Objective　To evaluate the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus combined vaccine formulated with 4 adjuvants Al(OH)₃, MF59, AS03 and QS21 in mice.Methods　Adjuvants Al(OH)₃, MF59, AS03 and QS21 were used respectively to prepare SARS-CoV-2 (inactivated) and tetravalent influenza virus (split) combined vaccine. BALB/c mice were immunized by intraperitoneal injection on day 0 (D0) and D14, respectively. Blood samples were collected on D14 and D28 to detect antibody titers against SARS-CoV-2 and hemagglutination inhibition titers of influenza. Spleen lymphocytes were isolated on D28 to detect cellular immune responses to both SARS-CoV-2 and influenza virus.Results　SARS-CoV-2 and influenza virus combined vaccine with different adjuvants induced both antigen-specific antibody responses and cellular immune responses in mice. At D28 post-initial immunization, MF59 adjuvant group induced high levels of SARS-CoV-2 binding antibodies and neutralizing antibodies, with geometric mean titers (GMTs) of 89 144 and 5 418, respectively, and MF59 group also induced high levels of hemagglutination-inhibiting antibodies against the quadrivalent influenza virus strains (H1N1, H3N2, BV, BY), with GMTs of 4 457, 5 120, 1 470 and 5 881, respectively. Both the MF59 and AS03 groups induced robust Th1-type (IFN-γ, IL-2) cellular immune responses against SARS-CoV-2, with spot forming units (SFUs) statistically significantly higher than those of Mock group （IFN-γ： H=16.69，P＜0.01； IL-2： H=15.21， P＜0.05）. The AS03 group induced a strong Th1-type (IFN-γ, IL-2) cellular immune response against the quadrivalent influenza virus strains (H1N1, H3N2, BV, BY), with SFUs statistically significantly higher than those of Mock group （IFN-γ： H=12.93, 12.17, 11.82, 13.61, P＜0.05； IL-2： H=12.24, 12.42, 11.72, 12.43， P＜0.05）.Conclusion　The immunogenicity as well as specific antibody and cellular immune responses of SARS-CoV-2 and influenza virus combined vaccine with different adjuvant formulations are different, indicating the importance of adjuvants in the development of combined vaccine formulations.

Objective　To evaluate the non-clinical safety of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) chicken egg yolk immunoglobulin (IgY) spray by investigating the systemic and local toxicities, skin sensitization and potential eye irritation through repeated nasal and oropharyngeal administration in animals. Methods　Toxicity in ICR mice was evaluated after nasal and oropharynx drop administration of anti-SARS-CoV-2 IgY (71.04, 142.08 μg/d) once daily for 2 weeks. After SD rats were administrated with anti-SARS-CoV-2 IgY (639.35, 1 278.70, 2 557.40 μg/d) by nasal drop and oropharyngeal spray twice daily for 4 weeks, toxicity, target organs, toxicokinetics, and recovery after 4 weeks withdrawal were assessed. Active skin anaphylaxis test was used to evaluate the allergenicity after application of 0.4 mL anti-SARS-CoV-2 IgY (2 367.96 µg/mL) on backs of guinea pigs. New Zealand rabbits were given anti-SARS-CoV-2 IgY eye drops (2 367.96 µg/mL) 3 times daily for 7 d to evaluate the eye irritability. Results　No significant systemic toxicity was observed in ICR mice of either dosage group in 2 weeks, and the no observed adverse effect level (NOAEL) was 142.08 μg/d. The drug-related local irritant reaction was observed in 142.08 μg/d group, and the safe local dosage (71.04 μg/d) was 31.17 times of the clinical intended dose. The blood concentration of anti-SARS-CoV-2 IgY was under the lower limit of quantitation (0.74 μg/mL) in all SD rats of any dosage group, and no obvious systemic toxic reaction was observed. The NOAEL for SD rats (2 557.40 μg/d) was 112.20 times of the clinical intended dose, with only high-dosage group male rats presented a reversible local irritant response on nasal mucosa and tunica propria. Active skin allergic reactions in guinea pigs and eye irritation in New Zealand rabbits were both negative. Conclusions　The anti-SARS-CoV-2 IgY spray shows good safety when administered through the nasal cavity and oropharynx. At more than 100 times of human clinical highest intended dose, no obvious systemic toxicity occurs. The local irritant reaction observed in high-dosage group SD rats is recoverable. At clinical concentration, the tested product does not cause anaphylactic response in skin or irritate eyes.

