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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl - transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl - transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl - concentration ([Cl - ] i ) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl - ] i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection., (© 2024. The Author(s).)

Background: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence., Objectives: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19., Methods: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms., Results: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported., Interpretation: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 ., (© 2023. The Author(s).)

Background: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes., Methods: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group., Results: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19., Conclusions: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl - is a crucial regulator of host defense, whereas the role of Cl - signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl - concentration ([Cl - ] i ) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl - ] i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl - ] i . Our findings suggested that Cl - acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl - signaling pathway might be a novel therapeutic strategy for COVID-19., (© 2022. The Author(s).)

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.

As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions., (© 2022 Published by Elsevier España, S.L.U. on behalf of SEPAR.)

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 ( P for trend = 0.001), and the association was independent of COPD ( P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P  = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P  < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases ( n  = 74) and test-negative controls ( n  = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

Competing Interests: Conflicts of Interest: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: All authors declare no conflict of interest. The Secretariat of the Independent Panel for Pandemic Preparedness and Response is independent.

Background: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19)., Objectives: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19., Methods: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization., Results: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without., Conclusion: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to ascertain the trends of injury mortality during the COVID-19 period in southern China., Methods: We conducted a population-based retrospective analysis to compare the mortality changes of all-cause injury and transport injuries, poisoning, falls, fire/heat/hot substances, drowning, self-harm and interpersonal violence, which were further stratified by sex and age. Comparisons were made between the COVID-19 period (between January 2020 and June 2020) and control period (between January 2019 and June 2019) in Guangdong province. We used the negative binomial models to explore the associations of deaths during the COVID-19 period, according to the different sex and age strata., Results: The all-cause injury mortality in Guangdong province decreased significantly from 28.65 per 100 000 population during the control period to 23.24 per 100 000 population during COVID-19 pandemic period. Similar results were found in specific injury categories. Mortality of self-harm increased by 139.26% in the 10-14 year group during the COVID-19 period as compared with the control period. Although mortality changes in some groups were not statistically significant, some increases were noteworthy during the COVID-19 period (ie, self-harm, transport injury and falls) in the 70-79 year group. The corresponding increase in mortality rate was 16.83%, 3.32% and 4.92%, respectively., Conclusion: The mortality of all-cause injury, transport injury and drowning during the COVID-19 pandemic was consistently decreased. However, the increase in mortality associated with falls, fire/heat/hot substance injury and self-harm in specific age populations warrant the targeted control and prevention measures for the population at risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As of 28 February 2022, China has vaccinated 87.64% of the whole population with at least two doses of SARS-CoV-2 vaccines, with 40.32% completing the third-dose boosting vaccination. The community-based dynamic zeroing policy has played a pivotal role in minimizing the number of laboratory-confirmed cases and deaths in mainland China. The transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the culprit pathogen of coronavirus disease 2019 (COVID-19), has resulted in more than 0.43 billion cases and 6 million deaths globally. [Extracted from the article]

Keywords: coronavirus; COVID-19; laboratory testing; prevention; therapy; transmission EN coronavirus COVID-19 laboratory testing prevention therapy transmission 657 658 2 05/28/20 20200601 NES 200601 The outbreak of coronavirus disease 2019 (Covid-19) has been rapidly spreading, causing a pandemic globally. We must ensure opportunities to develop targeted therapies to Covid-19 and other coronavirus diseases do not cease when the current outbreak is over. Coronavirus, COVID-19, laboratory testing, prevention, therapy, transmission. [Extracted from the article]