Divergent humoral responses in mild to moderate SARS-CoV-2 infection over time - indication of persistence of the virus?
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ABSTRACT:
SUBMITTER: Burgi JJ
PROVIDER: S-EPMC8570801 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
| S-EPMC7896046 | biostudies-literature
Project description:BackgroundThe symptoms of coronavirus disease 2019 (COVID-19) appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and to assess how symptom course predicts other symptom changes as well as clinical deterioration.MethodsOne hundred sixty-two participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because 9 participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles.ResultsTrajectories varied greatly between individuals, with many having persistently severe symptoms or developing new symptoms several days after being diagnosed. A typical trajectory was for a symptom to improve at a decremental rate, with most symptoms still persisting to some degree at the end of the reporting period. The pattern of symptoms over time suggested a fluctuating course for many patients. Participants who showed clinical deterioration were more likely to present with higher reports of severity of cough and diarrhea.ConclusionsThe course of symptoms during the initial weeks of COVID-19 is highly heterogeneous and is neither predictable nor easily characterized using typical survey methods. This has implications for clinical care and early-treatment clinical trials. Additional research is needed to determine whether the decelerating improvement pattern seen in our data is related to the phenomenon of patients reporting long-term symptoms and whether higher symptoms of diarrhea in early illness presages deterioration.
| S-EPMC7989225 | biostudies-literature
Project description:Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.
| S-EPMC8888837 | biostudies-literature
Project description:Background In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria triggered the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a previous study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April, representing an exceptionally high level of local seropositivity in Europe. We performed a follow-up study in Ischgl, which is the first to show persistence of immunity and protection against SARS-CoV-2 and some of its variants at a community level. Methods Of the 1259 adults that participated in the baseline study, 801 have been included in the follow-up in November 2020. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 and its variants in Ischgl was compared to the incidence in similar municipalities in Tyrol until April 2021. Findings For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9-54.9) to 45.4% (95% CI 42.0-49.0). Median antibody concentrations dropped considerably (5.345, 95% CI 4.833 - 6.123 to 2.298, 95% CI 2.141 - 2.527) but antibody avidity increased (17.02, 95% CI 16.49 - 17.94 to 42.46, 95% CI 41.06 - 46.26). Only one person had lost detectable antibodies and T cell responses. In parallel to this persistent immunity, we observed that Ischgl was relatively spared, compared to similar municipalities, from the prominent second COVID-19 wave that hit Austria in November 2020. In addition, we used sequencing data to show that the local immunity acquired from wild-type infections also helped to curb infections from variants of SARS-CoV-2 which spread in Austria since January 2021. Interpretation The relatively high level of seroprevalence (40-45%) in Ischgl persisted and might have been associated with the observed protection of Ischgl residents against virus infection during the second COVID-19 wave as well as against variant spread in 2021. Funding Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.
| S-EPMC8358264 | biostudies-literature
Project description:BackgroundUnderstanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches.MethodsWe evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test.FindingsIncreasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers.InterpretationHospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics.FundingAustin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.
| S-EPMC10723498 | biostudies-literature
Project description:ObjectiveTo determine the long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination.MethodsUsing longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL-1) and neutralising antibody titres against ten SARS-CoV-2 variants over 7 months following BNT162b2 in SARS-CoV-2-recovered (n = 118) and SARS-CoV-2-naïve (n = 289) healthcare workers with confirmed prior SARS-CoV-2 infection. A smaller group with (n = 47) and without (n = 60) confirmed prior SARS-CoV-2 infection receiving ChAdOx1 nCoV-19 was followed for 3 months. SARS-CoV-2-specific memory T-cell responses were investigated in a subset of SARS-CoV-2-naïve and SARS-CoV-2-recovered vaccinees.ResultsVaccination with both vaccine platforms resulted in substantially enhanced T-cell responses, anti-spike IgG responses and neutralising antibodies effective against ten SARS-CoV-2 variants in SARS-CoV-2-recovered participants as compared to SARS-CoV-2-naïve participants. The enhanced immune responses sustained over 7 months following vaccination.ConclusionThese findings imply that prior SARS-CoV-2 infection should be taken into consideration when planning booster doses and design of current and future COVID-19 vaccine programmes.
