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ObjectiveThis study explored the application of Yiqi Zengmian prescription as a vaccine adjuvant， aiming to provide a new scheme for the prevention and control of corona virus disease 2019（COVID-19） with traditional Chinese medicine （TCM）. By analyzing the compatibility and efficacy， this paper examines the compatibility effect of Yiqi Zengmian prescription， which is modified from the classic tonifying agent Si Junzitang， as a vaccine adjuvant. MethodUsing the Database of Ancient Classical Prescriptions， this paper analyzed the composition of Yiqi Zengmian prescription and probed into the theoretical basis for the compatibility of this prescription from the properties， medicine combination， and efficacy. Furthermore， the compatibility effect of this prescription with vaccines was analyzed. ResultAs a TCM prescription， Yiqi Zengmian prescription focuses on the lung and spleen and enhances the Qi in the two organs. The lung governs Qi movement. The body breathes fresh air through the lungs and exchanges the turbid gas in the lungs， and the gas circulates alternately in the lungs to ensure the normal breathing of the human body. The spleen governing transportation and transformation is the hub for Qi movement， and Qi is the embodiment of metabolic function. By regulating qi movement and enhancing the functions of Qi and blood， Yiqi Zengmian prescription can enhance the immunogenicity of the vaccine， which provides a theoretical basis for enhancing the immune effects of vaccines. ConclusionYiqi Zengmian prescription has the effects of replenishing Qi and invigorating spleen， regulating Qi and drying dampness， and enhancing immunity. The in-depth analysis of the TCM theory of Yiqi Zengmian prescription as a vaccine adjuvant and the results of clinical and laboratory studies suggest that Yiqi Zengmian prescription may enhance the induction of immune response after vaccination and maintain the immune memory. However， the mechanism of Yiqi Zengmian prescription in regulating the complex immune network remains to be elucidated.
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Objectives: In December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, as a respiratory tract infection causing symptoms, such as fever, chills, dry cough, fatigue, and shortness of breath. Despite the low mortality rate of COVID-19, patients with comorbidities such as hypertension, cardiovascular disease, and diabetes mellitus seem to be prone to more severe symptoms and to a higher mortality rate than others. Such patients are shown to benefit from usage of monoclonal antibodies. Casirivimab-imdevimab is a cocktail made up of two non-competing, neutralizing human immunoglobulin G1 antibodies that target the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and block viral entry into human cells. We assessed the clinical profile and outcome of 42 patients who received the antibody cocktail. Materials and Methods: Casirivimab-imdevimab was administered to COVID-positive patients with mild severity. Forty-two patients who satisfied the inclusion criteria received casirivimab-imdevimab and were included in the study. Demographic and clinical data were tabulated in Microsoft Excel and statistics were run in OpenEpi software. Results: No adverse reactions were seen in any of the patients. Among the 42 patients, there were no deaths. Twentytwo (52.3%) patients improved, while 20 (47.6%) worsened after receiving the antibody cocktail. Out of 21 (50%) patients who did not have any comorbidity, 13 (30.9%) worsened after receiving the drug and 8 (19%) improved, while among those with comorbidities, 7 (16.6%) worsened and 14 (33.3%) improved (P < 0.05). Thirteen (30.9%) unvaccinated patients improved, while 14 (33.3%) worsened, whereas 6 (14.2%) fully vaccinated patients improved while only 2 (4.7%) worsened. Among the patients who were administered the cocktail within 5 days of onset of symptoms, 12 (28.5%) improved and 10 (23.8%) worsened, whereas among those who received the drug between 6 and 10 days of symptom onset, ten improved, and ten worsened. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients. Conclusion: None of the 42 patients developed any reaction to casirivimab-imdevimab. There were no deaths in the study population. About 52.3% of the patients improved and 47.6% worsened after receiving the cocktail. About 33.3% of the comorbid patients improved. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients.
