Assessment of Long-Term Effects on Pulmonary Functions Between Severe and Non-Severe Convalescent COVID-19 Patients: A Single-Center Study in China.

Objective: To explore the long-term effects of SARS-Cov-2 infection on the pulmonary function in the severe convalescent COVID-19 patients for 6 to 9 months follow-up in Beijing, China. Methods: A total of 64 cases of COVID-19 patients were recruited for the study and discharged from the Beijing Ditan Hospital, Capital Medical University, for 6 to 9 months. COVID-19 patients were divided into non-severe (mild and moderate) and severe groups. The follow-up investigated the lung function tests, the novel coronavirus antibody (IgM and IgG), chest CT and blood tests. Results: About 25.00% (16/64) patients had pulmonary ventilation dysfunction and 35.9% (23/64) had diffusion dysfunction. In the severe group, 56.50% (13/23) individuals showed decreased diffusion function. The diffusion dysfunction of the severe group was significantly decreased than the non-severe group (P = 0.01). Among 56 cases, the positive rate of IgG titers was 73.2% (41/56). The result of chest CT showed 55.36% (31/56) cases in nodules, 44.64% (25/56) in strip-like changes, 37.5% (21/56) in-ground glass shadow, and 5.36% (3/56) in grid shadow, which was significantly different between the severe group and the non-severe group. Patients tended to have ground glass changes in the severe group while nodules in the non-severe group. Conclusion: For the 6 to 9 months in convalescent COVID-19 patients, 56.50% (13/23) of severe patients had pulmonary diffusion dysfunction. Convalescent COVID-19 patients should have their pulmonary function regularly tested, especially those with severe illness.

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.

To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial.

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.

Liver stiffness measurement is a potent predictor of histological fibrosis regression after hepatitis C virus clearance.

BACKGROUND: Most of the studies on fibrosis regression prediction were based on noninvasive fibrosis markers and differ greatly. The 'Beijing fibrosis classification' can use histological results to classify fibrosis into progressive or 'nonprogressive' according to fibrotic septal morphology. We use this standard which served as the gold standard in order to find fibrosis regression predictors. AIM: To study the predictors of fibrosis regression after hepatitis C virus clearance according to histological fibrosis staging by the 'Beijing fibrosis classification'. MATERIALS AND METHODS: This was a prospective cohort study. A total of 68 patients with advanced liver fibrosis or compensated cirrhosis who achieved sustained virological response were enrolled. Patients with the Ishak scores lower than 3 seemed to have fibrosis regression. The others were divided into the fibrosis progressive group and the nonprogressive group according to the 'Beijing fibrosis classification'. Predictors of fibrosis regression were studied by logistic regression using baseline factors and the dynamic change in noninvasive fibrosis factors. RESULTS: Eighteen patients were assigned to the progressive group, and the others were assigned to the nonprogressive group. The baseline liver stiffness measurements (LSMs) of the progressive and nonprogressive groups were 14.35 (11.3, 27.3) kPa and 11.3 (8.3, 14.2) kPa, respectively, P = 0.02. The baseline LSM was the only predictor of fibrosis progression. With a cutoff of 11.85 kPa, the AUC was 0.71 (0.5, 0.9), and the negative predictive value was 0.92. CONCLUSIONS: The baseline LSM was found to be the only predictor of fibrosis regression, 11.85 kPa is a possible 'hepatic fibrosis return point'.

Lower Circulating Interferon-Gamma Is a Risk Factor for Lung Fibrosis in COVID-19 Patients.

Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-γ (IFN-γ) levels were twofold lower than those without fibrosis (p > 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-γ levels with an estimate of 0.43 (p = 0.02). Per the 1-SD increase of basal IFN-γ level in circulation, the fibrosis volume decreased by 0.070% (p = 0.04) at the discharge of participants. The basal circulating IFN-γ levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-γ is a risk factor of lung fibrosis in COVID-19.

A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.

