A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases.

BACKGROUND: Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce. OBJECTIVES: To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination. METHODS: This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination. RESULTS: Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD. CONCLUSIONS: Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

Comparison of the immunogenicity of ChAdOx1 nCoV-19 vaccine against the wild-type and delta variants in kidney transplant recipients and healthy volunteers.

Little is known about immunogenicity after ChAdOx1 nCov-19 vaccination after transplantation. We assessed the vaccine response by antibody testing, surrogate neutralization test (sVNT) against wild-type (WT) and delta variant (DT), and T cell assay in 83 kidney transplant recipients (KTRs) and 52 healthy volunteers (HVs). For KTRs, a positive anti-RBD antibody was seen in 2.8% after one dose and 15.7% after two doses of the vaccine. After two doses, the positivity rate by sVNT was equal (4.9% each, for WT and DT) and was 13.4% by T cell response. Post two doses, KTRs had significantly lower geometric mean titer than HVs (1.93 [95% CI: 1.39-2.69] vs. 248.3 [95% CI: 203.7-302.6] BAU/ml, respectively, p < .001). Daily mycophenolate dose of ≥1000 mg significantly associated with negative seroconversion [risk ratio (RR) of 0.33, 95% CI: 0.15-0.72, p = .005]. Compared with cyclosporine, daily tacrolimus dose of ≤3 mg and >3 mg of tacrolimus significantly associated with negative seroconversion [RR = 0.38 (95% CI, 0.17-0.85, p = .018) and RR = 0.16 (95% CI, 0.37-0.73, p = .018)], respectively. The vaccine was safe and well-tolerated but the immune response after the two doses of ChAdOx1 nCov-19 vaccine in KTRs was very low.

Correlations between serum interleukin 6, serum soluble interleukin 6 receptor, and disease activity in systemic juvenile idiopathic arthritis patients treated with or without tocilizumab.

INTRODUCTION: Interleukin (IL)-6 is a proinflammatory cytokine involved in systemic juvenile idiopathic arthritis (SJIA). Since these patients are often treated with tocilizumab (TCZ), anti-IL-6 receptor (IL-6R) antibody, we investigated correlations between serum IL-6 and soluble IL-6R-levels and disease activity in SJIA patients treated with or without TCZ. MATERIAL AND METHODS: 164 serum samples were taken from 42 SJIA patients treated with or without TCZ (69 and 95 samples, respectively). Patients were assigned to three groups according to disease status: 1) systemic (patients with systemic features and/or arthritis), 2) arthritis (patients with arthritis but no systemic features), and 3) inactive (clinically inactive disease). Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27) at the time of blood collection. RESULTS: IL-6 levels were highest in SJIA patients with predominant systemic features, while serum sIL-6R levels were highest in patients with persistent arthritis. Serum IL-6 correlated with JADAS-27 in patients treated with and without TCZ (r = 0.38 and r = 0.65, respectively), whereas serum sIL-6R levels correlated with JADAS-27 in patients treated without (r = 0.30) but not with (r = -0.14) TCZ. The sIL-6R/IL-6 ratio negatively correlated with JADAS-27 in patients treated with and without TCZ (r = -0.49 and r = -0.56, respectively). CONCLUSIONS: Serum IL-6 levels correlated more strongly with disease activity parameters than did sIL-6R levels and could be useful for monitoring disease activity in SJIA patients. The sIL-6R/IL-6 ratio might be a promising disease activity marker in both SJIA patients treated with and without TCZ.

Immunogenicity of Intradermal Versus Intramuscular BNT162b2 COVID-19 Booster Vaccine in Patients with Immune-Mediated Dermatologic Diseases: A Non-Inferiority Randomized Controlled Trial.

The intradermal route has emerged as a dose-sparing alternative during the coronavirus disease 2019 (COVID-19) pandemic. Despite its efficacy in healthy populations, its immunogenicity has not been tested in immune-mediated dermatologic disease (IMDD) patients. This assessor-blinded, randomized-controlled, non-inferiority trial recruited patients with two representative IMDDs (i.e., psoriasis and autoimmune bullous diseases) to vaccinate with fractionated-dose intradermal (fID) or standard intramuscular (sIM) BNT162b2 vaccines as a fourth booster dose under block randomization stratified by age, sex, and their skin diseases. Post-vaccination SARS-CoV-2-specific IgG and interferon-γ responses measured 4 and 12 weeks post-intervention were serological surrogates used for demonstrating treatment effects. Mean differences in log-normalized outcome estimates were calculated with multivariable linear regression adjusting for their baseline values, systemic immunosuppressants used, and prior COVID-19 vaccination history. The non-inferiority margin was set for fID to retain >80% immunogenicity of sIM. With 109 participants included, 53 received fID (all entered an intention-to-treat analysis). The fID demonstrated non-inferiority to sIM in humoral (mean outcome estimates of sIM: 3.3, ΔfID-sIM [mean, 95%CI]: -0.1, -0.3 to 0.0) and cellular (mean outcome estimates of sIM: 3.2, ΔfID-sIM [mean, 95%CI]: 0.1, -0.2 to 0.3) immunogenicity outcomes. Two psoriasis patients from the fID arm (3.8%) developed injection-site Koebner's phenomenon. Fewer fID recipients experienced post-vaccination fever (fID vs. sIM: 1.9% vs. 12.5%, p = 0.027). The overall incidence of disease flare-ups was low without a statistically significant difference between groups. The intradermal BNT162b2 vaccine is a viable booster option for IMDD patients troubled by post-vaccination fever; its role in mitigating the risk of flare-ups remains unclear.

