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2.
Infectious Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1804323

ABSTRACT

Background : Since the outbreak of coronavirus disease (COVID-19), the high infection rate and mutation frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent, have contributed to the ongoing global pandemic. Vaccination has become the most effective means of controlling COVID-19. Traditional neutralizing tests of sera are complex and labor-intensive, therefore, a rapid test for detecting neutralizing antibodies and antibody status post-immunization is needed. Methods : Based on the fact that antibodies exhibit neutralizing activity by blocking the binding of the S protein receptor-binding domain (S-RBD) to ACE2, we developed a rapid neutralizing antibody test, ACE2-Block-ELISA. To evaluate the sensitivity and specificity, we used 54 positive and 84 negative serum samples. We also tested the neutralizing activities of monoclonal antibodies (mAbs) and 214 sera samples from healthy individuals immunized with the inactivated SARS-CoV-2 vaccine. Results : The sensitivity and specificity of the ACE2-Block ELISA were 96.3% and 100%, respectively. For neutralizing mAb screening, ch-2C5 was selected for its ability to block the ACE2–S-RBD interaction. A plaque assay confirmed that ch-2C5 neutralized SARS-CoV-2, with NT50 values of 4.19, 10.63, and 1.074 μg/mL against the SARS-CoV-2 original strain, and the Beta and Delta variants, respectively. For the immunized sera samples, the neutralizing positive rate dropped from 82.14% to 32.16% within 4 months post-vaccination. Conclusions : This study developed and validated an ACE2-Block-ELISA to test the neutralizing activities of antibodies. As a rapid, inexpensive and easy-to-perform method, this ACE2-Block-ELISA has potential applications in rapid neutralizing mAb screening and SARS-CoV-2 vaccine evaluation.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333031

ABSTRACT

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

4.
Research Square ; 2022.
Article in English | EuropePMC | ID: covidwho-1786456

ABSTRACT

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

5.
BMJ Open ; 12(4): e056345, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1784821

ABSTRACT

OBJECTIVE: To investigate the COVID-19 vaccination coverage rate and differences among various COVID-19 prevention primary healthcare (PHC) facilities in China and understand their attitudes towards COVID-19 vaccine. These findings are helpful to provide important suggestions to further improve national COVID-19 vaccination rate. DESIGN: A nationwide cross-sectional online survey was designed and conducted among COVID-19 prevention and control management teams at PHC facilities in mainland China. In the self-designed questionnaires, each subject was asked to evaluate on a 1-10 scale (10=extremely important/acceptable/influential) the COVID-19 vaccination importance, acceptance and factors related to vaccine hesitancy. SETTING: Subjects from 31 provinces and autonomous regions including minorities across mainland China were invited to complete the questionnaire between 22 February 2021 and 2 March 2021. PARTICIPANTS: Were selected by multistage stratified sampling, 998 valid questionnaires (valid rate 99.11%) were collected. The respondents were divided into group A (≤5 respondents within each PHC facility, n1=718) and group B (>5 respondents within each PHC facility, n2=280). OUTCOME MEASURES: Survey on vaccination rate and attitude towards COVID-19 vaccine included the following: (1) if the subjects think the vaccination is important in containment of COVID-19 pandemic (1-10 scale, 10=extremely important), (2) if they would accept COVID-19 vaccine (1-10 scale, 10=extremely acceptable) and (3) their opinions on 7 factors possibly related to vaccine hesitancy (1-10 scale, 10=extremely influential). All the items were designed based on the previous expert interviews. RESULTS: Our results showed vaccination rate was greater in group A (85.93%) than in group B (66.43%) (p<0.001). Detailed analyses revealed that in group A, male members were twice as likely to get vaccinated as compared with female members (adjusted OR (aOR): 2.07; 95% CI: 1.26 to 3.43, p=0.004). In group B, those who were at or under the median age had twice the odds of vaccination coverage compared with those who were over the median age (aOR: 2.29; 95% CI: 1.22 to 4.33, p=0.010). In addition, those who were specialised in traditional Chinese medicine were less likely to get vaccinated against COVID-19 compared with those who were specialised in general medicine, with the aOR: 0.10 (95% CI: 0.01 to 0.83, p=0.033). By analysing the factors that influenced the vaccination attitudes among the 998 respondents, we found no significant difference between the vaccinated and unvaccinated participants. However, further detailed analyses found that team members with undergraduate college education were less likely to score higher in COVID-19 vaccination importance than those with technical secondary school education (aOR: 0.35; 95% CI: 0.13 to 0.93, p=0.035); Furthermore, those with non-medical job titles had nearly twice the odds of giving a higher score for the uncertainty of vaccine efficacy compared with those with junior medical titles (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.016). Team members with a non-medical title were more likely to give a higher score for advice on social sources compared with those with a junior medical title (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.042). CONCLUSION: In PHC facilities, although there was a higher COVID-19 vaccination rate among COVID-19 prevention and control teams, some subgroups with different descriptive characters showed negative attitudes towards COVID-19 vaccination. Because primary care workers in China are highly expected to receive the vaccination, and support and educate the public for COVID-19 vaccination. Thus, it is important and necessary to continue to educate them about their vaccination concerns and change their attitudes towards vaccination. Our findings are highly beneficial for designing public vaccination education strategies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Attitude , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Pandemics , Primary Health Care , SARS-CoV-2 , Vaccination , Vaccination Coverage
6.
BMC Health Serv Res ; 22(1): 399, 2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-1765452

