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1.
Lancet HIV ; 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1756297

ABSTRACT

BACKGROUND: People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression. METHODS: In this prospective cohort study, adults (aged ≥18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose (day 69). Immunogenicity was assessed at baseline (day 0), before second vaccine (day 28), and 6 weeks after second vaccine dose (day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody (NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres (FI-GMT). We investigated whether HIV status and CD4 count (<500 or ≥500 cells per µL) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex. FINDINGS: Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 (42%) were people with HIV and 296 (58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose (day 69), 185 (91%) of 204 participants with HIV and 265 (97%) of 274 participants with no known immunosuppression had seroconversion (p=0·0055). 143 (71%) of 202 participants with HIV were NAb positive compared with 229 (84%) of 274 participants with no known immunosuppression (p=0·0008). Median IgG titres were 48·7 AU/mL (IQR 26·6-88·2) in people with HIV compared with 75·2 AU/mL (50·3-112·0) in people with no known immunosuppression (p<0·0001); and median NAb activity was 46·2% (26·9-69·7) compared with 60·8% (39·8-79·9; p<0·0001). In people with HIV who had CD4 counts less than 500 cells per µL seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per µL. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per µL and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per µL. No serious adverse reactions were reported during the study. INTERPRETATION: Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and B3-Bolsa de Valores do Brasil.

2.
Clin Rheumatol ; 2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1750715

ABSTRACT

INTRODUCTION: There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjögren's syndrome (pSS). OBJECTIVES: To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS. METHODS: Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile. RESULTS: Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p = 1.000) and mean age (53.5 ± 11.7 vs. 53.4 ± 11.4 years, p = 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p < 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p < 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p = 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p = 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p > 0.05). CONCLUSION: Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04754698. Key Points • Sinovac-CoronaVac vaccine is safe in pSS, without a detrimental effect on systemic disease activity, and has a moderate short-term humoral response • A booster dose should be considered in these patients.

3.
Ann Rheum Dis ; 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1741594

ABSTRACT

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.Trial registration number NCT04754698.

4.
J Appl Physiol (1985) ; 132(3): 682-688, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1731339

ABSTRACT

This randomized controlled study aimed to investigate whether a single bout of exercise before the homologous booster dose of a SARS-CoV-2 inactivated vaccine could enhance immunogenicity in patients with spondyloarthritis. We selected 60 consecutive patients with spondyloarthritis (SpA). Patients assigned to the intervention group performed an exercise bout comprising three exercises. Then, they remained at rest for 1 h before vaccination. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and 1 mo after (Post) the booster using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of neutralizing antibodies (NAb) positivity, and NAb activity. At Pre, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), and 1 mo after the booster dose, seropositivity occurred in 96% versus 100% of the cases. Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% versus 93%. GMT was comparable between groups at Pre. At Post, GMT increased similarly in both groups. Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis.NEW & NOTEWORTHY We tested the role of exercise as an adjuvant to a booster of a COVID-19 vaccine. Immunocompromised patients were immunized after an acute bout of exercise or not. Patients exhibited an excellent immunogenicity in response to the booster dose. Exercise did not add to the vaccine effects on IgG or neutralizing antibodies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , Humans , Immunocompromised Host , SARS-CoV-2 , Vaccines, Inactivated
5.
Ann Rheum Dis ; 2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1709161

ABSTRACT

OBJECTIVE: To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). METHODS: This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice. RESULTS: Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024). CONCLUSION: We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317874

