COVID-19, Asthma and Allergies — What We Know So Far
A new coronavirus (SARS-CoV-2) infection began to disseminate in Wuhan, China in early December 2019 and has rapidly spread to almost every country around the globe, with the number of confirmed cases increasing every day. The disease condition associated with this novel coronavirus is referred as coronavirus disease (or COVID-19), and this outbreak was declared as a pandemic on March 11, 2020 by the World Health Organization (WHO).1 The emergence of this coronavirus in 2019, poses a significant threat to human health and the economy, and requires global control measures. As of April 5, 2020, the outbreak of COVID-19 had reached 1,245,375 confirmed cases and 67,914 deaths, globally.2 These numbers are much greater than those registered during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) pandemics, which occurred in 2003 and 2013, respectively;3 despite the fact that proportion of COVID-19 deaths in relation to the number infected, is lower.2,3
While human strains of coronavirus are associated with a low percentage of cases of the common cold, SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death.3 After more than a decade of research, there are still no specific treatments for coronavirus, which highlights an urgent need to develop effective vaccines and/or post-exposure prophylaxis to prevent future epidemics.3
SARS-CoV-2 is the seventh known member of the family of coronaviruses to infect humans. Like SARS-CoV and MERS-CoV, SARS-CoV-2 is responsible for lower respiratory infection and can cause acute respiratory distress syndromes (ARDS). It appears to be more infectious than SARS-CoV or MERS-CoV, based on values calculated at the early stage of this outbreak, and it can survive for several hours in air particles, and for several days on plastic or metal surfaces. This RNA virus is most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses that had previously been found in bats in China.4 This outbreak highlights the ongoing ability of viral spill-over from wild animals to cause severe disease in humans.4
SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) receptors in host cells, as was also reported for another viral family member, SARS-CoV-1. ACE2 receptors are abundant in the lungs, heart, blood vessels, testes, brain, and intestine, and their numbers increase throughout life. In the lungs, the organ most vulnerable to SARS-CoV-2 infection in the current pandemic, ACE2 is localised to type II, and to a lesser extent, type I alveolar cells.5
COVID-19 mainly presents with respiratory symptoms, such as cough and shortness of breath, in addition to fever, fatigue, tiredness, aches and also gastrointestinal symptoms.6 Sudden losses of taste and smell can be an isolated clinical manifestation, and is generally reversible.7 Many patients with COVID-19 develop ARDS, which leads to pulmonary oedema and lung failure, in addition to liver, heart, and kidney damage. These severe symptoms are associated with a true cytokine storm and death can occur.6 Cardiovascular, endocrine and digestive system diseases are commonly reported co-morbidities; however, cases of pre-existing chronic respiratory diseases (e.g., chronic obstructive pulmonary disease [COPD]) are surprisingly low at this time (<2% of patients from China).6
The majority of infected individuals who do not have symptoms (asymptomatic), or those with only mild symptoms, are still capable of spreading viruses to others; which presents a serious challenging in preventing the spread of COVID-19. Therefore, intensive surveillance is vital for preventing sustained transmission. Mass testing, as proposed by WHO, can be an effective measure in mitigating the spread of COVID-19.
Asthma and viruses
Asthma and rhinitis are chronic inflammations of the airways, which can worsen as a result of several triggers. Symptoms include shortness of breath, wheezing, coughing, chest pressure, sneezing, itching and runny nose, nasal obstruction, and tiredness. Respiratory viruses can exacerbate asthma and are responsible for more than two-thirds of asthma exacerbations, mainly in children. This leads to the question, can a coronavirus like SARS-Cov2 trigger a severe asthma attack? The answer is very likely to be yes. Theoretically, it could even lead to pneumonia and cause ARDS. In fact, viral infections, from pre-school age to older adults, are well known risk factors for asthma exacerbations, especially if the disease is not controlled;8 and almost half of asthmatics have uncontrolled disease.9 Patients with uncontrolled disease may experience symptoms during the day and/or at night and limitations in their daily lives, they miss work or school days, they often use only relief medications, they go to emergency services very often, they are admitted to the hospital, and worldwide mortality rates are not decreasing.10
Pharmacological and non-pharmacological management of asthma results in minimal or almost non-existent inflammation. This means that symptoms do not arise and there are no exacerbations when the airways are triggered by external factors, as is the case when the airways are colonised with virus. Viruses can cause respiratory tract infections, which if severe, can lead to a visit to the emergency department and hospitalisation. This places a large burden on healthcare services in primary and secondary care, and also puts patients with chronic respiratory allergies at risk of an exacerbation, which can lead to death, as has been demonstrated with respiratory viruses such as influenza and respiratory syncytial, particularly in the young and in the elderly.11–14
With this in mind, identifying viruses and monitoring the severity of their effects will always remain a major scientific and clinical priority. Nevertheless, recent investigation from population-based databases shows that community respiratory viral epidemics are major drivers of emergency department visits and hospitalisations in patients with COPD, but are only a modest contributor to asthma severe exacerbations; in asthmatics the human rhinovirus was the main individual contributor and coronavirus was one of the less identified.15 In a literature review concerning virus detection during asthma exacerbations, Zheng et al. found that exacerbations were mainly associated with rhinovirus infection.16
Asthma, allergies and COVID-19
Extensive research has been conducted on coronavirus in recent weeks, with hundreds of articles published in high-impact journals. It is time to collaborate and disseminate the current knowledge.
