UK

Institute of Applied Molecular Medicine Hospitals Madrid Group San Pablo CEU University Madrid Spain

Institute of Pathophysiology and Allergy Research Center of Pathophysiology Infectiology and Immunology Medical University of Vienna Vienna Austria

Paediatric Allergy Group Department of Women and Children's Health School of Life Course Sciences St Thomas' Hospital King's College London London UK

Paediatric Allergy Group Peter Gorer Department of Immunobiology School of Immunology and Microbial Sciences Guys' Hospital King's College London London UK

Sean N Parker Center for Allergy and Asthma Research at Stanford University Stanford University Stanford CA USA

SKIN Research Group Department of Dermatology Vrije Universiteit Brussel Universitair Ziekenhuis Brussel Brussels Belgium

Swiss Institute of Allergy and Asthma Research University of Zurich Davos Switzerland

Translational Medicine Program Research Institute The Hospital for Sick Children Toronto ON Canada

University Heart Center Zurich University Hospital Zurich Zurich Switzerland

Zobrazit více v PubMed

Li W, Shi Z, Yu M, et al. Bats are natural reservoirs of SARS‐like coronaviruses. Science. 2005;310(5748):676‐679. PubMed

Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181‐192. PubMed PMC

Zhang YZ, Holmes EC. A genomic perspective on the origin and emergence of SARS‐CoV‐2. Cell. 2020;181(2):223‐227. PubMed PMC

Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel coronavirus (2019‐nCoV) originating in China. Cell Host Microbe. 2020;27(3):325‐328. PubMed PMC

Wang Q, Zhang Y, Wu L, et al. Structural and functional basis of SARS‐CoV‐2 entry by using human ACE2. Cell. 2020;181(4):894‐904.e9. PubMed PMC

van de Veerdonk FL, Netea MG, van Deuren M, et al. Kallikrein‐kinin blockade in patients with COVID‐19 to prevent acute respiratory distress syndrome. eLife. 2020;9. PubMed PMC

Hoffmann M, Kleine‐Weber H, Schroeder S, et al. SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271‐280.e8. PubMed PMC

Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015;116:76‐84. PubMed PMC

Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS‐CoV‐2. Proc Natl Acad Sci USA. 2020;117(21):11727‐11734. PubMed PMC

Radzikowska U, Ding M, Tan G, et al. Distribution of ACE2, CD147, CD26 and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors. Allergy. 2020. 10.1111/all.14429 PubMed DOI PMC

Sungnak W, Huang NI, Bécavin C, et al. SARS‐CoV‐2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26(5):681‐687. PubMed PMC

Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS‐CoV‐2 receptor ACE2 is an interferon‐stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181(5):1016–1035.e19. 10.1016/j.cell.2020.04.035 PubMed DOI PMC

Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135‐140. PubMed PMC

Wang K, Chen W, Zhou YS, et al. SARS‐CoV‐2 invades host cells via a novel route: CD147‐spike protein. bioRxiv. 2020;preprint:2020.2003.2014.988345.

Chen Z, Mi LI, Xu J, et al. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis. 2005;191(5):755‐760. PubMed PMC

Pushkarsky T, Zybarth G, Dubrovsky L, et al. CD147 facilitates HIV‐1 infection by interacting with virus‐associated cyclophilin A. Proc Natl Acad Sci USA. 2001;98(11):6360‐6365. PubMed PMC

Watanabe A, Yoneda M, Ikeda F, Terao‐Muto Y, Sato H, Kai C. CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells. J Virol. 2010;84(9):4183‐4193. PubMed PMC

Akkus MN, Ormam A, Seyis S, Baran C, Gorur A, Bilen MN. Plasma EMMPRIN levels in acute myocardial infarction and stable coronary artery disease. Clin Invest Med. 2016;39(3):E79‐87. PubMed

Yurchenko V, Constant S, Eisenmesser E, Bukrinsky M. Cyclophilin‐CD147 interactions: a new target for anti‐inflammatory therapeutics. Clin Exp Immunol. 2010;160(3):305‐317. PubMed PMC

Hibino T, Sakaguchi M, Miyamoto S, et al. S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis. Cancer Res. 2013;73(1):172‐183. PubMed

Kato N, Yuzawa Y, Kosugi T, et al. The E‐selectin ligand basigin/CD147 is responsible for neutrophil recruitment in renal ischemia/reperfusion. J Am Soc Nephrol. 2009;20(7):1565‐1576. PubMed PMC

Seizer P, Borst O, Langer H, et al. EMMPRIN (CD147) is a novel receptor for platelet GPVI and mediates platelet rolling via GPVI‐EMMPRIN interaction. Thromb Haemost. 2009;101(4):682‐686. PubMed

Huang W, Luo W‐J, Zhu P, et al. Modulation of CD147‐induced matrix metalloproteinase activity: role of CD147 N‐glycosylation. Biochem J. 2013;449(2):437‐448. PubMed

Slomiany MG, Grass GD, Robertson AD, et al. Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res. 2009;69(4):1293‐1301. PubMed PMC

Wathelet MG, Orr M, Frieman MB, Baric RS. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J Virol. 2007;81(21):11620‐11633. PubMed PMC

Tanaka Y, Sato Y, Sasaki T. Suppression of coronavirus replication by cyclophilin inhibitors. Viruses. 2013;5(5):1250‐1260. PubMed PMC

Whitworth KM, Rowland RRR, Petrovan V, et al. Resistance to coronavirus infection in amino peptidase N‐deficient pigs. Transgenic Res. 2019;28(1):21‐32. PubMed PMC

Holmes RS, Spradling‐Reeves KD, Cox LA. Mammalian glutamyl aminopeptidase genes (ENPEP) and proteins: Comparative studies of a major contributor to arterial hypertension. J Data Mining Genomics Proteomics. 2017;8(2). PubMed PMC

Yang Z‐Y, Huang Y, Ganesh L, et al. pH‐dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC‐SIGN. J Virol. 2004;78(11):5642‐5650. PubMed PMC

Wu C, Zheng M. Single‐cell RNA expression profiling shows that ACE2, the putative receptor for COVID‐2019, has significant expression in nasal and mounth tissue and is co‐expressed with TMPRSS2 and not co‐expressed with SLC6A19 in the tissues. PREPRINT (Version 1) available at Research Square. 12 March 2020.