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients.

Background: By depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines' humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear. Objective: To estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients. Methods: This retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2. Findings: Forty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients. Conclusions: Nine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.

Anti-HIV serological test algorithms to reduce false-positive and inconclusive results for low HIV prevalence and resource-limited areas.

A false-positive anti-human immunodeficiency virus (HIV) test result can have devastating consequences. Sequential HIV serological testing is a strategy that could be applied in resource-limited settings to reduce false-positive results when a nucleic acid test is not affordable. We aimed to compare the results of sequential anti-HIV testing algorithms recommended by the national guidelines and our hospital algorithm in the setting of low HIV prevalence. We retrospectively reviewed individuals whose anti-HIV tested positive by Architect HIV Ag/Ab Combo with a signal/cut-off ratio of 1.00-20.00 between January 2015 and June 2016 at a university hospital in Bangkok, Thailand. A total of 111,224 samples were requested for anti-HIV tests during the study period. Sixty-six adults and nine children/adolescents met the inclusion criteria of this study. Compared to the national guidelines, our hospital HIV diagnosis algorithm could identify two individuals with false-positive anti-HIV tests and a reduction of inconclusive diagnoses from 45 to one adult cases (p <.001). It also eliminated inconclusive diagnoses in four non-infected children with HIV-negative mothers. Our hospital HIV diagnosis algorithm can reduce the number of HIV misdiagnoses of serological tests in an area with low HIV prevalence. The sequential HIV serological test algorithms should be reviewed and evaluated in each institute.

Application of QuantiFERON ELISA for Detection of Interferon-Gamma Autoantibodies in Adult-Onset Immunodeficiency Syndrome.

OBJECTIVE: Patients who develop interferon-gamma autoantibodies (IFN-ɤ autoAbs) in adult-onset immunodeficiency (AOID) syndrome are more likely to develop opportunistic and recurrent intracellular infections. The assay to detect IFN-ɤ autoAbs is essential for the diagnosis and therapeutic monitoring of AOID syndrome. Therefore, this study applied the QuantiFERON assay for the detection of IFN-ɤ autoAbs. METHODS: Serum from patients with AOID syndrome (n = 19) and serum from healthy patients (n = 20) was collected and applied using 2 neutralizing platforms of enzyme-linked immunosorbent assay (ELISA) kits (the BD ELISA and the QuantiFERON ELISA) for IFN-ɤ autoAbs detection. RESULTS: The pooled serum from patients with AOID syndrome showed >50% inhibition at 1:5000 dilution (positive), whereas the pooled serum from healthy patients showed <50% inhibition at 1:5000 dilution (negative) according to the neutralizing QuantiFERON ELISA. Each specimen showed the same result according to both the neutralizing BD ELISA and the neutralizing QuantiFERON ELISA. Moreover, the patient serum showed a variation in titer ranging from 1:5000 to >1:5,000,000 according to the neutralizing QuantiFERON ELISA. CONCLUSION: The QuantiFERON ELISA kit could be applied for the detection of IFN-ɤ autoAbs for the diagnosis and therapeutic monitoring of AOID syndrome.

External quality assessment scheme for HbA1c assays in Thailand: A 5-year experience.

Background: Thailand National External Quality Assessment Scheme (NEQAS) for HbA1c was established to evaluate the quality of HbA1c assays in Thailand in 2016. Methods: HbA1c results from participating laboratories were compared to the target value assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system. Results: The pass rates of participating laboratories during 2016-2020 were72-88%. The mean bias ranged between -0.19 and 0.20% of HbA1c. SD ranged from 0.30 to 1.08% of HbA1c. The overall coefficients of variation ranged from 4.46-15.66%. Conclusions: Performance evaluation using IFCC assigned values indicated that different assay methods had an effect on HbA1c results. Participation in external quality assessment programs for HbA1c analysis is essential for improving laboratory quality and benefiting patient management.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

Short-Term Immunogenicity Profiles and Predictors for Suboptimal Immune Responses in Patients with End-Stage Kidney Disease Immunized with Inactivated SARS-CoV-2 Vaccine.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored. METHODS: We conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls. RESULTS: After two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses. CONCLUSIONS: Patients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3).

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136−3083) BAU/mL vs. 373 (188−607) BAU/mL) and PD (1093 (617−1911) BAU/mL vs. 180 (126−320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

A Prospective Study of Cytomegalovirus-Specific Cell-Mediated Immune Monitoring and Cytomegalovirus Infection in Patients With Active Systemic Lupus Erythematosus Receiving Immunosuppressants.

