1.Zhu, N., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 382, 727–733 (2020).
2.Wu, Z. & McGoogan, J. M. 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).
3.Wu, D., Wu, T., Liu, Q. & Yang, Z. The SARS-CoV–2 outbreak: What we know. Int J Infect Dis 94, 44–48 (2020).
4.Zou, L., et al. SARS-CoV–2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 382, 1177–1179 (2020).
5.Danis, K., et al. Cluster of coronavirus disease 2019 (Covid–19) in the French Alps, 2020. Clin Infect Dis (2020).
6.Lai, C. C., et al. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV–2): Facts and myths. J Microbiol Immunol Infect (2020).
7.Pan, X., et al. Asymptomatic cases in a family cluster with SARS-CoV–2 infection. Lancet Infect Dis 20, 410–411 (2020).
8.Furukawa, N. W., Brooks, J. T. & Sobel, J. Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic. Emerg Infect Dis 26(2020).
9.Ki, M. & Task Force for -nCo, V. Epidemiologic characteristics of early cases with 2019 novel coronavirus (2019-nCoV) disease in Korea. Epidemiol Health 42, e2020007 (2020).
10.Huang, C., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).
11.Wang, D., et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA (2020).
12.Shi, H., et al. Radiological findings from 81 patients with COVID–19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 20, 425–434 (2020).
13.He, G., et al. The clinical feature of silent infections of novel coronavirus infection (COVID–19) in Wenzhou. J Med Virol (2020).
14.Tian, S., et al. Characteristics of COVID–19 infection in Beijing. J Infect 80, 401–406 (2020).
15.Hu, Z., et al. Clinical characteristics of 24 asymptomatic infections with COVID–19 screened among close contacts in Nanjing, China. Sci China Life Sci 63, 706–711 (2020).
16.Mizumoto, K., Kagaya, K., Zarebski, A. & Chowell, G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID–19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 25(2020).
17.Giacomelli, A., et al. Self-reported olfactory and taste disorders in SARS-CoV–2 patients: a cross-sectional study. Clin Infect Dis (2020).
18.Lechien, J. R., 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).
19.CDC. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID–19). Vol. 2020 (2020).
20.Freedberg, D. E., et al. Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID–19 Patients: A Retrospective Cohort Study. medRxiv, 2020.2005.2001.20086694 (2020).
21.Borrell, B. New York clinical trial quietly tests heartburn remedy against coronavirus. Vol. 2020 (Science Magazine, 2020).
22.Daczkowski, C. M., et al. Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. J Mol Biol 429, 1661–1683 (2017).
23.Baez-Santos, Y. M., St John, S. E. & Mesecar, A.D. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res 115, 21–38 (2015).
24.Mielech, A.M., Chen, Y., Mesecar, A.D. & Baker, S. C. Nidovirus papain-like proteases: Multifunctional enzymes with protease, deubiquitinating and deISGylating activities. Virus Research 194, 184–190 (2014).
25.Han, Y. S., et al. Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): expression, purification, characterization, and inhibition. Biochemistry 44, 10349–10359 (2005).
26.Wu, C., et al. Analysis of therapeutic targets for SARS-CoV–2 and discovery of potential drugs by computational methods. Acta Pharm Sin B (2020).
27.Anson, B. J., et al. Broad-spectrum inhibition of coronavirus main and papain-like proteases by HCV drugs,. Research Square (2020).
28.Gordon, D. E., et al. A SARS-CoV–2 protein interaction map reveals targets for drug repurposing. Nature (2020).
29.Schmidt, H. R., et al. Crystal structure of the human σ1 receptor. Nature 532, 527–530 (2016).
30.Alon, A., et al. Identification of the gene that codes for the sigma2 receptor. Proc Natl Acad Sci U S A 114, 7160–7165 (2017).
