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1.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572660

ABSTRACT

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.


Subject(s)
Antibody-Dependent Enhancement/immunology , Leukocytes/virology , SARS-CoV-2/pathogenicity , COVID-19/immunology , Cells, Cultured , Gene Expression Profiling , Humans , Immune Sera/immunology , Leukocytes/metabolism , Receptors, IgG/metabolism , Virus Replication/immunology
2.
Front Pharmacol ; 12: 735223, 2021.
Article in English | MEDLINE | ID: covidwho-1551527

ABSTRACT

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying high anti-SFTSV efficacy, in which, toosendanin showed the highest inhibition potency. Mechanistic investigation indicated that toosendanin inhibited SFTSV infection at the step of virus internalization. The anti-viral effect of toosendanin against SFTSV was further verified in mouse infection models, and the treatment with toosendanin significantly reduced viral load and histopathological changes in vivo. The antiviral activity of toosendanin was further expanded to another bunyavirus and the emerging SARS-CoV-2. This study revealed a broad anti-viral effect of toosendanin and indicated its potential to be developed as an anti-viral drug for clinical use.

4.
ACS Infect Dis ; 7(6): 1409-1422, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1493008

ABSTRACT

Arenaviruses are a large family of enveloped negative-strand RNA viruses that include several causative agents of severe hemorrhagic fevers. Currently, there are no FDA-licensed drugs to treat arenavirus infection except for the off-labeled use of ribavirin. Here, we performed antiviral drug screening against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) using an FDA-approved drug library. Five drug candidates were identified, including mycophenolic acid, benidipine hydrochloride, clofazimine, dabrafenib, and apatinib, for having strong anti-LCMV effects. Further analysis indicated that benidipine hydrochloride inhibited LCMV membrane fusion, and an adaptive mutation on the LCMV glycoprotein D414 site was found to antagonize the anti-LCMV activity of benidipine hydrochloride. Mycophenolic acid inhibited LCMV replication by depleting GTP production. We also found mycophenolic acid, clofazimine, dabrafenib, and apatinib can inhibit the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Owing to their FDA-approved status, these drug candidates can potentially be used rapidly in the clinical treatment of arenavirus and SARS-CoV-2 infection.


Subject(s)
COVID-19 , Pharmaceutical Preparations , High-Throughput Screening Assays , Humans , SARS-CoV-2 , Virus Replication
5.
Med Sci Monit ; 27: e933381, 2021 Nov 14.
Article in English | MEDLINE | ID: covidwho-1488859

ABSTRACT

BACKGROUND Little is known of the changes in lung radiographic characteristics over time in patients recovering from COVID-19. This study analyzed the clinical features and temporal lung radiographic changes in patients with moderate and severe COVID-19 pneumonia who did not require invasive mechanical ventilation during the acute and convalescent periods. MATERIAL AND METHODS The data of 25 patients with COVID-19 pneumonia from January 29, 2020, to November 24, 2020, who did not require invasive mechanical ventilation and who were followed up were retrospectively collected. The 25 patients were divided into severe and moderate groups. Clinical characteristics and computed tomography (CT) manifestations were compared. A total of 121 consecutive thin-slice CT scans were collected at 4 weeks, 2 months, and 5 months after admission to evaluate lung abnormalities in the patients. The CT score was used to assess disease severity. RESULTS The severe group had a lower rate of nucleic acid conversion within 10 days of admission and higher D-dimer, creatine kinase, and lactate dehydrogenase values. In the severe group, hospital stay was longer and hospitalization costs were higher. The average CT score of the severe group peaked in the second week, while the moderate group peaked in the first week and then decreased over time. There were no statistically significant differences in the average CT score between the 2 groups at the 5-month follow-up. CONCLUSIONS The pulmonary lesions of patients recovering from COVID-19 and who do not require invasive mechanical ventilation were gradually absorbed and resolved over time.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/pathology , Lung/diagnostic imaging , Lung/physiology , Tomography, X-Ray Computed/methods , Adult , Case-Control Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
6.
Infect Dis Ther ; 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1482329