BACKGROUND: The effects of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) on CMV infection in patients with autoimmune diseases receiving immunosuppressants have not been explored. METHODS: Patients with active systemic lupus erythematosus (SLE) were preemptively monitored for clinically significant CMV infection (CsCMVI; defined as plasma CMV DNA loads >3 log10 IU/mL). CMV-specific CMI was assessed using an enzyme-linked immunosorbent assay (QuantiFERON-CMV [QF]) before as well as 1 and 3 months after intense immunosuppressive therapy. RESULTS: The study included 55 patients with active SLE; patients were a mean age (SD) of 34 (13) years and had a median SLE Disease Activity Index 2000 score (SD) of 14 (8), and 93% were female. Most patients had renal involvement (67%), received methylprednisolone (93%), and were CMV-seropositive (95%). Thirteen (23.6%) patients developed CsCMVI. Among patients with active SLE who were QF-negative (QF-) and QF-positive (QF+) before receiving immunosuppressive therapy, 28.6% and 25% developed CsCMVI, respectively (P = .69). However, 1 month postimmunosuppression, more QF- than QF+ patients developed CsCMVI (44.4% vs 11.8%; P = .03; adjusted hazard ratio, 4.97; 95% CI, 1.07-23.10; P = .04). CONCLUSIONS: Patients with active SLE and low CMV-specific T-cell responses could develop CMV infection after receiving immunosuppressants. Further studies should focus on CMV-specific CMI among patients with autoimmune diseases.

The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients.

BACKGROUND: Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. METHODS: Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. RESULTS: The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. CONCLUSION: Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

Inactivated COVID-19 Vaccine Induces a Low Humoral Immune Response in a Subset of Dermatological Patients Receiving Immunosuppressants.

Inactivated Sinovac-CoronaVac vaccine (Sinovac Life Sciences, Beijing) for coronavirus disease 2019 (COVID-19) has been used in many countries. However, its immunogenicity profile in immunosuppressed dermatological patients is lacking. This prospective observational case-control study compared the humoral immune response between adult dermatological patients receiving systemic immunosuppressive therapies (n = 14) and those who did not (n = 18); excluding patients with HIV infection, cancer, non-dermatological autoimmune conditions, previous COVID-19 infection, and positive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG prior to vaccination. The subjects were advised to withhold methotrexate for 1 week after each vaccine dose while continuing other therapies unadjusted. Anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (sNAb), and seroconversion rates (calculated from the percentages of participants in the group with positive sNAb) were used to assess immunogenicity. We found that participants using azathioprine, cyclosporin, mycophenolate mofetil, or prednisolone ≥ 10 mg/day had a lower level of serum anti-SARS-CoV-2 IgG antibody and sNAb than those received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day, or biologics (i.e., secukinumab, ixekizumab, omalizumab). Patients who received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day or the biologics had a similar immunogenicity profile to those without immunosuppressive therapies. Despite the lack of statistical significance, a reduction of humoral immune response was observed among the study participants who used ≥2 immunosuppressants or pemphigus patients. Our findings suggest that a subset of patients with immune-mediated skin conditions respond poorly to the vaccine despite having low-level immunosuppression. These patients could benefit from vaccines that trigger a greater level of immunogenicity or booster doses.

SARS-CoV-2 neutralizing antibodies decline over one year and patients with severe COVID-19 pneumonia display a unique cytokine profile.

OBJECTIVES: As coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity. METHODS: This study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups. RESULTS: Peak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups. CONCLUSIONS: The study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Performance of real-time PCR and immunofluorescence assay for diagnosis of Pneumocystis pneumonia in real-world clinical practice.

BACKGROUND: PCR is more sensitive than immunofluorescence assay (IFA) for detection of Pneumocystis jirovecii. However, PCR cannot always distinguish infection from colonization. This study aimed to compare the performance of real-time PCR and IFA for diagnosis of P. jirovecii pneumonia (PJP) in a real-world clinical setting. METHODS: A retrospective cohort study was conducted at a 1,300-bed hospital between April 2017 and December 2018. Patients whose respiratory sample (bronchoalveolar lavage or sputum) were tested by both Pneumocystis PCR and IFA were included. Diagnosis of PJP was classified based on multicomponent criteria. Sensitivity, specificity, 95% confidence intervals (CI), and Cohen's kappa coefficient were calculated. RESULTS: There were 222 eligible patients. The sensitivity and specificity of PCR was 91.9% (95% CI, 84.0%-96.7%) and 89.7% (95% CI, 83.3%-94.3%), respectively. The sensitivity and specificity of IFA was 7.0% (95% CI, 2.6%-14.6%) and 99.2% (95% CI, 95.6%-100.0%), respectively. The percent agreement between PCR and IFA was 56.7% (Cohen's kappa -0.02). Among discordant PCR-positive and IFA-negative samples, 78% were collected after PJP treatment. Clinical management would have changed in 14% of patients using diagnostic information, mainly based on PCR results. CONCLUSIONS: PCR is highly sensitive compared with IFA for detection of PJP. Combining clinical, and radiological features with PCR is useful for diagnosis of PJP, particularly when respiratory specimens cannot be promptly collected before initiation of PJP treatment.

The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99-26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16-8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.