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1.
J Clin Med ; 11(14)2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1938865

ABSTRACT

Immune escape of emerging SARS-CoV-2 variants of concern (VOCs) and waning immunity over time following the primary series suggest the importance and necessity of booster shot of COVID-19 vaccines. With the aim to preliminarily evaluate the potential of heterologous boosting, we conducted two pilot studies to evaluate the safety and immunogenicity of the V-01 or a bivalent V-01D-351 (targeting Delta and Beta strain) booster after 5-7 months of the primary series of inactivated COVID-9 vaccine (ICV). A total of 77 participants were enrolled, with 20 participants in the V-01D-351 booster study, and 27, 30 participants in the age stratified participants of V-01 booster study. The safety results showed that V-01 or V-01D-351 was safe and well-tolerated as a heterologous booster shot, with overall adverse reactions predominantly being absent or mild in severity. The immunogenicity results showed that the heterologous prime-boost immunization with V-01 or bivalent V-01D-351 booster induced stronger humoral immune response as compared with the homologous booster with ICV. In particular, V-01D-351 booster showed the highest pseudovirus neutralizing antibody titers against prototype SARS-CoV-2, Delta and Omicron BA.1 strains at day 14 post boosting, with GMTs 22.7, 18.3, 14.3 times higher than ICV booster, 6.2, 6.1, 3.8 times higher than V-01 booster (10 µg), and 5.2, 3.8, 3.5 times higher than V-01 booster (25 µg), respectively. The heterologous V-01 booster also achieved a favorable safety and immunogenicity profile in older participants. Our study has provided evidence for a flexible roll-out of heterologous boosters and referential approaches for variant-specific vaccine boosters, with rationally conserved but diversified epitopes relative to primary series, to build herd immunity against the ongoing pandemic.

3.
J Virol ; 96(8): e0201321, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1779314

ABSTRACT

The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332, developed by Pfizer, is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here, we report three crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome (MERS)-CoV bound to the inhibitor PF-07321332. The structures reveal a ligand-binding site that is conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV, providing insights into the mechanism of inhibition of viral replication. The long and narrow cavity in the cleft between domains I and II of the main protease harbors multiple inhibitor-binding sites, where PF-07321332 occupies subsites S1, S2, and S4 and appears more restricted than other inhibitors. A detailed analysis of these structures illuminated key structural determinants essential for inhibition and elucidated the binding mode of action of the main proteases from different coronaviruses. Given the importance of the main protease for the treatment of SARS-CoV-2 infection, insights derived from this study should accelerate the design of safer and more effective antivirals. IMPORTANCE The current pandemic of multiple variants has created an urgent need for effective inhibitors of SARS-CoV-2 to complement vaccine strategies. PF-07321332, developed by Pfizer, is the first orally administered coronavirus-specific main protease inhibitor approved by the FDA. We solved the crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and MERS-CoV that bound to the PF-07321332, suggesting PF-07321332 is a broad-spectrum inhibitor for coronaviruses. Structures of the main protease inhibitor complexes present an opportunity to discover safer and more effective inhibitors for COVID-19.


Subject(s)
Lactams , Leucine , Nitriles , Peptide Hydrolases , Proline , Antiviral Agents/chemistry , Antiviral Agents/metabolism , COVID-19/drug therapy , Humans , Lactams/chemistry , Lactams/metabolism , Leucine/chemistry , Leucine/metabolism , Middle East Respiratory Syndrome Coronavirus/chemistry , Middle East Respiratory Syndrome Coronavirus/enzymology , Nitriles/chemistry , Nitriles/metabolism , Peptide Hydrolases/chemistry , Peptide Hydrolases/metabolism , Proline/chemistry , Proline/metabolism , Protease Inhibitors/chemistry , Protease Inhibitors/metabolism , SARS Virus/chemistry , SARS Virus/enzymology , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331690

ABSTRACT

The unprecedented coronavirus disease (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective antiviral drug to control this severe infectious disease. Here, we found that the E, or M membrane proteins of coronavirus could be targeted by a 28-residue antibody mimetic by fusing two antibody Fab complementarity-determining regions (VHCDR1 and VLCDR3) through a cognate framework region (VHFR2) of the antibodies which recognize the coronavirus E or M proteins. We constructed a fusion protein, pheromonicin-covid-19 (PMC-covid-19), by linking colicin Ia, a bactericidal molecule produced by E.coli which kills target cells by forming a voltage-dependent channel in target lipid bilayers, to that antibody mimetic. The E, or M protein/antibody mimetic interaction initiated the formation of irreversible PMC-covid-19 channel in the covid-19 envelope and infected host cell membrane resulting in leakage of cellular contents. PMC-covid-19 demonstrates broad-spectrum protective efficacy against tested variants of coronavirus severe acute respiratory syndrome (p<0.01-0.0001). PMC-covid-19 significantly altered outcomes of in vivo fatal covid-19 challenge infection without evident toxicity, making it an appropriate candidate for further clinical evaluation.