31.Bertaccini, G., Coruzzi, G., Poli, E. & Adami, M. Pharmacology of the novel H2 antagonist famotidine: in vitro studies. Agents Actions 19, 180–187 (1986).
32.Alonso, N., et al. Physiological implications of biased signaling at histamine H2 receptors. Front Pharmacol 6, 45 (2015).
33.Irannejad, R. & von Zastrow, M. GPCR signaling along the endocytic pathway. Curr Opin Cell Biol 27, 109–116 (2014).
34.Jean-Charles, P. Y., Kaur, S. & Shenoy, S. K. G Protein-Coupled Receptor Signaling Through beta-Arrestin-Dependent Mechanisms. J Cardiovasc Pharmacol 70, 142–158 (2017).
35.Miao, M., De Clercq, E. & Li, G. Clinical significance of chemokine receptor antagonists. Expert Opin Drug Metab Toxicol 16, 11–30 (2020).
36.Fantuzzi, L., Tagliamonte, M., Gauzzi, M. C. & Lopalco, L. Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders. Cell Mol Life Sci 76, 4869–4886 (2019).
37.Zhou, Y. Q., et al. The Role of CXCR3 in Neurological Diseases. Curr Neuropharmacol 17, 142–150 (2019).
38.Nasi, A. & Chiodi, F. Mechanisms regulating expansion of CD8+ T cells during HIV–1 infection. J Intern Med 283, 257–267 (2018).
39.Lin, J. H., et al. Effects of antacids and food on absorption of famotidine. Br J Clin Pharmacol 24, 551–553 (1987).
40.Yeh, K. C., et al. Single-dose pharmacokinetics and bioavailability of famotidine in man. Results of multicenter collaborative studies. Biopharm Drug Dispos 8, 549–560 (1987).
41.Lin, J. H. Pharmacokinetic and pharmacodynamic properties of histamine H2-receptor antagonists. Relationship between intrinsic potency and effective plasma concentrations. Clin Pharmacokinet 20, 218–236 (1991).
42.Burde, R., Seifert, R., Buschauer, A. & Schultz, G. Histamine inhibits activation of human neutrophils and HL–60 leukemic cells via H2-receptors. Naunyn Schmiedebergs Arch Pharmacol 340, 671–678 (1989).
43.Gespach, C. & Abita, J. P. Human polymorphonuclear neutrophils. Pharmacological characterization of histamine receptors mediating the elevation of cyclic AMP. Mol Pharmacol 21, 78–85 (1982).
44.Rabier, M., et al. Inhibition by histamine of platelet-activating-factor-induced neutrophil chemotaxis in bronchial asthma. Int Arch Allergy Appl Immunol 89, 314–317 (1989).
45.Flamand, N., Plante, H., Picard, S., Laviolette, M. & Borgeat, P. Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: involvement of the H2 receptor and cAMP. Br J Pharmacol 141, 552–561 (2004).
46.Ezeamuzie, C. I. & Philips, E. Histamine H(2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol 131, 482–488 (2000).
47.Wadee, A. A., Anderson, R. & Sher, R. In vitro effects of histamine on eosinophil migration. Int Arch Allergy Appl Immunol 63, 322–329 (1980).
48.Clark, R. A., Gallin, J. I. & Kaplan, A. P. The selective eosinophil chemotactic activity of histamine. J Exp Med 142, 1462–1476 (1975).
49.Reher, T. M., Brunskole, I., Neumann, D. & Seifert, R. Evidence for ligand-specific conformations of the histamine H(2)-receptor in human eosinophils and neutrophils. Biochem Pharmacol 84, 1174–1185 (2012).
50.Lippert, U., et al. Human skin mast cells express H2 and H4, but not H3 receptors. J Invest Dermatol 123, 116–123 (2004).
51.Somogyi, A. & Gugler, R. Clinical pharmacokinetics of cimetidine. Clin Pharmacokinet 8, 463–495 (1983).