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Background: Coronavirus 2019 infection (COVID 19) is an ongoing pandemic caused by pathogenic RNA viruses called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). It has affected people of all ages, with high morbidity and mortality among the elderly and immunocompromised population. Limited information is available on the effects of COVID-19 infection on pregnancy. Aim: To describe the histopathological changes in the placental tissue of SARS-CoV-2 infected term mothers with no comorbidities and to correlate with neonatal outcome. Materials and Methods: This observational study was conducted in the Department of Pathology, KMCH institute of health sciences and research, Coimbatore from May 1, 2020 to November 30, 2020 for 6 months. Placental tissues of all COVID-19-positive term mothers with no comorbidities were included in this study. Histopathological examination of placentae was carried out and clinical data of mothers and newborn babies were obtained from medical records. Results: Histopathological examination of 64 placental tissue of COVID-19 mothers showed predominantly the features of fetal vascular malperfusion like stem villi vasculature thrombus, villous congestion, and avascular villi. No significant correlation was obtained in comparison with parity and symptomatic status of the mothers. However, histopathological changes were more prominent among symptomatic patients. The newborn babies born to these mothers showed no adverse outcome. Conclusion: This study concluded that though COVID-19 infection in normal term pregnant women was associated with increased prevalence of features of fetal vascular malperfusion, there was no significant morbidity in the health status of both COVID-19 mothers and their neonates.
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Introduction: To assess the status of bi-directional screening for COVID-19, tuberculosis and diabetes among people attending Non-communicable Disease (NCD), Directly Observed Treatment Short-course (DOTS), and flu clinics of a secondary care hospital in rural northern India. Material and Methods: A cross?sectional, analytical study was conducted among the eligible (aged ?18 years) population who attended the study clinics in a rural sub-district hospital. In the flu clinic, consecutive patients were assessed for screening for TB (symptom-based) and diabetes (random blood sugar) and status of referral to DOTS and NCD clinics. Similarly, the screening for diabetes and COVID-19, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in the DOTS clinic, and TB and COVID-19 in the NCD clinic were assessed. The independent association of factors with COVID-19 positivity were assessed by calculating the adjusted prevalence ratios (aPR) at 95% confidence interval (CI). Results: Of the 405 people assessed, 279 (68.9%), 102 (25.2%), and 24 (5.9%) were from flu, NCD, and DOTS clinics, respectively. 26 (25.5%) and 22 (91.7%) of NCD and DOTS clinic patients underwent RT-PCR for COVID-19. TB screening in NCD and flu clinics was done among 4 (3.9%) and 7 (12.5%), respectively. A total of 23 (9.0%) were found positive for COVID-19, and no factors other than the presence of COVID-19 symptoms (aPR: 2.89; 95% CI: 1.33–6.29) had any independent association with COVID-19 positive status. Conclusion: The low screening for TB in NCD and flu clinics indicates the need to strengthen the implementation the TB-DM and TB-COVID-19 bidirectional screening. Similarly, the low screening or testing for COVID-19 in the NCD clinic can be improved by the implementation of systematic screening strategies like TB-DM bidirectional screening.
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Abstract BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has several mechanisms of action related to inflammatory responses, especially in individuals diagnosed with obesity. This hyperinflammatory clinical profile resulting from the association between obesity and coronavirus disease 2019 (COVID-19) may be attenuated by regular physical activity. OBJECTIVE: The aim of this study was to review the evidence on the consequences of physical inactivity and physical activity on COVID-19 in patients with obesity. DESIGN AND SETTING: Narrative review at the Bahiana School of Medicine and Public Health in Salvador, Brazil. METHODS: We searched evidence on the association of COVID-19 with physical activity and obesity using the following keywords: "covid-19," "physical activity," and "obesity". The databases used were MEDLINE (PubMed), ScienceDirect, and Virtual Health Library. Studies published from 2019 to 2021 and available in Portuguese, English, and Spanish were included. The final search was conducted on September 26, 2021. RESULTS: We identified 661 studies in the database, among which 71 were considered for inclusion in the narrative review of the molecular aspects of COVID-19 and its relationship with physical activity and obesity. CONCLUSION: This literature review enabled the perception of the relationship between the molecular mechanisms of COVID-19 and obesity. Regular physical activity had various benefits for the inflammatory condition of the studied population, highlighting moderate-intensity.