6.
Microbiol Res ; 258: 126993, 2022 May.
Article in English | MEDLINE | ID: covidwho-1693103

ABSTRACT

Pseudoviruses are viral particles coated with a heterologous envelope protein, which mediates the entry of pseudoviruses as efficiently as that of the live viruses possessing high pathogenicity and infectivity. Due to the deletion of the envelope protein gene and the absence of pathogenic genes, pseudoviruses have no autonomous replication ability and can infect host cells for only a single cycle. In addition, pseudoviruses have the desired characteristics of high safety, strong operability, and can be easily used to perform rapid throughput detection. Therefore, pseudoviruses are widely employed in the mechanistic investigation of viral infection, the screening and evaluation of monoclonal antibodies and antiviral drugs, and the detection of neutralizing antibody titers in serum after vaccination. In this review, we will discuss the construction of pseudoviruses based on different packaging systems, their current applications especially in the research of SARS-CoV-2, limitations, and further directions.


Subject(s)
COVID-19 , Vaccines , Antibodies, Neutralizing , Antiviral Agents/pharmacology , COVID-19/prevention & control , Humans , SARS-CoV-2
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310365

ABSTRACT

Background: Since December 2019, China has carried out dramatic containment measures to control the spread of COVID-19. As of April 6, 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead. In this study, we aimed to understand environmental factors leading to COVID-19-related mortality outside of Hubei province, in mainland China. Methods We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level CFR of COVID-19 outside Hubei, China. Results Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P  < 0.001) and humidity (r=-0.607, P  = 0.002), while latitude was positively correlated with the CFR (r = 0.636, P  = 0.001). There were no statistically significant associations between CFR and the social environment factors. Conclusion Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317496

ABSTRACT

Background: More evidence in understanding the heterogeneity of COVID-19-associated acute respiratory distress syndrome (ARDS) and in improving strategy to increase the survival from the critical patients intubated is always needed. The study aimed to comprehensively explore the features of COVID-19-associated ARDS and the features and outcomes between the early and late intubation groups. Methods: : This retrospective cohort included 65 adult COVID-19 inpatients with ARDS at two hospitals in Hubei, China. The ARDS in these patients was diagnosed according to the Berlin criteria. We defined intubation within 7 days of ARDS diagnosis as ‘early’ intubation and that performed from the eighth day as ‘late’ intubation based on literatures. The outcomes were invasive mechanical ventilation and in-hospital death. The log-binomial regression models were used to explore the risk factors and the Kaplan-Meier statistic was used to estimate the risk of mortality. Results: : The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The early intubation and the late intubation had the differences in days from symptom onset/hospital admission/ARDS diagnosis to intubation (P = 0.023, P = 0.011, P < 0.001). Compared with the early-intubation group, the late-intubation group showed less severity at admission (median oxygenation index 159.0 95% CI 134.0-203.0 vs. 133.9 95% CI 98.3-183.2), but required more aggressive therapies (ICU 80% vs. 70%, CRRT 50% vs. 10%, prone-position 50% vs. 30%, and ECMO 50% vs. 10%) and had higher risk to die at hospital (RR, 3.18;95% CI 1.98-5.12). Conclusion: The ARDS caused by COVID-19 was not typical ARDS due to prolonged onset time, multiple organ injuries, and higher mortalities. The late-intubation group showed less severity at admission but higher risk of in-hospital death than the early-intubation group.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317495