ABSTRACT

Background: People living with HIV (PLWH) may have a poor or delayed response to vaccines, mainly when CD4+ T cell counts are low. There are limited data concerning the safety and immunogenicity of COVID-19 vaccines in PLWH.Methods: This prospective controlled study evaluated the safety and immunogenicity of the SARS-CoV-2 inactivated vaccine CoronaVac in PLWH compared with controls with no known immunosuppression. Immunogenicity was assessed with SARS-CoV-2 IgG seroconversion (SC), neutralizing antibodies (NAb) activity, and factor increase in IgG geometric mean titers (FI-GMT). We also investigated if levels of CD4+ T cell counts (< or ≥500 cells/mm3) were associated with CoronaVac immunogenicity.Findings: 511 participants (215 PLWH and 296 controls) were eligible for the immunogenicity analysis. At vaccine completion (D69), although the percentage of participants with SC and NAb positivity was high for both PLWH and controls, it was somewhat lower in PLWH. CD4+ T cell was identified as a relevant factor for immunogenicity, with lower SC and NAb positivity in PLWH with CD4+ counts <500 cells/mm3 compared to those with ≥500 cells/mm3. In a multivariable logistic regression model for NAb positivity after a complete two-dose regimen adjusted for age and sex, compared with PLWH with a CD4+ T cell count <500/mm3, those with CD4+ counts ≥500/mm3 had 2·26 times the odds of having positivity in NAb activity (95% CI 1·18-4·32;p=0·014), whereas controls had 3·21 times the odds of this outcome. No serious adverse reactions were reported during the study.Interpretation: Immunogenicity following CoronaVac in PLWH seems robust but reduced compared with controls;PLWH with CD4+ counts <500/mm 3 are at increased risk for a blunted antibody response following vaccination.Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP);Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq);and B3 - Bolsa de Valores do Brasil.Declaration of Interest: EGK is the Principal Investigator for the CoronaVac phase 3 clinical trial at University of Sao Paulo. VIAS is the Principal Investigator for the Janssen COVID-19 vaccine phase 3 clinical trial at University of Sao Paulo. INCOMPLETE, MISSING SOME AUTHORS FROM DOIEthical Approval: The national and local ethics committees approved the study.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311602

ABSTRACT

Immunocompromised individuals show lower vaccine immunogenicity, which may be modulated by physical activity. This prospective cohort study within a phase-4 vaccination trial investigated whether physical activity is associated with enhanced immunogenicity of Coronavac (SARS-CoV-2 inactivated vaccine) in patients with autoimmune rheumatic diseases (ARD) (n=898) and non-ARD (n=197) individuals without pre-existing immunogenicity to SARS-CoV-2 after receiving a two-dose vaccine schedule. Seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity were assessed. After controlling for covariates, active patients (≥150 min/week) exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary (≥150 min/week/<8h/day) vs. inactive/sedentary (<150 min/week/>8h/day) ARD. A dose-response was observed, with greater benefits for ≥350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4];41% [95%CI: 10-80%];35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised individuals.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308818

ABSTRACT

Background: Healthcare workers (HW) are a vulnerable group to develop burnout during the COVID-19 pandemic. The aims of this study were to evaluate the perception of HW about the antibody test, and, secondarily, the prevalence of burnout and factors associated with burnout among HW who took the test. Methods: : In this cross-sectional study, we evaluated burnout among HW in a 600-bed building entirely dedicated to COVID-19 inpatients care at Hospital das Clinicas (HC), located in São Paulo, Brazil. The HW answered an online questionnaire that included questions on burnout, a single-item scale based on the Maslach Burnout Inventory;demographic data, professional category, type of Protective Personal Equipment (PPE) used, distancing from social support;and emotional reactions to their serology result. Bivariate and multivariate analyses were done to evaluate the risk of burnout. Outcomes: Among 4,417 HW tested, 528 (12.0%) were positive for SARS-CoV-2 and 1,945 answered the questionnaire. Burnout was reported by 308 (15.8%);anxiety, tenseness, and depression associated with COVID-19 were reported by 344 (17.7%);292 (15.1%);and 181(9.3%) of the participants, respectively. The risk factors for burnout were: being a physician [adjOR:1.604;(95%CI 1.604-1.080;p=0.019)];a physiotherapist [adjOR:2.047;(95%CI:1.285–3.261;p=0.003)];perceiving a decrease in public safety[adjOR:1.983;(95%CI:1.229–3.199;p=0.005)];anxiety [adjOR:2.721;(95%CI:1.812–4.085;p=<0.001)], and depression associated with COVID-19[adjOR:2.071;(95%CI:1.308–3.279;p=0.002)];and having negative feeling towards had a previously negative SARS-CoV-2 serology[adjOR:1,989;(95%CI:1.484-2.664;p<0.001)]. Interpretation: Routine serological testing was one of the strategies used in our hospital to promote the well-being of HW. We observed that those who had negative feeling regarding testing negative to COVID-19 in previous serologies were at higher risk of burnout, suggesting that the risk of contracting the disease is a major stressor for HW.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307113

