Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response (preprint)

Phosgene, a highly dangerous chemical warfare agent, is widely used as an industrial chemical. Phosgene inhalation causes acute lung injury (ALI), which may further progress into pulmonary edema. Currently, there is no known antidote for phosgene poisoning. Alpha-1 antitrypsin (α1-AT) is a protease inhibitor that has been used to treat emphysema patients, who are deficient in α1-AT, for decades. Recent studies have shown that α1-AT has both anti-inflammatory and anti-SARS-CoV-2 effects. In this study, we aimed to investigate the role of α1-AT in phosgene-induced ALI. We observed a time-dependent increase in α1-AT expression and secretion in the lungs of rats exposed to phosgene. Interestingly, α1-AT was derived from neutrophils, but not from macrophages or alveolar type II cells, and α1-AT knockdown aggravated phosgene- and lipopolysaccharide (LPS)-induced inflammation and cell death in human bronchial epithelial cells (BEAS-2B). Conversely, α1-AT administration suppressed the inflammatory response and prevented death in LPS- and phosgene-exposed BEAS-2B cells. Furthermore, α1-AT treatment increased the expression of the inhibitor of DNA binding (ID1) gene, which suppressed NF-κB pathway activation, reduced inflammation, and inhibited cell death. These data demonstrate that neutrophil-derived α1-AT protects against phosgene-induced ALI by activating the ID1-dependent anti-inflammatory response. This study may provide novel strategies for the treatment of patients with phosgene-induced ALI.

Immunogenicity and Safety of Inactivated SARS-CoV-2 Vaccine in People Living with HIV: A Cross-Sectional Study (preprint)

Background: To analyze the efficacy and safety of SARS-CoV-2 inactivated vaccine in people living with HIV (PLWH).Methods: A total of 143 PLWH were included in the study. All patients were confirmed with HIV-1 infection. We also enrolled 50 healthy individuals vaccinated with two doses of SARS-CoV-2 vaccine as controls. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detected serum IgG and IgM against SARS-CoV-2.Findings: Serum levels of SARS-CoV-2-specific IgG were significantly higher in the control group than in the PLWH group (P=0.001). Overall, 76% of individuals in the control group achieved IgG seroconversion after vaccination compared with 58% in the PLWH group (P=0.024). The time after vaccination in IgG seronegative PLWH was significantly longer compared with PLWH with IgG seropositive (43.38 ± 34.96 vs 30.27 ± 20.12 days, P=0.005). In PLWH with IgG seropositivity, CD4+ T cell counts before antiretroviral therapy (ART) (P=0.015) and at IgG detection (P<0.001) were higher. Multivariable analysis indicated CD4+ T cells at IgG detection (OR=1.004, P=0.006) and time after vaccination (OR=0.977, P=0.014) were independently associated with humoral response in PLWH after vaccination. Neutralizing antibody (NeuAb) titers in PLWH against wild type SARS-CoV-2 were similar compared with the Control group (P=0.160). The proportion of seropositive NeuAb against wild type SARS-CoV-2 were also similar (95% in Control group vs 97% in PLWH group, P=0.665). Similar results were obtained when NeuAb were detected against the delta variants with similar titers (P=0.355) and with similar proportion of humoral response (P=0.588). All side effects observed in our study were mild and self-limiting. There was no significant difference in occurrence of side effects in the control and PLWH groups. Interpretation: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in PLWH.Funding: This study was supported by Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (No. LC2016PY003).Declaration of Interest: None of the authors have competing interests to disclose.Ethical Approval: The study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Nanfang Hospital (NFEC-2021-178).

Research progress in drugs for Corona Virus Disease 2019

This article summarizes the research progress in treatment drugs for Corona Virus Disease -2019 (COVID-19) by retrieving and referring to the latest clinical data and literature reports, so as to provide reference for clinical treatment. Therapeutic drugs recommended by the latest guidelines were alpha-interferon, lopinavir/ritonavir, and ribavirin combination therapy. In addition, chloroquine, arbidol, as well as bian zheng lun zhi, i. e. diagnosis and treatment based on overall analysis of symptoms and signs, causes, nature and locations of illness and patient physical conditions according to the basic theories of traditional Chinese medicine, can be applied for the treatment of COVID-19. The symptoms of 2 patients treated with lopinavir/ritonavir and redisevir were improved. Theoretically, barretinib could be used as a treatment drug for COVID-19. In vitro experiments have confirmed that darunavir, abidol, fusion peptide (EKl), ABL kinase inhibitors (including imatinib), tenofovir± lavamidine have a certain effect on COVID-19. The combined application of multiple antiviral drugs might be appropriate. The efficacy and safety of the drugs for the treatment of COVID-19 demands further confirmed through clinical trials. [ABSTRACT FROM AUTHOR] Copyright of Pharmaceutial Care & Research is the property of Editorial Board of Pharmaceutial Care & Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Analysis of similarities and differences between coronavirus disease 2019 and severe acute respiratory syndrome

Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are epidemic, contagious, sudden, and publicly harmful diseases. The whole-genome nucleotide identity of the pathogens causing the two diseases reached 79.5%. The mechanism and treatment of COVID-19 are still under investigation. Combining the experiences of SARS prevention and treatment in 2003, and the case data and literature of COVID-19, the similarities and differences between the two diseases in terms of causes, susceptible people, characteristics, dialectical mode, and treatment were analyzed. The two diseases are both plagues in terms of Chinese medicine. The cause of SARS was 'heat poison,' and its pathogenesis was 'heat poison, stasis, and qi and yin deficiency.' Therefore the treatment regimen was mainly to clear away heat, detoxicate, and expel evil. While the cause of COVID-19 was 'wet poison,' and its pathogenesis was 'wet, poison, heat, stasis, close, syncope, and yang collapse.' Hence the basic treatment strategy was to declare lung and remove dampness. Treatment of COVID-19 was clearing away evil qi as soon as possible, with the basic treatment regimen, which was declaring lung, removing dampness, and dispelling the evil. Combined with Traditional Chinese medicine's (TCM's) understanding and experience in SARS prevention and treatment, and Chinese clinical cured cases, we try to provide strategies for people all over the world to understand and respond to COVID-19, through the analysis and comparison. To improve COVID-19 prevention and treatment regimen and give full play to the advantages of TCM.

ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China (preprint)

Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. Methods: In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Results: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age [≥] 60 years and CRP [≥] 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age [≥] 60 years and CRP < 34 mg/L; age < 60 years and CRP [≥] 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P <0.001), respectively. Conclusion: The ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas.