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Many new Omicron sub-lineages have been reported to evade neutralizing antibody response, including BA.2, BA.2.12.1, BA.4 and BA.5. Most recently, another emerging sub-lineage BA.2.75 has been reported in multiple countries. In this study, we constructed a comprehensive panel of pseudoviruses (PsVs), including wild-type, Delta, BA.1, BA.1.1, BA.2, BA.3, BA.2.3.1, BA.2.10.1, BA.2.12.1, BA.2.13, BA.2.75 and BA.4/BA.5, with accumulate coverage reached 91% according to the proportion of sequences deposited in GISAID database since Jan 1st, 2022. We collected serum samples from healthy adults at day14 post homologous booster with BBIBP-CorV, or heterologous booster with ZF2001, primed with two doses of BBIBP-CorV, or from convalescents immunized with three-dose inactivated vaccines prior to infection with Omicron BA.2, and tested their neutralization activity on this panel of PsVs. Our results demonstrated that all Omicron sub-lineages showed substantial evasion of neutralizing antibodies induced by vaccination and infection, although BA.2.75 accumulated the largest number of mutations in its spike, BA.4 and BA.5 showed the strongest serum escape. However, BA.2 breakthrough infection could remarkably elevated neutralization titers against all different variants, especially titers against BA.2 and its derivative sub-lineages.
ABSTRACT
The SARS-CoV-2 Omicron variant has been partitioned into four sub-lineages designated BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide recently by outcompeting BA.1 and BA.1.1. We and others have reported the striking antibody evasion of BA.1 and BA.2, but side-by-side comparison of susceptibility of all the major Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are urgently needed. Using VSV-based pseudovirus, we found that sera from individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed very weak to no neutralization activity, while a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) markedly improved the neutralization titers against all Omicron variants. The comparison between sub-lineages indicated that BA.1.1, BA.2 and BA.3 had comparable or even greater antibody resistance than BA.1. We further evaluated the neutralization profile of a panel of 20 mAbs, including 10 already authorized or approved, against these Omicron sub-lineages as well as viruses with different Omicron spike single or combined mutations. Most mAbs lost their neutralizing activity completely or substantially, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, reflecting their antigenic difference. Taken together, our results suggest all four Omicron sub-lineages threaten the efficacies of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters to combat the emerging SARS-CoV-2 variants.
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ObjectiveTo describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. DesignA retrospective descriptive study SettingChina ParticipantsEpidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measurePrevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fishers exact test, t test or Mann-Whitney U test were used in statistical analysis. ResultsCOVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. ConclusionStrict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction.
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BackgroundThe recent outbreak of infections by the 2019 novel coronavirus (2019-nCoV), the third zoonotic CoV has raised great public health concern. The demand for rapid and accurate diagnosis of this novel pathogen brought significant clinical and technological challenges. Currently, metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) are the most widely used molecular diagnostics for 2019-nCoV. Methods2019-nCoV infections were confirmed in 52 specimens by mNGS. Genomic information was analyzed and used for the design and development of an isothermal, CRISPR-based diagnostic for the novel virus. The diagnostic performance of CRISPR-nCoV was assessed and also compared across three technology platforms (mNGS, RT-PCR and CRISPR) Results2019-nCoVs sequenced in our study were conserved with the Wuhan strain, and shared certain genetic similarity with SARS-CoV. A high degree of variation in the level of viral RNA was observed in clinical specimens. CRISPR-nCoV demonstrated a near single-copy sensitivity and great clinical sensitivity with a shorter turn-around time than RT-PCR. ConclusionCRISPR-nCoV presents as a promising diagnostic option for the emerging pathogen.