Yan R, Zhang Y, Li Y, Xia L, Zhou Q. Structure of dimeric full‐length human ACE2 in complex with B0AT1. bioRxiv. 2020;preprint:2020.2002.2017.951848.

Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1‐23. PubMed PMC

Gordon DE, Jang GM, Bouhaddou M, et al. A SARS‐CoV‐2 protein interaction map reveals targets for drug repurposing. Nature. 2020. 10.1038/s41586-020-2286-9 PubMed DOI PMC

Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID‐19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1‐9. PubMed

Zissler UM, Chaker AM, Effner R, et al. Interleukin‐4 and interferon‐γ orchestrate an epithelial polarization in the airways. Mucosal Immunol. 2016;9(4):917‐926. PubMed

Finlay BB, McFadden G. Anti‐immunology: Evasion of the host immune system by bacterial and viral pathogens. Cell. 2006;124(4):767‐782. PubMed

DeDiego ML, Nieto‐Torres JL, Jimenez‐Guardeño JM, et al. Coronavirus virulence genes with main focus on SARS‐CoV envelope gene. Virus Res. 2014;194:124‐137. PubMed PMC

Schoggins JW. Interferon‐stimulated genes: What do they all do? Annu Rev Virol. 2019;6(1):567‐584. PubMed

Prokunina‐Olsson L, Alphonse N, Dickenson RE, et al. COVID‐19 and emerging viral infections: The case for interferon lambda. J Exp Med. 2020;217(5). PubMed PMC

Chu H, Chan JF‐W, Wang Y, et al. Comparative replication and immune activation profiles of SARS‐CoV‐2 and SARS‐CoV in human lungs: An ex vivo study with implications for the pathogenesis of COVID‐19. Clin Infect Dis. 2020. 10.1093/cid/ciaa410 PubMed DOI PMC

Channappanavar R, Fehr A, Vijay R, et al. Dysregulated type I interferon and inflammatory monocyte‐macrophage responses cause lethal pneumonia in SARS‐CoV‐infected mice. Cell Host Microbe. 2016;19(2):181‐193. PubMed PMC

Kindler E, Thiel V, Weber F. Interaction of SARS and MERS coronaviruses with the antiviral interferon response. Adv Virus Res. 2016;96:219‐243. PubMed PMC

Menachery VD, Debbink K, Baric RS. Coronavirus non‐structural protein 16: Evasion, attenuation, and possible treatments. Virus Res. 2014;194:191‐199. PubMed PMC

Versteeg GA, Bredenbeek PJ, van den Worm SH, Spaan WJ. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology. 2007;361(1):18‐26. PubMed PMC

Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631‐637. PubMed PMC

Zhang H, Kang Z, Gong H, et al. Digestive system is a potential route of COVID‐ 19: an analysis of single‐cell coexpression pattern of key proteins in viral entry process. Gut. 2020;69(6):1010‐1018.

Zang R, Castro MFG, McCune BT, et al. TMPRSS2 and TMPRSS4 mediate SARS‐CoV‐2 infection of human small intestinal enterocytes. bioRxiv. 2020; preprint:2020.2004.2021.054015. PubMed PMC

Zheng H‐C, Takahashi H, Murai Y, et al. Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 2006;95(10):1371‐1378. PubMed PMC

Darmoul D, Voisin T, Couvineau A, et al. Regional expression of epithelial dipeptidyl peptidase IV in the human intestines. Biochem Biophys Res Commun. 1994;203(2):1224‐1229. PubMed

Pan L, Mu MI, Yang P, et al. Clinical characteristics of COVID‐19 patients with digestive symptoms in Hubei, China: A descriptive, cross‐sectional. Multicenter Study. Am J Gastroenterol. 2020;115(5):766‐773. PubMed PMC

Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID‐19 patients. Proc Natl Acad Sci USA. 2020;117(17):9490‐9496. PubMed PMC

D'Amico F, Baumgart DC, Danese S, Peyrin‐Biroulet L. Diarrhea during COVID‐19 infection: Pathogenesis, epidemiology, prevention and management. Clin Gastroenterol Hepatol. 2020;18(8):1663‐1672. PubMed PMC

Leung WK, To KF, Chan PK, et al. Enteric involvement of severe acute respiratory syndrome‐associated coronavirus infection. Gastroenterology. 2003;125(4):1011‐1017. PubMed PMC

Zhang B, Liu S, Tan T, et al. Treatment with convalescent plasma for critically Ill patients with severe acute respiratory syndrome coronavirus 2 infection. Chest. 2020;158(1):e9–e13. 10.1016/j.chest.2020.03.039 PubMed DOI PMC

Zhou J, Li C, Zhao G, et al. Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus. Sci Adv. 2017;3(11):eaao4966. PubMed PMC

Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID‐2019. Nature. 2020;581(7809):465‐469. PubMed

Li LY, Wu W, Chen S, et al. Digestive system involvement of novel coronavirus infection: prevention and control infection from a gastroenterology perspective. J Dig Dis. 2020;21(4):199‐204. PubMed PMC

Recalcati S. Cutaneous manifestations in COVID‐19: A first perspective. J Eur Acad Dermatol Venereol. 2020;34(5). PubMed

Bouaziz JD, Duong T, Jachiet M, et al. Vascular skin symptoms in COVID‐19: A french observational study. J Eur Acad Dermatol Venereol. 2020. 10.1111/jdv.16544 PubMed DOI PMC

Marzano AV, Genovese G, Fabbrocini G, et al. Varicella‐like exanthem as a specific COVID‐19–associated skin manifestation: Multicenter case series of 22 patients. J Eur Acad Dermatol Venereol. 2020;83(1):280–285. 10.1016/j.jaad.2020.04.044 PubMed DOI PMC

Mazzotta FT, Troccoli T. Acute acro‐ischemia in the child at the time of COVID‐19. Eur J Pediat Dermatol. 2020;30(2):71–74.

