Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection

Abstract

BackgroundSARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses. A multi-antigen immunoassay to define the complex serological landscape and clinical associations is essential.MethodsWe developed a multiplex immunoassay and evaluated serum/plasma from adults with RT-PCR-confirmed SARS-CoV-2 infections during acute illness (N=52) and convalescence (N=69); and pre-pandemic (N=106) and post-pandemic (N=137) healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 Nucleocapsid (N), Spike domain 1 (S1), receptor binding domain (S1-RBD) and S1-N-terminal domain (S1-NTD).ResultsTo diagnose infection, the combined [IgA+IgG+IgM] or IgG for N, S1, and S1-RBD yielded AUC values −0.90 by ROC curves. From days 6-30 post-symptom onset, the levels of antigen-specific IgG, IgA or [IgA+IgG+IgM] were higher in patients with severe/critical compared to mild/moderate infections. Consistent with excessive concentrations of antibodies, a strong prozone effect was observed in sera from severe/critical patients. Notably, mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared to severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 months.ConclusionThis SARS-CoV-2 multiplex immunoassay measures the magnitude, complexity and kinetics of the antibody response against multiple viral antigens. The IgG and combined-isotype SARS-CoV-2 multiplex assay is highly diagnostic of acute and convalescent disease and may prognosticate severity early in illness.One Sentence SummaryIn contrast to patients with moderate infections, those with severe COVID-19 develop prominent, early antibody responses to S1 and N proteins.

High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids

“…We used Venice, a recent algorithm designed to overcome some of the challenges with mixed cell states/rare populations being represented by mean gene expression values 48 . BioTuring BBrowser 49 was used to identify markers in tissue-derived PNs (pooled time points) and organoid-derived PNs, identifying 10.2% shared marker expression (977 genes logFC > 0.001, Supplementary Table S33, Supplementary Figure S20b). The ‘Unknown’ cluster, which previously clustered alongside human tissue PNs (Supplementary Figure S9), also showed diffuse clustering and overlap with more than one human tissue PN region (Supplementary Figure S20c).…”

Detection of Anti-Nucleocapsid Antibody in COVID-19 Patients in Bangladesh Is not Correlated with Previous Dengue Infection

“…Anti-SARS-CoV-2 antibodies measured in different countries throughout the COVID-19 pandemic reveal three distinguishing features: first, the titers of anti-S-protein and anti-N-protein antibodies among severe cases in ICU or hospitalization are higher than titers among mild or moderate COVID-19 disease [ 33 , 34 , 35 , 36 ]. The percentage of positivity of anti-S-protein antibodies are greater than the percent positivity of anti-N-protein antibodies measured on the Luminex trimeric S protein immunoassay within the first 30 days post-onset of COVID-19 symptoms [ 37 ].…”

“…On March 8, 2020, the first COVID-19 case in Bangladesh was reported. Between March 2020 and August 2020, the COVID-19 incidence in Dhaka City and Narayanganj districts was estimated at 151 and 73 SARS-CoV-2 by rT-PCR confirmed cases per 100,000 inhabitants, respectively [ 31 , 32 , 33 ]. These two districts have the highest population density in Bangladesh and were identified as the country’s epicentre.…”

Endothelial cell-activating antibodies in COVID-19

“…Beyond aPL Abs, autoantibodies against the type I interferon response (31,32) and platelets (33) have been described in moderate-to-severe COVID-19, with both demonstrating potentially important functional properties in vitro. At the same time, the circulating B cell compartment of COVID-19 appears reminiscent of the autoimmune disease lupus whereby naïve B cells rapidly take an extrafollicular route to becoming antibody-producing cells (34,35), and in doing so bypass the normal tolerance checkpoints against autoimmunity provided by the germinal center.…”