ABSTRACT

CoronaVac(SARS-CoV-2 inactivated vaccine) has been largely used as the main immunogen for COVID-19 in several countries. However, its immunogenicity in immunocompromised individuals has not been established. This was a prospective controlled study of 910 adult ARD patients and 182 age- and sex-matched control group(CG) who received two doses of CoronaVac in a 28-days interrval. Anti-SARS-Cov-2 IgG and neutralizing antibodies were assessed at each vaccine shot and 6 weeks after the 2nd dose. Vaccine adverse events(AE) were similar in both groups. We observed significant lower anti-SARS-Cov-2 IgG seroconversion(70.4% vs. 95.5%,p < 0.001) and titers[12.1(95%CI 11.0-13.2) vs. 29.7(95%CI 26.3–33.5),p < 0.001], frequency of neutralizing antibodies(56.3% vs. 79.3%),p < 0.001) and median (interquartile range) neutralization activity [58.7(43.1–77.2) vs. 64.5(48.4–81.4),p = 0.013] in ARD patients compared to CG. A significant decline in the number of COVID-19 cases (p < 0.0001) were observed 10 days after the second dose, with a predominant P1 variant. Safety analysis revealed no moderate/severe AEs. In conclusion, CoronaVac has an excellent safety profile and reasonable rates of quantitative serology(70.4%)/neutralization(56.3%) in ARD patients. The impact of this reduced immunogenicity in vaccine effectiveness warrants further evaluation.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305026

ABSTRACT

Background: Limited information is available on response to Covid-19 vaccines in autoimmune rheumatic disease patients(ARD) previously exposed to the SARS-CoV-2. We compared the dynamics of vaccine induced antibody production after immunization with CoronaVac in SARS-CoV-2 - seropositive ARD patients(ARD+) with two age/sex balanced groups: SARS-CoV-2 naïve ARD patients(NAÏVE-ARD) and SARS-CoV-2-seropositive control group(CTRL+).Methods: Participants of this phase 4 prospective controlled study were vaccinated with two doses of CoronaVac(28-days interval). Primary objective was immunogenicity dynamics evaluated by median neutralizing activity(NAb-activity)/anti-SARS-Cov-2 ln(IgG) titers[ln(IgG)] from D0-D28 and from D28-D69. Secondary objectives included safety and other immunogenicity parameters.Findings: Disease and therapy were similar in ARD+ and NAÏVE-ARD groups(p>0·05). A comparable dynamics was observed for ARD+ and CTRL+ with a plateau increase occurring from D0-D28[ARD+, NAb-activity:59·1% to 81·8%, mean difference -12·1%,p=0·002 and anti-S1/S2-GMT:52·3 to 128·9, ln(IgG) mean difference -0·9,p<0·001] and [CTRL+, NAb-activity:57·5 to 91·9%, mean difference -25·2%,p<0·001 and anti-S1/S2-GMT: 53·3 to 202·0, ln(IgG) mean difference -1·33,p<0·001]. Insignificant increments occurred from D28-D69 for ARD+ and CTRL+ regarding NAb-activity(p>0·999) and anti-S1/S2-GMT(p<0·999). In contrast, a distinct pattern was observed for NAÏVE-ARD with negligible increase from D0-D28 [NAÏVE-ARD: NAb-activity:15 vs. 15%, mean difference -8·3%,p<0·001 and anti-S1/S2-GMT:2·3 vs. 5·7, ln(IgG) mean difference -0·93,p<0·001] and a moderate increase from D28-D69[NAÏVE-ARD: NAb-activity:15·0 vs. 39·4%, mean difference -19·2%,p<0·001 and anti-S1/S2-GMT:5·7 vs. 29·6, ln(IgG) mean difference -1·65,p<0·001]. Supporting these findings, significant differences in NAb activity/ln(IgG) anti-S1/S2-GMT were observed between ARD+ vs. NAÏVE-ARD at D0:43·8%/3·14,p<0·001, D28:47·5%/3·12,p<0·001 and D69:29%/1·53,p<0·001, whereas no difference occurred between ARD+ vs. CTRL+ at D0:-0·5%/-0·02,p>0·999 and D69:-12·3%,p=0·167/0·32%,p=0·258 with minor difference at D28:-13·6%, p=0·067/-0·45,p=0·006.Interpretation: ARD+ patients mount a robust plateau response after a single dose of inactivated SARS-CoV-2 vaccine, independent of pre-existing ARD/therapy, whereas NAÏVE-ARD patients require the second dose to ensure a moderate antibody production. Our findings raise the possibility of a single dose regimen in ARD patients previously exposed to SARS-CoV-2.[clinicaltrials.gov#NCT04754698]Funding: FAPESP/CNPq/B3-Bolsa de Valores-Brasil.Declaration of Interest: The authors declare no competing interests.Ethical Approval: The protocol was approved by the National and Institutional Ethical Committee (CAAE: 42566621.0.0000.0068)