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Objective:To analyze the clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections in children, and to provide reference basis for the SARS-CoV-2 vaccination in children.Methods:A total of 97 children aged 3 to 14 years and diagnosed with coronavirus disease 2019 (COVID-19) admitted to Xi′an People′s Hospital (Xi′an Fourth Hospital) from December 27, 2021 to February 7, 2022 were included. According to the COVID-19 vaccination status, the enrolled children were divided into unvaccinated group, partially vaccinated group and fully vaccinated group, and the clinical data of the children in the three groups were collected and compared. Chi-square test, two independent sample t-test and Kruskal-Wallis H test were used for statistical analysis. Results:Totally 97 children including 49 males and 48 females were enrolled, with 87(89.7%) children of mild type, 10(10.3%) children of common type, and no severe or critical case. The proportions of unvaccinated, partially vaccinated and fully vaccinated preschool-aged children (3 to 6 years old) were 56.5%(13/23), 30.8%(12/39) and 17.1%(6/35), respectively, while those of school-aged children (7 to 14 years old) were 43.5%(10/23), 69.2%(27/39) and 82.9%(29/35), respectively. The vaccination proportion in preschool-aged children was significantly lower than that in school-age children ( χ2=9.94, P=0.007). The proportion of the children with fever in fully vaccinated group was 17.1%(6/35), which was lower than that in unvaccinated group (43.5%, 10/23), and the difference was statistically significant ( χ2=4.82, P=0.028). The cycle threshold (Ct) values of the open reading frame ( ORF)1 ab gene in the unvaccinated, partially vaccinated and fully vaccinated groups were 33.77(26.87, 36.58), 35.23 (33.45, 38.57) and 37.12 (34.91, 39.39), respectively, and there was a statistically significant difference among the groups ( H=7.76, P=0.021). The Ct values of the nucleocapsid protein ( N) gene in the three groups were 32.26(25.85, 36.18), 35.12(33.18, 37.96) and 37.26(34.27, 39.24), respectively, and the difference among the groups was statistically significant ( H=7.84, P=0.020). The Ct values of ORF1 ab gene and N gene in fully vaccinated group were higher than those in unvaccinated group, and the differences were statistically significant ( Z=-2.69, P=0.007 and Z=-2.39, P=0.017, respectively). The duration of viral shedding in fully vaccinated children was (9.9±4.1) d, which was shorter than that in unvaccinated children ((12.8±3.7) d), and the difference was statistically significant ( t=2.72, P=0.009). Conclusions:The majority of children with breakthrough infections with SARS-CoV-2 are mild. Vaccination may effectively shorten the duration of viral shedding. And fully vaccination is associated with mild clinical symptoms and lower serum viral load compared to unvaccinated children.
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@#Abstract: Viral shedding of SARS-CoV-2 is a continuous dynamic process, which can be divided into latent stage, initial stage, peak stage and decreasing stage according to the characteristics of viral shedding. After being infected with SARS-CoV-2, the infected person generally stays in the latent period for 1-3 days, which is characterized by continuous negative nucleic acid test results and no infectiousness, and the risk of infection for close contacts is very low. At the initial stage of viral shedding is characterized by a rapid decline in the Ct value of nucleic acid tests in a short time, and clinical symptoms gradually appear. The infectiousness of the infected person gradually increases during this period, and the risk of infection for close contacts also gradually increases, but it is still in the early stage of infection, the possibility of viral shedding is low, and the risk of infection of secondary close contacts is low. The peak of viral shedding is characterized by low Ct value in nucleic acid test and obvious clinical symptoms; during this period, the infected person is the most infectious, and the risk of infection of the contact is the highest, so the scope of close contacts should be expanded appropriately. The decreasing period is characterized by the gradual increase of Ct value of nucleic acid test and the gradual disappearance of clinical symptoms; during this period, the infectiousness of the infected person gradually decreases to disappear. In an outbreak, an infected person in the decreasing phase is more likely to be an early infected person in the transmission chain. If infected individuals in the decreasing phase are found in an area without a SARS-CoV-2 epidemic, it suggests that the local outbreak epidemic has been spreading for some time and may be larger in scale. According to the characteristics of viral shedding, risk personnel can be determined more scientifically and accurately, so as to minimize the risk and reduce the waste of epidemic prevention resources.