Nucleic acid testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical and effective measure to quickly identify the source of infection, control the infected cases and block the transmission route. The capability of clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR associated protein (Cas) system to edit targeted gene presents broad application prospects in pathogen detection, especially Cas13 and Cas12, proteins targeting RNA and DNA, respectively. Relying on their collateral cleavage activity with fluorescent reporter systems, they have been utilized to detect SARS-CoV-2 nucleic acid and perform remarkably in sensitivity, specificity, portability, economy and ease of operation. This paper summarizes systematically the technology progress for SARS-CoV-2 detection based on CRISPR-Cas system, including mechanisms, improvement measures and their advantages, to evaluate the feasibility of the technology application. This also provides a reference for developing pathogen detection tools based on CRISPR-Cas system.

Objective  To construct and identify the recombinant BCG vaccine with nucleocapsid(N) protein gene of severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）. Methods  SARS-CoV-2 N protein gene was obtained from plasmid pUC57-N(Kan⁺) by PCR. The N gene was connected to the shuttle expression plasmid pMV261 of Escherichia coli and BCG vaccine, and identified by enzyme digestion, PCR and sequencing. The recombinant plasmid was transformed into the competent state of BCG, and the expression of the target antigen in the recombinant BCG was identified by Western blot. Results  N gene with 1 260 bp was obtained by PCR amplification, and the recombinant plasmid pMV261-N had complete sequense,and the fragment inserted was consistent with N gene full size and sequence of America National Center for Biotechnology Information. The recombinant plasmid could express the target protein in BCG, and its relative molecular weight was about 46 000. Western blot showed that the protein could be recognized by anti-N protein monoclonal antibody. Conclusion  The recombinant BCG can express the fusion protein stably, which lays the foundation for the development of recombinant SARS-CoV-2 N protein BCG vaccine.

Omicron variant has become the most prevalent strain of severe acute respiratory syndrome coronavirus 2. The extensive mutations in the spike protein endow the variant with new characteristics, which bring great challenges to public health. This article describes the infection mechanism and some epidemiological characteristics of Omicron variant, the effectiveness analysis of existing vaccines against Omicron-induced diseases, the risk analysis of breakthrough infections, and the prospect of vaccine improvement, research and development. The entry mode of Omicron variant has changed from membrane fusion to endocytosis pathway. The generation of new mutations endows this variant with strong transmission, short incubation period and recovery period, mild symptoms, and susceptibility to vaccination and convalescence, which seriously affects vaccine effectiveness and increases the risk of breakthrough infection. New requirements have been put forward for the future improvement, research and development of vaccines.

Objective  To choose 2019 novel coronavirus （2019-nCoV）nucleic acid extraction kits by comparing their extraction efficiency and to investigate the suitability of detection method for nucleic acid in plasma sample. Methods  The 2019-nCoV nucleic acid in plasma was extracted using 3 different nucleic acid extraction kits. The open reading frame 1a/b (ORF1ab) and nucelocapcid (N) genes were amplified and detected using same nucleic acid detection kit. Results  The correlation coefficients of ORF1ab and N gene fragments standard curve were both ≥ 0.999. Extraction kit A had a recovery rate of 91% for ORF1ab and  38% for N. Kit B had a recovery rate of 104% for ORF1ab and 44% for N. Kit C had a recovery rate of 0% for ORF1ab and 12% for N. The accuracies of kits A and B were both 100%, while kit C was 62.5% attributing to false negative results. Conclusion  Except for kit C, both kits A and B can be used with 2019-nCoV nucleic acid detection kit for virus nucleic acid detection in COVID-19 convalescent plasma.

COVID-19 pandemic has caused severe public health crisis worldwide. To prevent the adverse health effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on people in various countries, different types and production processes of SARS-CoV-2 vaccines, including live attenuated, nucleic acid, virus vectored, inactivated and recombinant protein vaccines, primarily focusing on viral surface spike protein, have been successively developed. This review describes the structure, function and immunological properties of the SARS-CoV-2 spike protein, as well as the research status, safety and applicability of spike protein-related SARS-CoV-2 vaccine, and discusses solutions for potential issues.