ABSTRACT

Background: The reviews on the risk factors with ARDS and the worse outcomes concluded lacking robust data of risk factors to prevent COVID-19 and identified an urgent need for large sample and high-quality research in this area, as well as the features of the ARDS. Methods: : This retrospective cohort study included 333 COVID-19 inpatients at two hospitals in Hubei of China in 2020. The COVID-19-related ARDS was diagnosed according to the Berlin criteria. The outcomes were ARDS development and the intubation or in-hospital death. The cox proportional hazard ratio (HR) models were employed to determine the significant risk factors. Results: : The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The survival patients on invasive mechanical ventilation (IMV) had been intubated earlier since ARDS diagnosis than those who had not survived (5.5 median days, IQR 4.0-7.0 days versus 11.5 median days, IQR 6.0-14.0 days, P < 0.001). Males and all abnormal laboratory indices associated with the higher risk of ARDS (P<0.05) but were not linked with the risk of intubation or death (P>0.05). The sensitivity analyses found that lymphocyte count of < 1000 per mm3 at hospital admission were still significantly associated with developing ARDS when adjusting for age and male gender (HR, 4.10;95% CI, 2.40-7.10), and oxygenation index (OI) ratio < 150 were more likely to predict the intubation/death after age adjustment (HR, 2.50;95% CI, 1.17-5.30). Conclusion: The SARS-CoV-2-caused ARDS was not the typical ARDS according to Berlin criteria. The alive patients with IMV had been intubated earlier since ARDS diagnosis than those who had not survived. We identified male gender and abnormal laboratory indices associated with the ARDS but were not linked with the intubation/death. Sensitivity analysis concluded lymphocyte count of < 1000 per mm3 could predict ARDS while OI ratio less than 150 could predict intubation/death.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315497

ABSTRACT

Background: Large-scale epidemics have changed people’s medical behavior, and patients tend to delay non-urgent medical needs. However, the impact of the pandemic on the use of complementary and alternative medicine remains unknown. Methods: : This retrospective study aimed to analyze the changes in the number of traditional Chinese medicine (TCM) patients and examine the epidemic prevention policy during the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the number of TCM patients in Taipei City Hospital from January 2017 to May 2020. We tallied the numbers of patients in each month and compared them with those in the same months last year. We calculated the percentage difference in the number of patients to reveal the impact of the COVID-19 pandemic on TCM utilization. We used the Mann­–Whitney U test to examine whether there was a significant difference in the number of patients during the COVID-19 pandemic. Results: : We included a total of 41 months and 1,935,827 patients in this study. During the COVID-19 pandemic, the number of patients decreased significantly, except in February 2020. The numbers of patients during the COVID-19 pandemic had fallen by more than 15% compared with those in the same months last year. March and April had the greatest number of patient losses, with falls of 32.8% and 40%, respectively. TCM patients declined significantly during the COVID-19 pandemic, and mobile medicine provided to rural areas fell considerably. Among all the TCM specialties, pediatrics and traumatology, as well as infertility treatment, witnessed the most significant decline in the number of patients. However, the number of cancer patients has reportedly increased. Conclusions: : The COVID-19 pandemic decreased the utilization rate of TCM, especially for mobile healthcare in rural areas. We suggest that the government pay attention to the medical disparity between urban and rural areas, which are affected by the pandemic, as well as allocate adequate resources in areas deprived of medical care.

11.
J Virol ; 96(1): e0125321, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1639525

ABSTRACT

Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro; also known as 3CLpro) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/chemistry , Catalytic Domain , Coronavirus/classification , Coronavirus/enzymology , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Molecular Docking Simulation , Naphthoquinones/chemistry , Protein Binding
12.
BMC Health Serv Res ; 21(1): 1268, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1613236

ABSTRACT

BACKGROUND: Internet medical care has been advancing steadily, especially during the coronavirus disease 2019 pandemic, the development momentum of Internet medical care in China is more vigorous. This study aimed to explore the factors associated with using the Internet for medical information, to examine the popularisation and implementation of Internet medical treatment and feasible strategies, and promote the further development of Internet medical treatment. METHODS: A cross-sectional study was conducted on 408 medical patients who had used online medical services. The one-way analysis of variance or independent samples t-test was used to compare the differences in the influence of demographic characteristics on behavioural intentions of different people seeking medical care. Pearson's correlation was used to evaluate the correlation between different measurement variables. A mediation regression analysis was used to explore the mediating role of trust in Internet medical care. RESULTS: The difference in the influence of Internet medical use frequency on the behavioural intention of different participants was statistically significant (F = 3.311, P = 0.038). Among the influencing factors, personal trust propensity (r = 0.387, P < 0.01), website credibility (r = 0.662, P < 0.01), hospital credibility (r = 0.629, P < 0.01), doctor's credibility (r = 0.746, P < 0.01), and online patient trust (r = 0.874, P < 0.01) were positively correlated with patients' behavioural intentions. In the analysis of intermediary factors, the total effect of the credibility of the diagnosis and treatment website on the behavioural intention of patients was 0.344. The total effect of the credibility of the diagnosis and treatment hospital on the behavioural intention of patients was 0.312; the total effect of the service doctor's credibility on the patient's behavioural intention was 0.385; the total effect of the personal trust tendency on the patient's behavioural intention was 0.296. CONCLUSIONS: This study found defects in various factors that produce distrust in Internet medical treatment. It also reveals the positive effect of trust factors on the development and implementation of Internet medical treatment and provides some ideas for improving the use of Internet medical treatment by the masses.


