BackgroundTimely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated.MethodSerial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described.ResultsThe seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0–7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays.ConclusionsA typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.
Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.
The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 μg) with the inclusion of an aluminium adjuvant. Higher doses (20 μg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.
23Pandemic coronavirus disease 2019 is caused by the emerging severe 24 acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no 25 efficacious vaccines or therapeutics that are urgently needed. We expressed three 26 versions of spike (S) proteins-receptor binding domain (RBD), S1 subunit and S 27 ectodomain-in insect cells. RBD appears monomer in solutions, whereas S1 and S 28 associate into homotrimer with substantial glycosylation. The three proteins confer 29 excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron 30 microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a 31 unique conformation distinguished from the classic prefusion conformation of 32 coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral 33 membrane. Such conformation is proposed as an early prefusion state for the SARS-34 CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine 35 development.36
Coronavirus disease 2019 (COVID-19) is the most important global public health issue that we currently face. We aimed to explore the clinical features of patients with COVID-19 and compared them with those of hospitalized community-acquired pneumonia (CAP) patients caused by influenza virus during the same period. From Jan 1, to Mar 4, 2020, patients with COVID-19 or CAP caused by influenza virus who were admitted to the First Affiliated Hospital of Xiamen University were consecutively screened for enrollment. A total of 35 COVID-19 patients and 22 CAP patients caused by influenza virus were included in this study. Most of COVID-19 patients had characteristics of familial clustering (63%), however, in the other group, there was no similar finding. The percentages of patients with a high fever (the highest recorded temperature was ≥39.0°C; 11% vs 45% [COVID-19 vs CAP groups, respectively]), dyspnea (9% vs 59%), leukocytosis (3% vs 32%), elevated C-reactive protein concentrations (>10 mg/L, 48% vs 86%), elevated procalcitonin levels (>0.1 ng/ml, 15% vs 73%), PaO 2 /FiO 2 <200 mm Hg (4% vs 22%), and infiltration on imaging (29% vs 68%) in the COVID-19 group were less than those same indices in the hospitalized CAP patients caused by influenza virus. Ground-glass opacity with reticular pattern (63%) and interlobular septal thickening (71%) in chest CT were commonly observed in the COVID-19 group. COVID-19 and CAP caused by influenza virus appear to share some similarities in clinical manifestaions but they definitely have major distinctions. Influenza infection remains a health problem even during COVID-19 pandemic.
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