Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.
We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of adaptation to humans.
An immunoassay (IA) that simultaneously detects both antibody to human immunodeficiency virus (HIV) and HIV p24 antigen (Architect HIV Ag/Ab Combo) was evaluated for its ability to detect HIV infection by using a panel of specimens collected from individuals recently infected with HIV type 1 (HIV-1). This IA was found to be capable of detecting the majority (89%) of infections, including 80% of those considered acute infections based on the presence of HIV RNA and the lack of detectable antibody to HIV. Substantial improvements in detection of recent infections by the Architect HIV Ag/Ab Combo relative to previous generations of IAs as well as the capacity to detect acute infections have important implications for HIV prevention strategies.
As the epidemiological epicenter of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43.02%), but 7 other subtypes (33.14%), 20 circulating recombinant forms (CRFs; 11.63%), and 20 unclassified (11.63%) sequences were also found. Of the rare and unclassified subtypes, 18 specimens were selected for next-generation sequencing (NGS) by a modified HIV-switching mechanism at the 5′ end of the RNA template (SMART) method to obtain full-genome sequences. NGS produced 14 new complete genomes, which included pure subtype C (n = 2), D (n = 1), F1 (n = 1), H (n = 3), and J (n = 1) genomes. The two subtype C genomes and one of the subtype H genomes branched basal to their respective subtype branches but had no evidence of recombination. The remaining 6 genomes were complex recombinants of 2 or more subtypes, including subtypes A1, F, G, H, J, and K and unclassified fragments, including one subtype CRF25 isolate, which branched basal to all CRF25 references. Notably, all recombinant subtype H fragments branched basal to the H clade. Spatial-geographical analysis indicated that the diverse sequences identified here did not expand globally. The full-genome and subgenomic sequences identified in our study population significantly increase the documented diversity of the strains involved in the continually evolving HIV-1 pandemic.IMPORTANCE Very little is known about the ancestral HIV-1 strains that founded the global pandemic, and very few complete genome sequences are available from patients in the Congo Basin, where HIV-1 expanded early in the global pandemic. By sequencing a subgenomic fragment of the HIV-1 envelope from study participants in the DRC, we identified rare variants for complete genome sequencing. The basal branching of some of the complete genome sequences that we recovered suggests that these strains are more closely related to ancestral HIV-1 strains than to previously reported strains and is evidence that the local diversification of HIV in the DRC continues to outpace the diversity of global strains decades after the emergence of the pandemic.
Antibodies to asialoglycoprotein receptor have diagnostic specificity for autoimmune hepatitis, but it is uncertain if they are complementary or redundant markers of the disease. Our aims were to assess their frequency and significance in type 1 autoimmune hepatitis and determine their contribution to the evaluation of these patients. Sera from 54 well-characterized patients were evaluated for antibodies to asialoglycoprotein receptor by a radioimmunofiltration assay based on rabbit-derived protein. Forty-four patients (82%) were seropositive. Seropositive patients were distinguished from seronegative counterparts by having higher serum gamma globulin (3.7 +/- 0.2 g/dl vs 2.3 +/- 0.3 g/dl, P = 0.0007) and immunoglobulin G levels (3707 +/- 179 mg/dl vs 2203 +/- 263 mg/dl, P = 0.0005) at presentation and a greater frequency of relapse after drug withdrawal (88% vs 33%, P = 0.01). Seropositivity for smooth muscle and/or antinuclear antibodies did not define treatment outcomes and antinuclear antibodies occurred less frequently than the other markers. Concurrent testing for antibodies to asialoglycoprotein receptor and smooth muscle identified all patients. We conclude that antibodies to asialoglycoprotein receptor are common in type 1 autoimmune hepatitis and they identify patients with a high frequency of relapse after corticosteroid withdrawal. Concurrent testing for these antibodies and smooth muscle antibodies has the same diagnostic sensitivity as testing for antinuclear and smooth muscle antibodies but a greater prognostic implication.
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