Risk and management of patients with mastocytosis and MCAS in the SARS-CoV-2 (COVID-19) pandemic: Expert opinions
Authors: Peter Valent, Cem Akin, Patrizia Bonadonna, Knut Brockow, Marek Niedoszytko, Boguslaw Nedoszytko, Joseph H. Butterfield, Ivan Alvarez-Twose, Karl Sotlar, Juliana Schwaab, Mohamad Jawhar, Andreas Reiter, Mariana Castells, Wolfgang R. Sperr, Hanneke C. Kluin-Nelemans, Olivier Hermine, Jason Gotlib, Roberta Zanotti, Sigurd Broesby-Olsen, Hans-Peter Horny, Massimo Triggiani, Frank Siebenhaar, Alberto Orfao, Dean D. Metcalfe, Michel Arock, Karin Hartmann
Journal: Journal of Allergy and Clinical Immunology (2020)

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19–induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation–related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti–mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider. The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19–induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation–related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti–mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider. Mast cells (MCs) are proinflammatory effector cells of the immune system.1Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (448) Google Scholar, 2Galli S.J. Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.Eur J Immunol. 2010; 40: 1843-1851Crossref PubMed Scopus (322) Google Scholar, 3Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (350) Google Scholar Upon activation by an allergen, microbes (including viruses), or toxins, MCs release a number of proinflammatory substances and lipid mediators, thereby contributing to tissue inflammation and allergic reactions.1Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (448) Google Scholar, 2Galli S.J. Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.Eur J Immunol. 2010; 40: 1843-1851Crossref PubMed Scopus (322) Google Scholar, 3Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (350) Google Scholar Mastocytosis is a group of neoplasms characterized by an uncontrolled expansion and accumulation of neoplastic MCs in various organs, including the skin, the bone marrow, and the gastrointestinal tract.1Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (448) Google Scholar,3Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (350) Google Scholar, 4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar Mastocytosis is divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM).4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar Most patients with CM are children,8Hartmann K. Escribano L. Grattan C. Brockow K. Carter M.C. Alvarez-Twose I. et al.Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.J Allergy Clin Immunol. 2016; 137: 35-45Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar whereas adult patients are usually diagnosed with SM.4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar Most patients with SM carry an activating KIT mutation, typically D816V.4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar,9Arock M. Sotlar K. Akin C. Broesby-Olsen S. Hoermann G. Escribano L. et al.KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis.Leukemia. 2015; 29: 1223-1232Crossref PubMed Scopus (223) Google Scholar In a smaller subset of patients, an advanced form of the disease is diagnosed.4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar These patients are usually older. In addition, patients with mastocytosis may suffer from the consequences of a massive release of MC-derived mediators.4Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (664) Google Scholar, 6Arock M. Akin C. Hermine O. Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.Eur J Haematol. 2015; 94: 474-490Crossref PubMed Scopus (62) Google Scholar, 7Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (497) Google Scholar, 8Hartmann K. Escribano L. Grattan C. Brockow K. Carter M.C. Alvarez-Twose I. et al.Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.J Allergy Clin Immunol. 2016; 137: 35-45Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar, 9Arock M. Sotlar K. Akin C. Broesby-Olsen S. Hoermann G. Escribano L. et al.KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis.Leukemia. 2015; 29: 1223-1232Crossref PubMed Scopus (223) Google Scholar In severe cases, an MC activation syndrome (MCAS) may be diagnosed.10Akin C. Valent P. Metcalfe D.D. Mast cell activation syndrome: proposed diagnostic criteria.J Allergy Clin Immunol. 2010; 126: 1099-1104Abstract Full Text Full Text PDF PubMed Scopus (264) Google Scholar, 11Valent P. Akin C. Arock M. Brockow K. Butterfield J.H. Carter M.C. et al.Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal.Int Arch Allergy Immunol. 2012; 157: 215-225Crossref PubMed Scopus (502) Google Scholar, 12Valent P. Mast cell activation syndromes: definition and classification.Allergy. 