Objective　To investigate the best immune effectiveness of the virus-like structure (VLS) mRNA vaccine against severe acute respiratory syndrorme coronavirus 2 in mice, using vaccine containing different dosages of mRNA and protein, to determine the drugability of this vaccine. Methods　ADT-lipid nanoparticle delivery system was applied to encapsulate different doses of mRNA and protein. It was used to transfect different cell lines for detecting the expression of antigens coded by mRNA and immunize BALB/c mice to evaluate antibody response elicited by VLS vaccine. Result　Dendritic cell activation was found in BALB/c mice immunized by VLS vaccine encapsulated 10-20 μg mRNA and 5 μg protein in vivo, while the activation of innate and adaptive immunity was observed in mice. Conclusion　The VLS mRNA vaccine can become a novel candidate vaccine, with potent immunogenicity and antibody stimulating ability in mice.

Viral infection is one of the main causes for many human diseases. Viruses are widely distributed and generally highly harmful. Vitamin D, an essential substance for human body, is an important participant in immune regulation, and plays an important role in the prevention and treatment of viral infection. This article mainly discusses the latest clinical research progress of vitamin D in the prevention and treatment of several common viral infections. The prospects of COVID-19 prevention and treatment by vitamin D are also discussed.

Objective  To explore the existance of antibody-dependent enhancement (ADE) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on hamster model, which would provide an experimental support for vaccine development and application. Methods  SARS-CoV-2 infected Syrian hamster models were established and divided into mock group, infection group, twice-infection group and immunization group. ELISA was used to measure levels of total antibodies and cytokines IL-6/transforming growth factor β (TGF-β) in hamster sera. Neutralization test was used to detect anti-virus neutralizing antibodies of hamster sera. Western blotting and quantitative reverse transcriptase PCR were used to detect virus in lung tissues. Hematoxylin eosin staining was utilized to evaluate pathological changes of hamster lung tissues. Hamster primary peritoneal macrophages were isolated and cultured, then used to detect whether immunization sera promote SARS-CoV-2 infection of macrophages. Results  Total antibody titers of the hamster sera were similar between twice-infection group and immunization group (P>0.05), while sera neutralizing antibody titers of immunization group were far lower than that of twice-infection group (P<0.001). Compared with infection group, the body weight of twice-infection group and immunization group infected by SARS-CoV-2 remained stable (P<0.01) and inflammation of lung tissues was much milder. SARS-CoV-2 was only detected at the day 2 post infection in lung tissues of immunization group. There was no significant difference of pro-inflammatory factor IL-6 and anti-inflammatory factor TGF-β in the hamster sera measured by ELISA (P>0.05). SARS-CoV-2 could not infect hamster peritoneal macrophages with or without hamster immune sera, but be engulfed by macrophages. Conclusion  The preliminary experiments do not support the macrophage-mediated ADE during SARS-CoV-2 infection based on hamster models.

Objective  To establish and validate a reverse transcription PCR (RT-PCR) method for the specific identification of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta strain vaccine bulk.  Methods  Primers S3F/S3R were designed based on the sequence of upstream and downstream conserved regions to 3 specific mutation sites in the receptor binding domain（RBD） of spike (S) gene of Beta strain, and an 843 bp target DNA band was amplified by RT-PCR. The amplified bands were sequenced and compared with the S gene sequence of prototype strain. The Beta strain was identified by three characteristic mutations. The repeatability, specificity, durability and sensitivity of the method were verified. Results  Target DNA bands of 843 bp were amplified, identical to the Beta strain gene sequence and containing 3 characteristic mutations. A batch of Beta strain bulk was taken for PCR 6 times, and the sequencing results showed that the nucleotide sequence was consistently identical to that of Beta strain. S3F/S3R primers only amplified the RBD region of SARS-CoV-2 S. The target bands could still be amplified when the original solution of Beta strain was kept at 4 ℃ and -70 ℃, respectively, for 8 weeks, and the sequencing results were consistent. The extracted RNA was diluted into different concentrations for RT-PCR, and the minimum detection limitation was 0.032 ng/µL.   Conclusions  The established method has good specificity, repeatability, durability and sensitivity and can successfully distinguish SARS-CoV-2 prototype strain from Beta strain. It can be used for the identification of vaccine bulk in the production of COVID-19 vaccine.

