Neutrophil elastase: From mechanisms to therapeutic potential.

Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Spatial-temporal clustering of an outbreak of SARS-CoV-2 Delta VOC in Guangzhou, China in 2021.

Background: In May 2021, the SARS-CoV-2 Delta variant led to the first local outbreak in China in Guangzhou City. We explored the epidemiological characteristics and spatial-temporal clustering of this outbreak. Methods: Based on the 153 cases in the SARS-CoV-2 Delta variant outbreak, the Knox test was used to analyze the spatial-temporal clustering of the outbreak. We further explored the spatial-temporal clustering by gender and age groups, as well as compared the changes of clustering strength (S) value between the two outbreaks in Guangzhou. Results: The result of the Knox analysis showed that the areas at short distances and brief periods presented a relatively high risk. The strength of clustering of male-male pairs was higher. Age groups showed that clustering was concentrated in cases aged ≤ 18 years matched to 18-59 years and cases aged 60+ years. The strength of clustering of the outbreak declined after the implementation of public health measures. The change of strength of clustering at time intervals of 1-5 days decreased greater in 2021 (S = 129.19, change rate 38.87%) than that in 2020 (S = 83.81, change rate 30.02%). Conclusions: The outbreak of SARS-CoV-2 Delta VOC in Guangzhou has obvious spatial-temporal clustering. The timely intervention measures are essential role to contain this outbreak of high transmission.

When and How to Adjust Non-Pharmacological Interventions Concurrent with Booster Vaccinations Against COVID-19 - Guangdong, China, 2022.

Introduction: With the large-scale roll-out of the coronavirus disease 2019 (COVID-19) booster vaccination effort (a vaccine dose given 6 months after completing primary vaccination) in China, we explore when and how China could lift non-pharmacological interventions (NPIs) against COVID-19 in 2022. Methods: Using a modified susceptible-infectious-recovered (SIR) mathematical model, we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province, China. Results: If the number of people entering from overseas recovers to 20% of the number in 2019, the epidemic in 2022 could be controlled at a low level by a containment (215 local cases) or suppression strategy (1,397 local cases). A mitigation strategy would lead to 21,722 local cases. A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong's medical system. With 50% or 100% recovery of the 2019 level of travelers from overseas, the epidemic could also be controlled with containment or suppression, but enormous resources, including more hotel rooms for border quarantine, will be required. However, coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases. Discussion: With booster vaccinations, the number of travelers from overseas could increase slightly in 2022, but a suppression strategy would need to be maintained to ensure a controllable epidemic.

Reduction of air pollutants and associated mortality during and after the COVID-19 lockdown in China: Impacts and implications.

Although strict lockdown measurements implemented during the COVID-19 pandemic have dramatically reduced the anthropogenic-based emissions, changes in air quality and its health impacts remain unclear in China. We comprehensively described air pollution during and after the lockdown periods in 2020 compared with 2018-2019, and estimated the mortality burden indicated by the number of deaths and years of life lost (YLL) related to the air pollution changes. The mean air quality index (AQI), PM10, PM2.5, NO2, SO2 and CO concentrations during the lockdown across China declined by 18.2 (21.2%), 27.0 µg/m3 (28.9%), 10.5 µg/m3 (18.3%), 8.4 µg/m3 (44.2%), 13.1 µg/m3 (38.8%), and 0.3 mg/m3 (27.3%) respectively, when compared to the same periods during 2018-2019. We observed an increase in O3 concentration during the lockdown by 5.5 µg/m3 (10.4%), and a slight decrease after the lockdown by 3.4 µg/m3 (4.4%). As a result, there were 51.3 (95%CI: 32.2, 70.1) thousand fewer premature deaths (16.2 thousand during and 35.1 thousand after the lockdown), and 1066.8 (95%CI: 668.7, 1456.8) thousand fewer YLLs (343.3 thousand during and 723.5 thousand after the lockdown) than these in 2018-2019. Our findings suggest that the COVID-19 lockdown has caused substantial decreases in air pollutants except for O3, and that substantial human health benefits can be achieved when strict control measures for air pollution are taken to reduce emissions from vehicles and industries. Stricter tailored policy solutions of air pollution are urgently needed in China and other countries, especially in well-developed industrial regions, such as upgrading industry structure and promoting green transportation.

The time-varying transmission dynamics of COVID-19 and synchronous public health interventions in China.

OBJECTIVES: We aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City, and Guangdong province, and compare to that of severe acute respiratory syndrome (SARS). METHODS: Data on COVID-19 cases in China up to 20 March 2020 was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing, and Hong Kong during 2002-3 was also obtained. We estimated the doubling time, basic reproduction number (R0), and time-varying reproduction number (Rt) of COVID-19 and SARS. RESULTS: As of 20 March 2020, 80,739 locally acquired COVID-19 cases were identified in mainland China, with most cases reported between 20 January and 29 February 2020. The R0 value of COVID-19 in China and Wuhan was 5.0 and 4.8, respectively, which was greater than the R0 value of SARS in Guangdong (R0 = 2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). At the start of the COVID-19 epidemic, the Rt value in China peaked at 8.4 and then declined quickly to below 1.0 in one month. With SARS, the Rt curve saw fluctuations with more than one peak, the highest peak was lower than that for COVID-19. CONCLUSIONS: COVID-19 has much higher transmissibility than SARS, however, a series of prevention and control interventions to suppress the outbreak were effective. Sustained efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.

Risk factors associated with COVID-19 infection: a retrospective cohort study based on contacts tracing.

This study aimed to estimate the attack rates, and identify the risk factors of COVID-19 infection. Based on a retrospective cohort study, we investigated 11,580 contacts of COVID-19 cases in Guangdong Province from 10 January to 15 March 2020. All contacts were tested by RT-PCR to detect their infection of SARS-COV-2. Attack rates by characteristics were calculated. Logistic regression was used to estimate the risk factors of infection for COVID-19. A total of 515 of 11,580 contacts were identified to be infected with SARS-COV-2. Compared to young adults aged 20-29 years, the infected risk was higher in children (RR: 2.59, 95%CI: 1.79-3.76), and old people aged 60-69 years (RR: 5.29, 95%CI: 3.76-7.46). Females also had higher infected risk (RR: 1.66, 95%CI: 1.39-2.00). People having close relationship with index cases encountered higher infected risk (RR for spouse: 20.68, 95%CI: 14.28-29.95; RR for non-spouse family members: 9.55, 95%CI: 6.73-13.55; RR for close relatives: 5.90, 95%CI: 4.06-8.59). Moreover, contacts exposed to index case in symptomatic period (RR: 2.15, 95%CI: 1.67-2.79), with critically severe symptoms (RR: 1.61, 95%CI: 1.00-2.57), with symptoms of dizzy (RR: 1.58, 95%CI: 1.08-2.30), myalgia (RR: 1.49, 95%CI: 1.15-1.94), and chill (RR: 1.42, 95%CI: 1.05-1.92) had higher infected risks. Children, old people, females, and family members are susceptible of COVID-19 infection, while index cases in the incubation period had lower contagiousness. Our findings will be helpful for developing targeted prevention and control strategies to combat the worldwide pandemic.