ABSTRACT

INTRODUCTION: Since the global outbreak of COVID-19, there has been a significant reduction in pediatric outpatient and emergency visits for infectious diseases. The purpose of this study was to analyze the changes in respiratory viruses in children with community-acquired pneumonia (CAP) in Shanghai in the past 10 years, especially in the first year after COVID-19. METHODS: We conducted a retrospective, observational study; the results for eight common respiratory viruses (respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza virus 1-3 (PIV), adenovirus (ADV) and human metapneumovirus) tested by direct fluorescent antibody assays in hospitalized CAP cases in Children's Hospital of Fudan University during 2010-2020 were analyzed. RESULTS: Of the 5544 hospitalized CAP patients included in this study, 20.2% (1125/5544) were positive for the eight respiratory viruses. The top three pathogens were RSV, PIV3 and ADV, detected from 9.8% (543/5544), 5.3% (294/5544) and 2.0% (111/5544) of the samples, respectively. RSV had the highest positive rates among children < 2 years old. In 2020, the detection rate of all viruses showed a sharp decline from February to August compared with the previous 9 years. When the Shanghai community reopened in August 2020, the detection rate of eight viruses rebounded significantly in September. CONCLUSIONS: These eight respiratory viruses, especially RSV and PIV, were important pathogens of CAP in Shanghai children in the past 10 years. The COVID-19 pandemic had a significant impact on the detection rates for eight respiratory viruses in children with CAP in Shanghai.

7.
Sustainability ; 13(20):11308, 2021.
Article in English | ProQuest Central | ID: covidwho-1480958

ABSTRACT

Based on the data of the 283 prefecture-level cities in China from 2003 to 2018, this paper examines the impact of Internet development on environmental quality. The results show that China’s urban PM2.5 has a significant spatial spillover effect. In general, the Internet has a significant negative direct effect on urban environmental pollution, which means that the development of the Internet can improve urban environmental quality. This result remains robust under different methods. As the Internet has evolved over the years, its influence on environmental quality has increased and became more and more significant. In terms of regions, the spatial spillover effect of PM2.5 shows a pattern of eastern region < central region < western region < northeast region, where the eastern region is the only region with a statistically significant negative value for the coefficient, which indicates the direct effects of Internet development on the environmental quality. In addition, the statistic testing on mediating effect shows that the Internet’s effect on urban environment quality is mainly transmitted through the upgrading of industrial structure. With the industrial structure being used as the threshold variable, the influence of Internet development on environmental quality could be divided into two stages.

8.
J Control Release ; 339: 361-380, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1454255

ABSTRACT

Fungal infections affect millions of people globally and are often unreceptive to conventional topical or oral preparations because of low drug bioavailability at the infection site, lack of sustained therapeutic effect, and the development of drug resistance. Amphotericin B (AmB) is one of the most potent antifungal agents. It is increasingly important since fungal co-infections associated with COVID-19 are frequently reported. AmB is only administered via injections (IV) and restricted to life-threatening infections due to its nephrotoxicity and administration-related side effects. In this work, we introduce, for the first time, dissolving microneedle patches (DMP) loaded with micronised particles of AmB to achieve localised and long-acting intradermal delivery of AmB for treatment of cutaneous fungal infections. AmB was pulverised with poly (vinyl alcohol) and poly (vinyl pyrrolidone) to form micronised particles-loaded gels, which were then cast into DMP moulds to form the tips. The mean particle size of AmB in AmB DMP tips after pulverisation was 1.67 ± 0.01 µm. This is an easy way to fabricate and load microparticles into DMP, as few steps are required, and no organic solvents are needed. AmB had no covalent chemical interaction with the excipients, but the crystallinity of AmB was reduced in the tips. AmB was completely released from the tips within 4 days in vitro. AmB DMP presented inhibition of Candida albicans (CA) and the killing rate of AmB DMP against CA biofilm inside porcine skin reached 100% within 24 h. AmB DMP were able to pierce excised neonatal porcine skin at an insertion depth of 301.34 ± 46.86 µm. Ex vivo dermatokinetic and drug deposition studies showed that AmB was mainly deposited in the dermis. An in vivo dermatokinetic study revealed that the area under curve (AUC0-inf) values of AmB DMP and IV (Fungizone® bolus injection 1 mg/kg) groups were 8823.0 d∙µg/g and 33.4 d∙µg/g, respectively (264-fold higher). AmB remained at high levels (219.07 ± 102.81 µg/g or more) in the skin until 7 days after the application of AmB DMP. Pharmacokinetic and biodistribution studies showed that AmB concentration in plasma, kidney, liver, and spleen in the AmB DMP group was significantly lower than that in the IV group. Accordingly, this system addressed the systemic side effects of intravenous injection of AmB and localised the drug inside the skin for a week. This work establishes a novel, easy and effective method for long-acting and localised intradermal drug delivery.