 Objective  To establish the enzyme-linked quantitative detection method of anti-2019-nCoV neutralizing antibody for test of convalescent plasma, plasma bluk and final products in the development of COVID-19 human immunoglobulin for intravenous use. Methods  Using COVID-19 convalescent plasma with a known neutralizing activity as a reference standard,  the indirect ELISA kit coated with receptor-binding domain antigen was selected, and double log-fit curve was used to establish a quantitative ELISA, and its optimal linear range was determined.Indoor quality control was prepared and calibrated. Dilution linearity, parallelism, accuracy, precision of the method were verified. Three batches of convalescent plasma, plasma bluk and final products were tested by the method, and the correlation with the results of chemiluminescence immunoassay and neutralization experiment was analyzed. Results The standard curve range was determined as dilution factor 1-8. The intra-batch accuracy was 88.50% ~ 108.58%. The inter-batch accuracy was 100.98% ~ 103.98%. The intra-batch precision was within 3.83% ~ 14.68%. The inter-batch precision was 5.67% ~ 13.15%. Parallelism of standard substance with convalescent plasma, plasma bluk and final products good. Correlation of the method with chemiluminescence immunoassay and neutralization experiment was good. Conclusions  The method established meets the requirements, and can be used for the potency test of COVID-19 human intravenous immunoglobulin as an internal release test.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is one of the important ways to the prevention of COVID-19. However, with the emergence of SARS-CoV-2 variants, especially Omicron variant, the preventive effect of the vaccine has been reduced. The public yearn for the timely updated vaccine in sync with the virus mutation. In this paper, based on the relationship between the characteristics of SARS-CoV-2 infection and mucosal immunity, the positive effect and innate deficiency of the first-generation SARS-CoV-2 vaccine in preventing the severe symptoms caused by the variants is discussed. A new interference drastic mutation hypothesis is proposed for the evolution of Omicron variants, hoping to draw attention to the unnatural acceleration of virus evolution. Although the COVID-19 epidemic has come to an end, over the past three years, the research on a vaccine for the SARS-CoV-2 variant has lagged behind the speed of the virus' evolution. Therefore, this article boldly proposes a forward-looking study on the green channel of vaccine upgrade and emergency use for the approval of variant vaccine upgrade under emergency circumstances. It is imperative to study the feasibility of vaccine upgrade reform from the perspective of regulations and policies. When rapidly changing emergencies such as the COVID-19 outbreak occur again, it is necessary to respond through timely vaccine upgrades in the future.

Coronavirus disease 2019 (COVID-19) is still in the stage of global pandemic, and vaccination is an important means to stop the spread of the epidemic. The vaccination of COVID-19 vaccines developed on multiple platforms around the world is being actively carry out. The strategy of boost immunization is particularly important in the current situation of coping with the continuous mutation of SARS-CoV-2 epidemic strain. In particular, the immunogenicity and protective effect of homologous and heterologous booster vaccination have received much attention. This paper mainly introduces the results of clinical studies and real world studies on boost immunization with vaccines of different platforms, providing reference for immunization strategies.

The current COVID-19 epidemic is still in a global pandemic, and the number of confirmed cases and deaths continues to rise. How to effectively control the spread of the virus and reduce the infection rate and the mortality rate is an urgent problem for all mankind at present. On the one hand, we need fast, reliable, and economic detection methods to find severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） infection in time. On the other hand, it is necessary to find novel and effective COVID-19 treatment and prevention strategies. A variety of new-generation gene-editing technologies based on clustered regularly interspaced short palindromic repeat and associated protein (CRISPR-Cas) systems provide rapid, portable, economical, and efficient features for rapid genetic diagnosis of COVID-19 solution. The CRISPR-Cas system can accurately recognize and degrade SARS-CoV-2 nucleic acid, which provides a potential technical solution for the development of new treatment and prevention methods for COVID-19. This paper analyzes the current situation of diagnosis and treatment of COVID-19, and briefly describes the research progress of molecular diagnosis, treatment, and prevention strategies of COVID-19 based on CRISPR-Cas system.