Yan Y, Chen H, Chen L, et al. Consensus of Chinese experts on protection of skin and mucous membrane barrier for health‐care workers fighting against coronavirus disease. Dermatol Ther. 2019;2020:e13310. PubMed PMC

Prescott SL, Larcombe D‐L, Logan AC, et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10(1):29. PubMed PMC

Wang A, Chiou J, Poirion OB, et al. Nucleus multiomic profiling reveals age‐dynamic regulation of host genes associated with SARS‐CoV‐2 infection. bioRxiv. 2020; preprint:2020.2004.2012.037580.

Blanco‐Melo D, Nilsson‐Payant BE, Liu W‐C, et al. Imbalanced host response to SARS‐CoV‐2 drives development of COVID‐19. Cell. 2020;181(5):1036–1045.e9. 10.1016/j.cell.2020.04.026. PubMed DOI PMC

Liao M, Liu Y, Yuan J, et al. The landscape of lung bronchoalveolar immune cells in COVID‐19 revealed by single‐cell RNA sequencing. medRxiv. 2020; preprint: 2020.2002.2023.20026690.

Yilla M, Harcourt BH, Hickman CJ, et al. SARS‐coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005;107(1):93‐101. PubMed PMC

Chen Y, Feng Z, Diao B, et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) directly decimates human spleens and lymph nodes . medRxiv. 2020; preprint: 2020.2003.2027.20045427.

Lozach PY, Burleigh L, Staropoli I, Amara A. The C type lectins DC‐SIGN and L‐SIGN: receptors for viral glycoproteins. Methods Mol Biol. 2007;379:51‐68. PubMed PMC

Cai G, Cui X, Zhu X, Zhou J. A hint on the COVID‐19 Risk: population disparities in gene expression of three receptors of SARS‐CoV. In. www.preprints.org, 10.20944/preprints202002.0408.v12020 DOI

Park MD. Macrophages: a Trojan horse in COVID‐19? Nat Rev Immunol. 2020;20(6):351. PubMed PMC

Ratajczak MZ, Kucia M. SARS‐CoV‐2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine "storm" and risk factor for damage of hematopoietic stem cells. Leukemia. 2020;1‐4. PubMed PMC

Chen IY, Moriyama M, Chang MF, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019;10:50. PubMed PMC

Zhou Y, Fu B, Zheng X, et al. Pathogenic T‐cells and inflammatory monocytes incite inflammatory storms in severe COVID‐19 patients. National Sci Rev. 2020;7(6):998–1002. 10.1093/nsr/nwaa041 PubMed DOI PMC

He L, Ding Y, Zhang Q, et al. Expression of elevated levels of pro‐inflammatory cytokines in SARS‐CoV‐infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS. J Pathol. 2006;210(3):288‐297. PubMed PMC

Liu LI, Wei Q, Lin Q, et al. Anti‐spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS‐CoV infection. JCI Insight. 2019;4(4). PubMed PMC

McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin‐6 in COVID‐19 induced pneumonia and macrophage activation syndrome‐like disease. Autoimmun Rev. 2020;19(6):102537. PubMed PMC

Zhou M, Zhang X, Qu J. Coronavirus disease 2019 (COVID‐19): A clinical update. Front Med. 2020;14(2):126‐135. PubMed PMC

Nairz M, Theurl I, Swirski FK, Weiss G. "Pumping iron"‐how macrophages handle iron at the systemic, microenvironmental, and cellular levels. Pflugers Arch. 2017;469(3–4):397‐418. PubMed PMC

Soares MP, Hamza I. Macrophages and iron metabolism. Immunity. 2016;44(3):492‐504. PubMed PMC

Velavan TP, Meyer CG. Mild versus severe COVID‐19: Laboratory markers. Int J Infect Dis. 2020;95:304‐307. PubMed PMC

Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061. PubMed PMC

Barnes BJ, Adrover JM, Baxter‐Stoltzfus A, et al. Targeting potential drivers of COVID‐ 19: Neutrophil extracellular traps. J Exp Med. 2020;217(6). PubMed PMC

Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in Covid‐19: The first autopsy series from new orleans. medRxiv. 2020; preprint: 2020.2004.2006.20050575.

Jesenak M, Banovcin P, Diamant Z. COVID‐19, chronic inflammatory respiratory diseases and eosinophils – Observationsfrom reported clinical case series. Allergy. 2020;75:1819‐1822. 10.1111/all.14353 PubMed DOI

Zhang J‐J, Dong X, Cao Y‐Y, et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy. 2020;75:1730‐1741. 10.1111/all.14238 PubMed DOI

Du Y, Tu L, Zhu P, et al. Clinical features of 85 fatal cases of COVID‐19 from Wuhan. A retrospective observational study. American Journal of Respiratory and Critical Care Medicine. 2020;201(11):1372–1379. 10.1164/rccm.202003-0543oc PubMed DOI PMC

Lippi G, Henry BM. Eosinophil count in severe coronavirus disease 2019. QJM: An International Journal of Medicine. 2020. 10.1093/qjmed/hcaa137 PubMed DOI PMC

Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses during COVID‐19 infections and coronavirus vaccination. J Allergy Clin Immuno. 2020;146(1):1–7. 10.1016/j.jaci.2020.04.021 PubMed DOI PMC

Barton LM, Duval EJ, Stroberg E, Ghosh S, Mukhopadhyay S. COVID‐19 Autopsies, Oklahoma, USA. Am J Clin Pathol. 2020;153(6):725‐733. PubMed PMC

Kortekaas Krohn I, Shikhagaie MM, Golebski K, et al. Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications. Allergy. 2018;73(4):837‐850. PubMed

Morita H, Moro K, Koyasu S. Innate lymphoid cells in allergic and nonallergic inflammation. J Allergy Clin Immunol. 2016;138(5):1253‐1264. PubMed

Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS‐CoV‐2 infected patients. EBioMedicine. 2020;55:102763. PubMed PMC

Wang F, Nie J, Wang H, et al. Characteristics of peripheral lymphocyte subset alteration in COVID‐19 pneumonia. J Infect Dis. 2020;221(11):1762‐1769. PubMed PMC

Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2(‐) mesenchymal stem cells improves the outcome of patients with COVID‐19 pneumonia. Aging Dis. 2020;11(2):216‐228. PubMed PMC

Thevarajan I, Nguyen THO, Koutsakos M, et al. Breadth of concomitant immune responses prior to patient recovery: A case report of non‐severe COVID‐19. Nat Med. 2020;26(4):453‐455. PubMed PMC

Giamarellos‐Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID‐19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992‐1000.e3. PubMed PMC

Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID‐19) in Wuhan, China. Clinical Infectious Diseases. 2020. 10.1093/cid/ciaa248 PubMed DOI PMC

Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID‐19 patients. Cell Mol Immunol. 2020;17(5):533‐535. PubMed PMC

van Montfoort N, Borst L, Korrer MJ, et al. NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines. Cell 2018;175(7):1744‐1755.e1715. PubMed PMC

Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID‐19 infection: a report of five cases. Transl Res. 2020;220:1‐13. PubMed PMC

Gralinski LE, Sheahan TP, Morrison TE, et al. complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. MBio. 2018;9(5). PubMed PMC

Mulvey JJ, Magro CM, Ma LX, Nuovo GJ, Baergen RN. Analysis of complement deposition and viral RNA in placentas of COVID‐19 patients. Ann Diagn Pathol. 2020;46:151530. PubMed PMC

Netea MG, Quintin J, van der Meer JW. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9(5):355‐361. PubMed

Sanchez‐Ramon S, Conejero L, Netea MG, Sancho D, Palomares O, Subiza JL. Trained immunity‐based vaccines: A new paradigm for the development of broad‐spectrum anti‐infectious formulations. Front Immunol. 2018;9:2936. PubMed PMC

Kleinnijenhuis J, Quintin J, Preijers F, et al. Long‐lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2014;6(2):152‐158. PubMed PMC

Jensen KJ, Larsen N, Biering‐Sørensen S, et al. Heterologous immunological effects of early BCG vaccination in low‐birth‐weight infants in Guinea‐Bissau: A randomized‐controlled trial. J Infect Dis. 2015;211(6):956‐967. PubMed PMC

Gursel M, Gursel I. Is global BCG vaccination‐induced trained immunity relevant to the progression of SARS‐CoV‐2 pandemic?. Allergy. 2020;75:1815‐1819. 10.1111/all.14345 PubMed DOI PMC

Ozdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID‐19?. Allergy. 2020;75:1824‐1827. 10.1111/all.14344 PubMed DOI

O'Neill LAJ, Netea MG. BCG‐induced trained immunity: Can it offer protection against COVID‐19? Nat Rev Immunol. 2020;20(6):335‐337. PubMed PMC

Retamal‐Díaz A, Covián C, Pacheco GA, et al. Contribution of resident memory CD8(+) T cells to protective immunity against respiratory syncytial virus and their impact on vaccine design. Pathogens. 2019;8(3):147. PubMed PMC

Murali‐Krishna K, Altman JD, Suresh M, et al. Counting antigen‐specific CD8 T cells: A reevaluation of bystander activation during viral infection. Immunity. 1998;8(2):177‐187. PubMed

Libraty DH, O'Neil KM, Baker LM, Acosta LP, Olveda RM. Human CD4(+) memory T‐lymphocyte responses to SARS coronavirus infection. Virology. 2007;368(2):317‐321. PubMed PMC

Ng O‐W, Chia A, Tan AT, et al. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post‐infection. Vaccine. 2016;34(17):2008‐2014. PubMed PMC

Grifoni A, Weiskopf D, Ramirez SI, et al. Targets of T cell responses to SARS‐CoV‐2 coronavirus in humans with COVID‐19 disease and unexposed individuals. Cell. 2020;181(7):1489–1501.e15. 10.1016/j.cell.2020.05.015 PubMed DOI PMC

Braun J, Loyal L, Frentsch M, et al. Presence of SARS‐CoV‐2 reactive T cells in COVID‐19 patients and healthy donors. medRxiv. 2020:2020.2004.2017.20061440.

Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID‐19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420‐422. PubMed PMC

Cameron MJ, Bermejo‐Martin JF, Danesh A, Muller MP, Kelvin DJ. Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res. 2008;133(1):13‐19. PubMed PMC

Xiong Y, Liu Y, Cao L, et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID‐19 patients. Emerg Microbes Infect. 2020;9(1):761‐770. PubMed PMC

Zhao J, Zhao J, Legge K, Perlman S. Age‐related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest. 2011;121(12):4921‐4930. PubMed PMC

Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus‐induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte‐derived macrophages and dendritic cells. J Virol. 2009;83(7):3039‐3048. PubMed PMC

Zhao J, Zhao J, Van Rooijen N, Perlman S. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS‐CoV‐infected mice. PLoS Pathog. 2009;5(10):e1000636. PubMed PMC

Bahl K, Kim SK, Calcagno C, et al. IFN‐induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections. J Immunol. 2006;176(7):4284‐4295. PubMed

Bermejo‐Martin JF, Almansa R, Menendez R, Mendez R, Kelvin DJ, Torres A. Lymphopenic community acquired pneumonia as signature of severe COVID‐19 infection. J Infect. 2020;80(5):e23‐e24. PubMed PMC