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321525

ABSTRACT

Background: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). The recent reports of thrombosis associated with the adenovirus-based vaccines raises concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger a dysregulated immune response with possible clotting complications. Therefore, the objectives of this study were to assess immunogenicity, aPL production and safety of Sinovac-Coronavac in PAPS patients. Methods: This prospective controlled phase 4 study of SARS-CoV-2-naïve PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69. Safety and aPL production were also assessed. Results: Forty-four PAPS patients and 132 CG had comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092) and GMT [50.2(95%CI 34.5-73.2) vs. 61.7 (95%CI 52.8-72.3), p=0.249] as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity [64.3% (49.0-77.0) vs. 60.9% (45.6-81.3), p=0.689]. Of note, for D28, the antibody response was very low and also similar in both groups SC (25.8% vs. 30.6% p=0.609). Antiphospholipid levels remained stable throughout the study at D0 vs D28 vs D69 (IgG aCL, p=0.058;IgM aCL, p=0.091;IgG aβ2GPI, p=0.513 and IgM aβ2GPI, p=0.468). Thrombotic event up to 6 months or other moderate/severe side effects were not observed. Conclusions: We provide novel evidence that Sinovac-CoronaVac vaccine has a high immunogenicity and excellent safety profile in PAPS. We further demonstrated that this vaccine did not trigger thrombosis or induced changes in aPL-related antibodies production. Our findings strongly support the recommendation of SARS-CoV-2 vaccination for PAPS patients. Trial registration : ClinicalTrials.gov - Identifier: NCT04754698 first registered on February 8 th , 2021.

12.
Ann Rheum Dis ; 81(5): 710-719, 2022 May.
Article in English | MEDLINE | ID: covidwho-1685510

ABSTRACT

OBJECTIVES: To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included. RESULTS: Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies. CONCLUSIONS: Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population. TRIAL REGISTRATION DETAILS: NCT04754698.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Abatacept/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines , Drug Therapy, Combination , Humans , Immunoglobulin G/therapeutic use , Methotrexate/therapeutic use , Middle Aged , Prospective Studies , SARS-CoV-2 , Treatment Outcome , Vaccines, Inactivated
13.
Lancet Rheumatol ; 4(2): e113-e124, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1649499

ABSTRACT

Background: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. Methods: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. Findings: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. Interpretation: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. Translation: For the Portuguese translation of the abstract see Supplementary Materials section.