Subject(s)
COVID-19 , Trust , Cross-Sectional Studies , Humans , Internet , SARS-CoV-2
13.
Virol J ; 19(1): 2, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1608023

ABSTRACT

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Mice , SARS-CoV-2/immunology
15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292562

ABSTRACT

Background: As of April 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead in China. We aimed to understand environmental factors leading to COVID-19-related mortality in non-Hubei region.Methods:: We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level case fatality rate (CFR) of COVID-19 outside Hubei, China.Results: Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P <0.001) and humidity (r=-0.607, P =0.002), while latitude was positively correlated with the CFR (r=0.636, P =0.001). There were no statistically significant associations between CFR and the social environment factors.Conclusion: Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

16.
Front Immunol ; 12: 689065, 2021.
Article in English | MEDLINE | ID: covidwho-1502324

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US FDA has approved several therapeutics and vaccines worldwide through the emergency use authorization in response to the rapid spread of COVID-19. Nevertheless, the efficacies of these treatments are being challenged by viral escape mutations. There is an urgent need to develop effective treatments protecting against SARS-CoV-2 infection and to establish a stable effect-screening model to test potential drugs. Polyclonal antibodies (pAbs) have an intrinsic advantage in such developments because they can target rapidly mutating viral strains as a result of the complexity of their binding epitopes. In this study, we generated anti-receptor-binding domain (anti-RBD) pAbs from rabbit serum and tested their safety and efficacy in response to SARS-CoV-2 infection both in vivo and ex vivo. Primary human bronchial epithelial two-dimensional (2-D) organoids were cultured and differentiated to a mature morphology and subsequently employed for SARS-CoV-2 infection and drug screening. The pAbs protected the airway organoids from viral infection and tissue damage. Potential side effects were tested in mouse models for both inhalation and vein injection. The pAbs displayed effective viral neutralization effects without significant side effects. Thus, the use of animal immune serum-derived pAbs might be a potential therapy for protection against SARS-CoV-2 infection, with the strategy developed to produce these pAbs providing new insight into the treatment of respiratory tract infections, especially for infections with viruses undergoing rapid mutation.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , Binding Sites , Bronchi/cytology , COVID-19/genetics , COVID-19/therapy , Epithelial Cells , Gene Expression Profiling , Humans , Immunization, Passive , Mice , Mutation , Neutralization Tests , Organoids , Rabbits , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
18.
Clin Hemorheol Microcirc ; 78(2): 199-207, 2021.
Article in English | MEDLINE | ID: covidwho-1352794

ABSTRACT

INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes.


Subject(s)
COVID-19/complications , Carbon Dioxide/isolation & purification , Extracorporeal Circulation/methods , Hemofiltration/methods , Hypercapnia/therapy , Respiratory Distress Syndrome/therapy , SARS-CoV-2/isolation & purification , Aged , COVID-19/transmission , COVID-19/virology , Humans , Hypercapnia/physiopathology , Hypercapnia/virology , Male , Positive-Pressure Respiration , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/virology
19.
Cell Res ; 31(9): 1011-1023, 2021 09.
Article in English | MEDLINE | ID: covidwho-1315592

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunogenicity, Vaccine/immunology , Protein Binding/immunology , Protein Domains/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antiviral Agents/immunology , Cell Line , Chlorocebus aethiops , Double-Blind Method , Female , HEK293 Cells , Humans , Interferons/immunology , Macaca mulatta , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Middle Aged , Vaccination/methods , Vero Cells , Young Adult
20.
Clin Infect Dis ; 71(16): 2027-2034, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153138

ABSTRACT

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.


Subject(s)
COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Adult , Aged , Antibodies, Viral/metabolism , Antibody Formation/physiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Male , Middle Aged , Pandemics , Serologic Tests
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