Exacerbation of Chronic Spontaneous Urticaria Following Coronavirus Disease 2019 (COVID-19) Vaccination in Omalizumab-Treated Patients.

BACKGROUND: The rapid development and rollout of vaccines against coronavirus disease 2019 (COVID-19) has led to more than half of the world's population being vaccinated to date. Real-world data have reported various adverse cutaneous reactions, including delayed-onset urticaria, which was highly ranked as a common manifestation across studies. However, the impact of these novel mRNA or viral vector COVID-19 vaccines on preexisting chronic spontaneous urticaria (CSU) remains largely unknown. OBJECTIVE: To investigate the impact of COVID-19 vaccination on the clinical status of patients with relatively stable CSU who are undergoing omalizumab treatment and to identify risk factors for exacerbation. METHODS: We conducted a questionnaire-based cross-sectional study in a tertiary hospital. Adult patients with relatively stable CSU under regular omalizumab treatments who had received at least one COVID-19 vaccination were included. RESULTS: There were 105 study subjects who received 230 COVID-19 vaccinations between March and December 2021. Fifteen patients (14.3%) experienced aggravation of urticaria at least once after COVID-19 vaccination. The demographics and clinical characteristics of the patients were comparable regardless of the exacerbation of CSU. However, case-level analysis revealed that the presence of urticaria (vs none) before vaccination (odds ratio [OR] = 4.99; 95% CI, 1.57-15.82) and the development of systemic reactogenicity (OR = 4.57; 95% CI, 1.62-12.90) were associated with a higher risk for exacerbation. CONCLUSIONS: The novel COVID-19 vaccination induced exacerbation in more than one-tenth of patients with well-controlled CSU. The establishment of a proper management strategy during COVID-19 vaccination is necessary for patients with CSU.

Clinical Characteristics of Post-COVID-19 Persistent Cough in the Omicron Era.

Cough is one of the most common symptoms of acute coronavirus disease 2019, but cough may persist for weeks or months. This study aimed to examine the clinical characteristics of patients with post-coronavirus disease (COVID) persistent cough in the Omicron era. We conducted a pooled analysis comparing 3 different groups: 1) a prospective cohort of post-COVID cough (> 3 weeks; n = 55), 2) a retrospective cohort of post-COVID cough (> 3 weeks; n = 66), and 3) a prospective cohort of non-COVID chronic cough (CC) (> 8 weeks; n = 100). Cough and health status was assessed using patient-reported outcomes (PROs). Outcomes, including PROs and systemic symptoms, were longitudinally evaluated in the prospective post-COVID cough registry participants receiving usual care. A total of 121 patients with post-COVID cough and 100 with non-COVID CC were studied. Baseline cough-specific PRO scores did not significantly differ between post-COVID cough and non-COVID CC groups. There were no significant differences in chest imaging abnormality or lung function between groups. However, the proportions of patients with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb were 44.7% in those with post-COVID cough and 22.7% in those with non-COVID CC, which were significantly different. In longitudinal assessment of the post-COVID registry (n = 43), cough-specific PROs, such as cough severity or Leicester Cough Questionnaire (LCQ) scores, significantly improved between visits 1 and 2 (visit interval: median 35 [interquartile range, IQR: 23-58] days). In the LCQ score, 83.3% of the patients showed improvement (change ≥ +1.3), but 7.1% had worsened (≤ -1.3). The number of systemic symptoms was median 4 (IQR: 2-7) at visit 1 but decreased to median 2 (IQR: 0-4) at visit 2. In summary, post-COVID persistent cough was similar in overall clinical characteristics to CC. Current cough guideline-based approaches may be effective in most patients with post-COVID cough. Measurement of FeNO levels may also be useful for cough management.

Clinical Characteristics of Post-COVID-19 Persistent Cough in the Omicron Era.

Cough is one of the most common symptoms of acute coronavirus disease 2019, but cough may persist for weeks or months. This study aimed to examine the clinical characteristics of patients with post-coronavirus disease (COVID) persistent cough in the Omicron era. We conducted a pooled analysis comparing 3 different groups: 1) a prospective cohort of post-COVID cough (> 3 weeks; n = 55), 2) a retrospective cohort of post-COVID cough (> 3 weeks; n = 66), and 3) a prospective cohort of non-COVID chronic cough (CC) (> 8 weeks; n = 100). Cough and health status was assessed using patient-reported outcomes (PROs). Outcomes, including PROs and systemic symptoms, were longitudinally evaluated in the prospective post-COVID cough registry participants receiving usual care. A total of 121 patients with post-COVID cough and 100 with non-COVID CC were studied. Baseline cough-specific PRO scores did not significantly differ between post-COVID cough and non-COVID CC groups. There were no significant differences in chest imaging abnormality or lung function between groups. However, the proportions of patients with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb were 44.7% in those with post-COVID cough and 22.7% in those with non-COVID CC, which were significantly different. In longitudinal assessment of the post-COVID registry (n = 43), cough-specific PROs, such as cough severity or Leicester Cough Questionnaire (LCQ) scores, significantly improved between visits 1 and 2 (visit interval: median 35 [interquartile range, IQR: 23-58] days). In the LCQ score, 83.3% of the patients showed improvement (change ≥ +1.3), but 7.1% had worsened (≤ -1.3). The number of systemic symptoms was median 4 (IQR: 2-7) at visit 1 but decreased to median 2 (IQR: 0-4) at visit 2. In summary, post-COVID persistent cough was similar in overall clinical characteristics to CC. Current cough guideline-based approaches may be effective in most patients with post-COVID cough. Measurement of FeNO levels may also be useful for cough management.