In previous SARS outbreaks, patients with asthma, predominantly children, appeared to be less susceptible to the coronavirus with a low rate of asthma exacerbations described, with a good prognosis.17 In contrast, during influenza epidemics, asthma is implicated in more severe cases, including with the need of mechanical ventilation, including in patients of paediatric age.18 The exact reasons for this remain unknown.
In the current COVID-19 pandemic, there is a dearth of data regarding the effects of the disease in patients with allergies and asthma. Among patients with chronic respiratory diseases, asthmatics, despite being part of a group classified as high risk, seem to be not significantly affected, and have a good prognosis; the same situation has been found in relation to other allergic diseases such as allergic rhinitis and atopic dermatitis.19 Hundreds of thousands of people are being affected by COVID-19, and children, who account for up to 5% of diagnosed cases, often have a milder disease, with few developing severe pneumonia, and death being extremely rare.20 New-born infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission is scarce, although not impossible.
Of 171 children treated at Wuhan Children’s Hospital, three (1.8%) required intensive care and mechanical ventilation; all of those had underlying diseases. There was one case of hydronephrosis, one child was undergoing chemotherapy for leukaemia, and another had intussusception,21 with no asthma reference. The same picture was described in a recent report from China.22
In a survey of 140 hospitalised patients in China, the clinical characteristics and allergy status of patients were investigated. An approximately 1:1 ratio of male (50.7%) and female patients with COVID-19 was found, with an overall median age of 57.0 years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations; and hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Patients with COPD (1.4%) and current smokers (1.4%) were rare and the authors concluded that allergic diseases, asthma, and COPD were not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities (cardio-vascular and metabolic), and more prominent laboratory abnormalities were associated with more severe patients.23
In a retrospective, multicentre cohort study, 191 adult inpatients with confirmed COVID-19 (Wuhan, China) who had been discharged (n=135) or had died (n=56), 48% patients had a comorbidity, with hypertension being the most common, followed by diabetes and coronary heart disease. The longest observed duration of viral shedding in survivors was 37 days.24 In a sample of 355 patients with COVID-19 who died in Italy, with a mean age of 79.5 years, it was reported that comorbidities may have increased the mortality risk: 30% had ischaemic heart disease, 35.5% had diabetes, 20.3% had active cancer, 24.5% had atrial fibrillation, 6.8% had dementia, and 9.6% had a history of stroke. Once again, no reference to chronic respiratory diseases, namely asthma or COPD.25
Dong et al. described eleven cases of patients with COVID-19, children and adults, demonstrating the profile complexity and different clinical presentations, from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Patients with common allergic diseases, such as rhinitis or atopic dermatitis, did not develop distinct symptoms and severe courses; however, cases with a pre-existing condition of COPD or complicated with a secondary bacterial pneumonia were more severe.19 The authors stressed the importance of identification all the positive cases, including those with mild symptoms, that need quarantine allowing an efficient containment of the pandemic.19
Very recently, Bhatraju et al. from Seattle, USA, reported 24 patients with confirmed SARS-CoV-2, admitted to the intensive care unit (ICU), with a mortality rate of 50%. As coexisting disorders, 58% had diabetes mellitus, 22% were current or former tobacco smoke, 21% had chronic kidney disease, and 14% had asthma, corresponding to three cases of mild asthmatics. In the week prior to ICU admission, the patients with asthma received systemic steroids, as outpatients, for presumed asthma exacerbation. These patients were subsequently admitted to the ICU with severe respiratory failure requiring invasive mechanical ventilation.26 These data stress the importance of the recognition and differentiation of asthma acute symptoms versus COVID-19 symptoms, as previous studies have shown that systemic steroids can be associated with a higher subsequent viral load, resulting in worse clinical outcomes in previous coronavirus outbreaks.27,28
The available data regarding asthma and allergies reveal that this patient population seem to be at no greater risk of infection with COVID-19.19,23,29 However, these underlying conditions may worsen the disease course of COVID-19, should infection occur, namely if oral rescue steroids are prescribed.26 It is crucial that patients always maintain their controller medication without making any dose adjustments or stopping medication. Patients should also ensure that they have enough medicine for the next few weeks to months.29 New data are emerging daily, rapidly updating our understanding of this novel coronavirus.30
- World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020. Available at: www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020 (accessed 7 April 2020).