| S-EPMC9015077 | biostudies-literature
Project description:Plants respond to salinity by altering their physiological parameters in order to maintain their water balance. The reduction in root hydraulic conductivity is one of the first responses of plants to the presence of salt in order to minimize water stress. Although its regulation has been commonly attributed to aquaporins activity, osmotic adjustment and the toxic effect of Na+ and Cl- have also a main role in the whole process. We studied the effects of 30 mM NaCl on Phaseolus vulgaris plants after 9 days and found different responses in root hydraulic conductivity over-time. An initial and final reduction of root hydraulic conductivity, stomatal conductance, and leaf water potential in response to NaCl was attributed to an initial osmotic shock after 1 day of treatment, and to the initial symptoms of salt accumulation within the plant tissues after 9 days of treatment. After 6 days of NaCl treatment, the increase in root hydraulic conductivity to the levels of control plants was accompanied by an increase in root fructose content, and with the intracellular localization of root plasma membrane aquaporins (PIP) to cortex cells close to the epidermis and to cells surrounding xylem vessels. Thus, the different responses of bean plants to mild salt stress over time may be connected with root fructose accumulation, and intracellular localization of PIP aquaporins.
| S-EPMC3942473 | biostudies-literature
Project description:Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence. Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays (CLIA). All patients were positive for the anti-SARS-CoV-2 IgM/IgG at the onset of COVID-19 symptoms, and the IgG antibody persisted in all the patients during the convalescence. However, only approximately 25% of patients can detect the IgM antibodies, IgM against N protein (N-IgM) and receptor binding domain of S protein (RBD-IgM) at the 27th week. The titers of IgM, N-IgM and RBD-IgM reduced to 16.7%, 17.6% and 15.2% of their peak values respectively. In contrast, the titers of IgG, N-IgG and RBD-IgG peaked at 4-5th week and reduced to 85.9%, 62.6% and 87.2% of their peak values respectively at the end of observation. Dynamic behavior of antibodies and their correlation in age, gender and severity groups were investigated. In general, the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients. Only a few patients with antibody reducing to an undetectable level which needs further attention. The humoral immune response against SARS-CoV-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.
| S-EPMC7931792 | biostudies-literature
Project description:We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95% of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.
| S-EPMC8401673 | biostudies-literature
Project description:BackgroundThe identification of key genes and regulatory networks in the transcriptomic responses of blood cells to antigen stimulation could facilitate the understanding of host defence and disease resistance. Moreover, genetic relationships between immunocompetence and the expression of other phenotypes, such as those of metabolic interest, are debated but incompletely understood in farm animals. Both positive and negative associations between immune responsiveness and performance traits such as weight gain or lean growth have been reported. We designed an in vivo microarray study of transcriptional changes in porcine peripheral blood mononuclear cells (PBMCs) during the immune response to tetanus toxoid (TT) as a model antigen for combined cellular (Th1) and humoral (Th2) responses. The aim of the study was to investigate the responsiveness of PBMCs against the background of divergent lean growth (LG) performance and anti-TT antibody (AB) titers and to compare lean growth and humoral immune performance phenotypes.ResultsIn general, high LG phenotypes had increased cellular immune response transcripts, while low AB phenotypes had increased transcripts for canonical pathways that represented processes of intracellular and second messenger signaling and immune responses. Comparison of lean growth phenotypes in the context of high AB titers revealed higher cellular immune response transcripts in high LG phenotypes. Similar comparisons in the context of low AB titers failed to identify any corresponding pathways. When high and low AB titer phenotypes were differentially compared, low AB phenotypes had higher cellular immune response transcripts on a low LG background and higher cell signaling, growth, and proliferation transcripts on a high LG background.ConclusionsDivergent phenotypes of both lean growth performance and humoral immune response are affected by significant and functional transcript abundance changes throughout the immune response. The selected high-performance phenotypes demonstrated both high AB titers and increased transcript abundance of cellular immune response genes, which were possibly offset by lower expression of other cellular functions. Further, indications of compensatory effects were observed between cellular and humoral immune responses that became visible only in low-performance phenotypes.
| S-EPMC3805897 | biostudies-literature