First patient management of COVID-19 in Changsha, China: a case report.

BACKGROUND: In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report. CASE PRESENTATION: A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020. CONCLUSIONS: Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed.

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract.

BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. CONCLUSIONS: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.

Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study.

This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9-11) vs. 11 (95% CI 10-12) vs. 9 (95% CI 8-12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8-10) vs. 10 (95% CI 9.48-11) vs. 8.708 (95% CI 7.51-11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11-13) vs. 13 (95% CI 12-14) vs. 12 (95% CI 10-14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs.

Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism.

Backgrounds and Purpose: The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia. Methods: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFß1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism. Results: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism. Conclusions: FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder.

The role of endoplasmic reticulum stress in emphysema results from cigarette smoke exposure.

Apoptosis is of considerable importance in the pathogenesis of emphysema, and recent studies show that endoplasmic reticulum (ER) stress is involved in emphysema. In our research, we investigated the role of protein kinase RNA (PKR)-like ER kinase (PERK)/ eukaryotic initiation factor 2 alpha (eIF2α) pathway, the CCAAT enhancer-binding protein-homologous protein (CHOP) expression, caspase-12 activation and apoptosis in emphysema results from cigarette smoke (CS) exposure. Expression of phosphorylated-PERK (p-PERK), phospholated-eIF2α (p-eIF2α),CHOP and caspase-12 as well as the apoptosis rate are remarkably increased in rats after exposure to 2 months CS compared with control rats, significantly elevated in rats exposed to 4 months CS over rats exposed only to 2 months CS, and slightly decreased in ex-smoking rats in contrast to rats exposed to 4 months CS. Taken together, our results show that CS induces ER stress in lung epithelial cells, which may subsequently lead to lung injury in rats, and this might be a novel target for protection of pulmonary epithelial cells from ER stress injury in emphysema.

Case Report: Clinical Features of a COVID-19 Patient With Cirrhosis.

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China in December 2019. At present, COVID-19 has emerged as a global pandemic. The clinical features of this disease are not fully understood, especially the interaction of COVID-19 and preexisting comorbidities and how these together further impair the immune system. In this case study, we report a COVID-19 patient with cirrhosis. A 73-year-old woman with cirrhosis reported a fever and cough on February 6, 2020. CT of the chest indicated an infection in her bilateral lungs. She tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The woman was treated with lopinavir and ritonavir tablets and interferon alpha-2b injection, but there was no obvious effect. Although this patient was basically asymptomatic after 2 days in the hospital, the inflammation of the bilateral lungs was slow to subside as shown in CT of the chest. In addition, the white blood cell count (WBC), absolute neutrophil count, and absolute lymphocyte count remained decreased and the result of real-time reverse transcription polymerase chain reaction (PCR) (rRT-PCR) assay was still positive for SARS-CoV-2 on hospital day 28. After infusion of plasma from a recovered COVID-19 patient four times, the patient tested negative for SARS-CoV-2. She was discharged on March 13, 2020. This patient tested negative for SARS-CoV-2 after infusion of plasma from a recovered COVID-19 patient four times. Cirrhosis could impair the homeostatic role of the liver in the systemic immune response, which may affect the removal of SARS-CoV-2. This could lead to a diminished therapeutic effect of COVID-19. Thus, clinicians should pay more attention to COVID-19 patients with cirrhosis.

[Effect of Xuebijing injection on inflammatory markers and disease outcome of coronavirus disease 2019].