Diao B, Wang C, Tan Y, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID‐19). medRxiv. 2020;preprint. PubMed PMC

Diao B, Wang C, Tan Y, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID‐19). Frontiers Immunol. 2020;11(827). PubMed PMC

McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG. T‐cell exhaustion, co‐stimulation and clinical outcome in autoimmunity and infection. Nature. 2015;523(7562):612‐616. PubMed PMC

Huang AT, Garcia‐Carreras B, Hitchings MDT, et al. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv. 2020; preprint: 2020.2004.2014.20065771. PubMed PMC

Breedveld A, van Egmond M. IgA and FcαRI: Pathological roles and therapeutic opportunities. Front Immunol. 2019;10:553. PubMed PMC

Tan YJ, Goh PY, Fielding BC, et al. Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers. Clin Diagn Lab Immunol. 2004;11(2):362‐371. PubMed PMC

Temperton NJ, Chan PK, Simmons G, et al. Longitudinally profiling neutralizing antibody response to SARS coronavirus with pseudotypes. Emerg Infect Dis. 2005;11(3):411‐416. PubMed PMC

Casadevall A, Pirofski L‐A. The convalescent sera option for containing COVID‐19. J Clin Investig. 2020;130(4):1545‐1548. PubMed PMC

Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically Ill patients with COVID‐19 with convalescent plasma. JAMA. 2020;323(16):1582. PubMed PMC

Ahn JY, Sohn Y, Lee SH, et al. Use of convalescent plasma therapy in two COVID‐19 patients with acute respiratory distress syndrome in Korea. J Korean Med Sci. 2020;35(14):e149. PubMed PMC

Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID‐19. Nat Rev Immunol. 2020;20(6):339–‐41. PubMed PMC

Wilk AJ, Rustagi A, Zhao NQ, et al. A single‐cell atlas of the peripheral immune response to severe COVID‐19. medRxiv. 2020:2020.2004.2017.20069930. PubMed PMC

Corcoran LM, Tarlinton DM. Regulation of germinal center responses, memory B cells and plasma cell formation‐an update. Curr Opin Immunol. 2016;39:59‐67. PubMed

Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS‐CoV‐2 in clinical samples. Lancet Infect Dis. 2020;20(4):411‐412. PubMed PMC

Zou L, Ruan F, Huang M, et al. SARS‐CoV‐2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;382(12):1177‐1179. PubMed PMC

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID‐19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363‐374. PubMed PMC

Xu Y‐H, Dong J‐H, An W‐M, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS‐CoV‐2. J Infect. 2020;80(4):394‐400. PubMed PMC

Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early‐phase 2019 novel coronavirus (COVID‐19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020;15(5):700‐704. PubMed PMC

Vardhana SA, Wolchok JD. The many faces of the anti‐COVID immune response. J Exp Med. 2020;217(6). PubMed PMC

George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID‐19: The potential role for antifibrotic therapy. Lancet Respir Med. 2020. 10.1016/s2213-2600(20)30225-3 PubMed DOI PMC

Spagnolo P, Balestro E, Aliberti S, et al. Pulmonary fibrosis secondary to COVID‐ 19: a call to arms? Lancet Respir Med. 2020. PubMed PMC

Liu PP, Blet A, Smyth D, Li H. The science underlying COVID‐19: Implications for the cardiovascular system. Circulation. 2020. 10.1161/circulationaha.120.047549 PubMed DOI

Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID‐19. Lancet. 2020;395(10234):1417‐1418. PubMed PMC

Oudit GY, Kassiri Z, Jiang C, et al. SARS‐coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest. 2009;39(7):618‐625. PubMed PMC

Sala S, Peretto G, Gramegna M, et al. Acute myocarditis presenting as a reverse Tako‐Tsubo syndrome in a patient with SARS‐CoV‐2 respiratory infection. Eur Heart J. 2020;41(19):1861‐1862. PubMed PMC

Deng Q, Hu BO, Zhang Y, et al. Suspected myocardial injury in patients with COVID‐ 19: Evidence from front‐line clinical observation in Wuhan, China. Int J Cardiol. 2020;19:116‐121. PubMed PMC

Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS‐CoV‐2. N Engl J Med. 2020. 10.1056/nejmc2011400 PubMed DOI PMC

Bikdeli B, Madhavan MV, Jimenez D, et al. COVID‐19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow‐up. J Am Coll Cardiol. 2020;75(23):2950‐2973. PubMed PMC

Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID‐19, SARS‐CoV‐1, MERS‐CoV and lessons from the past. J Clin Virol. 2020;127:104362. PubMed PMC

Lippi G, Plebani M. Laboratory abnormalities in patients with COVID‐2019 infection. Clin Chem Lab Med. 2020;58(7):1131‐1134. PubMed

Liu Y, Sun W, Guo Y, et al. Retrospective cohort study. Platelets. 2020;31(4):490‐496. PubMed PMC

Lippi G, Favaloro EJ. D‐dimer is associated with severity of coronavirus disease 2019: A pooled analysis. Thromb Haemost. 2020;120(05):876‐ 878. PubMed PMC

Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID‐19): A meta‐analysis. Clin Chim Acta. 2020;505:190‐191. PubMed PMC

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094‐1099. PubMed PMC

Ito T. PAMPs and DAMPs as triggers for DIC. J Intensive Care. 2014;2(1):67. PubMed PMC

Ranucci M, Ballotta A, Di Dedda U, et al. The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome. J Thromb Haemost. 2020. PubMed PMC

Chen R, Sang L, Jiang M, et al. Longitudinal hematologic and immunologic variations associated with the progression of COVID‐19 patients in China. J Allergy Clin Immunol. 2020;146(1):89–100. 10.1016/j.jaci.2020.05.003 PubMed DOI PMC

Schwartz M, Baruch K. The resolution of neuroinflammation in neurodegeneration: Leukocyte recruitment via the choroid plexus. EMBO J. 2014;33(1):7‐22. PubMed PMC

Michalicová A, Bhide K, Bhide M, Kováč A. How viruses infiltrate the central nervous system. Acta Virol. 2017;61(4):393‐400. PubMed

Archibald LK, Quisling RG. Central nervous system infections. In: Layon JA, Gabrielli A, Friedman WA, eds. Textbook of Neurointensive Care. London, UK: Springer; 2013:427‐517.

Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID‐19 and other coronaviruses. Brain Behav Immun. 2020;87:18‐22. PubMed PMC

Ding Y, He LI, Zhang Q, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: Implications for pathogenesis and virus transmission pathways. J Pathol. 2004;203(2):622‐630. PubMed PMC

Gu J, Gong E, Zhang BO, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202(3):415‐424. PubMed PMC

Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264‐7275. PubMed PMC

Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID‐19‐associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. 2020;201187. PubMed PMC

Zhou B, She J, Wang Y, Ma X. A case of coronavirus disease 2019 with concomitant acute cerebral infarction and deep vein thrombosis. Frontiers Neurol. 2020;11. PubMed PMC

China. NHCotPsRo . Diagnosis and treatment protocol for novel coronavirus pneumonia (7th Interim Edition). 2020. China NHCOTPSRO. http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989/files/ce3e6945832a438eaae415350a8ce964.pdf

Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683. PubMed PMC

Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and Ageusia: Common Findings in COVID‐19 Patients. Laryngoscope. 2020. PubMed PMC

Giacomelli A, Pezzati L, Conti F, et al. Self‐reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: A cross‐sectional study. Clin Infect Dis. 2020. 10.1093/cid/ciaa330 PubMed DOI PMC

Lechien JR, Chiesa‐Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild‐to‐moderate forms of the coronavirus disease (COVID‐19): A multicenter European study. Eur Arch Otorhinolaryngol. 2020. 10.1007/s00405-020-05965-1 PubMed DOI PMC

Pei G, Zhang Z, Peng J, et al. Renal Involvement and early prognosis in patients with COVID‐19 pneumonia. J Am Soc Nephrol. 2020;31(6):1157‐1165. PubMed PMC

Rovin BH, Ronco P, Editors A, Kidney TEE. International and the COVID‐19 infection. Kidney Int. 2020;97(5):823. PubMed PMC

Magrone T, Magrone M, Jirillo E. Focus on receptors for coronaviruses with special reference to angiotensin‐converting enzyme 2 as a potential drug target ‐ A perspective. Endocr Metab Immune Disord Drug Targets. 2020. PubMed

Monteil V, Kwon H, Prado P, et al. Inhibition of SARS‐CoV‐2 infections in engineered human tissues using clinical‐grade soluble human ACE2. Cell. 2020;181(4):905‐913.e7. PubMed PMC

Qu X, Wang C, Zhang J, Qie G, Zhou J. The roles of CD147 and/or cyclophilin A in kidney diseases. Mediators Inflamm. 2014;2014:728673. PubMed PMC

Pfefferle S, Schöpf J, Kögl M, et al. The SARS‐coronavirus‐host interactome: Identification of cyclophilins as target for pan‐coronavirus inhibitors. PLoS Pathog. 2011;7(10):e1002331. PubMed PMC

Wang B, Li R, Lu Z, Huang Y. Does comorbidity increase the risk of patients with COVID‐19: Evidence from meta‐analysis. Aging (Albany NY). 2020;12(7):6049‐6057. PubMed PMC

Dong X, Cao Y‐Y, Lu X‐X, et al. Eleven faces of coronavirus disease 2019. Allergy. 2020. Jul;75(7):1699‐1709. 10.1111/all.14289. PubMed DOI PMC

Guan W‐J, Liang W‐H, Zhao Y, et al. Comorbidity and its impact on 1590 patients with COVID‐19 in China: A nationwide analysis. Eur Respir J. 2020;55(5):2000547. 10.1183/13993003.00547-2020 PubMed DOI PMC

Chen X, Hu W, Ling J, et al. Hypertension and diabetes delay the viral clearance in COVID‐19 patients. medRxiv. 2020;preprint.

Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS‐CoV infection. JCI Insight. 2019;4(20). PubMed PMC

Michalovich D, Rodriguez‐Perez N, Smolinska S, et al. Obesity and disease severity magnify disturbed microbiome‐immune interactions in asthma patients. Nat Commun. 2019;10(1):5711. PubMed PMC

Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47(3):193‐199. PubMed PMC

Chakrabarty B, Das D, Bulusu G, Roy A. Network‐based analysis of fatal comorbidities of COVID‐19 and potential therapeutics. ChemRxiv. preprint. 10.26434/chemrxiv.12136470.v1 PubMed DOI PMC

Bao W, Min D, Twigg SM, et al. Monocyte CD147 is induced by advanced glycation end products and high glucose concentration: Possible role in diabetic complications. Am J Physiol Cell Physiol. 2010;299(5):C1212‐1219. PubMed

Wang J, Luo Q, Chen R, Chen T, Li J. Susceptibility Analysis of COVID‐19 in Smokers Based on ACE2. Preprintsorg. 2020;preprint.