2013; 68: 417-424Crossref PubMed Scopus (102) Google Scholar The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan (China)13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar and its pandemic spread with substantial morbidity and mortality in numerous countries have raised fears and concerns in patients with MC disorders and their physicians. These concerns relate to the questions as to whether patients with mastocytosis and/or MCAS have an increased risk to acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or an increased risk to develop a more severe course of COVID-19, whether MC mediator–related symptoms are aggravated by the viral infection, and how treatment of MC diseases might affect the course of COVID-19. In addition, patients are concerned about potential side effects that could be provoked by antiviral agents. Because solid data to answer these questions are as yet scant, and based on the complexity of CM/SM and MCAS, there is thus a need for expert advice and recommendations. In this article, we provide a first expert opinion–based estimate of the risk and a guide and proposal for the management of MC diseases during the COVID-19 pandemic, based on case observations, reports of patients, and recommendations provided in other, similar, disease entities. In addition, we discuss risk factors concerning transmission and fatality of COVID-19 and propose therapeutic strategies in mastocytosis and MCAS that may help reduce the overall impact. The clinical course of a SARS-CoV-2 infection ranges from asymptomatic or mild upper respiratory tract illness to severe viral COVID-19 pneumonia, leading to respiratory failure and death due to acute respiratory distress syndrome and multiorgan failure.13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar More than 80% of all patients with SARS-CoV-2 infection have a mild form of the disease.13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar However, about 15% to 20% of the patients need hospitalization, and up to 5% develop a life-threatening pneumonia.13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar The most commonly reported symptoms are fever (>70%) and dry cough (>60%) (Table I).13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar Other typical symptoms are sore throat, anosmia and agneusia, and a skin rash (Table I).13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zhang J. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 17Chen N. Zhou M. Dong X. Qu J. Gong F. Han Y. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 18Wu 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 [published online ahead of print February 24, 2020]. JAMA. https://doi.org/10.1001/jama.2020.2648.Google Scholar, 19Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (803) Google Scholar Dyspnea, tachycardia, and fatigue are usually recorded when the disease progresses, and in the advanced phase of COVID-19, patients often need intensive care with or without oxygen supply. Less frequently reported symptoms are increased sputum production, headache, urticaria, myalgia, arthralgia, abdominal discomfort, vomiting, and diarrhea. Abdominal symptoms and headache are also seen frequently in patients with MC disorders (Table I). However, other symptoms and findings typically recorded in mastocytosis and/or MCAS, such as pruritus, flushing, or hypotension, are not considered typical presenting symptoms of a COVID-19 infection (Table I).Table IClinical symptoms typically associated with local or systemic MCA and comparison to symptoms of COVID-19SymptomTypically found in patients withMCA∗In patients with MCA, the symptoms are typically episodic and recurrent and cannot be explained by other known disorders or conditions. In severe cases, an MCAS may be diagnosed.COVID-19†Most of the COVID-19–related symptoms are recorded only during the infection period, and are transient; however, chronic pulmonary damage with persistent dyspnea may be seen in rare, severe, COVID-19 cases.Urticaria+−Flushing+−Pruritus+−Measles-like rash−±Angioedema+−Nasal congestion±±Wheezing+±Anosmia−++Cough−++Dyspnea±++Hoarseness±±Sore throat±+Throat swelling±±Agneusia−++Fever−±Headache±±Hypotensive episode±−Tachycardia±±Abdominal cramping±−Diarrhea±±MCA, Mast cell activation.Score: ++, high specificity; +, moderate specificity; ±, low specificity; −, not considered to be indicative of MCA or COVID-19 when recoded as an individual symptom.∗ In patients with MCA, the symptoms are typically episodic and recurrent and cannot be explained by other known disorders or conditions. In severe cases, an MCAS may be diagnosed.† Most of the COVID-19–related symptoms are recorded only during the infection period, and are transient; however, chronic pulmonary damage with persistent dyspnea may be seen in rare, severe, COVID-19 cases. Open table in a new tab MCA, Mast cell activation. Score: ++, high specificity; +, moderate specificity; ±, low specificity; −, not considered to be indicative of MCA or COVID-19 when recoded as an individual symptom. Severe illness and death due to SARS-CoV-2 are more commonly documented in elderly patients and those with preexisting comorbidities.13Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance [published online ahead of print January 30, 2020]. JAMA. https://doi.org/10.1001/jama.2020.1097.Google Scholar, 14Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 15Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 16Wang D. Hu B. Hu C. Zhu F. Liu X. Zh