OBJECTIVE: To observe the influence of Xuebijing injection on the inflammatory markers and prognosis of coronavirus disease 2019 (COVID-19) patients. METHODS: Sixty severe COVID-19 patients admitted to Changsha Public Health Treatment Center (North Hospital of the First Hospital of Changsha City) from January to March in 2020 were randomly divided into routine treatment group, Xuebijing 50 mL group and Xuebijing 100 mL group, with 20 cases in each group. The routine treatment group was treated according to the National Health Commission's guide for COVID-19. On the basis of conventional treatment, Xuebijing injection was injected by 50 mL twice a day for 7 days in Xuebijing 50 mL group, while by 100 mL twice a day for 7 days in Xuebijing 100 mL group. The blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acute physiology and chronic health evaluation II (APACHE II) score, 2019 novel coronavirus (2019-nCoV) nucleic acid test and disease classification of three groups before and 8 days after treatment were observed. RESULTS: (1) After treatment, the white blood cell count (WBC) and lymphocyte count (LYM) of three groups increased, meanwhile CRP and ESR decreased. Compared with routine treatment group, the WBC count of Xuebijing 100 mL group after treatment significantly increased (×109/L: 7.12±0.55 vs. 5.67±0.51, P < 0.05), and the levels of CRP and ESR in Xuebijing 50 mL and 100 mL groups significantly decreased [CRP (mg/L): 32.3±4.6, 28.0±6.2 vs. 37.3±5.9; ESR (mm/1 h): 45.9±5.7, 40.5±7.4 vs. 55.3±6.6, all P < 0.05]. Compared with Xuebijing 50 mL group, the increase of WBC, and the decrease of CRP and ESR were more significant in Xuebijing 100 mL group [WBC (×109/L): 7.12±0.55 vs. 5.82±0.49, CRP (mg/L): 28.0±6.2 vs. 32.3±4.6, ESR (mm/1 h): 40.5±7.4 vs. 45.9±5.7, all P < 0.05]. (2) After treatment, the APACHE II score of three groups decreased. In Xuebijing 100 mL group, the APACHE II score after treatment was significantly lower than those in routine treatment and Xuebijing 50 mL groups (12.3±1.5 vs. 16.5±1.6, 15.9±1.4, both P < 0.05). After treatment, the 2019-nCoV nucleic acid test in three groups partly turned negative, with 9 cases in routine treatment group, 8 cases in Xuebijing 50 mL group and 9 cases in Xuebijing 100 mL group, without significant difference (P > 0.05). The conditions of patients in the three groups were improved after treatment, among them, 8 cases in the routine treatment group were transformed into common type, 1 case into critical type; 9 cases and 12 cases of Xuebijing 50 mL group and 100 mL group were transformed into common type respectively. Xuebijing 100 mL group was improved more obviously than Xuebijing 50 mL group and routine treatment group (both P < 0.05). CONCLUSIONS: The Xuebijing injection can effectively improve the inflammatory markers and prognosis of severe COVID-19 patients.

Effectiveness of Convalescent Plasma Therapy for COVID-19 Patients in Hunan, China.

OBJECTIVE: To investigate clinical efficacy and safety of convalescent plasma (CP) therapy in coronavirus disease 2019 (COVID-19) patients. METHODS: We included 4 severe patients and 3 critical patients. The date of admission to hospital ranged from January 30 to February 19, 2020. We retrospectively collected clinical and outcome data. Relative parameters were compared. RESULTS: After CP therapy, the symptoms and respiratory functions were improved. Median PaO2/FIO2 increased from 254 (142-331) to 326 (163-364), and dependence of oxygen supply decreased. Median time to lesion's first absorption was 5 (2-7) days, undetectable viral RNA was 11 (3.5-15.7) days. Median lymphocyte count (0.77 × 109/L vs 0.85 × 109/L) and albumin level (31g/L vs 36 g/L) were elevated, C-reactive protein (44 mg/L vs 18 mg/L), D-dimer (5.9 mg/L vs 4 mg/L) and lactate dehydrogenase (263 U/L vs 245 U/L) decreased. No obvious adverse reactions were observed. At the follow-up on June 14, 2020, 6 patients had completely recovered and one died from terminal disease. CONCLUSION: CP therapy for COVID-19 was effective and safe. Three patients who did not combine with antiviral therapy after CP also obtained viral clearance and clinical improvement. However, CP therapy failed to save the life of a terminally ill patient.

Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study.

