In May 2023, WHO declared that COVID-19 was no longer a public health emergency of international concern. In 2024, COVID-19 certainly has not gone away, but we can now take a more reflective look at the pandemic. This issue of the Monograph does just that, bringing together a truly international group of experts, as befits a global illness, to consider areas such as: long-term sequelae in airway disease, interstitial lung disease, and in the immunocompromised; therapeutics in the community, in hospital and in the intensive care unit; and the pathophysiology and management of long COVID. The Guest Editors also consider the impact of COVID-19 on clinical research and scientific publishing, as well as looking to the future, considering what can be learnt from the pandemic.
- Page 1AbstractCorresponding author: Clare Williams (clare.williams@europeanlung.org)
The COVID-19 pandemic exerted multifaceted effects on patients. Many felt apprehensive regarding the potential consequences of contracting COVID-19 on their respiratory health, observing a dearth of pertinent information for those with pre-existing lung conditions. Self-isolation, while deemed necessary for mitigating viral transmission, presented challenges. Patients with respiratory conditions reported changes in healthcare service delivery, with some encountering difficulty accessing appropriate and timely care. Those who contracted COVID-19 frequently reported enduring sequelae, including long COVID. Even as the pandemic ended, many with lung conditions continued to harbour concerns, with mixed attitudes towards vaccination. Prospective pandemic preparedness strategies should include enhanced dissemination of tailored information targeting individuals with pulmonary conditions, alongside expedited interventions by healthcare systems and governments to safeguard patient welfare. This chapter aims to capture patients' perspectives on the COVID-19 pandemic. It combines data from a search of published qualitative studies, along with patient perspectives from group discussions, interviews and case studies.
Cite as: Williams C. The patient perspective of the pandemic. In: Chalmers JD, Cilloniz D, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 1–15 [https://doi.org/10.1183/2312508X.10018723].
- Page 16AbstractCorresponding author: Wei-Jie Guan (battery203@163.com)
The COVID-19 pandemic has had a significant impact on global health since its emergence in December 2019. During this pandemic, SARS-CoV-2 variants with different transmissibility and pathogenicity have evolved continuously and caused multiple waves globally. This ongoing evolution underscores the need for persistent genomic surveillance to effectively detect and respond to new mutations. Understanding these patterns and the factors driving variant emergence can enhance public health strategies and preparedness for future outbreaks. In this chapter, we review the timeline of the COVID-19 global pandemic and highlight the continuous evolution of different variants. The driving forces underlying the emergence of SARS-CoV-2 variants are also discussed. Furthermore, we summarise the key trends associated with the transmissibility and pathogenicity of the variants, thereby outlining the trajectory of evolution and management strategies.
Cite as: Liu Y-X, Luo J-Y, Liu R-B, et al. Timeline of the pandemic: epidemiology, global spread, variants and waves. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 16–25 [https://doi.org/10.1183/2312508X.10018823].
- Page 26AbstractCorresponding author: Bin Cao (caobin_ben@163.com)
COVID-19 is a multi-system disease caused by infection of the respiratory virus SARS-CoV-2. Widespread COVID-19 vaccination and population immunity from previous infections have reduced disease severity. The clinical presentations have also changed as the virus is constantly evolving. Most infections are asymptomatic or only lead to mild upper respiratory tract symptoms. A small proportion of patients, however, develop pulmonary and extrapulmonary complications in the acute stage, often with exacerbation of pre-existing illness, some of whom progress to respiratory failure and even death. Special populations, especially immunocompromised hosts, have different clinical presentations including prolonged virus shedding or persistent infection. COVID-19 also has long-term health impacts, including long-term sequalae or long COVID. Although the COVID-19 pandemic has already ended, it is still an international disease of great importance. Careful management and longitudinal follow-up is still necessary.
Cite as: Xu J, Li J, Jin Y, et al. COVID-19 in adults: spectrum of illness and clinical presentation. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 26–43 [https://doi.org/10.1183/2312508X.10019623].
- Page 44AbstractCorresponding author: Charles Dela Cruz (delacruz@pitt.edu)
The extensive research conducted during the pandemic provided an immense understanding of the complex but important cell-specific responses to SARS-CoV-2. Cellular responses to the virus are performed in a coordinated manner, in which multiple immune cell types, both resident and recruited, and pulmonary structural cells participate in the antiviral response. SARS-CoV-2 preferentially infects cells based on cell receptor ACE2 expression. Important cells are involved in the control of the virus at the initial site of exposure in the nasopharyngeal space, limiting viral spread. Infection can progress to involve cells in the conducting airways and the upper respiratory tract and, for some, can migrate into the lower respiratory tract, involving alveolar cells in the lung parenchyma. Virus infection of alveolar epithelial cells causes cell death and triggers exuberant inflammatory cellular activation and recruitment, leading to tissue destruction and causing clinical respiratory failure.