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@#Abstract: Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature, and to provide early warning signs for the variation of SARS-CoV-2 in clinical work. Methods From Jan 2, 2021 to Jun 30, 2021, a total of 105 COVID-19 patients were included in the study using a case-control method. Nasal swab samples were collected from the study subjects, the viral genes were sequenced, and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences. Clinically relevant data were collected from the two groups, and indicators such as days of hospitalization, age distribution, lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, and IL-10 were compared; subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping, and differences in immunological characteristics were compared, including lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, IL-10, etc. Results The theoretical hospitalization days of Delta variant group were (22.2±8.33) d, which were significantly longer than (17.6±10.50) d of non-Delta variant group (t=2.396, P<0.05). The total lymphocyte count and IL-4 of Delta variant group were (1.22±0.86) ×109/L and (0.80±0.23) ng/mL, which were significantly lower than corresponding (1.91±0.70) ×109/L and (1.59±0.59) ng/mL of non-Delta variant group (t=4.329, 9.072, P<0.05), while IL-10 was (7.16±7.77) ng/mL, which was significantly higher than (4.26±3.91) ng/mL of non-Delta mutation group (t=1.980, P<0.05). Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were (1.04±0.60) ×109/L and (0.74±0.25) ng/ml, which were significantly lower than corresponding (1.62±0.56) ×109/L and (1.56±0.52) ng/mL in non-Delta variant group, in patients with delayed discharge (P<0.05). Conclutions SARS-CoV-2 variant has an impact on clinical manifestations. The patient's B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within 12 hours of admission indicated variant virus infection. The decrease of total lymphocyte count, especially T lymphocyte reduction, strongly suggests discharge delay due to viral clearance disorder.
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@#The rapid spread of Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has had a devastating impact on public health and the global economy. Tremendous efforts had been put on urgent development of prophylactic or therapeutic drugs against SARS-CoV-2,mainly smallmolecule antiviral drugs and monoclonal antibodies,to reduce the impact and burden of COVID-19. Currently,National Medical Products Administration(NMPA)of China or Food and Drug Administration(FDA)of the United States have approved three small-molecule drugs and three monoclonal antibodies for use. This paper reviews the clinical research progress and challenges of the main drugs against SARS-CoV-2 on the market at present.