OBJECTIVES: To investigate factors associated with the duration of viral shedding in patients with COVID-19, outside of Wuhan. METHODS: In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment, and outcome were retrieved. Univariate and multivariate analyses were performed to explore potential factors. RESULTS: Overall, 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset until the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12-21). Multivariate Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200; 95% confidence interval [CI]: 1.190-22.726; p = 0.028), time from symptom onset to admission (OR, 1.740; 95% CI: 1.296-2.337; p < 0.001) and hospital length of stay (OR, 1.604; 95% CI: 1.262-2.040; p < 0.001) were risk factors for prolonged duration of viral shedding. CONCLUSIONS: This study, with a relatively large sample size, focused on the duration of viral shedding and related factors in patients with COVID-19, outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantining infected patients.

Epidemiological and clinical features of 201 COVID-19 patients in Changsha city, Hunan, China.

In December 2019, a cluster of coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The present study was conducted to report the clinical characteristics of 201 COVID-19 patients in Changsha, China, a city outside of Wuhan. All of the patients with confirmed COVID-19 were admitted to the First Hospital of Changsha City, the designated hospital for COVID-19 assigned by the Changsha City Government. The clinical and epidemiological characteristics, data of laboratory, radiological picture, treatment, and outcomes records of 201 COVID-19 patients were collected using electronic medical records. This study population consisted of 201 hospitalized patients with laboratory-confirmed COVID-19 in Changsha by April 28, 2020. The median age of the patients was 45 years (IQR 34-59). About half (50.7%) of the patients were male, and most of the infected patients were staff (96 [47.8%]). Concerning the epidemiologic history, the number of patients linked to Wuhan was 92 (45.8%). The most common symptoms were fever (125 [62.2%]), dry cough (118 [58.7%]), fatigue (65 [32.3%]), and pharyngalgia (31 [15.4%]). One hundred and forty-four (71.6%) enrolled patients showed bilateral pneumonia. Fifty-four (26.9%) patients showed unilateral involvement, and three (1.5%) patients showed no abnormal signs or symptoms. The laboratory findings differed significantly between the Intensive Care Unit (ICU) and non-ICU groups. Compared with non-ICU patients, ICU patients had depressed white blood cell (WBC), neutrocytes, lymphocytes, and prolonged prothrombin time (PT). Moreover, higher plasma levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALA), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase-MB (CK-MB), creatinine (CREA), and lactate dehydrogenase (LDH) were detected in the ICU group. In this single-center study of 201 COVID-19 patients in Changsha, China, 22.4% of patients were admitted to ICU. Based on our findings, we propose that the risk of cellular immune deficiency, hepatic injury, and kidney injury should be monitored. Previous reports focused on the clinical features of patients from Wuhan, China. With the global epidemic of COVID-19, we should pay more attention to the clinical and epidemiological characteristics of patients outside of Wuhan.

Lymphopenia predicted illness severity and recovery in patients with COVID-19: A single-center, retrospective study.

The outbreak of SARS-CoV-2 began in December 2019 and rapidly became a pandemic. The present study investigated the significance of lymphopenia on disease severity. A total of 115 patients with confirmed COVID-19 from a tertiary hospital in Changsha, China, were enrolled. Clinical, laboratory, treatment and outcome data were gathered and compared between patients with and without lymphopenia. The median age was 42 years (1-75). Fifty-four patients (47.0%) of the 115 patients had lymphopenia on admission. More patients in the lymphopenia group had hypertension (30.8% vs. 10.0%, P = 0.006) and coronary heart disease (3.6% vs. 0%, P = 0.029) than in the nonlymphopenia group, and more patients with leukopenia (48.1% vs 14.8%, P<0.001) and eosinopenia (92.6% vs 54.1%, P<0.001) were observed. Lymphopenia was also correlated with severity grades of pneumonia (P<0.001) and C-reactive protein (CRP) level (P = 0.0014). Lymphopenia was associated with a prolonged duration of hospitalization (17.0 days vs. 14.0 days, P = 0.002). Lymphocyte recovery appeared the earliest, prior to CRP and chest radiographs, in severe cases, which suggests its predictive value for disease improvement. Our results demonstrated the clinical significance of lymphopenia for predicting the severity of and recovery from COVID-19, which emphasizes the need to dynamically monitor lymphocyte count.