Cite as: Sharma L, Kim J, Dela Cruz C. Cellular response in the pathogenesis of COVID-19. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 44–64 [https://doi.org/10.1183/2312508X.10019823].
- Page 65AbstractCorresponding author: Adamantia Liapikou (mliapikou@yahoo.com)
The development of effective antiviral therapy for COVID-19 is critical to protect high-risk populations, including people aged >65 years old, individuals with overweight or obesity, immunocompromised individuals or those with comorbidities, or unvaccinated individuals. This chapter summarises the approved antiviral therapies for COVID-19 inpatients and outpatients. The three antivirals approved for the treatment of COVID-19 in outpatients are remdesivir, molnupiravir, and nirmatrelvir/ritonavir. The therapeutic value of remdesivir lies on its ability to inhibit viral replication, and it may prevent severe illness in patients with COVID-19 and high-risk factors. In hospital settings, the recommended antivirals are remdesivir, tocilizumab (an IL-6 receptor antagonist) and baricitinib (which inhibits JAK enzymes). In hospitalised patients with disease progression and rapidly increasing oxygen needs, the WHO suggests the use of baricitinib and tocilizumab in combination with corticosteroids.
Cite as: Liapikou A, Lerikou M. Antiviral therapy for COVID-19. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 65–78 [https://doi.org/10.1183/2312508X.10020023].
- Page 79AbstractCorresponding author: Adrian Ceccato (aaceccato@tauli.cat)
The development of effective vaccines against SARS-CoV-2 changed the course of the pandemic. Vaccines were shown to be safe and were highly effective against the development of severe disease, preventing many deaths worldwide. Several vaccine types were introduced, which had different mechanisms of action and variable efficacy. However, waning immunity and the emergence of new variants of concern with considerable immune escape have increased the need for additional boosters. In this chapter, we summarise the most recent evidence, including important studies and recommendations regarding COVID-19 vaccines in the post-pandemic era, focusing on their effectiveness against severe disease, which should be the ultimate goal of vaccination. Knowledge gaps are still being filled and important questions remain to be answered. For now, available evidence suggests a need for regular boosters, particularly for those at increased risk of severe events.
Cite as: Lazar Neto F, Ceccato A, Ranzani OT. Vaccination against COVID-19 in a post-pandemic era. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 79–103 [https://doi.org/10.1183/2312508X.10020223].
- Page 104AbstractCorresponding author: Nicolas Roche (nicolas.roche@aphp.fr)
The proportion of patients with COVID-19 requiring hospitalisation has decreased dramatically since the start of the pandemic, while the population has been gaining immunity. In parallel, variants have also evolved. Most patients included in large-scale RCTs were recruited during the 2 first years of the pandemic, and the extent to which the corresponding evidence is still applicable is not fully clear. The pharmacological treatment for severe COVID-19 currently includes systemic corticosteroids (dexamethasone), associated with anti-IL-6 agents and/or the JAK inhibitor baricitinib, and with prophylactic or therapeutic heparin regimen. Remdesivir can be administered. Other agents are not recommended. When oxygen therapy is not sufficient to obtain adequate gas exchange, high-flow nasal therapy or NIV are indicated and can be used alternately. Resources need to be mobilised to provide adequate supportive measures, including palliative care and rehabilitation. Adequate protective measures are needed when providing nebulised therapy.
Cite as: Roche N, Chalmers JD. Therapeutics in hospitalised adult patients with COVID-19. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 104–121 [https://doi.org/10.1183/2312508X.10020423].
- Page 122AbstractCorresponding author: Despoina Koulenti (deskogr@yahoo.gr)
COVID-19 management in the ICU has been significantly improved due to the evidence that has become available, since the beginning of the pandemic. Among other factors, this has improved outcomes and has increased ICU survival rates. This chapter provides a thorough and up-to-date overview of COVID-19 management in critical care settings. It describes the epidemiology of severe disease and the criteria that define this entity. Additionally, this chapter presents the most updated evidence on specific clinical manifestations, on clinical and laboratory monitoring and on different aspects of severe COVID-19 management, including the sedation and analgesia, the ventilation and oxygenation, the use of ECMO, the haemodynamic monitoring and support, and the pharmacological interventions that are indicated in COVID-19 patients requiring ICU admission. Finally, it discusses usual and more rare complications that are seen in this population and concludes by describing specific long-term complications that ICU survivors develop after ICU discharge.