52.Echizen, H. & Ishizaki, T. Clinical pharmacokinetics of famotidine. Clin Pharmacokinet 21, 178–194 (1991).
53.Administration, U. F.a.D. PEPCID® (famotidine) tablets, for oral use. Vol. 2020 (1986).
54.Luo, T., et al. Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function. Basic Res Cardiol 108, 342 (2013).
55.Di Lorenzo, A., Fernandez-Hernando, C., Cirino, G. & Sessa, W. C. Akt1 is critical for acute inflammation and histamine-mediated vascular leakage. Proc Natl Acad Sci U S A 106, 14552–14557 (2009).
56.Panula, P., et al. International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors. Pharmacol Rev 67, 601–655 (2015).
57.Krystel-Whittemore, M., Dileepan, K. N. & Wood, J. G. Mast Cell: A Multi-Functional Master Cell. Front Immunol 6, 620 (2015).
58.Du, Y., Guo, M., Whitsett, J. A. & Xu, Y. ‘LungGENS’: a web-based tool for mapping single-cell gene expression in the developing lung. Thorax 70, 1092–1094 (2015).
59.Tian, S., et al. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID–19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol 15, 700–704 (2020).
60.Zeng, Z., et al. Pulmonary Pathology of Early Phase COVID–19 Pneumonia in a Patient with a Benign Lung Lesion. Histopathology n/a(2020).
61.Marone, G., Columbo, M., Triggiani, M., Vigorita, S. & Formisano, S. Forskolin inhibits the release of histamine from human basophils and mast cells. Agents Actions 18, 96–99 (1986).
62.Couzin-Frankel, J. The mystery of the pandemic’s ‘happy hypoxia’. Science 368, 455–456 (2020).
63.Schweitzer, W., et al. Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID–19. Forensic Imaging 21, 200378 (2020).
64.Eliezer, M., et al. Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID–19. JAMA Otolaryngology–Head & Neck Surgery (2020).
65.Cohen, P. A., Hall, L., Johns, J. N. & Rapoport, A. B. The Early Natural History of SARS-CoV–2 Infection: Clinical Observations From an Urban, Ambulatory COVID–19 Clinic. Mayo Clinic Proceedings.
66.Gattinoni, L., Chiumello, D. & Rossi, S. COVID–19 pneumonia: ARDS or not? Critical Care 24, 154 (2020).
67.Mao, L., et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol (2020).
68.Filatov, A., Sharma, P., Hindi, F. & Espinosa, P. S. Neurological Complications of Coronavirus Disease (COVID–19): Encephalopathy. Cureus 12, e7352 (2020).
69.Qureshi, A. I., et al. Management of acute ischemic stroke in patients with COVID–19 infection: Report of an international panel. Int J Stroke, 1747493020923234 (2020).
70.Long, B., Brady, W. J., Koyfman, A. & Gottlieb, M. Cardiovascular complications in COVID–19. Am J Emerg Med (2020).
71.Mahmud, E., et al. Management of Acute Myocardial Infarction During the COVID–19 Pandemic. J Am Coll Cardiol (2020).
72.Carsana, L., et al. Pulmonary post-mortem findings in a large series of COVID–19 cases from Northern Italy. medRxiv, 2020.2004.2019.20054262 (2020).
73.Magro, C., et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID–19 infection: a report of five cases. Transl Res (2020).
74.Oudkerk, M., et al. Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID–19: Report of the National Institute for Public Health of the Netherlands. Radiology, 201629 (2020).
75.Panigada, M., et al. Hypercoagulability of COVID–19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis. J Thromb Haemost (2020).
76.Ranucci, M., et al. The procoagulant pattern of patients with COVID–19 acute respiratory distress syndrome. J Thromb Haemost (2020).
77.The Method of Multiple Working Hypotheses. Science 15, 92–96 (1890).
78.Alphonsus, C. S. & Rodseth, R. N. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia 69, 777–784 (2014).
