Increased serum levels of HSP27 as a marker for incipient chronic obstructive pulmonary disease in young smokers.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is amongst the leading causes of morbidity and mortality, no biomarkers for its early detection are known. We have recently demonstrated that COPD is accompanied by elevated serum heat shock protein (HSP) 27 levels as compared to a control population. OBJECTIVES: In an open prospective study, we investigated whether elevated HSP27 levels are associated with the early radiological signs of COPD, i.e., air trapping (AT), emphysema (E) and impaired lung function. METHODS: In total, 120 apparently healthy smokers underwent lung function testing and serum sampling. Serum levels of HSP27, phospho-HSP27, CXCR2 chemokines and proteins related to inflammation, tissue remodeling and apoptosis were evaluated by ELISA. Of these 120 subjects, 94 voluntarily underwent a high-resolution computed tomography scan. RESULTS: AT or AT and E were detected in 57.45%. Subjects with AT and E (n = 23) showed significantly higher HSP27 levels than those without any pathology [i.e., nothing abnormal detected (NAD)] (4,618 +/- 1,677 vs. 3,282 +/- 1,607 pg/ml; p = 0.0081). In a univariate logistic regression model including NAD and AT and E, the area under the curve of HSP27 in the receiver-operating-characteristic curve was 0.724, (0.594­0.854, 95% CI; p = 0.0033). Interestingly, proinflammatory IL-8 was elevated in those subjects with evidence of AT and E compared to those with AT and NAD. Lung function did not correlate with increased HSP27 levels or pathological radiological findings. CONCLUSIONS: HSP27 serum levels correlated with the early radiological signs of COPD, whereas lung function did not match with radiological findings or HSP27 serum levels. Serum HSP27 levels may serve as a potential marker to identify the early signs of COPD independent of lung function in young smokers.

SARS-CoV-2-Specific Antibody (Ab) Levels and the Kinetic of Ab Decline Determine Ab Persistence Over 1 Year.

In a SARS-CoV-2 seroprevalence study conducted with 1,655 working adults in spring of 2020, 12 of the subjects presented with positive neutralization test (NT) titers (>1:10). They were here followed up for 1 year to assess their Ab persistence. We report that 7/12 individuals (58%) had NT_50 titers ≥1:50 and S1-specific IgG ≥50 BAU/ml 1 year after mild COVID-19 infection. S1-specific IgG were retained until a year when these levels were at least >60 BAU/ml at 3 months post-infection. For both the initial fast and subsequent slow decline phase of Abs, we observed a significant correlation between NT_50 titers and S1-specific IgG and thus propose S1-IgG of 60 BAU/ml 3 months post-infection as a potential threshold to predict neutralizing Ab persistence for 1 year. NT_50 titers and S1-specific IgG also correlated with circulating S1-specific memory B-cells. SARS-CoV-2-specific Ab levels after primary mRNA vaccination in healthy controls were higher (Geometric Mean Concentration [GMC] 3158 BAU/ml [CI 2592 to 3848]) than after mild COVID-19 infection (GMC 82 BAU/ml [CI 48 to 139]), but showed a stronger fold-decline within 5-6 months (0.20-fold, to GMC 619 BAU/ml [CI 479 to 801] vs. 0.56-fold, to GMC 46 BAU/ml [CI 26 to 82]). Of particular interest, the decline of both infection- and vaccine-induced Abs correlated with body mass index. Our data contribute to describe decline and persistence of SARS-CoV-2-specific Abs after infection and vaccination, yet the relevance of the maintained Ab levels for protection against infection and/or disease depends on the so far undefined correlate of protection.

Neutralising SARS-CoV-2 RBD-specific antibodies persist for at least six months independently of symptoms in adults.

Background: In spring 2020, at the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Europe, we set up an assay system for large-scale testing of virus-specific and neutralising antibodies including their longevity. Methods: We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at three time points over six months. Results: We detect immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n = 168) of the participants. In total, 0.97% (n = 16) are positive for S1-IgG, 0.91% (n = 15) were S1-IgG- borderline and 8.28% (n = 137) exhibit only S1-IgA antibodies. Of the 168 S1-reactive sera, 8.33% (n = 14) have detectable RBD-specific antibodies and 6.55% (n = 11) NCP-specific antibodies. The latter correlates with NTs (kappa coefficient = 0.8660) but start to decline after 3 months. RBD-specific antibodies correlate most closely with the NT (kappa = 0.9448) and only these antibodies are stable for up to six months. All participants with virus-neutralising antibodies report symptoms, of which anosmia and/or dysgeusia correlate most closely with the detection of virus-neutralising antibodies. Conclusions: RBD-specific antibodies are most reliably detected post-infection, independent of the number/severity of symptoms, and correlate with neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both antibody reactivity and virus neutralisation.