- Worldometer. COVID-19 Coronavirus Pandemic. Available at: www.worldometers.info/coronavirus/ (accessed 7 April 2020).
- Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020. doi: 10.1002/jmv.25748.
- Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–9.
- Abassi ZA, Skorecki K, Heyman SN, et al. Covid-19 infection and mortality – A physiologist’s perspective enlightening clinical features and plausible interventional strategies. Am J Physiol Lung Cell Mol Physiol. 2020; doi:10.1152/ajplung.00097.2020. [Epub ahead of print]
- Lupia T, Scabini S, Mornese Pinna S, et al. 2019 novel coronavirus (2019-nCoV) outbreak: A new challenge. J Glob Antimicrob Resist. 2020;21:22–7.
- Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020; doi: 10.4193/Rhin20.114. [Epub ahead of print]
- Oliver BG, Robinson P, Peters M, Black J. Viral infections and asthma: an inflammatory interface? Eur Resp J. 2014;44:1666–81.
- van der Molen T, Fletcher M, Price D. Identifying patient attitudinal clusters associated with asthma control: The European REALISE Survey. J Allergy Clin Immunol Pract. 2018;6:962–71.
- Ebmeier S, Thayabaran D, Braithwaite I, et al. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993-2012). Lancet. 2017;390:935–45.
- Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86.
- van Asten L, van den Wijngaard C, van Pelt W, et al. Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons. J Infect Dis. 2012;206:628–39.
- Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–55.
- Byington CL, Wilkes J, Korgenski K, Sheng X. Respiratory syncytial virus–associated mortality in hospitalized infants and young children. Pediatrics. 2015;135:24–31.
- Satia I, Cusack R, Greene JM, et al. Prevalence and contribution of respiratory viruses in the community to rates of emergency department visits and hospitalizations with respiratory tract infections, chronic obstructive pulmonary disease and asthma. PLoS One. 2020;15:e0228544.
- Zheng X-Y, Xu Y-J, Guan W-J, Lin L-F. Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review. Arch Virol. 2018;163:845–53.
- van Bever HP, Chng SY, Goh DY. Childhood severe acute respiratory syndrome, coronavirus infections and asthma. Pediatr Allergy Immunol. 2004;15:206–9.
- Tokuhira N, Shime N, Inoue M, et al, Writing Committee of AH1N1 Investigators; Japanese Society of Intensive Care Medicine Pediatric Intensive Care Unit Network. Mechanically ventilated children with 2009 pandemic Influenza A/H1N1: results from the national pediatric intensive care registry in Japan. Pediatr Crit Care Med. 2012;13:294–8.
- Dong X, Cao YY, Lu XX, et al. Eleven faces of coronavirus disease 2019. Allergy. 2020; doi: 10.1111/all.14289. [Epub ahead of print].
- Ludvigsson JF. Systematic review of COVID-19 in children show milder cases and a better prognosis than adults. Acta Paediatr. 2020; doi: 0.1111/apa.15270. [Epub ahead of print].
- Lu X, Zhang L, Du H, et al; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 infection in children. N Engl J Med. 2020; doi: 10.1056/NEJMc2005073. [Epub ahead of print].
- Zheng F, Liao C, Fan QH, et al. Clinical characteristics of children with coronavirus disease 2019 in Hubei, China. Curr Med Sci. 2020; doi: 10.1007/s11596-020-2172-6. [Epub ahead of print].
- Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020; doi: 10.1111/all.14238. [Epub ahead of print]
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.
- Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020; doi: 10.1001/jama.2020.4683. [Epub ahead of print]
- Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in critically ill patients in the Seattle region — case series. N Engl J Med. 2020; doi: 10.1056/NEJMoa2004500. [Epub ahead of print]
- Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31:304–9.
- Arabi YM, Mandourah Y, Al-Hameed F, et al. Saudi Critical Care Trial Group. Corticosteroid therapy for critically ill patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018;197:757–67.
- World Allergy Organization. Allergic patients during COVID-19 pandemic. 2020. Available at: www.worldallergy.org/UserFiles/file/Allergic_patients_during_COVID-19.pdf (accessed 7 April 2020).
- Niederman MS, Richeldi L, Chotirmall SH, Bai C. Rising to the challenge of the novel SARS-coronavirus-2 (SARS-CoV-2): Advice for pulmonary and critical care and an agenda for research. Am J Respir Crit Care Med. 2020; doi: 10.1164/rccm.202003-0741ED. [Epub ahead of print]
Mário Morais-Almeida, Head of Immunoallergy, Hospital CUF Descobertas, Lisbon, Portugal; World Allergy Organization, secretary-general; Ignacio Ansotegui, Head of the Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao-Erandio, Spain; World Allergy Organization, past-president.
Disclosures: Mário Morais-Almeida and Ignacio Ansotegui have no financial or non-financial relationships or activities to declare in relation to this article.
Support: Commissioned, edited and supported by Touch Medical Media.
Published: 7 April 2020
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