14.
Brain Behav Immun ; 101: 49-56, 2022 03.
Article in English | MEDLINE | ID: covidwho-1623304

ABSTRACT

OBJECTIVES: To investigate whether physical activity is associated with enhanced immunogenicity of a SARS-CoV-2 inactivated vaccine (Coronavac) in patients with autoimmune rheumatic diseases (ARD) (n = 898) and in non-ARD (n = 197) individuals without pre-existing immunogenicity to SARS-CoV-2. METHODS: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial. Immunogenicity was assessed after vaccination by measuring seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity. Physical activity (active being defined as ≥ 150 min/week) and sedentary behavior (>8h/day) were assessed by questionnaire. RESULTS: Physically active ARD patients (n = 494) were younger and less frequently used prednisone/biologics than inactive patients (n = 404). After controlling for covariates, active patients exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary vs. inactive/sedentary ARD patients. A dose-response was observed, with greater benefits for the group of patients performing ≥ 350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively) vs. the least active group (≤30 min/week). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. CONCLUSIONS: A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised patients. TRIAL REGISTRATION: Clinicaltrials.gov #NCT04754698.


Subject(s)
COVID-19 , Rheumatic Diseases , COVID-19 Vaccines , Exercise , Humans , Prospective Studies , SARS-CoV-2 , Vaccines, Inactivated
15.
Am J Infect Control ; 2021 Dec 25.
Article in English | MEDLINE | ID: covidwho-1588519

ABSTRACT

This study assessed, using a self-reported questionnaire, the adherence to PPE (mask, gowns, and gloves) at the workplace, as well as to non-pharmacological preventive measures (NPPM) (physical distance defined as hardly ever and/or never approaches other people within 1.5 meters, social isolation as leaving home less than once a week, hand hygiene was defined as performing hand hygiene ≥ 6 times per period, and adherence to the use of a mask outside of the workplace was defined as on all outings and hardly ever and/or never removes the mask) outside of the workplace among 1,296 health care workers (HCWs), including if NPPM adherence was associated with COVID-19 in HCWs. High adherence to PPE was independently associated with younger age, professional category, work in an area of direct patient assistance; use of public transportation, or adherence to NPPM outside of the workplace.

16.
Rheumatology (Oxford) ; 2021 Dec 11.
Article in English | MEDLINE | ID: covidwho-1566059

ABSTRACT

OBJECTIVE: To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome-Coronavirus-2(SARS-CoV-2) vaccination in patients with systemic sclerosis (SSc). METHODS: This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the 2nd dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants. RESULTS: Patients and controls had comparable median ages [48(38.5-57) vs 48(38-57) years, p= 0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly mycophenolate mofetil (MMF) (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, p< 0.001) and NAb positivity (53.8% vs 76.9%; p= 0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both SC (p= 0.958) and NAb positivity (p= 0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC : 31.3% vs 90%, p< 0.001) and NAb : 18.8% vs 85%, p< 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95%CI 0.009-0.034), p= 0.002] and NAb positivity [OR = 0.047(95%CI 0.007-0.036), p= 0.002]. No moderate/severe side-effects were observed. CONCLUSION: CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294296

ABSTRACT

We provide novel data on anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine(D210) in 828 autoimmune rheumatic diseases(ARD) patients compared with 223 age/sex-balanced control group(CG). From D69 to D210, anti-S1/S2IgG positivity and GMT reduced 23.8% and 38% in ARD(p<0.001/p<0.001) and 20% and 51% in CG(p<0.001/p<0.001). From D69 to D210 NAb positivity and activity declined 41% and 54% in ARD(p<0.001/p<0.001) and 39.7% and 47% in CG(p<0.001/p<0.001). Multivariate logistic regression analysis showed that male(OR=0.56;95%CI0.40-0.79;p<0.001), prednisone(OR=0.56;95%CI0.41-0.76;p<0.001), anti-TNF(OR=0.66;95%CI0.45-0.96;p=0.031), abatacept(OR=0.29;95%CI0.15-0.56;p<0.001) and rituximab(OR=0.32;95%CI0.11-0.90;p=0.031) use were associated with a substantial reduction on IgG response at D210 in ARD patients. A decrease of COVID-19 cases(from 27.5 to 8.1/100 person-years;p<0.001) occurred during the study despite the Delta variant spread. In conclusion, after 6-months of Sinovac-CoronaVac 2nd dose, immunogenicity of ARD patients was markedly reduced, particularly in males and those under prednisone/biological therapies, without a concomitant rise in COVID-19 cases(NCT04754698).