ERJ Open Research receives its first impact factor and plans for the next step.

ERJ Open Research received its first impact factor of 4.2. We thank everyone whose commitment has helped the journal to grow and succeed. The journal will continue to contribute to the wider dissemination of relevant, robust and up-to-date knowledge. https://bit.ly/3g9X0lR.

Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.

Cough hypersensitivity and chronic cough.

Chronic cough is globally prevalent across all age groups. This disorder is challenging to treat because many pulmonary and extrapulmonary conditions can present with chronic cough, and cough can also be present without any identifiable underlying cause or be refractory to therapies that improve associated conditions. Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. Cough hypersensitivity presents as excessive coughing often in response to relatively innocuous stimuli, causing significant psychophysical morbidity and affecting patients' quality of life. Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.

Impact of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap on the prognosis of coronavirus disease 2019.

Background: The effects of asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACO) on coronavirus disease 2019 (COVID-19) remain unclear. Objective: We aimed to investigate the effects of chronic obstructive airway diseases such as asthma, COPD, and ACO on COVID-19. Methods: In total, 5625 hospitalized patients with COVID-19 were divided into asthma, COPD, ACO, and control groups. A multivariate logistic regression analysis was performed to identify factors affecting the COVID-19 mortality rate. To find out whether chronic obstructive airway diseases such as asthma, COPD, and ACO affect COVID-19 mortality, 1:4 matching was performed, except for the ACO group alone due to a small number of patients. Results: The mortality rates of asthma, COPD, and ACO groups were about 2.3, 4.8, and 5.5 times higher than that of the control group, respectively. Although not statistically significant, the survival probability tended to decrease (asthma, COPD, and combined groups of asthma and ACO, hazard ratio [HR]: 1.84, 1.31, and 1.89, respectively). The survival probability of the combined groups of COPD, ACO, and asthma and the combined groups of COPD and ACO was significantly lower than that of the matched control group (HR: 3.00 and 1.99, respectively). Conclusion: Compared to patients with COVID-19 without chronic obstructive airway disease, patients with these comorbidities are more likely to require oxygen and mechanical ventilators and have a higher mortality rate, which can be considered when classifying and monitoring patients in the era of COVID-19. Therefore, further studies are needed to evaluate the effect of chronic obstructive airway disease, especially ACO, on COVID-19 mortality.

Long-COVID severe refractory cough: discussion of a case with 6-week longitudinal cough characterization.

Long coronavirus disease (COVID) refers to an array of variable and fluctuating symptoms experienced after acute illness, with signs and symptoms that persist for 8-12 weeks and are not otherwise explicable. Cough is the most common symptom of acute COVID-19, but cough may persist in some individuals for weeks or months after recovery from acute phase. Long-COVID cough patients may get stigmatised because of the public fear of contagion and reinfection. However, clinical characteristics and longitudinal course of long-COVID cough have not been reported in detail, and evidence-based treatment is also lacking. In this paper, we describe a case of long-COVID severe refractory cough with features of laryngeal hypersensitivity and dysfunction. We characterized cough using patient-reported outcomes and engaged in continuous cough frequency monitoring. Through the case study, we discuss potential mechanisms, managements, and clinical implications of long-COVID refractory cough problems.

Epidemiology of adult chronic cough: disease burden, regional issues, and recent findings.

Chronic cough is a common medical condition that has a significant impact on patients' quality of life. Although it was previously considered a symptom of other disorders, it is now regarded as a pathologic state that is characterized by a deviation from the intrinsic protective functions of the cough reflex, especially in adults. There are several factors that may underlie the cough reflex hypersensitivity and its persistence, such as age, sex, comorbidities, viral infection, exposure to irritants or environmental pollutants, and their interactions may determine the epidemiology of chronic cough in different countries. With a deeper understanding of disease pathophysiology and advanced research methodology, there are more attempts to investigate cough epidemiology using a large cohort of healthcare population data. This is a narrative overview of recent findings on the disease burden, risk factors, Asia-Pacific issues, and longitudinal outcomes in adults with chronic cough. This paper also discusses the approaches utilizing routinely collected data in cough research.

Soluble ACE2 and TMPRSS2 Levels in the Serum of Asthmatic Patients.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. METHODS: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. RESULTS: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. CONCLUSION: The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

Impact and disease burden of chronic cough.

Cough is an important physiological mechanism to protect the lower airways, but it is also one of the most common symptoms that lead patients to seek medical consultations. Chronic cough, usually defined by cough duration longer than 8 weeks in adults, is prevalent in the community and impairs quality of life in individual patients. There are several characteristics that may differentiate pathologic coughs from protective cough responses, including cough duration, frequency, hypersensitivity, impaired cough suppressibility, or treatment refractoriness. However, the impact of cough, or its perceived severity, is a sum of the patient's experience of coughing and is a factor that may finally define cough as a disease. Social isolation is a major impact of chronic cough, which is now worse due to the coronavirus disease 2019 pandemic and a widespread fear of cough as a source of contagion. Emotional impact and economic impact (medical cost, reduced work productivity, and job loss) are also important complications of chronic cough, and they interact in a vicious cycle, aggravated by social isolation and treatment failures. This paper is a narrative review that aims to address the impact and disease burden of chronic cough in adult patients. We review the literature, but also introduce the findings from recent qualitative interviews and the patients' experiences of the impact and burden of chronic cough and discuss unmet needs in these patients.