From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay.

There have been several false-positive results in the antibody detection of COVID-19. This study aimed to analyze the distribution characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M (IgM) and immunoglobulin G (IgG) in false-positive results using chemiluminescent immunoassay. The characteristics of false-positive results in SARS-CoV-2 IgM and IgG tests were analyzed. The false-positive proportion of single SARS-CoV-2 IgM-positive results was 95.88%, which was higher than those of single SARS-CoV-2 IgG-positive results (71.05%; p < 0.001) and SARS-CoV-2 IgM- and IgG-positive results (39.39%; p < 0.001). The S/CO ratios of SARS-CoV-2 IgM and IgG in false-positive results ranged from 1.0 to 50.0. The false-positive probability of SARS-CoV-2 IgM in the ratios of specimen signals to the cutoff value (S/CO) range (1.0-3.0) was 95.06% (77/81), and the probability of false-positive results of SARS-CoV-2 IgG in the S/CO range (1.0-2.0) was 85.71% (24/28). Dynamic monitoring showed that the S/CO values of IgM in false-positive results decreased or remained unchanged, whereas the S/CO values of IgG in false-positive results decreased. The possibility of false-positive single SARS-CoV-2 IgM-positive and single SARS-CoV-2 IgG-positive results was high. As the value of S/CO ratios decreased, the probability of false-positives consequently increased, especially among the single SARS-CoV-2 IgM-positive results.

The analytical strategy of GICA and CLIA combination in SARS-CoV-2 antibodies detection

To evaluate the effect of colloidal gold immunochromatographic assay (GCIA) combined with chemiluminescent immunoassay (CLIA) in reducing the false positive of antibodies against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Thirty-three serum samples from 19 patients with SARS-CoV-2 infection at different times, and 55 serum samples from 55 patients not infected with SARS-CoV-2. but infected instead with other pathogens or suffering from autoimmune diseases were collected from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital from 22 January to 5 March 2020. Serum IgM and IgG against SARS-CoV-2 were detected by GICA and CLIA respectively, and the results were analyzed. The sensitivity of GCIA for detection of IgM and IgG against SARS - CoV - 2 was 100.0% and 94.74%. respectively, values that were similar with those for CLIA (92.86% and 100.0%) (P = 1.000). The specificity of GCIA for IgM and IgG against SARS-CoV-2 was 70.91% and 74.55% respectively, which was significantly lower than that of CLIA (98.18% and 89.09%) (P < 0.01). The results of IgM and IgG against SARS-CoV-2 detected by the two methods were consistent (P=0.000) . and their Kappa was 0.434 and 0.406. respectively. Analyses of ROC curves showed that the AUC of IgM and IgG against SARS-CoV-2 detected by GCIA was 0.855 and 0.846. respectively, which was significantly lower than that of CLIA (0.955 and 0.945, respectively) (PC0.05). The sensitivity of combined detection of IgM and IgG against SARS -CoV-2 was 92.86% and 94.74%. and the specificity was 100.0% and 100.0%, respectively. Analyses of ROC curves showed that the AUC of combined detection of IgM and IgG against SARS-CoV-2 was 0.964 and 0.974. respectively, which was higher titan that of each method alone. GCIA combined with CLIA can improve the specificity of detection of IgM and IgG against SARS-CoV-2, which may merit clinical application.

Effect of urea dissociation on reducing the number of false-positive results of IgM and IgG antibodies against SARS-CoV -2