79.Becker, B. F., Chappell, D., Bruegger, D., Annecke, T. & Jacob, M. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc Res 87, 300–310 (2010).
80.Nelson, A., Berkestedt, I., Schmidtchen, A., Ljunggren, L. & Bodelsson, M. Increased levels of glycosaminoglycans during septic shock: relation to mortality and the antibacterial actions of plasma. Shock 30, 623–627 (2008).
81.Jackson, S. P., Darbousset, R. & Schoenwaelder, S. M. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 133, 906–918 (2019).
82.Zwickl, H., Zwickl-Traxler, E. & Pecherstorfer, M. Is Neuronal Histamine Signaling Involved in Cancer Cachexia? Implications and Perspectives. Front Oncol 9, 1409 (2019).
83.Becker, S., et al. Olfactory dysfunction in seasonal and perennial allergic rhinitis. Acta Otolaryngol 132, 763–768 (2012).
84.Suthar, M. S., et al. Rapid generation of neutralizing antibody responses in COVID–19 patients. medRxiv, 2020.2005.2003.20084442 (2020).
85.Mongkolsapaya, J., et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 9, 921–927 (2003).
86.Merad, M. & Martin, J. C. Pathological inflammation in patients with COVID–19: a key role for monocytes and macrophages. Nature Reviews Immunology (2020).
87.Vabret, N., et al. Immunology of COVID–19: current state of the science. Immunity (2020).
88.McGonagle, D., O’Donnell, J. S., Sharif, K., Emery, P. & Bridgewood, C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID–19 pneumonia. The Lancet Rheumatology (2020).
89.Kritas, S., et al. Mast cells contribute to coronavirus-induced inflammation: New anti-inflammatory strategy. Journal of biological regulators and homeostatic agents 34(2019).
90.Bissonnette, E. Y. Histamine inhibits tumor necrosis factor alpha release by mast cells through H2 and H3 receptors. Am J Respir Cell Mol Biol 14, 620–626 (1996).
91.Afrin, L. B., et al. Diagnosis of mast cell activation syndrome: a global “consensus–2”. Diagnosis (Berl) (2020).
92.Weiler, C. R. Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis. J Allergy Clin Immunol Pract 8, 498–506 (2020).
93.Weinstock, L. B., Pace, L. A., Rezaie, A., Afrin, L. B. & Molderings, G. J. Mast Cell Activation Syndrome: A Primer for the Gastroenterologist. Dig Dis Sci (2020).
94.Butterfield, J. H. Survey of Mast Cell Mediator Levels from Patients Presenting with Symptoms of Mast Cell Activation. Int Arch Allergy Immunol 181, 43–50 (2020).
95.Guzman, M. G. & Harris, E. Dengue. Lancet 385, 453–465 (2015).
96.Redoni, M., et al. Dengue: Status of current and under-development vaccines. Rev Med Virol, e2101 (2020).
97.Kounis, N. G., et al. Anaphylaxis-induced atrial fibrillation and anesthesia: Pathophysiologic and therapeutic considerations. Ann Card Anaesth 23, 1–6 (2020).
98.Kounis, N. G. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 54, 1545–1559 (2016).
99.Gonzalez-de-Olano, D., et al. Mast cell activation disorders presenting with cerebral vasospasm-related symptoms: a “Kounis-like” syndrome? Int J Cardiol 150, 210–211 (2011).
100.Fidan, C. & Aydogdu, A. As a potential treatment of COVID–19: Montelukast. Med Hypotheses 142, 109828 (2020).
101.Theoharides, T. C., Tsilioni, I. & Ren, H. Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? Expert Rev Clin Immunol 15, 639–656 (2019).
102.Lindner, H. A., et al. The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. J Virol 79, 15199–15208 (2005).
103.Swatek, K. N., et al. Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies. Proc Natl Acad Sci U S A 115, 2371–2376 (2018).