Subject(s)
Amphotericin B , COVID-19 , Animals , Antifungal Agents , Drug Delivery Systems , Humans , SARS-CoV-2 , Swine , Tissue Distribution
9.
Signal Transduct Target Ther ; 6(1): 346, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1437668

ABSTRACT

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11-20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Animals , Cell Line, Tumor , Female , Humans , Male , Mice , Middle Aged
11.
J Virol ; 95(17): e0074721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1356909

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase , Interferon-beta , Promoter Regions, Genetic , SARS-CoV-2 , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , HEK293 Cells , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon-beta/antagonists & inhibitors , Interferon-beta/biosynthesis , Interferon-beta/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
12.
J Virol ; 95(17): e0074721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1350002

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase , Interferon-beta , Promoter Regions, Genetic , SARS-CoV-2 , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , HEK293 Cells , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon-beta/antagonists & inhibitors , Interferon-beta/biosynthesis , Interferon-beta/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
13.
Int J Environ Res Public Health ; 18(13)2021 06 26.
Article in English | MEDLINE | ID: covidwho-1288859

ABSTRACT

To assess the effectiveness of the containment strategies proposed in Japan, an SEIAQR (susceptible-exposed-infected-asymptomatic-quarantined-recovered) model was established to simulate the transmission of COVID-19. We divided the spread of COVID-19 in Japan into different stages based on policies. The effective reproduction number Re and the transmission parameters were determined to evaluate the measures conducted by the Japanese Government during these periods. On 7 April 2020, the Japanese authority declared a state of emergency to control the rapid development of the pandemic. Based on the simulation results, the spread of COVID-19 in Japan can be inhibited by containment actions during the state of emergency. The effective reproduction number Re reduced from 1.99 (before the state of emergency) to 0.92 (after the state of emergency). The transmission parameters were fitted and characterized with quantifiable variables including the ratio of untracked cases, the PCR test index and the proportion of COCOA app users (official contact confirming application). The impact of these variables on the control of COVID-19 was investigated in the modelling analysis. On 8 January 2021, the Japanese Government declared another state of emergency. The simulated results demonstrated that the spread could be controlled in May by keeping the same strategies. A higher intensity of PCR testing was suggested, and a larger proportion of COCOA app users should reduce the final number of infections and the time needed to control the spread of COVID-19.


Subject(s)
COVID-19 , Humans , Japan , Pandemics , Quarantine , SARS-CoV-2
14.
Signal Transduct Target Ther ; 6(1): 181, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1223081

ABSTRACT

Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming "herd-immunity" through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.


Subject(s)
Antibodies, Viral/immunology , Asymptomatic Infections/epidemiology , COVID-19/immunology , Immunity/immunology , Aged , Antibodies, Viral/blood , Antibodies, Viral/genetics , COVID-19/blood , COVID-19/physiopathology , COVID-19/virology , China/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
15.
Psychosom Med ; 83(4): 373-379, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1218021

ABSTRACT

OBJECTIVE: The outbreak of COVID-19 that commenced in December 2019 in Wuhan, China, has caused extensive public health concerns and posed substantial challenges to health professionals, especially for those in the center of the epidemic. The current study aimed to assess the prevalence, related factors, and mechanism of acute stress disorder (ASD) among health professionals in Wuhan during this critical period. METHODS: The study used a cross-sectional design. Self-administered questionnaires were distributed to the frontline health professionals in Wuhan hospitals from January 28 to February 1, 2020. Mental health-related measurements included ASD, depression, anxiety, conflict experiences, hostility, and psychosomatic symptoms. Structural equation modeling was used to analyze the factors associated with ASD among health professionals. RESULTS: A total of 332 frontline health professionals were included in the analysis (mean [standard deviation] age = 32.21 [8.77] years; 78.0% women). ASD was a prominent mental health problem in the health professionals surveyed, with a prevalence of 38.3%. Anxiety (24.7%) and depression (20.2%) were also common. Structural equation modeling analyses revealed that emotional distress (i.e., anxiety and depressive symptoms) fully mediated the association between conflicts with ASD (the standardized indirect coefficient ß = 0.47, p = .016). The most common reported symptom was chest pain (51.2%). ASD was significantly associated with psychosomatic symptoms. The majority (67.8%) reported being easily annoyed or irritated, and ASD was associated with hostility. CONCLUSIONS: During the COVID-19 outbreak, a substantial number of health professionals in Wuhan suffered from ASD. Furthermore, ASD was found to be associated with psychosomatic symptoms as well as the hostility. The poor mental health of health professionals has detrimental impacts both on the well-being of staff in health care systems and may adversely affect the quality of patient care. We call for interventions that aim to relieve the psychological and occupational stress. Considering that most of our participants were young, female frontline health professionals, the results may not be generalized to more heterogenous samples.