This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.

Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals.

The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.

[A clinical analysis of 137 cases of influenza A(H1N1)].

OBJECTIVE: To analyze the epidemiology and clinical characteristics of influenza A (H1N1). METHODS: A retrospective analysis was performed on the clinical data of 137 cases of influenza A (H1N1) admitted into our hospital during May to August 2009. RESULTS: In the early stage, most cases were imported from the US, Australia, Canada and the UK. While in the later stage, most of them were secondary. The patients were mainly children and youngsters. And the most common clinical manifestations were fever (n = 108), cough (n = 93) and sore throat (n = 67) while the most common signs congestive throat (n = 99) and swelling tonsil (n = 46). The average fever period was 3.3 ± 1.5 days. The clinical symptoms vanished in 4.4 ± 1.9 days. And the average length of stay was 5.5 ± 2.1 days. Laboratory tests: the count of leukocytes declined while that of lymphocytes increased in 39 cases (39.5%). The test of influenza A (H1N1) nucleic acid was positive. The chest radiograph showed intensive pulmonary markings or patchy pneumonia-like signs. TREATMENTS: the groups of patients using Chinese herbs, western medicine plus Chinese herbs, symptomatic relief and placebo showed no significant difference in fever period, recovery time and the negative-converting period of influenza A (H1N1) nucleic acid tests became negative. CONCLUSION: Influenza A (H1N1) may be recessive or dominant. Despite a strong infectivity, the clinical symptoms are mild and the clinical course is self-limited, similar to the seasonal influenza.

[A follow up study of total IgM, IgG, nucleoprotein and spike protein antibodies against severe acute respiratory syndrome (SARS) coronavirus in patients with SARS].

OBJECTIVE: To survey the dynamic changing and persistence of the special antibodies, including total IgM, IgG, nucleocapsid protein and spike protein antibodies, against severe acute respiratory syndrome coronavirus (SARS-CoV) in patients with SARS. METHODS: 146 cases, all clinically diagnosed as SARS with positive SARS-CoV IgG, were followed up. 362 serum samples were collected from the onset of the disease to 660 days afterward. Total IgM and IgG against SARS-CoV were tested with commercial ELISA kits. For recombinant nucleoprotein and spike protein, we developed an ELISA to test these two antibodies. RESULTS: Within 20 days of the onset, the positive rate of anti-SARS-CoV IgM was 46.5% (20/43); it reached a peak after 21 - 40 days (80.6%, 25/31). Then, the positive rate of IgM went down gradually to 8.2% (6/73) until 550 days after the onset. The patient's IgG positive rate was lower (34.9%, 15/43) than that of IgM within 20 days of the onset. Then it went up rapidly to 100%. It remained positive (98.6%, 70/71) until 600 - 660 days after the onset. When N-IgG and S-IgG were tested 40 days after the onset of the disease at three different times, the positive rate of N-IgG (92.5%, 37/40) was higher than that of S-IgG (67.5%, 27/40), but the two structure protein antibodies were always lower than the total IgG. CONCLUSIONS: In SARS patients with definite clinical and etiological diagnosis, the highest positive rate of the antibodies against SARS-CoV was found at 21 - 40 days after the onset. IgM disappeared almost 500 days (91.8%) after the onset. Total IgG positive rate could reach 100% and 98.6% and the positivity might persist nearly two years. So it is speculated that the total IgG antibody may be positive 3 to 5 years after infection, but it seems that N-IgG and S-IgG keep positive shorter in time than total IgG antibody.

[Psychological and physical presentations of severe acute respiratory syndrome].