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@#Objective To prepare and verify a uniform antigen content detection kit for recombinant protein vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods Using goat anti-S protein polyclonal antibody prepared by National Institutes for Food and Drug Control(NIFDC) as coating antibody,one of four monoclonal antibodies(14C8,15F9,17A7 and 20D8)with high receptor-binding domain(RBD)binding activity and broad-spectrum resistance against major variants as HRP-labeled antibody,a uniform double-antibody sandwich ELISA kit for antigen content detection of recombinant SARS-CoV-2 vaccine was prepared,and the dilution of coating antibody(1∶125 ～ 1∶4 000)and enzymelabeled antibody(1∶250 ～ 1∶32 000)were optimized by chessboard titration. The specificity,linear range,accuracy,precision and durability of the kit were verified. The prepared uniform detection kits were distributed to 12 laboratories to detect15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions(including 11 batches of stock solutions designed with WT strain and 4 batches of designed with Beta,Gamma and Delta variants as reference sequence)from different expression systems(CHO cells,Pichia pastoris,Sf9 cells or E. coli)and target proteins(RBD or S protein)prepared by each laboratory.Results Monoclonal antibody 20D8 was used as the enzyme-labeled antibody with the optimal dilution of 1 : 4 000,and the optimal dilution of coating antibody was 1 : 500. The uniform detection kit showed no cross reaction with recombinant S protein of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS). The first generation national standard for recombinant SARS-CoV-2 protein vaccine antigen(national standard for short)showed a concentration of 0. 16 ～ 2. 50 U/mL with a good linear relationship with A450/630,and the linear equation was:y = 0. 791 x-0. 100 4,R2= 0. 993 7;The recoveries of 0. 16 ～ 2. 50 U/mL national standard in 6 repeated tests were 95% ～ 104% and the coefficients of variation(CVs)were less than 15%;The CVs in 3 repeated tests by 2 experimenters at different time were 4. 4% ～6. 6% and the recoveries were in the range of 80% ～ 120% under different temperature and time conditions. The antigen content of 15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions showed good parallelism with the national standard. Conclusion The uniform detection kit for antigen content developed in this study had good specificity,accuracy,precision and durability,and might be used for the detection of antigen content of recombinant SARS-CoV-2 protein vaccines.
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@#Objective To construct a single-chain fragment variable(scFv)phage display library against receptor-binding domain(RBD)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike protein(S)to screen specific scFv and identify the function.Methods m RNA was extracted from spleen cells of mice immunized with RBD protein and reversely transcribed into c DNA,with which as template,genes of the hight chain fragment of variable(VH)and light chain fragment of variable(VL)of scFv were amplified and then assembled into scFv gene fragment through splicing overlap extension PCR(SOE-PCR).The scFv gene fragment was inserted to phage vector to construct scFv phage display library.After four rounds of biopanning,the scFv gene with strong binding ability to RBD was screened and expressed recombinantly,purified and identified for biological activity.Results The constructed scFv phage library showed a titer of 6.0×10(11)pfu/m L.After four rounds of biopanning,four scFv strains with strong binding to RBD were selected,namely scFv11,scFv12,scFv25and scFv28.scFv was mainly expressed in the form of inclusion body with a relative molecular mass of about 27 000,a concentration of 2.4 mg/m L and a purity of about 90%,which bound specifically to mouse monoclonal antibody against His labeled by HRP after purification.All four scFv strains bound specifically to RBD recombinant protein,among which the other 3 scFv strains bound to the S protein of wild type and multiple mutant strains except scFv28.All four strains showed dose-dependent interaction with RBD,with affinity dynamic fitting dissociation constants(K_Ds)8.9,5.92,10.67and 2.36 nmol/L,and steady-state fitting dissociation constants(K_Ds)of 5.3,6.5,8.7 and 5.8 nmol/L,respectively.scFv11,scFv12 and scFv25 simultaneously identified three independent RBD polypeptides,including RBD2(S(11)pfu/m L.After four rounds of biopanning,four scFv strains with strong binding to RBD were selected,namely scFv11,scFv12,scFv25and scFv28.scFv was mainly expressed in the form of inclusion body with a relative molecular mass of about 27 000,a concentration of 2.4 mg/m L and a purity of about 90%,which bound specifically to mouse monoclonal antibody against His labeled by HRP after purification.All four scFv strains bound specifically to RBD recombinant protein,among which the other 3 scFv strains bound to the S protein of wild type and multiple mutant strains except scFv28.All four strains showed dose-dependent interaction with RBD,with affinity dynamic fitting dissociation constants(K_Ds)8.9,5.92,10.67and 2.36 nmol/L,and steady-state fitting dissociation constants(K_Ds)of 5.3,6.5,8.7 and 5.8 nmol/L,respectively.scFv11,scFv12 and scFv25 simultaneously identified three independent RBD polypeptides,including RBD2(S(334～353)),RBD9(S(334～353)),RBD9(S(439～458))and RBD13(S(439～458))and RBD13(S(499～518)).Homologous model of scFv constructed by online server SWISS-MODEL showed a good quality and was used for molecular docking.The interface at which scFv11 interacted with RBD only partially coincided with the interaction interface of human angiotensin converting enzyme 2(ACE2)and RBD,and the interaction interfaces of scFv12 and scFv25 with RBD were quite different from that of ACE2.Conclusion In this study,scFv specifically bound to SARS-Co V-2 RBD was screened and prepared through constructing scFv phage library against SARS-CoV-2 RBD,which provided experimental basis for further development of anti-SARS-CoV-2 drugs and detection reagents.
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@#ObjectiveTo construct self-amplifying RNA(saRNA)vaccine of severe acute respiratory syndrome coronavirus2(SARS-CoV-2)Delta mutant strain(B.1.617.2)based on Coxsackievirus-A5(CV-A5)replicon and evaluate its immunogenicity.MethodsThe recombinant plasmids pDelta-S10,pDelta-S5 and pDelta-S1(10,5 and 1 amino acid residues at the upstream of S-VP1/2A cleavage site of the fusion polyprotein respectively)were constructed by In-fusion cloning of the plasmids containing the full-length genome sequence of CV-A5 and substituting the S protein gene of SARS-CoV-2 Delta mutant for the P1 structural protein gene of CV-A5 with different lengths.Three RNA molecules,Delta-S10,Delta-S5 and Delta-S1,were obtained by in vitro transcription of linearized recombinant plasmids and transfected into HEK-293T cells respectively,which were analyzed for the expression of S protein by Western blot.The RNA molecule with the highest expression of S protein was screened out and detected for the self-amplification in HEK-293T cells by qPCR.BALB/c mice(female,6 ～ 8 weeks old and five for each group)were immunized i.m.with two doses(0.5 and 2.5 μg)of the screened Delta-S packaged with lipid nanoparticles for once on day 1 and day 14 seperately.Blood samples were collected on days 14and 28,detected for serum binding antibody titers by ELISA,and detected for neutralizing antibody titers by micro neutralization method.The spleens were harvested on day 42 and detected for the level of IFNγ secreted by mouse spleen cells by enzyme linked enzyme linked immunospot assay(ELISPOT).ResultsThe recombinant RNA molecule Delta-S10showed the highest expression of S protein and self-amplified in HEK-293T cells,which of both high and low doses induced specific binding antibody against SARS-CoV-2 Delta S1 protein in mice with obvious dose effect and enhanced immune effect;The high dose of Delta-S10 induced neutralizing antibodies and cellular immune responses in mice.ConclusionThe SARS-CoV-2 Delta mutant(B.1.617.2)saRNA vaccine Delta-S10 based on CV-A5 replicon was successfully constructed,which induced humoral and cellular immune responses in mice,laying a foundation of the further study of the construction of SARS-CoV-2 saRNA vaccine by enterovirus replication elements.
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@#Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)seriously threatens human health and public health safety.Vaccination plays an important role in effectively controlling the epidemic situation.More than 150 SARS-CoV-2 vaccines have entered the clinical trial stage and 38 have been approved for emergency use or marketing.Neutralizing antibody level is the main index for evaluation of the immunogenicity of vaccines,but there has been no standardized detection method for SARS-CoV-2 neutralizing antibody till now,which makes it difficult to compare the neutralizing antibody levels among different laboratories and different products horizontally,and seriously restricts the development and evaluation of vaccines and antibody therapeutic drugs.With the rapid sale of the first generation of standards for SARS-CoV-2 antibody and the emergence of variants of concern(VOC)of SARS-CoV-2,WHO and China carried out the development of the second generation of standards simultaneously in 2022.This paper reviews the development and application progress of the standards for SARS-CoV-2 antibody in WHO and China.