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Cities , Humans , Pandemics/prevention & control , Primary Health Care
7.
J Med Virol ; 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1756617

ABSTRACT

SARS-CoV-2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS-CoV-2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS-CoV-2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well-understood SARS-CoV-2 mouse-adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor-binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS-CoV-2 from humans to mice during the continued evolution of SARS-CoV-2, and that the key amino acid mutations in the RBD of mouse-adapted strains may be referenced as an early-warning indicator for predicting the spillover risk of newly emerging SARS-CoV-2 variants.

8.
Front Immunol ; 13: 796682, 2022.
Article in English | MEDLINE | ID: covidwho-1731771

ABSTRACT

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Hepatitis A Virus Cellular Receptor 2/immunology , Natural Killer T-Cells/immunology , SARS-CoV-2/immunology , Humans , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-4/immunology , Signal Transduction/immunology
9.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1728092

ABSTRACT

Uncontrolled severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 infection is closely related to disorders of the innate immune and delayed adaptive immune systems. Dendritic cells (DCs) “bridge” innate immunity and adaptive immunity. DCs have important roles in defending against SARS-CoV-2 infection. In this review, we summarize the latest research concerning the role of DCs in SARS-CoV-2 infection. We focus on the complex interplay between DCs and SARS-CoV-2: pyroptosis-induced activation;activation of the renin–angiotensin–aldosterone system;and activation of dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin. We also discuss the decline in DC number, the impaired antigen-presentation capability, and the reduced production of type-I interferon of DCs in severe SARS-CoV-2 infection. In addition, we discuss the potential mechanisms for pathological activation of DCs to understand the pattern of SARS-CoV-2 infection. Lastly, we provide a brief overview of novel vaccination and immunotherapy strategies based on DC targeting to overcome SARS-CoV-2 infection.

10.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
11.
Lancet Microbe ; 3(3): e193-e202, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1721237

ABSTRACT

Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. Interpretation: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. Funding: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

12.
Future Med Chem ; 14(6): 393-405, 2022 03.
Article in English | MEDLINE | ID: covidwho-1715941

ABSTRACT

Background: Since December 2019, SARS-CoV-2 has continued to spread rapidly around the world. The effective drugs may provide a long-term strategy to combat this virus. The main protease (Mpro) and papain-like protease (PLpro) are two important targets for the inhibition of SARS-CoV-2 virus replication and proliferation. Materials & methods: In this study, deep reinforcement learning, covalent docking and molecular dynamics simulations were used to identify novel compounds that have the potential to inhibit both Mpro and PLpro. Results & conclusion: Three compounds were identified that can effectively occupy the Mpro protein cavity with the PLpro protein cavity and form high-frequency contacts with key amino acid residues (Mpro: His41, Cys145, Glu166; PLpro: Cys111). These three compounds can be further investigated as potential lead compounds for SARS-CoV-2 inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Deep Learning , Drug Evaluation, Preclinical , SARS-CoV-2/drug effects , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/pharmacology
13.
J Immunol ; 208(2): 321-327, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1708204

ABSTRACT

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.


Subject(s)
8-Hydroxy-2'-Deoxyguanosine/blood , Community-Acquired Infections/pathology , Pneumonia/blood , Pneumonia/mortality , Severity of Illness Index , Aged , Biomarkers/blood , Community-Acquired Infections/blood , Critical Care/statistics & numerical data , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Oxidative Stress/physiology , Pneumonia/pathology , Prognosis , Prospective Studies , Respiration, Artificial/statistics & numerical data
14.
Cell Res ; 32(4): 375-382, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1707327

ABSTRACT

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/prevention & control , Cricetinae , Humans , Liposomes , Mice , Nanoparticles , Pandemics/prevention & control , RNA, Messenger/genetics , Spike Glycoprotein, Coronavirus
15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318617

ABSTRACT

Background: To analyze the clinical features and the possible risk factors of secondary infection, and explore their impact on prognosis of COVID-19. Methods: : A total of 165 severe and critical hospitalized patients diagnosed with COVID-19 were included. The clinical characteristics, laboratory tests, imaging data, secondary infections and outcomes were analyzed. Results: : The mean age of total patients was (57.3±15.2) years, of which 111 were males (67.3%). 108 cases were with basic diseases (65.5%), and 1 death (0.6%). The secondary infection rate in critical patients was significantly higher than in severe patients ( P <0.05). The secondary infections were mainly lung infections. The pathogens were principally Burkholderia multivorans, Stenotrophomonas maltophilia, Acinetobacter baumannii and Klebsiella pneumoniae. The recovery rate of 28 days in the infected group was significantly lower than that in the non-infected group ( p < 0.001).The utilization rate and usage time of invasive ventilator, and deep vein catheterization, catheter indwelling and ECMO were the risk factors for the secondary infected patients. Conclusion: Secondary infection is an extremely common complication in critically ill patients and a trigger point for exacerbation of the disease. An effective control on the secondary infection will do good to the prognosis of COVID-19 patients.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310721