Cite as: Koulenti D, Almyroudi M-P, Andrianopoulos I, et al. Management of severe COVID-19 in the ICU. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 122–152 [https://doi.org/10.1183/2312508X.10020523].
- Page 153AbstractCorresponding author: Bin Cao (caobin_ben@163.com)
A considerable proportion of hospitalised COVID-19 patients have sepsis, with ARDS as the most common organ dysfunction. The clinical presentation of sepsis is similar regardless of the underlying cause. However, key differences exist in the pathobiology between viral and bacterial sepsis. Damage-associated molecular patterns (DAMPs) play a key role in the pathology of severe COVID-19 by initiating an inflammatory response. Delayed but exaggerated type I IFN responses can exacerbate inflammation and contribute to the severe progression of COVID-19. A broad range of immune cells are involved in viral sepsis pathogenesis. Severe or critical COVID-19 patients are in a prothrombotic state with impaired fibrinolysis due to endothelial injury and dysfunction; therefore, anticoagulant therapy is an important part of the treatment strategy for COVID-19-related sepsis. Low-dose corticosteroids prove beneficial for COVID-19-related sepsis, whereas higher dose corticosteroids significantly increase the risk of death. Both the similarities and unique phenotypic characteristics of viral and bacterial sepsis should be considered to optimise treatment outcomes.
Cite as: Li H, Yu J, Xu J, et al. Viral sepsis and SARS-CoV-2. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 153–161 [https://doi.org/10.1183/2312508X.10020623].
- Page 162AbstractCorresponding author: Tommaso Francesco Aiello (tfaiello@recerca.clinic.cat)
This chapter explores secondary infections in COVID-19, emphasising their clinical significance and evolving epidemiology. Secondary infections, including co-infections and superinfections, occur simultaneously or after SARS-CoV-2 infection, increasing morbidity and mortality, particularly in critically ill patients and those with comorbidities. Initially rare, the prevalence of these infections has surged, especially in severe cases. Bacterial respiratory tract infections are most common, followed by bloodstream and urinary tract infections, mainly related to hospital stay. Key risk factors include ICU admission, mechanical ventilation and immunosuppression. The pathophysiology involves immune dysregulation, epithelial barrier disruption and microbiome alterations. Diagnosing these infections is complex, often requiring advanced techniques. Empirical antibiotic use is widespread, although guidelines advocate for prudent prescribing. This chapter highlights the need for targeted antimicrobial therapy and enhanced diagnostic strategies to manage secondary infections in COVID-19 patients effectively, aiming to mitigate their substantial impact on patient outcome. This comprehensive overview underscores the importance of ongoing vigilance and research in this critical aspect of COVID-19 management.
Cite as: Aiello TF, Chumbita M, Monzó-Gallo P, et al. Secondary infection after COVID-19. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 162–173 [https://doi.org/10.1183/2312508X.10021123].
- Page 174AbstractCorresponding author: Kristina Crothers (crothk@uw.edu)
Immunocompromised individuals represent a large group of people who are at very high risk of SARS-CoV-2 infection and severe COVID-19. The impact of an impaired immune system on vaccine responsiveness and clinical outcome is highly variable, depending on what aspects of the immune system are compromised. Understanding the biological and clinical manifestations of COVID-19 in different immunocompromised states has significant implications for personalised management of immunosuppressed patients as well as our understanding of COVID-19 in general. These insights could inform future prevention and treatment approaches for COVID-19 that have the potential to impact the entire population. In this chapter, we discuss the mechanisms of host immunological risk, epidemiology, vaccine responsiveness and treatment considerations for the five most common immunocompromising conditions: HIV, solid organ transplant, cellular therapies, cancer, and autoimmune/inflammatory diseases.
Cite as: Morrell ED, Mabrey FL, Goodman JS, et al. COVID-19 in the immunocompromised host. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 174–197 [https://doi.org/10.1183/2312508X.10020823].
- Page 198AbstractCorresponding author: James D. Chalmers (j.chalmers@dundee.ac.uk)
COPD, asthma and bronchiectasis patients are an increased risk of respiratory infections, and in 2020 they were assumed to be more vulnerable to COVID-19 morbidity and mortality. However, evidence suggests that these patients were not over-represented among those hospitalised during the pandemic, although considerable variability in prevalence has been observed. COPD is associated with increased mortality and more severe outcomes from COVID-19, potentially related to increased expression of ACE2, the primary receptor for SARS-CoV-2 entry into host cells. Whether asthma increases the risk of severe COVID-19 is less clear, and evidence suggests that a type 2 high endotype may offer some protection against SARS-CoV-2 infection. Currently, guidance suggests that the continuation of usual maintenance therapies, including inhaled corticosteroids and biologics, is safe in SARS-CoV-2 infection. Public health measures taken during the COVID-19 pandemic reduced the circulation of other respiratory viruses and, as a consequence, reduced the frequency of exacerbations, including hospitalisations, for people with airways diseases.