Objective  To investigate the efficacy and safety of human immunoglobulin for intravenous injection (IVIG) in treating COVID-19 patients by Meta-analysis. Methods Between 1 January 2020 and 31 July 2021, randomized controlled trials (RCTs) and cohort studies referred to IVIG and COVID-19 were searched from Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI) and China Biology Medicine disc (CBM). Quality evaluation was performed according to Cochrane Handbook for Systematic Reviews and Meta-analysis was conducted with RevMan 5.3 Software. Results Eleven studies were retrieved, including 4 RCTs and 7 cohort studies. The result of the Meta-analysis showed that the mortality rate of critical ill COVID-19 patients could be relieved significantly by IVIG [risk ratio (RR)=0.67, 95% confidence interval (CI): 0.52-0.85, P=0.001, I²=7%].In severe patients, IVIG could also improve patients’ survival though significant statistical difference was not achieved [RR=0.78, 95% CI: 0.52-1.18, P=0.24, I²=49%]. The incidence of adverse reactions of IVIG in patients with COVID-19 was 0.0%-5.9%, and the majority was manifested in mild to moderate palpitation, dizziness, rash, and swelling at infusion site. Conclusion IVIG can improve the survival of critical ill COVID-19 patients effectively, with excellent safety. In severe patients, it is necessary to further explore the starting time and recommended dosage of IVIG, thus serving clinical practice better.

Since first reported,COVID-19 caused by 2019 novel coronavirus (2019-nCoV) infection has spread rapidly around the world. 2019-nCoV can results in severe pneumonia and endanger patients' lives. Currently, there are no specific drugs for 2019-nCoV infection. The structures of 2019-nCoV spike protein and its receptor angiotension-converting enzyme 2 have been resolved, providing basis for drug development. Many 2019-nCoV-specific neutralizing antibodies have been obtained by single B cell antibody technology from human peripheral blood as well as other antibody screening technologies. The development of antibody drugs provides new options for the prevention and treatment of COVID-19. This article briefly reviews the research and development of antibody drugs for 2019-nCoV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not only seriously affects human immunity, but also may induce autoimmune diseases in genetically susceptible people. The research progresses of five major types of autoantibodies produced in SARS-CoV-2 infected patients, the autoimmune diseases that may be caused by autoantibodies, the excessive activation of the patients’ autoimmune system, and the possible mechanisms that autoimmunity induced by SARS-CoV-2 infection were summarized in this review, which aims to provide a theoretical basis for the study of SARS-CoV-2-related autoimmune injury and diseases.

Objective  To explore the production and quality standard of an inactivated plasma of anti-2019 novel coronavirus(2019-nCoV) prepared from convalescent plasma of COVID-19 patients. Methods  Four hundred and forty-one convalescent samples were collected from COVID-19 patients in Wuhan, China from January to March 2020 and screend for pathogens including 2019-nCoV, HIV, Treponema pallidum and so on. Qualified plasma samples were inactivated by methylene blue light. By carrying out protein content of plasma , anti-2019-nCoV antibody, coagulation factor Ⅷ activity and other tests, the effect of methylene blue light inactivation on plasma was determined and the quality standard was dstablished. Results  Protein content of inactivated plasma did not change significantly before and after methylene blue irradiation inactivation ,coagulation factor Ⅷ activity was ≥ ≥0.50 I U/ml.Antibody titer did not show a significant decrease.All test results met the queality requeirement. Conclusion  The key quality control and process parameters of anti-2019-nCoV inactivated plasma prepared from the plasma of COVID-19 convalescent patients are established.

Objective  To investigate the neutralization and inhibitory effect of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) chicken egg yolk antibodies (IgYs) on SARS-CoV-2 and its variants in vitro, and to explore the possibility of using anti-SARS-CoV-2 IgYs to prevent and block SARS-CoV-2 infection as a nasal or oral spray. Methods  Indirect ELISA was used for detecting the anti-spike (S) titers of anti-SARS-CoV-2 IgYs stock and final product. The neutralization activity of the IgYs on live SARS-CoV-2 was tested by microcytopathic assay. The blocking potency of IgYs on pseudotyped SARS-CoV-2 was evaluated by luciferase luminescence method. Results  The anti-S antigen titers of anti-SARS-CoV-2 IgYs bulk ranged from 1:32 000 to 1:64 000, and that of IgYs final products ranged from 1:16 000 to 1:32 000. The neutralization titers of 2 anti-SARS-CoV-2 IgYs bulks against live virus were 1:128 and 1:256, and the corresponding median inhibitory concentration (IC₅₀) values were 36.22 μg/ml and 36.50 μg/ml, respectively. The mean IC₅₀ values of IgYs final products against pseudotyped SARS-CoV-2 were 4.57 μg/ml (WT) and 6.07 μg/ml (D614G), and the IC₅₀ values for pseudotyped SARS-CoV-2 variants were 15.09-29.94 μg/ml (B.1.1.7), 41.71-55.56 μg/ml (B.1.351) and 16.66-32.33 μg/ml (B.1.617.2), respectively. Conclusions  The anti-SARS-CoV-2 IgYs can effectively bind to SARS-CoV-2 S protien, and show potent inhibitory activity against live SARS-CoV-2, pseudotyped SARS-CoV-2 and its variants infection in vitro. The anti-SARS-CoV-2 IgYs have good potential to be further developed to prevent and control SARS-CoV-2 infection.

