The safety and immunogenicity of a two-dose schedule of CoronaVac, and the immune persistence of vaccination for six months, in people living with HIV: A multicenter prospective cohort study.

Background: People living with HIV (PLWH) are more vulnerable to SARS-CoV-2. However, evidence on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in this population is insufficient. The objective of this study is to assess the immunogenicity and safety of the two-dose schedule of Sinovac CoronaVac for 6 months postvaccination in PLWH. Methods: We conducted a multicenter prospective cohort study among PLWH and HIV-negative adults in China. Participants who received two doses of CoronaVac prior to the recruitment were allocated into two groups and followed up for 6 months. The neutralizing antibodies (nAbs), immunoglobulin G against the receptor-binding domain of the spike protein (S-IgG), and gamma-interferon (IFN-γ) were measured to assess the associations among CoronaVac immunogenicity and related factors. Adverse reactions were collected to evaluate the safety profile of vaccination. Results: A total of 203 PLWH and 100 HIV-negative individuals were enrolled. A small portion of participants reported mild or moderate adverse reactions without serious adverse events. Median nAbs level in PLWH (31.96 IU/mL, IQR: 12.34-76.40) was lower than that in the control group (46.52 IU/mL, IQR: 29.08-77.30) at the 2-4 weeks postvaccination (P=0.002), and the same trend was presented for median S-IgG titer (37.09 vs. 60.02 IU/ml) (both P <0.05). The nAbs seroconversion rate in the PLWH group was also lower than in the control group (75.86% vs. 89.00%). After then, the immune responses reduced over time in term of only 23.04% of PLWH and 36.00% of HIV-negative individuals had a positive seroconversion for nAbs at 6-month. The multivariable generalized estimating equation analysis showed that PLWH with CD4+T count≥350 cells/µL presented higher immune response than PLWH with CD4+T count <350 cells/µL in terms of antibody seroconversion and titers. The immunogenicity did not differ in participants with low or high HIV viral load. The S-antigen specific IFN-γ immunity was generally stable and had a slow attenuation in both two groups for 6 months postvaccination. Conclusion: The Sinovac CoronaVac was generally safe and immunogenic in PLWH, but the immunity response was inferior and the antibodies vanished faster compared to HIV-negative individuals. This study suggested a shorter than 6-month interval of prime-boost vaccination for PLWH to ensure a better protection.

Dynamics of Anti-S IgG Antibodies Titers after the Second Dose of COVID-19 Vaccines in the Manual and Craft Worker Population of Qatar.

There is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibody titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. A total of 300 male participants who received any of the following vaccines BNT162b2/Comirnaty, mRNA-1273, ChAdOx1-S/Covishield, COVID-19 Vaccine Janssen/Johnson, or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan-Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibody titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. Participants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13,720.9 AU/mL (IQR 6426.5 to 30,185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/mL; IQR, 3757.9 to 16,577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. This evidence on anti-S IgG antibody titers should be considered for informing decisions on the durability of the neutralizing activity and thus protection against infection after the full course of primary vaccination in individuals receiving different type (mRNA verus non-mRNA) vaccines and those with natural infection.

Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution.

BACKGROUND: We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group). METHODS: This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1-negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined. RESULTS: At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4-654.9) and 171.9 (61.8-425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145-824) and 555.8 (166.4-1751) BAU/mL in the HIV>500 group and 274.7 (193.7-680.4) and 281.6 (181-831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01). CONCLUSIONS: One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.

Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers.

INTRODUCTION: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). METHODS: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. RESULTS: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70-0.85) for BI in the previous six months to 0.83 (95% CI 0.67-0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). CONCLUSIONS: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects.

Assessment of humoral immune response to two mRNA SARS-CoV-2 vaccines (Moderna and Pfizer) in healthcare workers fully vaccinated with and without a history of previous infection.

AIMS: Presence of anti-S1 region of SARS-CoV-2 spike protein was analysed, at two and eight months, in 477 immunocompetent healthcare workers in Zaragoza, Spain, vaccinated with mRNA-1273 (Moderna) or BNT162b2 (Pfizer). METHODS AND RESULTS: Antibody analysis was performed with Alinity i System (Abbott). At 2 months, 100% of vaccinated had anti-S1 IgG (mean = 13,285 AU ml-1 ). This value was significantly higher with Moderna (18,192 AU ml-1 ) than with Pfizer (10,441 AU ml-1 ). The mean value of anti-S1 IgG after vaccination was significantly higher in patients with than without previous infection (18,539 vs. 7919 AU ml-1 ); in both groups was significantly higher with Moderna than with Pfizer (21,881 vs. 15,733 AU ml-1 and 11,949 vs. 6387 AU ml-1 ), respectively. At 8 months, 100% of patients were IgG positive, with higher levels with Moderna than with Pfizer. Nevertheless, in ensemble of cases, a mean decrease of antibody levels of 11,025 AU ml-1 was observed. CONCLUSION: At 2 and 8 months after vaccination, IgG response persists with both vaccines but with important decrease which suggests the need for revaccination. SIGNIFICANCE AND IMPACT OF STUDY: The study contributes to know the immune status after vaccination with two of more used anti-SARS-CoV-2 vaccines. This knowledge is important for establishing the best vaccination strategy.

Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on residents of long-term care facilities (LTCFs) has been dramatic on global scale as older age and comorbidities pose an increased risk of severe disease and death. METHODS: Aim of this study was to evaluate SARS-CoV-2 Spike-specific IgG (S-IgG) antibody titers in 478 residents and 649 health care workers of a large Italian long-term care facility two months after complete vaccination with BNT162b2. Associations among resident-related factors and predictors of humoral response were investigated. RESULTS: By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of residents had high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Residents with documented previous COVID-19 and those with SARS-CoV-2 nucleocapsid-specific IgG (N-IgG) positive serology showed higher level of serological response, while significant associations were observed for cancer with suboptimal response (p = 0.005) and the administration of corticosteroid for suboptimal response (p = 0.028) and a null one (p = 0.039). According to multivariate logistic regression, predictors of an increased risk of null response were advanced age (Odd ratio, OR: 2.630; Confidence interval, CI: 1.13-6.14; p = 0.025), corticosteroid therapy (OR: 4.964; CI: 1.06-23.52; p = 0.042) and diabetes mellitus (OR:3.415; CI:1.08-10.8; p = 0.037). In contrast, previous diagnosis of COVID-19 was strongly associated with a reduced risk of null response to vaccination (OR:0.126; CI:0.02-0.23; p < 0.001). CONCLUSIONS: SARS-CoV-2 specific antibodies in elderly individuals should be consider when deciding the need of a third dose of vaccine for prevention of reinfections in LTCFs despite the maintenance of barrier measures.

Seroprevalence, Waning and Correlates of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Large-Scale Study of 35,193 Blood Donors Conducted between June 2020 and September 2021.

There is uncertainty about the seroprevalence of anti-SARS-CoV-2 antibodies in the general population of Austria and about the waning of antibodies over time. We conducted a seroepidemiological study between June 2020 and September 2021, enrolling blood donors aged 18-70 years across Tyrol, Austria (participation rate: 84.0%). We analyzed serum samples for antibodies against the spike or the nucleocapsid proteins of SARS-CoV-2. We performed a total of 47,363 samples taken from 35,193 individuals (median age, 43.1 years (IQR: 29.3-53.7); 45.3% women; 10.0% with prior SARS-CoV-2 infection). Seroprevalence increased from 3.4% (95% CI: 2.8-4.2%) in June 2020 to 82.7% (95% CI: 81.4-83.8%) in September 2021, largely due to vaccination. Anti-spike IgG seroprevalence was 99.6% (95% CI: 99.4-99.7%) among fully vaccinated individuals, 90.4% (95% CI: 88.8-91.7%) among unvaccinated individuals with prior infection and 11.5% (95% CI: 10.8-12.3%) among unvaccinated individuals without known prior infection. Anti-spike IgG levels were reduced by 44.0% (95% CI: 34.9-51.7%) at 5-6 months compared with 0-3 months after infection. In fully vaccinated individuals, they decreased by 31.7% (95% CI: 29.4-33.9%) per month. In conclusion, seroprevalence in Tyrol increased to 82.7% in September 2021, with the bulk of seropositivity stemming from vaccination. Antibody levels substantially and gradually declined after vaccination or infection.

Durable antibody response one year after hospitalization for COVID-19: A longitudinal cohort study.

OBJECTIVES: Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of antibody titres decline and seroreversion. METHODS: Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients' discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively. RESULTS: 80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.059 [0.05-0.067], p < 0.001), inversely with WHO severity score (coefficient [95% CI] -0.042 [-0.079/-0.004], p = 0.033), and there was a trivial positive association with age (coefficient [95% CI] 0.002 [0-0.005], p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.091 [0.078-0.105], p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53-0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00-1.33; p = 0.062). CONCLUSION: Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies.

Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study.

BACKGROUND: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. METHODS: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. FINDINGS: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0•016) and SARS-CoV-2 viral load (p<0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15-0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35-7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11-0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9-5] for S-IgG; and HR 3•0 [1•9-4•9] for N-IgG; log-rank p<0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41-6•0]) nor N-IgG (HR 0•96 [0•26-3•5]) responses in an adjusted propensity score analysis. INTERPRETATION: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. FUNDING: Instituto de salud Carlos III (Spain).