ABSTRACT

Background: There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the association of SARS-CoV-2-induced myocardial injury with death risk of COVID-19 is unclear. Methods: : This prospective case-cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected. Myocardial injury was evaluated and its prognosis was followed up. Results: Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe and 52 critically ill patients. On admission, 220 (62.0%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Using multivariate logistic regression, male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 220 COVID-19 patients with myocardial injury, 33 (15.0%) died on mean 10.9 day after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (15.0% vs 1.74%, RR =8.625, P <0.001). Follow-up study observed that at least one myocardial index of 21.3% patients remained abnormal 14 days after discharge. Conclusion: Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered 14 days after discharge.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306305

ABSTRACT

COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient's symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324427

ABSTRACT

Background: In fulfilling the COVID-19 containment, primary health care (PHC) facilities in China played an important role. We sought to investigate the exact tasks performed at the PHC facilities and the processes of COVID-19 prevention and control. Methods: Semi-structured face-to-face interviews for primary care physicians (PCPs) and a simple survey for residents were conducted in the field survey. Based-on purposive stratified sampling, 32 PCPs were selected from 22 PHC facilities in Wuhan as a high-risk city, in Shanghai as medium-risk city and in Zunyi as low-risk city. In the field survey, semi-structured face-to-face interviews were conducted with PCPs to summarize the tasks of COVID-19 prevention and control at the PHC facilities. A simple survey was used to investigate the local residents’ awareness about COVID-19 prevention and control. Results: In pre-outbreak period, the PHC facilities mainly engaged in storing medical supplies;in out-break period, they were responsible for screening, transferring, quarantine and treatment;in regular prevention and control period, attention was given to the employees and items of cold-chain & fresh food markets, etc. In Wuhan, PHC facilities focused on graded diagnoses and treatments of patients;in Shanghai, they were mainly engaged in at-home/centralized quarantine;in Zunyi, they focused on the screening of high-risk individuals. In urban areas, COVID-19 were more likely to be transmitted;in urban-rural areas, it was difficult to perform screening on the migrant populations;in rural areas, the risk was much lower. The community residents had satisfactory compliance with the preventive measures. Conclusion: We identified differences in the prevention and control tasks performed at the PHC facilities in China. During the different phases of the pandemic, the tasks were adjusted depending on the gradually comprehensive understanding of COVID-19. Among the cities at different risk levels, screening, quarantine, transferring or treatment was chosen to be a priority accordingly. Located in different intra-city geographic locations at different risk levels, the PHC facilities conducted their own tasks accordingly. Additionally, compliance on the part of the local community residents could not be overemphasized in COVID-19 prevention and control.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324222

ABSTRACT

Introduction: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains unclear. Materials: and methods: This prospective case-cohort study analyzed 154 COVID-19 patients from the Second People’s Hospital of Fuyang City in Anhui Province. Clinical and demographic information were collected. Renal function was evaluated and its prognosis was followed up. Results: Of 154 hospitalized patients with COVID-19, 125 were common and 29 were severe patients. On admission, 16 (10.4%) patients were with renal dysfunction. Serum creatinine and cystatin C were increased, eGFR was decreased in severe patients compared with those in common patients. Renal dysfunction was more common in severe patients. By multivariate logistic regression, male, higher age and hypertension were three importantly independent risk factors of renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in two weeks after discharge. Conclusion: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in two weeks after discharge.

20.
Molecules ; 27(3)2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1649980

ABSTRACT

COVID-19 has spread around the world and caused serious public health and social problems. Although several vaccines have been authorized for emergency use, new effective antiviral drugs are still needed. Some repurposed drugs including Chloroquine, Hydroxychloroquine and Remdesivir were immediately used to treat COVID-19 after the pandemic. However, the therapeutic effects of these drugs have not been fully demonstrated in clinical studies. In this paper, we found an antimalarial drug, Naphthoquine, showed good broad-spectrum anti-coronavirus activity. Naphthoquineinhibited HCoV-229E, HCoV-OC43 and SARS-CoV-2 replication in vitro, with IC50 = 2.05 ± 1.44 µM, 5.83 ± 0.74 µM, and 2.01 ± 0.38 µM, respectively. Time-of-addition assay was also performed to explore at which stage Naphthoquine functions during SARS-CoV-2 replication. The results suggested that Naphthoquine may influence virus entry and post-entry replication. Considering the safety of Naphthoquine was even better than that of Chloroquine, we think Naphthoquine has the potential to be used as a broad-spectrum drug for coronavirus infection.


Subject(s)
1-Naphthylamine/analogs & derivatives , Aminoquinolines/pharmacology , Antiviral Agents/pharmacology , Coronavirus/drug effects , SARS-CoV-2/drug effects , 1-Naphthylamine/pharmacology , Animals , Cell Line , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus NL63, Human/drug effects , Coronavirus OC43, Human/drug effects , Humans , In Vitro Techniques , Vero Cells , Virus Replication/drug effects
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