As of February of 2021, the COVID-19 globe pandemic caused by 2019 novel coronavirus infection has resulted in over 100 million reported cases and 2 million fatal cases worldwide. With the advance in studies on clinical treatment, pathology, epidemiology, and basic molecular biology of the pathogen, vaccine development has made great breakthroughs. Several COVID-19 vaccines have been granted emergency use or conditional license. This review analyzes the safety, immunogenicity and primary efficacy of more advanced candidate vaccines based on their clinical study results. The challenges and strategies of different kinds of vaccines are discussed, focusing on mRNA vaccine using novel technology platform and traditional inactivated vaccines.

objective To investigate the effect of different types of coated gold-labeled antigens on the quality of anti-2019 novel coronavirus (2019-noV) antibody rapid detection test cassettes. Methods An anti-2019-nCoV antibody sample panel was used to test colloidal gold test cassettes coated with different gold-labeled antigens from manufacturer L. The sensitivity, specificity, accuracy and correctness index of the product were compared. For the time being, the eligibility standard was set at accuracy>95% and correctness index >0.85. Results For the 6 batches of test cassettes from manufacturer L coated with recombinant 2019nCoV spike (S)+ nucleocapsid (N) proteins (L002)receptor-binding domain (RBD)+ N proteins (L003), N protein(L004),RBD protein( L006), S protein(L007), N+ S proteins (L008), the accuracies/correctness indexes of detecting lgG were 98.38%/0.966.97.30%/0.946,97.84%/0. 954,90.82%/0.873,97. 86%/0. 958, 95. 72%/0. 919, respectively, and those of detecting IgM were 90.51%/0.736,95.57%/0. 890,73. 10%/0. 298, 68. 37%/0. 331,83.96%/0.533,87.17%/0.658,respectively. Conlusions Test cassettes coated with all kinds of gold-labeled antigens are qualified for lgG detection, but only the combination of RBD and N proteins coated test cassette is qualified for lgM detection. The quality of lgM detection can be improved by optimizing the types of gold-labeled antigens coated.

With the rapid development of COVID-19 vaccines, dozens of new COVID-19 vaccines have entered the clinical research stage and several different types of COVID-19 vaccines have been approved for use in different countries and regions. Vaccine safety has always been one of the focuses that experts and the public are paying close attention to. In this review, publicly or officially released safety data of new COVID-19 vaccines before and after authorization are systematically summarized, to help for fully understanding the safety of COVID-19 vaccines, enhancing the public's confidence in COVID-19 vaccines, and better implementing vaccines safety surveillance and safety signal detection after large-scale immunization.

Objective  To systematically verify the detection method of 2019 novel coronavirus (2019-nCoV)nucleic acid detection in convalescent plasma (CP) samples of COVID-19 patients. Methods  According to actual situation of plasma samples and requirements of the kit, a realtime fluorescent quantitative PCR detection method for 2019-nCoV nucleic acid was established. The method was systematically verified from specificity, detection limit, repeatability and intermediate precision.The method performance was validated by measurements of 20 CP samples. Results  The specificity results showed that both positive and negative samples were detected effectively. The detection limit results revealed that the open reading frame 1a/b and nucleocapsid genes were positive in all of 19 times tests of 1×LOD-2×LOD concentration enterprise reference materials. Repeatability and intermediate precision results showed that the relative standard deviations of cycle threshold values for both positive control genes and internal quality control in different fluorescence channels all met the requirements. The performance validation results displayed that 20 CP samples were all negative for 2019-nCoV nucleic acid. Conclusion  The method is specific, stable, reliable and repeatable, and can be applied for the detection of 2019-nCoV nucleic acid in COVID-19CP samples.