ABSTRACT
Background: The immunogenicity and safety of mRNA-based vaccination in people living with HIV have yet to be clarified. We aimed to describe the impact of SARS-CoV-2 mRNA vaccination on safety, HIV-RNA control, and humoral immune responses after two doses of vaccine. Methods: From January 2021 to April 2021, vaccination with mRNA1273 (Moderna) and BNT162b2 (BioNTech/Pfizer) was offered to every individual with HIV registered at our institution who fulfilled vaccination criteria and consented to routine vaccination. HIV-1 RNA levels and anti-SARS-CoV-2 S total Ig (Elecsys®, Roche Diagnostics, Rotkreuz, Switzerland) were measured at the time of the first and second doses, 30 days later, and at 6 months after the first dose. Results: The study sample included 131 individuals (median age: 54 years [interquartile range (IQR): 47-60.5]);male: 70.2%;median baseline CD4-T cell: 602 cells/μ l [IQR: 445.0-825.5]). HIV viral load data were collected for 129 patients at the time of the first dose (M0) and 30 days later (M1);for 124 patients, 30 days after the second dose (M2);and for 42 patients, 6 months after the first dose (M6). Twenty (15.5%) of 129 patients had detectable HIV-1 RNA (>20 copies/ml;IQR: 24.0-43.5) at M0, 13/129 (10.1%) at M1 (among which 5 were newly detected), 15/124 (12.1%) at M2 (among which 4 were newly detected), and 6/42 (14.3%) at M6. HIV-RNA levels returned below the detection threshold of 20 copies/mL at the subsequent measure. All analyzed patients showed a positive anti-SARS-CoV-2 S Ig after vaccination with geometric mean titers (GMT) of 131.8 U/ml (95% CI: 130.4-133.2) 30 days after the first dose and 2003.4 U/ml (95% CI: 2002.3-2004.4) 30 days after the second dose. Six months after the first dose, 75/131 patients were analyzed, and they were all still positive for anti-SARS-CoV-2 S Ig, with GMT of 1132.2 U/ml (95% CI: 1131.0-1133.4). We found no statistical significance in anti-SARS-CoV-2 S Ig titers between patients with detectable and undetectable HIV-1 RNA. No serious adverse effects were reported. Conclusion: In a patient population on effective antiretroviral drugs, only minor or transient effects of mRNA vaccines on HIV-1 RNA levels were observed. All patients developed anti-SARS-CoV-2 S total antibodies after two-dose vaccination and antibodies were detectable in all analyzed patients 6 months after the first dose.
ABSTRACT
Background: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose:We want to determine i) the degree of homology between SARSCoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods: We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, antiapoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARSCoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
ABSTRACT
OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2;p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0;p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6;p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4;p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.
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OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.