Leung JM, Yang CX, Tam A, et al. ACE‐2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID‐19. European Respiratory Journal. 2020;55(5). 10.1183/13993003.00688-2020 PubMed DOI PMC

Ji HL, Zhao R, Matalon S, Matthay MA. Elevated Plasmin(ogen) as a COMMON RISK FACTOR for COVID‐19 susceptibility. Physiol Rev. 2020;100(3):1065‐1075. PubMed PMC

Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83(1):308‐309. PubMed PMC

Wang LS, Williamson SR, Zhang SB, et al. Increased androgen receptor gene copy number is associated with TMPRSS2‐ERG rearrangement in prostatic small cell carcinoma. Mol Carcinogen. 2015;54(9):900‐907. PubMed

Kwetkat A, Heppner HJ. Comorbidities in the elderly and their possible influence on vaccine response. Interdiscip Top Gerontol Geriatr. 2020;43:73‐85. PubMed

Samson LD, Boots AMH, Verschuren WMM, Picavet HSJ, Engelfriet P, Buisman AM. Frailty is associated with elevated CRP trajectories and higher numbers of neutrophils and monocytes. Exp Gerontol. 2019;125. PubMed

Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A new immune‐metabolic viewpoint for age‐related diseases. Nat Rev Endocrinol. 2018;14(10):576‐590. PubMed

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395(10223):507‐513. PubMed PMC

Guan W‐J, Ni Z‐Y, Hu YU, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708‐1720. PubMed PMC

Huang C, Wang Y, Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):496. PubMed PMC

Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID‐19) outbreak in China: Summary of a report of 72314 cases from the chinese center for disease control and prevention. JAMA. 2020;323(13):1239. PubMed

CDC . Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020. 2020; https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm. Accessed May 7, 2020 PubMed PMC

Bousquet J, Akdis C, Jutel M, et al. Intranasal corticosteroids in allergic rhinitis in COVID‐19 infected patients: An ARIA‐EAACI statement. Allergy 2020;75:2511‐2515. PubMed

Klimek L, Jutel M, Akdis C, et al. Handling of allergen immunotherapy in the COVID‐19 pandemic: An ARIA‐EAACI statement. Allergy. 2020;75(7):1546‐1554. 10.1111/all.14336 PubMed DOI PMC

Johnston SL. Asthma and COVID‐19: is asthma a risk factor for severe outcomes? Allergy 2020. PubMed PMC

Jackson DJ, Busse WW, Bacharier LB, et al. Association of respiratory allergy, asthma and expression of the SARS‐CoV‐2 receptor, ACE2. J Allergy Clin Immunol. 2020. PubMed PMC

Mehta P, McAuley DF, Brown M, et al. COVID‐19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034. PubMed PMC

Sotgiu G, Gerli AG, Centanni S, et al. Advanced forecasting of SARS‐CoV‐2‐related deaths in Italy, Germany, Spain, and New York State. Allergy. 2020;75:1813‐1815. PubMed PMC

Yang Y, Shen C, Li J, et al. Exuberant elevation of IP‐10, MCP‐3, and IL‐1ra during SARS‐CoV‐2 infection is associated with disease severity and fatal outcomes. med Rxiv preprint. 2020.

Liu M, Song Z, Xiao K. High‐resolution computed tomography manifestations of 5 pediatric patients with 2019 novel coronavirus. J Comput Assist Tomogr. 2020;44(3):311‐ 313. PubMed PMC

Jones TC, Mühlemann B, Veith T, et al. An analysis of SARS‐CoV‐2 viral load by patient age. submitted. 2020. 10.1101/2020.06.08.20125484 DOI

Maddux AB, Douglas IS. Is the developmentally immature immune response in paediatric sepsis a recapitulation of immune tolerance? Immunology 2015;145(1):1‐10. PubMed PMC

Riphagen S, Gomez X, Gonzalez‐Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID‐19 pandemic. Lancet. 2020;395(10237):1607‐1608. PubMed PMC

WHO . Multisystem inflammatory syndrome in children and adolescents temporally related to COVID‐19. https://www.who.int/news‐room/commentaries/detail/multisystem‐inflammatory‐syndrome‐in‐children‐and‐adolescents‐with‐covid‐19: WHO; 2020.

WHO . Report of the WHO‐China Joint Mission on Coronavirus Disease 2019 (COVID‐19). https://www.who.int/publications‐detail/report‐of‐the‐who‐china‐joint‐mission‐on‐coronavirus‐disease‐2019‐(covid‐19): WHO; 2020.

Vogel G. These are answers we need. WHO plans global study to discover true extent of coronavirus infections. Science. 2020.

Alberici F, Delbarba E, Manenti C, et al. A single center observational study of the clinical characteristics and short‐term outcome of 20 kidney transplant patients admitted for SARS‐CoV2 pneumonia. Kidney International. 2020;97(6):1083–1088. 10.1016/j.kint.2020.04.002 PubMed DOI PMC

Capra R, De Rossi N, Mattioli F, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID‐19 related pneumonia. Eur J Intern Med. 2020;76:31‐35. PubMed PMC

Colaneri M, Bogliolo L, Valsecchi P, et al. Tocilizumab for treatment of severe COVID‐19 patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms. 2020;8(5):695. PubMed PMC

Di Giambenedetto S, Ciccullo A, Borghetti A, et al. Off‐label use of tocilizumab in patients with SARS‐CoV‐2 infection. J Med Virol. 2020. PubMed PMC

Jacobs JP, Stammers AH, St. Louis J, et al. Extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in COVID‐19: Experience with 32 patients. ASAIO J. 2020. PubMed PMC

Klopfenstein T, Zayet S, Lohse A, et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID‐19 patients. Med Mal Infect. 2020. PubMed PMC

Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID‐19: A single center experience. J Med Virol. 2020;92(7):814‐818. PubMed PMC

Mazzitelli M, Arrighi E, Serapide F, et al. Use of subcutaneous tocilizumab in patients with COVID‐19 pneumonia. J Med Virol. 2020. PubMed PMC

Pereira MR, Mohan S, Cohen DJ, et al. COVID‐19 in solid organ transplant recipients: Initial report from the US Epicenter. Am J Transplant. 2020. PubMed PMC

Piva S, Filippini M, Turla F, et al. Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in Brescia. Italy. J Crit Care. 2020;58:29‐33. PubMed PMC