Cite as: Marshall L, Johnson E, Chalmers JD. COVID-19 in patients with airways disease: COPD, asthma and bronchiectasis. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 198–214 [https://doi.org/10.1183/2312508X.10005024].
- Page 215AbstractCorresponding author: Bruno Crestani (bruno.crestani@aphp.fr)
Patients with ILD have both impaired lung function and an increased risk of acute exacerbations driven by viral infection. COVID-19 disease is of particular concern for ILD patients, including those with idiopathic ILDs and with ILDs associated with systemic autoimmune diseases, hypersensitivity pneumonitis and others. Although data about the prevalence of COVID-19 in ILD patients remains limited, evidence from several published studies and meta-analyses shows that COVID-19 infection is associated with increased rates of hospitalisation and mortality. Several factors, such as male sex, older age, usual interstitial pneumonia pattern, ILD subtype, and immunosuppressants are associated with the prognosis from COVID-19. Digital health provided a promising alternative approach during the pandemic, with tele-rehabilitation showing an important benefit for the quality of life of ILD patients.
Cite as: Vasarmidi E, Le Guen P, Goletto T, et al. COVID-19 in patients with interstitial lung disease. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 215–226 [https://doi.org/10.1183/2312508X.10021023].
- Page 227AbstractCorresponding author: Joan B. Soriano (jbsoriano2@gmail.com)
There are many unknowns surrounding COVID-19 and long COVID. Even >4 years after the outbreak of the COVID-19 pandemic, the sequelae and long-term consequences of acute SARS-CoV-2 infection, often referred to as long COVID, remain poorly understood. Despite mounting evidence, denial and nihilism from some health systems persist, dismissing patients' symptoms as psychosomatic or failing to recognise and treat long COVID. Discrepancies in terminology and definitions further complicate efforts to characterise this condition. The natural history of long COVID varies widely and requires more research. Beyond any lingering respiratory problems, a myriad of persistent, fluctuating, new-onset symptoms prevail, ranging from fatigue to cognitive dysfunction, and presenting in virtually any system and organ. Epidemiological estimators, such as incidence, prevalence and remission rates, offer valuable insights into the population distribution of long COVID, although variability across populations persists. Identifying risk (and protective) factors is crucial, yet uncertainties abound, highlighting the need for ongoing research and surveillance. As we navigate the complexities of long COVID, a concerted effort is required to prevent, diagnose and manage this condition effectively, and eventually to cure such patients, while preparing for future challenges in a rapidly evolving landscape of infectious and post-viral diseases.
Cite as: Soriano JB, Rodríguez-Ledo P, Ancochea J. Long COVID: epidemiology and clinical impact. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 227–239 [https://doi.org/10.1183/2312508X.10021323].
- Page 240AbstractCorresponding author: Rosemary J. Boyton (r.boyton@imperial.ac.uk)
Efforts to address the global challenge of long COVID are progressing, with urgent attempts to decode its pathophysiology. Among the mechanisms that have been investigated are organ damage through viral cytotoxicity or inflammation, downstream consequences of stimulation by a persistent tissue reservoir of uncleared virus, immune perturbations that include changes in immune subsets, immune exhaustion and raised inflammatory biomarkers, downstream consequences of reactivating endogenous herpesviruses, perturbations of the vascular endothelium and coagulation, autoimmunity, allergy, and microbiota dysbiosis. The hypothesis that long COVID symptoms result from a tissue reservoir of persistent SARS-CoV-2 is, of all the proposed immunopathogenic mechanisms, perhaps the most widely favoured and investigated. A limiting factor is that studies have had to rely on invasive procedures such as biopsy or on positron emission tomography imaging. There is a need to translate biomarker discovery studies into an agreed, accessible, standardised combination set for use in diagnosis and trial design. The aim now is to implement RCTs based on the evidenced pathophysiology.
Cite as: Boyton RJ, Altmann DM. Long COVID: pathological mechanisms. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 240–249 [https://doi.org/10.1183/2312508X.10021423].