OBJECTIVE: To study the relation between psychological symptoms and physical parameters in patients with severe acute respiratory syndrome (SARS) at different stages of the disease. METHODS: Physical parameters such as SCL-90, chest CT, T lymphocytes and subset and SaO2 were studied in 29 SARS patients at three different stages (initial stage, serious stage, rehabilitating stage). RESULTS: Patients with SARS showing severe psychological symptoms constituted about 41% (group I) and patients with SARS showing mild psychological symptoms (group II) constituted about 59%. There were no change of the psychological symptoms at the three stages in group I and II (P > 0.05). Statistical differences were found between physical parameters of group I and II in rehabilitating stage. CONCLUSIONS: Severe psychological symptoms such as obsession, depression and anxiety were found in a minority of patients with SARS and the psychological symptoms were not related with the change of physical parameters. The majority of the patients with SARS did not have severe psychological symptoms. Whether or not psychological symptoms were related to their personality needs further study.

[Liver histological changes after lamivudine treating in chronic hepatitis B patients with HBeAg positive].

OBJECTIVES: To investigate the histological changes in liver biopsy tissues taken from chronic hepatitis B patients with HBsAg and HBeAg positive and ALT abnormal after lamivudine therapy for one year. METHODS: Lamivudine was given orally at the dose of 100 mg once a day for one year. 101 patients were enrolled into this open-label study. Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine were studied. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index(HAI). RESULTS: 53.5% (54/101), 51.5% (52/101) and 31.7% (32/101) patients had a reduction of their total hepatic HAI score, necroinflammation and fibrosis scores by >or=2 points or 1 points at the end of one year of lamivudine therapy, compared with their pretreatment values, respectively. There were significant reduction of HAI score, necroinflammation and fibrosis scores from 8.0+/-4.7 to 5.2+/-3.3 (t=7.358, P<0.01), from 5.9+/-3.8 to 3.6+/-2.5 (t=7.298, P<0.01), and from 2.1+/-1.2 to 1.6+/-1.2 (t=3.827, P<0.01), respectively. The histological improvement was independent on the HBeAg seroconvertion during the therapy. CONCLUSION: Significant improvement in liver histology, both necroinflammation and fibrosis, can be obtained in the majority of patients treated with lamivudine for one year.

[Clinical manifestation, treatment, and outcome of severe acute respiratory syndrome: analysis of 108 cases in Beijing].

OBJECTIVE: To investigate the clinical manifestations, treatment, and outcome of severe acute respiratory syndrome (SARS). METHODS: The clinical data of 108 SARS in-patients were analyzed. RESULTS: Among the 108 cases, 35 males (32.4%) and 73 females (67.6%), aged 37 +/- 9 (range 13 approximately 83 years), most were white-collar workers, medical workers accounting for 28.7%. 87.0% had a definite contact history. 20.4% were complicated by other internal diseases. The main clinical manifestations included fever, cough, pectoralgia, chest distress, headache, etc. Involvement of multiple organs was often. The incubation period was 2 approximately 14 days. The course included early stage, progressive stage, climax, and convalescence. Mild type accounted for 4.6%, common type 39.8%, severe type 20.4%, and extremely severe type 35.2%. At the early stage, white blood cell count, lymphocyte count and ratio of lymphocyte, proalbumin, transferring, CD(3)(+), CD(4)(+), CD(8)(+) cell count were remarkably decreased, and C-reactive protein, alpha-acid glycoprotein, and alpha(2)-globulin were remarkably increased. X-ray chest film showed solitary or multiple local exudative changes, mostly in pulmonary lower field. During the progressive stage the hyaline or consolidation images were enlarged. High solution CT showed solitary or multiple cotton wadding like images and ground glass-like or consolidation images. Hypoxemia was common. At the progressive stage application of adrenocortical hormones and non-invasive mechanical ventilation helped stop the progress of disease. Ninety-four cases were discharged, 14 cases died. Traditional Chinese medicine (TCM) regards SARS as one of epidemic febrile diseases. Treatment by combination of TCM and Western medicine was effective. CONCLUSION: SARS mainly affects youth and people in their prime of life. It has its own characteristic clinical manifestations. The classification system of 5 types and 4 stages helps judge the condition. Treatment by combination of TCM and Western medicine is encouraged.