Kuypers DRJ, de Jonge H, Naesens M, Vanrenterghem Y. A prospective, open‐label, observational clinical cohort study of the association between delayed renal allograft function, tacrolimus exposure, and CYP3A5 genotype in adult recipients. Clinical Therapeutics. 2010;32(12):2012–2023. 10.1016/j.clinthera.2010.11.010 PubMed DOI

Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID‐19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia. Italy. Autoimmun Rev. 2020:102568. PubMed PMC

Xu X, Han M, Li T, et al. Effective treatment of severe COVID‐19 Patients with tocilizumab. Proc Natl Acad Sci. 2020;117(20):10970‐10975. PubMed PMC

Zhang X, Song K, Tong F, et al. First case of COVID‐19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv. 2020;4(7):1307‐1310. PubMed PMC

Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS‐coronavirus 2. Science. 2020. PubMed PMC

Morrison AR, Johnson JM, Ramesh M, Bradley P, Jennings J, Smith ZR. Letter to the Editor: Acute hypertriglyceridemia in patients with COVID‐19 receiving tocilizumab. J Med Virol. 2020. PubMed PMC

Michot J‐M, Albiges L, Chaput N, et al. Tocilizumab, an anti‐IL6 receptor antibody, to treat Covid‐19‐related respiratory failure: A case report. Ann Oncol. 2020. PubMed PMC

Fontana F, Alfano G, Mori G, et al. Covid‐19 pneumonia in a kidney transplant recipient successfully treated with Tocilizumab and Hydroxychloroquine. Am J Transplant. 2020. PubMed PMC

De Luna G, Habibi A, Deux J‐F, et al. Rapid and SEvere Covid‐19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab. Am J Hematol. 2020;95(7):876‐878. PubMed PMC

Cellina M, Orsi M, Bombaci F, Sala M, Marino P, Oliva G. Favorable changes of CT findings in a patient with COVID‐19 pneumonia after treatment with tocilizumab. Diagn Interv Imaging. 2020;101(5):323‐324. PubMed PMC

Aouba A, Baldolli A, Geffray L, et al. Targeting the inflammatory cascade with anakinra in moderate to severe COVID‐19 pneumonia: Case series. Ann Rheum Dis. 2020. PubMed

Cavalli G, De Luca G, Campochiaro C, et al. Interleukin‐1 blockade with high‐dose anakinra in patients with COVID‐19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325‐e331. PubMed PMC

Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe covid‐19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe. 2020. 10.1016/j.chom.2020.05.007 PubMed DOI PMC

Cantini F, Niccoli L, Matarrese D, Nicastri E, Stobbione P, Goletti D. Baricitinib therapy in COVID‐19: A pilot study on safety and clinical impact. J Infect. 2020. PubMed PMC

Ye M, Fu D, Ren YI, et al. Treatment with convalescent plasma for COVID‐19 patients in Wuhan, China. J Med Virol. 2020. PubMed PMC

Diurno F, Numis FG, Porta G, et al. Eculizumab treatment in patients with COVID‐19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040‐4047. PubMed

Andreakos E, Tsiodras S. COVID‐19: lambda interferon against viral load and hyperinflammation. EMBO Mol Med. 2020. PubMed PMC

Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer‐Smadja N. Type 1 interferons as a potential treatment against COVID‐19. Antiviral Res. 2020;178:104791. PubMed PMC

Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682‐687. PubMed

Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3–potential mechanisms of action. Nat Rev Immunol. 2015;15(1):45‐56. PubMed

Lunjani N, Satitsuksanoa P, Lukasik Z, Sokolowska M, Eiwegger T, O'Mahony L. Recent developments and highlights in mechanisms of allergic diseases: Microbiome. Allergy. 2018;73(12):2314‐2327. PubMed

Wypych TP, Wickramasinghe LC, Marsland BJ. The influence of the microbiome on respiratory health. Nat Immunol. 2019;20(10):1279‐1290. PubMed

Barcik W, Boutin RCT, Sokolowska M, Finlay BB. The role of lung and gut microbiota in the pathology of asthma. Immunity. 2020;52(2):241‐255. PubMed PMC

Roduit C, Frei R, Ferstl R, et al. High levels of butyrate and propionate in early life are associated with protection against atopy. Allergy. 2019;74(4):799‐809. PubMed

Trompette A, Gollwitzer ES, Pattaroni C, et al. Dietary Fiber Confers Protection against Flu by Shaping Ly6c(‐) Patrolling Monocyte Hematopoiesis and CD8(+) T Cell Metabolism. Immunity. 2018;48(5):992‐1005.e8. PubMed

Gou W, Fu Y, Yue L, et al. Gut microbiota may underlie the predisposition of healthy individuals to COVID‐19. medRxiv. 2020;preprint.

WHO . Strategic and Technical Advisory Group for Infectious Hazards (STAG‐IH). 2020; https://www.who.int/emergencies/diseases/strategic‐and‐technical‐advisory‐group‐for‐infectious‐hazards/en/. Accessed May 7, 2020

Bedford J, Enria D, Giesecke J, et al. COVID‐19: towards controlling of a pandemic. Lancet. 2020;395(10229):1015‐1018. PubMed PMC

Lurie N, Saville M, Hatchett R, Halton J. Developing Covid‐19 vaccines at pandemic speed. N Engl J Med. 2020;382(21):1969‐1973. PubMed

WHO . DRAFT landscape of COVID‐19candidate vaccines – 20 April 2020. 2020; https://www.who.int/blueprint/priority‐diseases/key‐action/novel‐coronavirus‐landscape‐ncov.pdf?ua=1

El Zowalaty ME, Jarhult JD. From SARS to COVID‐19: A previously unknown SARS‐ related coronavirus (SARS‐CoV‐2) of pandemic potential infecting humans ‐ Call for a One Health approach. One Health. 2020;9:100124. PubMed PMC

Bian H, Zheng ZH, Wei D, et al. Meplazumab treats COVID‐19 pneumonia: an open‐labelled, concurrent controlled add‐on clinical trial. medRxiv. 2020.

Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID-19

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