Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants.

Background: COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain. Methods: The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group. Results: In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01). Conclusions: Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

B-Cell Receptor Features and Database Establishment in Recovered COVID-19 Patients by Combining 5'-RACE with PacBio Sequencing.

BACKGROUND: Antibodies induced by viral infection can not only prevent subsequent virus infection, but can also mediate pathological injury following infection. Therefore, understanding the B-cell receptor (BCR) repertoire of either specific neutralizing or pathological antibodies from patients convalescing from Coronavirus disease 2019 (COVID-19) infection is of benefit for the preparation of therapeutic or preventive antibodies, and may provide insight into the mechanisms of COVID-19 pathological injury. METHODS: In this study, we used a molecular approach of combining 5' Rapid Amplification of cDNA Ends (5'-RACE) with PacBio sequencing to analyze the BCR repertoire of all 5 IgH and 2 IgL genes in B-cells harvested from 35 convalescent patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: We observed numerous BCR clonotypes within most COVID-19 patients, but not in healthy controls, which validates the association of the disease with a prototypical immune response. In addition, many clonotypes were found to be frequently shared between different patients or different classes of antibodies. CONCLUSIONS: These convergent clonotypes provide a resource to identify potential therapeutic/prophylactic antibodies, or identify antibodies associated with pathological effects following infection with SARS-CoV-2.

Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants

Background COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain. Methods The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group. Results In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01). Conclusions Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

Lymphocytes screening on admission is essential for predicting in-hospital clinical outcome in COVID-19 patients: A retrospective cohort study.

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.

Neutrophil-to-lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID-19.

INTRODUCTION: Monitoring of laboratory indicators is important for predicting changes in disease severity and clinical outcomes. We aimed to identify the critical predictors that can effectively assess the disease conditions of patients with COVID-19 by analyzing the clinical characteristics and laboratory findings of patients with SARS-CoV-2 infection. METHODS: All consecutive patients (n = 294) with confirmed SARS-CoV-2 infection admitted to the General Hospital of Central Theater Command of the PLA from February 6 to February 21, 2020, were enrolled. These patients were divided into the severe group and the nonsevere group according to disease severity during hospitalization. RESULTS: The median neutrophil-to-lymphocyte ratio (NLR) value of the severe patients was dramatically higher than that of the nonsevere patients (10.4 vs 2.6; P < .001). The NLR value equal to 5 was a boundary value worthy of reference, because more than 80% severe patients had an NLR value greater than 5 and over 80% nonsevere patients had an NLR value less than 5. The NLR value of these COVID-19 patients was positively and respectively correlated with the values of C-reactive protein (R = .5921, P < .001), lactate dehydrogenase (R = .4509, P < .001), procalcitonin (R = .5504, P < .001), fibrinogen (R = .4710, P < .001), and D-dimers (R = .4425, P < .001). However, the NLR value was merely and positively correlated with the interleukin-6 value (R = .3594, P < .05), but had no correlations with the values of interleukin-10, interleukin-4, interleukin-17, interferon-γ, and tumor necrosis factor-α (P > .05). DISCUSSION: Neutrophil-to-lymphocyte ratio is a critical predictor for assessment of disease severity in patients with COVID-19, and it has a close relation with the laboratory indicators related to disease conditions.

Clinical application of Chemiluminescence Microparticle Immunoassay for SARS-CoV-2 infection diagnosis.

BACKGROUND: The unsatisfactory accuracy and capacity of real time RT-PCR depends on several unavoidable reasons, which cannot meet the demands for COVID-19 diagnosis. METHODS: 206 serum samples were collected from patients who were treated in the General Hospital of the Central Theater Command of the PLA between January 18 and April 4, 2020. 270 serum samples from healthy blood donors were used as control. IgM and total antibodies (Ab) against SARS-CoV-2 were detected by Chemiluminescence Microparticle Immunoassay (CMIA). RESULTS: Among the 206 patients, the positive rate of IgM and Ab were 149/206 (72.3 %) and 187/206 (90.8 %), respectively. And the specificity of IgM and Ab detection were 99.3 % and 98.9 %, respectively. The sensitivity of CMIA for Ab detection was significantly higher than that of IgM. An increase of the positive rate and S/CO value for detecting IgM and Ab accompanied with the increasing of days post-disease onset (d.p.o.) were observed. The positive rate of Ab detected by CMIA increased rapidly after 7 d.p.o., while that of IgM was obviously increased after 14 d.p.o.. In addition, the age and gender of these patients did not affect the seroconversion and titer of antibodies during the whole course. The disease-severity of patients had no effect on the seroconversion of antibodies. However, the critical patients possessed a much higher antibody titers than the no-critical cases after 14 d.p.o.. CONCLUSIONS: The CMIA can provide important complementation to nucleic acid assay and help to enhance the accuracy and capacity of diagnosis of SARS-CoV-2 infection.

Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies against SARS-CoV-2.

At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease (COVID-19) diagnosis. Two hundred fourteen confirmed COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command of the People's Liberation Army between 18 January and 26 February 2020 were recruited. Two enzyme-linked immunosorbent assay (ELISA) kits based on recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness, 0 to 10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o., so it could be an important supplementary method for COVID-19 diagnosis.