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1.
Immunol Cell Biol ; 2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2136876

ABSTRACT

The long-term health consequences of SARS-CoV-2 infection are still being understood. The molecular and phenotypic properties of SARS-CoV-2 antigen-specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen-specific memory B cell (MBC) population has not yet been analysed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe COVID-19. Here, we performed single cell molecular analysis of the SARS-CoV-2 receptor-binding domain (RBD) specific MBC population in three subjects after severe COVID-19 and four subjects after mild/moderate COVID-19. We analysed the transcriptomic and B cell receptor repertoire profiles at ~two months and ~four months post symptom onset. Transcriptomic analysis revealed a higher level of TNF-α signaling via NF-κB in the severe group, involving CD80, FOS, CD83, TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80hi TNFAIP3hi and CD11chi CD95hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long-term RBD-specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID-19 severity.

2.
Intern Med J ; 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2115639

ABSTRACT

BACKGROUND: Diabetes has been recognised as a major risk factor for COVID-19 mortality and hospital complications in earlier studies. AIMS: To examine the characteristics of hospitalised COVID-19 patients with diabetes and the impact of diabetes and hyperglycaemia on hospital outcomes. METHODS: This was a retrospective cohort study. Admission glucose levels, HbA1c, diabetes status and hospital outcomes were determined for subjects admitted from June to November 2021 by matching a pathology data set, a clinical data set and the hospital administrative database. The outcomes of interest were death, intensive care unit (ICU) admission and length of stay (LOS). RESULTS: There were 1515 individuals admitted with COVID-19 with 49 deaths (3.2%) and 205 (13.5%) ICU admissions. The median length of hospital stay was 3.7 days. Three hundred and ten patients (20%) had diabetes, with 46 (15%) newly diagnosed. Patients with diabetes had a higher mortality than patients who did not have diabetes (8% vs 2%, P < 0.001), were more likely to be admitted to ICU (20% vs 12%, P = 0.001) and have longer median LOS stay (6.6 (interquartile range (IQR) 2.9-12.5) vs 2.9 (IQR 0.5-7.1) days, P < 0.001). In multivariate models, neither diabetes nor admission glucose predicted death. Admission glucose level but not diabetes was an independent predictor of ICU admission and LOS. CONCLUSIONS: There is a high prevalence of diabetes among patients hospitalised with COVID-19, with worse outcomes. In contrast to previous studies, the association of diabetes with mortality was not significant when adjusted for other variables. This is possibly related to the benefits of vaccination and current medical and ICU interventions.

3.
J Immunol ; 209(8): 1499-1512, 2022 Oct 15.
Article in English | MEDLINE | ID: covidwho-2055634

ABSTRACT

Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and role remain to be fully elucidated. In this study of 62 acute and convalescent patients, we found that patients with acute coronavirus disease 2019 can mount a phagocytic response to autologous plasma-opsonized Spike protein-coated microbeads as early as 10 d after symptom onset, while heat inactivation of this plasma caused 77-95% abrogation of the phagocytic response and preblocking of Fc receptors showed variable 18-60% inhibition. In convalescent patients, phagocytic response significantly correlated with anti-Spike IgG titers and older patients, while patients with severe disease had significantly higher phagocytosis and neutralization functions compared with patients with asymptomatic, mild, or moderate disease. A longitudinal subset of the convalescent patients over 12 mo showed an increase in plasma Ab affinity toward Spike Ag and preservation of phagocytic and neutralization functions, despite a decline in the anti-Spike IgG titers by >90%. Our data suggest that early phagocytosis is primarily driven by heat-liable components of the plasma, such as activated complements, while anti-Spike IgG titers account for the majority of observed phagocytosis at convalescence. Longitudinally, a significant increase in the affinity of the anti-Spike Abs was observed that correlated with the maintenance of both the phagocytic and neutralization functions, suggesting an improvement in the quality of the Abs.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Antiviral Agents , Humans , Immunoglobulin G , Receptors, Fc , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Cell Rep ; 38(6): 110345, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1654153

ABSTRACT

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%-76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection.


Subject(s)
Broadly Neutralizing Antibodies/metabolism , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Australia , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , COVID-19/immunology , Cohort Studies , Female , Humans , Immunity/immunology , Immunity, Humoral/immunology , Male , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology
7.
Virus Evol ; 6(1): veaa027, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-1388022

ABSTRACT

The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea, and Iran. Phylogenetic analyses of whole-genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases.

8.
Cell Rep Med ; 2(4): 100228, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195472

ABSTRACT

Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort's neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/pathology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Asymptomatic Diseases , COVID-19/immunology , COVID-19/virology , Female , Humans , Limit of Detection , Male , Middle Aged , Neutralization Tests , Protein Domains/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Time Factors , Young Adult
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