We wished to explore the interference factors causing false-positive results for immunoglobulin M (IgM) and IgG antibodies in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by the gold immunochromatography assaym (GICA). In this way, we wanted to improve the detection method and scheme of laboratory detection. Seventy-four serum samples from outpatients and inpatients from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital in China from 2 January 2020 to 5 March 2020 were collected 19 patients with the nucleic acids of SARS-CoV-2;10 cases with IgM antibodies against other respiratory viruses;10 patients with IgM antibodies against hepatitis viruses;20 patients with IgM antibodies against rheumatoid factor (RF);15 patients with antinuclear antibody (ANA). Colloidal GICA (kit A and kit B) was used to detect IgM and IgG antibodies against SARS-CoV-2 in patient sera. Positive results of SARS-CoV-2 IgM or SARS-CoV -2 IgG antibodies were analyzed, and possible factors causing false-positive results were found. Then, the sera of SARS- CoV - 2 IgM/IgG positive and 3 early coronavirus disease 2019 (COVID-19) patients were dissociated with an appropriate concentration of urea, and levels of IgM and IgG antibodies against SARS-CoV-2 were redetermined. SPSS v19.0 was used to analyze data. In the sera of 19 patients with SARS-CoV-2 infection 15 of SARS -CoV-2 IgM antibodies and 18 cases SARS-CoV-2 IgG antibodies were detected in kit A;12 cases of SARS-CoV-2 IgM antibodies and 12 cases of SARS-CoV-2 IgG antibodies were detected in kit B;16 cases of SARS-CoV-2 IgM antibodies and 14 cases of SARS-CoV -2 IgG antibodies were detected in 20 patients who had IgM antibodies against RF. In the sera of 15 patients with high - titer ANA, SARS-CoV- 2 IgG antibodies were detected in four cases using kit B. When the urea dissociation concentration was 2 mol/L, 14 of 16 RF- IgM - positive sera detected using kit A turned negative, 13 of 14 SARS- CoV- 2 IgG antibodies turned negative, but patients with COVID-19 detected by kit A did not show negative conversion of IgM or IgG antibodies. When the urea dissociation concentration was 4 mol/L, ANA -positive serum detected by kit B turned negative in four cases, whereas SARS-CoV-2 IgM and IgG antibodies in patients with COVID-19 did not turn negative. After urea dissociation, the SARS-CoV- 2 IgM antibodies detected by kit A and kit B in the sera of three patients with early COVID- 19 did not turn negative. RF could cause false-positive results for SARS-CoV-2 IgM and IgG antibodies detected by kit A, and a high titer of ANA could cause false-positive results of SARS-CoV-2 IgG antibodies detected by kit B. Urea dissociation could be helpful for reducing the probability of false-positive results of SARS-CoV-2 IgM and IgG antibodies. The effect of urea dissociation on the detection sensitivity of early COVID-19 merits further study.

A Method To Prevent SARS-CoV-2 IgM False Positives in Gold Immunochromatography and Enzyme-Linked Immunosorbent Assays.

We set out to investigate the interference factors that led to false-positive novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM detection results using gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA) and the corresponding solutions. GICA and ELISA were used to detect SARS-CoV-2 IgM in 86 serum samples, including 5 influenza A virus (Flu A) IgM-positive sera, 5 influenza B virus (Flu B) IgM-positive sera, 5 Mycoplasma pneumoniae IgM-positive sera, 5 Legionella pneumophila IgM-positive sera, 6 sera of HIV infection patients, 36 rheumatoid factor IgM (RF-IgM)-positive sera, 5 sera from hypertensive patients, 5 sera from diabetes mellitus patients, and 14 sera from novel coronavirus infection disease 19 (COVID-19) patients. The interference factors causing false-positive reactivity with the two methods were analyzed, and the urea dissociation test was employed to dissociate the SARS-CoV-2 IgM-positive serum using the best dissociation concentration. The two methods detected positive SARS-CoV-2 IgM in 22 mid-to-high-level-RF-IgM-positive sera and 14 sera from COVID-19 patients; the other 50 sera were negative. At a urea dissociation concentration of 6 mol/liter, SARS-CoV-2 IgM results were positive in 1 mid-to-high-level-RF-IgM-positive serum and in 14 COVID-19 patient sera detected using GICA. At a urea dissociation concentration of 4 mol/liter and with affinity index (AI) levels lower than 0.371 set to negative, SARS-CoV-2 IgM results were positive in 3 mid-to-high-level-RF-IgM-positive sera and in 14 COVID-19 patient sera detected using ELISA. The presence of RF-IgM at mid-to-high levels could lead to false-positive reactivity of SARS-CoV-2 IgM detected using GICA and ELISA, and urea dissociation tests would be helpful in reducing SARS-CoV-2 IgM false-positive results.