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292836

ABSTRACT

Objectives: To evaluate the effect on immunogenicity and safety of 2-week methotrexate(MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in rheumatoid arthritis(RA) patients. Methods: This was a single-center, prospective, randomized, investigator-blinded, intervention study (# NCT04754698 , CoronavRheum), including adult RA patients(stable CDAI<10, prednisone<7.5mg/day), randomized(1:1) to withdraw MTX(MTX-hold) for 2 weeks after each vaccine dose or maintain MTX(MTX-maintain), evaluated at D0, D28 and D69. Co-primary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion(SC) and neutralizing antibody(NAb) positivity at D69. Secondary outcomes were GMT and changes in disease activity scores. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those unable to hold MTX twice(CDAI>10 at D28). Results: Randomization included 138 patients with 9 exclusions(5 COVID-19, 4 protocol violations). Safety evaluation included 60(MTX-hold) and 69(MTX-maintain) patients. Further exclusions consisted of 27 patients[13(21.7%) vs. 14(20.3%),p=0.848] with positive baseline IgG/NAb and 10 patients(21.3%) in MTX-hold with CDAI>10 at D28. At D69, a higher increase in SC[29(78.4%) vs 30(54.5%),p=0.019] was observed in MTX-hold(n=37) in comparison to MTX-maintain(n=55), with parallel augmentation in GMT[34.2(25.2-46.4) vs 16.8(11.9-23.6),p=0.006]. No differences were observed for NAb positivity[23(62.2%) vs 27(49.1%),p=0.217]. Longitudinal variations in disease activity scores were alike in both groups(CDAI,p=0.144;DAS28-CRP,p=0.718). Conclusion: We provided novel data that 2-week MTX withdrawal after each vaccine dose improves anti-SARS-CoV-2 immunogenicity. The comparable longitudinal variations of disease activity in both groups suggest that discontinuation is a feasible and efficient strategy in well-controlled RA patients, and may be even safer for vaccines with longer interval between doses or single dose schedules.

19.
Arthritis Care Res (Hoboken) ; 74(4): 562-571, 2022 04.
Article in English | MEDLINE | ID: covidwho-1527408

ABSTRACT

OBJECTIVE: To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS-CoV-2 vaccine (Sinovac-CoronaVac) and the influence of different medications in SLE. Safety was also assessed. METHODS: We conducted a prospective controlled study of 232 SARS-CoV-2-naive SLE patients and 58 SARS-CoV-2-naive controls who were vaccinated with 2 doses of Sinovac-CoronaVac with a 28-day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed. RESULTS: Patients and controls were well balanced for age (P = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P < 0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108-0.427], P < 0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107-0.378], P < 0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC (P = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC (P < 0.001) and NAb positivity (P < 0.001). Safety analysis revealed no moderate/severe adverse events. CONCLUSION: Sinovac-CoronaVac has a moderate immunogenicity in SARS-CoV-2-naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine-booster dose (ClinicalTrials.gov identifier: NCT04754698).


Subject(s)
COVID-19 Vaccines , Lupus Erythematosus, Systemic , Antibodies, Viral/therapeutic use , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Lupus Erythematosus, Systemic/immunology , Prospective Studies , SARS-CoV-2
20.
Nat Med ; 27(10): 1744-1751, 2021 10.
Article in English | MEDLINE | ID: covidwho-1526090

ABSTRACT

CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.


Subject(s)
Antibodies, Viral/biosynthesis , Autoimmune Diseases/complications , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Rheumatic Diseases/complications , Adult , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/complications , COVID-19/virology , Female , Humans , Male , Middle Aged
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