Subject(s)
COVID-19/psychology , Health Personnel/psychology , Occupational Stress/etiology , Stress Disorders, Traumatic, Acute/etiology , Adult , COVID-19/complications , COVID-19/epidemiology , China/epidemiology , Disease Outbreaks , Female , Health Personnel/statistics & numerical data , Humans , Male , Medically Unexplained Symptoms , Models, Statistical , Occupational Stress/epidemiology , Prevalence , Stress Disorders, Traumatic, Acute/epidemiology , Surveys and Questionnaires
17.
Front Psychiatry ; 12: 575005, 2021.
Article in English | MEDLINE | ID: covidwho-1178040

ABSTRACT

Background: The outbreak of coronavirus disease 2019 (COVID-19) resulted in a substantial workload and stress for frontline health professionals in high-risk areas. Little research has investigated the mechanism of occupational burnout among the frontline health professionals located in the center of the epidemic in Wuhan, China. Methods: A total of 199 frontline health professionals from Wuhan Jinyintan Hospital completed the cross-sectional survey. Mechanisms of occupational burnout (according to the Maslach Burnout Inventory-General Survey, MBI-GS) among the health professionals in Jinyintan Hospital during the COVID-19 outbreak were examined using a structural equation model (SEM). Results: The levels of the three burnout dimensions (emotional exhaustion, cynicism, and professional efficacy) were high at 34.2, 50.8, and 35.2%, respectively. Frontline health professionals in this stressful period reported significantly greater emotional exhaustion (p < 0.001) and job-related cynicism (p < 0.001), but no significant difference in professional efficacy (p = 0.449), when compared to employees in a large multinational company. The SEM results revealed that both acute stress symptoms and psychosomatic symptoms significantly predicted the emotional exhaustion and occupation cynicism dimensions of burnout. Conclusion: The study reveals the occupational burnout mechanism of frontline health professionals during the COVID-19 peak at the time of the outbreak. This study provides an important contribution to understanding the future psychological interventions necessary for frontline health professionals during an epidemic crisis.

18.
JCI Insight ; 6(4)2021 02 22.
Article in English | MEDLINE | ID: covidwho-1039950

ABSTRACT

The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst public health crisis in a century. However, knowledge about the dynamics of antibody responses in patients with COVID-19 is still poorly understood. In this study, we performed a serological study with serum specimens collected at the acute and the convalescent phases from 104 patients with severe COVID-19 who were part of the first wave of COVID-19 cases in Wuhan, China. Our findings revealed that neutralizing antibodies to SARS-CoV-2 are persistent for at least 6 months in patients with severe COVID-19, despite that IgG levels against the receptor binding domain (RBD) and nucleocapsid protein (N) IgG declined from the acute to the convalescent phase. Moreover, we demonstrate that the level of RBD-IgG is capable of correlating with SARS-CoV-2-neutralizing activities in COVID-19 serum. In summary, our findings identify the magnitude, functionality, and longevity of antibody responses in patients with COVID-19, which sheds light on the humoral immune response to COVID-19 and would be beneficial for developing vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/blood , Antibodies, Viral/isolation & purification , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , China , Cohort Studies , Female , Humans , Immune Sera , Immunity, Humoral , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Male , Middle Aged , Survivors , Time Factors
19.
Sens Actuators B Chem ; 331: 129415, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1009880

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic continues to ravage the world. In epidemic control, dealing with a large number of samples is a huge challenge. In this study, a point-of-care test (POCT) system was successfully developed and applied for rapid and accurate detection of immunoglobulin-G and -M against nucleocapsid protein (anti-N IgG/IgM) and receptor-binding domain in spike glycoprotein (anti-S-RBD IgG/IgM) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Any one of the IgG/IgM found in a sample was identified as positive. The POCT system contains colloidal gold-based lateral flow immunoassay test strips, homemade portable reader, and certified reference materials, which detected anti-N and anti-S-RBD IgG/IgM objectively in serum within 15 min. Receiver operating characteristic curve analysis was used to determine the optimal cutoff values, sensitivity, and specificity. It exhibited equal to or better performances than four approved commercial kits. Results of the system and chemiluminescence immunoassay kit detecting 108 suspicious samples had high consistency with kappa coefficient at 0.804 (P < 0.001). Besides, the levels and alterations of the IgG/IgM in an inpatient were primarily investigated by the POCT system. Those results suggested the POCT system possess the potential to contribute to rapid and accurate serological diagnosis and epidemiological survey of COVID-19.

20.
Cell Discov ; 6(1): 96, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-989763

ABSTRACT

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

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