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Objective To investigate the epidemiological and clinical characteristics of 91 cases of dengue fever outbreak in Jiangxi Province in 2019,and to strengthen the management and prevention of dengue fever.Methods The clinical data,laboratory results and etiology tests of 91 patients with dengue fever from the Ninth Hospital of Nanchang,Zhangshu People's Hospital,Fengcheng People' s Hospital and Nanchang County People's Hospital from July 31,2019 to September 27,2019 were retrospectively collected.The t test was used for continuous variables and chi-square test was used for categorical variables.Results A total of 91 dengue fever patients were reviewed.The patients age ranged from 4 to 87 years old,and the majority were adult patients.Most patients were farmers and they all had mosquito-biting history.Local cases were the major source of this outbreak.The incubation time was(5.19±2.96)days.All patients had fever over 38℃.Thirty-eight(41.8％)patients developed rashes,mainly distributed on the limbs and trunk,and 15 patients(16.5％)developed myalgia and fatigue.The incidence of rashes in patients admitted in September was 15.9％(7/44),which was significantly lower than 68.1％(32/47)in July and August(x2 = 25.262,P ＜0.01).The incidence of headache in patients admitted in September was 27.3％(12/44),which was significantly lower than 78.7％(37/47)in July and August(x2=24.206,P ＜ 0.01).Among the 91 patients,64(70.3％)patients had white blood cell counts less than 4×109/L,14(15.4％)patients had platelet counts less than 50×109/L.The positive rate of dengue non-structural protein 1(NS1)antigen was 100.0％(37/37),the positive rates of dengue antibody IgM and IgG were 50.0％(11/22)and 13.6％(3/22),respectively.Among the 113 serum samples tested for dengue virus RNA,106 were identified with dengue virus type-1 and two were dengue virus type-2.In 22 patients who received tests within 7 days,the positive rate of NS1 antigen was 100.0％(22/22),the IgM and IgG positive rates were 50.0％(11/22)and 13.6％(3/22),respectively,and 19 patients were infected with dengue type-1.Among the IgM antibody positive cases,the onset days before sampling was(5.09±1.64)days,longer than that of IgM antibody negative cases((2.82± 1.83)days),with statistical significance(t = 3.063,P = O.007).The onset time before sampling in dengue virus RNA-positive group was(3.53±1.87)days,which was shorter than that of RN A-negative group((6.67± 0.58)days),and the difference was statistically significant(t = 2.839,P = 0.013).Conclusions The dengue fever outbreak cases in Jiangxi Province in 2019 have typical clinical manifestations of dengue fever.Using the NS1 antigen test,IgM and IgG antibody tests and real-time fluorescent quantitative polymerase chain reaction for dengue virus genotyping during early onset of the disease can assistant clinicians in clinical management,controlling infectious source and stopping disease transmission.
ABSTRACT
Objective@#To investigate the epidemiological and clinical characteristics of 91 cases of dengue fever outbreak in Jiangxi Province in 2019, and to strengthen the management and prevention of dengue fever.@*Methods@#The clinical data, laboratory results and etiology tests of 91 patients with dengue fever from the Ninth Hospital of Nanchang, Zhangshu People′s Hospital, Fengcheng People′s Hospital and Nanchang County People′s Hospital from July 31, 2019 to September 27, 2019 were retrospectively collected. The t test was used for continuous variables and chi-square test was used for categorical variables.@*Results@#A total of 91 dengue fever patients were reviewed. The patients age ranged from 4 to 87 years old, and the majority were adult patients. Most patients were farmers and they all had mosquito-biting history. Local cases were the major source of this outbreak. The incubation time was (5.19±2.96) days. All patients had fever over 38 ℃. Thirty-eight (41.8%) patients developed rashes, mainly distributed on the limbs and trunk, and 15 patients (16.5%) developed myalgia and fatigue. The incidence of rashes in patients admitted in September was 15.9% (7/44), which was significantly lower than 68.1% (32/47) in July and August (χ2=25.262, P<0.01). The incidence of headache in patients admitted in September was 27.3%(12/44), which was significantly lower than 78.7% (37/47) in July and August (χ2 =24.206, P<0.01). Among the 91 patients, 64 (70.3%) patients had white blood cell counts less than 4×109/L, 14(15.4%) patients had platelet counts less than 50×109/L. The positive rate of dengue non-structural protein 1 (NS1) antigen was 100.0%(37/37), the positive rates of dengue antibody IgM and IgG were 50.0%(11/22) and 13.6%(3/22), respectively. Among the 113 serum samples tested for dengue virus RNA, 106 were identified with dengue virus type-1 and two were dengue virus type-2. In 22 patients who received tests within 7 days, the positive rate of NS1 antigen was 100.0% (22/22), the IgM and IgG positive rates were 50.0%(11/22) and 13.6% (3/22), respectively, and 19 patients were infected with dengue type-1. Among the IgM antibody positive cases, the onset days before sampling was (5.09±1.64) days, longer than that of IgM antibody negative cases ((2.82±1.83) days), with statistical significance (t=3.063, P=0.007). The onset time before sampling in dengue virus RNA-positive group was (3.53±1.87) days, which was shorter than that of RNA-negative group ((6.67±0.58) days), and the difference was statistically significant (t=2.839, P=0.013).@*Conclusions@#The dengue fever outbreak cases in Jiangxi Province in 2019 have typical clinical manifestations of dengue fever. Using the NS1 antigen test, IgM and IgG antibody tests and real-time fluorescent quantitative polymerase chain reaction for dengue virus genotyping during early onset of the disease can assistant clinicians in clinical management, controlling infectious source and stopping disease transmission.