- Page 250AbstractCorresponding author: Felicity Liew (felicity.liew16@imperial.ac.uk)
Long COVID is a chronic and debilitating condition with limited treatment options, suffered by millions of people globally. In the absence of diagnostic biomarkers and defined pathobiological mechanisms, symptom control and rehabilitation are currently the mainstays of management. A variety of clinical trials are underway, but many fail to take into account the pathogenic subgroups of long COVID. Characterising these subgroups and elucidating their associated pathophysiology would enable targeted trials of disease-modifying treatments. Adaptive multidisciplinary trials using defined disease subgroups, biomarkers and end-points are required to optimise clinical interventions.
Cite as: Liew F, Openshaw PJM. Long COVID: current management and future prospects. In: Chalmers JD, Cilloniz D, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 250–277 [https://doi.org/10.1183/2312508X.10021523].
- Page 278AbstractCorresponding author: Jamie Stobo (jstobo001@dundee.ac.uk)
The COVID-19 pandemic was an unprecedented healthcare event. With a novel pathogen and no proven treatments, it also represented an unprecedented challenge for clinical research, with an urgent need for life-saving treatments and vaccines. In the absence of outstanding candidate therapeutics, trial designs were required which could rapidly evaluate multiple therapies in heterogeneous patient populations. Adaptive platform trials (randomised trials with multiple treatment arms and a single control group) were ideal to deliver this. This approach was heavily used in fields such as oncology pre-pandemic, but was less common in respiratory medicine or infectious diseases. Trials such as RECOVERY and REMAP-CAP delivered dexamethasone, tociliuzumab, baricitinib and antibody therapies as effective treatments for hospitalised patients with COVID-19, while demonstrating lack of effectiveness for a number of drugs that were widely used empirically. The success of adaptive platform trials during COVID-19 has increased interest in their application to other diseases post-pandemic, which may be a lasting legacy of the pandemic for clinical research.
Cite as: New BJM, Chalmers JD, Stobo J. COVID-19 platform trials: insight and lessons in clinical trial design. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 278–294 [https://doi.org/10.1183/2312508X.10021223].
- Page 295AbstractCorresponding author: Martin Kolb (kolbm@mcmaster.ca)
Health systems and medical service providers faced many challenges during the COVID pandemic. This included the medical publishing field. Many medical journals, especially those in general medicine, respirology and critical care, and infectious disease, were forced to evaluate high numbers of manuscripts, at times exceeding the typical average of daily submissions by a factor of 3–5. This was the challenge faced by the flagship journals of the European Respiratory Society (ERS) and the American Thoracic Society (ATS), which had the goal of publishing useful information, and doing it rapidly, while maintaining scientific quality and integrity. As most society journals rely heavily on volunteer reviewers and non-professional editors, considerable stress was put upon the peer review system. Pre-print publications noted a surge in activity during this period and, not surprisingly, journal Impact Factors became inflated due to highly cited COVID-related papers. These effects were temporary, and a few years after the end of the pandemic, medical publishing is now back to previous levels: sound and effective, but intrinsically vulnerable to larger challenges.
Cite as: Kolb M, Wedzicha JA, Chalmers JD. Publishing the pandemic: the impact of COVID-19 on science and scientific publishing. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 295–299 [https://doi.org/10.1183/2312508X.10021623].
- Page 300AbstractCorresponding author: Catia Cilloniz (catiacilloniz@yahoo.com)
Pandemics have claimed the lives of millions of people throughout history. Over the last millennium, different respiratory pathogens have caused several global pandemics. The Black Death that killed ∼50 million European people, the Columbian Exchange with an estimated 48 million people dead, the Spanish influenza, which had an estimated death toll of 50–100 million, and COVID-19, which killed 7 million people, are foremost examples. Far from being past threats, future pandemics by emerging or re-emerging pathogens are expected. Factors such as increasing global trade and international travel, climate change, loss of biodiversity, the excessive use of antibiotics, exposure to animal, social and economic problems, and mounting health inequalities are the backbone of pathogen spillover and rapid zoonotic dissemination associated with a high latent pandemic potential against which we should prepare at both national and global levels. The SARS, Ebola, MERS, H1N1 and COVID-19 outbreaks, among other recent viral outbreaks, have directed global organisations such as the WHO to lead new programmes on preparedness in the face of new pandemics. In this chapter, we discuss the foundations of pandemic prevention and preparedness, from local easily applicable measures to global intersectoral strategies.
Cite as: Cilloniz C, Pericas JM, Čivljak R. Future perspectives: preventing the next pandemic. In: Chalmers JD, Cilloniz C, Cao B, eds. COVID-19: An Update (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 300–320 [https://doi.org/10.1183/2312508X.10021723].