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@#Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)seriously threatens human health and public health safety.Vaccination plays an important role in effectively controlling the epidemic situation.More than 150 SARS-CoV-2 vaccines have entered the clinical trial stage and 38 have been approved for emergency use or marketing.Neutralizing antibody level is the main index for evaluation of the immunogenicity of vaccines,but there has been no standardized detection method for SARS-CoV-2 neutralizing antibody till now,which makes it difficult to compare the neutralizing antibody levels among different laboratories and different products horizontally,and seriously restricts the development and evaluation of vaccines and antibody therapeutic drugs.With the rapid sale of the first generation of standards for SARS-CoV-2 antibody and the emergence of variants of concern(VOC)of SARS-CoV-2,WHO and China carried out the development of the second generation of standards simultaneously in 2022.This paper reviews the development and application progress of the standards for SARS-CoV-2 antibody in WHO and China.
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Since 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)posed a great threat to human health and social economy, which has brought out hundreds of millions infection and caused millions of deaths worldwide. With the increasing research on SARS-CoV-2, angiotensin-converting enzyme 2(ACE2)has been regarded as a significant functional receptor for SARS-CoV-2 invasion. ACE2 is distributed in many tissues of human body, not only expressed in lung, cardiovascular, kidney tissues, but also in conjunctiva, cornea, uvea, retina and optic nerve tissue. More and more cases of SARS-CoV-2 infection through ocular tissues have been found; however, whether ocular ACE2 plays a role in SARS-CoV-2 infection is not completely clear. Therefore, study on expression and distribution of ACE2 in the ocular tissues can not only provide an in-depth understanding of the mechanism of SARS-CoV-2 infection, but also supply a comprehensive acquaintance with the mechanism of ACE2 action in the ocular tissues. In this paper, we review recent research progress about the expression and distribution of ACE2 in ocular tissues and hope to better understand the mechanism of ACE2 in the pathophysiological processes of ocular tissues.
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The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.
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Humans , Antibodies, Viral , Blood Donors , China/epidemiology , COVID-19/immunology , Immunoglobulin G , Immunoglobulin M , Pandemics , SARS-CoV-2ABSTRACT
China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.
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Acute necrotizing encephalopathy (ANE) is a subtype of acute encephalopathy presented with disturbance of consciousness and symmetric bilateral thalamic necrosis in neuroradiology.Patients with ANE had a high mortality or severe neurological sequela.ANE usually secondary to virus infectious disease, in which influenza is a common etiology.During the 3 years of the worldwide pandemic of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection, ANE has become a severe complication and cause of death in children, which has aroused much concern.Here is a review of the research progress of epidemiology, pathogenesis, diagnosis, treatments and prognosis of ANE, in order to improve the knowledge of clinicians on this disease.
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Non-pharmaceutical interventions (NPIs) implemented during the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic have been proven to be effective in blocking the spread of the epidemic.While reducing SARS-CoV-2 transmission, NPIs also reduce children exposure to other pathogens, leading to a decline in the incidence of many viral and bacterial infections.The reduction in contact with viruses and bacteria and the delay or interruption of routine immunization during SARS-CoV-2 epidemic have resulted in insufficient immune stimulation of pathogens on the population, leading to an increase in susceptible populations and a decline in herd immunity, forming the immune debt during SARS-CoV-2 epidemic.After reducing or lifting NPIs, the incidence of some viral or bacterial infectious diseases was significantly higher than pre-epidemic.In this review, the definition, source, impact and strategies of immune debt during epidemic period were expounded, inorder to improve clinicians′ attention and understanding of immune debt and optimize the prevention of children′s infectious diseases.
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@#Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1 × 107IU/mL)and Remdesivir of the maximum concentration(150 μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC_(50))of human IFNα1b eye drops and human IFNα1b sprays were 29 958 and 37 550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.314 7,0.291 0 and0.300 3 μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.320 5,0.274 4 and 0.304 1 μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.