Anti-spike antibody level is associated with the risk of clinical progression among subjects hospitalized with COVID-19 pneumonia: results from a retrospective cohort study.

PURPOSE: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear. METHODS: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status. RESULTS: The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p < 0.001). After 30 days, 134 patients experienced death or MV. Among vaccinated individuals, higher anti-S levels correlated significantly with lower death/MV risk (per log2 increase, OR 0.88, 95%CI 0.81-0.97), irrespective of age and solid malignancies. Among unvaccinated, a marginally protective effect was observed (OR 0.86, 95%CI 0.73-1.01), independent of age, immunosuppressive therapy, and diabetes. Adjustment for monoclonal antibody treatment strengthened the association (OR 0.81, 95%CI 0.68-0.96). CONCLUSION: This study suggests that levels of anti-S antibodies can predict critical or fatal outcomes in COVID-19 pneumonia patients, regardless of vaccination. Whether anti-S Ab could guide risk assessment and vaccination boosting merits further evaluation.

Seroprevalence of SARS-CoV-2 in pediatric hematology-oncology patients.

BACKGROUND: The COVID-19 pandemic disproportionately affected persons with underlying medical conditions. SARS-CoV-2 infection susceptibility and vaccine effectiveness in pediatric hematology-oncology patients were unknown. METHODS: From February to July 2022, anti-spike and anti-nucleocapsid Ig were assayed in 354 pediatric hematology-oncology subjects, including 53 oncology patients receiving chemotherapy (cancer), 150 patients with sickle cell disease (SCD), and 151 benign consult and long-term follow-up patients (controls). Participants completed a questionnaire. RESULTS: Frequencies of COVID-19 infection, defined by positive PCR/antigen test or anti-nucleocapsid Ig, were 62% in cancer, 71% in SCD, 52% in controls, with SCD statistically different than controls (p = .001). Infection was associated with COVID-19 exposure, Hispanic/Latino or Black/African American ethnicity, multi-family dwelling, sports participation; COVID-19 booster decreased association with infection. In COVID-19-positive cancer patients, 58% had positive anti-nucleocapsid and 76% had positive anti-spike (≥10 U/mL), compared to essentially 100% seroconversion in SCD and controls (p < .0001, p = .01, respectively). Infection led to high anti-spike (≥2500 U/mL) in 12% cancer, 14% SCD, and 15% controls (p = .93). Vaccination resulted in anti-spike positivity in 90% cancer, 100% SCD, and 100% controls (p = .06), and in high anti-spike in 20% cancer, 47% SCD, and 41% controls (p = .36). Of boosted subjects, one of two cancer, 6/6 SCD, and 19/19 controls exhibited high anti-spike. CONCLUSIONS: Cancer patients demonstrated similar SARS-CoV-2 infection frequency as controls, but diminished antibody response to infection and vaccination. SCD patients exhibited seroconversion indistinguishable from controls. Vaccination was associated with higher frequency of high anti-spike than infection; vaccination plus booster was most effective in eliciting high anti-spike antibody detectable beyond 90 days.

Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Multisystem Inflammatory Syndrome in Adult after First Dose of mRNA Vaccine.

A 32-year-old man in Japan experienced respiratory failure after receiving the first dose of coronavirus disease (COVID-19) vaccine. He was treated with noninvasive ventilation and corticosteroids. Serologic test results suggested previous COVID-19; therefore, he received a diagnosis of multisystem inflammatory syndrome. COVID-19 vaccination could be a trigger for this condition.

Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. MATERIALS AND METHODS: In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. RESULTS: Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. CONCLUSION: Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Evaluation of response to different COVID-19 vaccines in vaccinated healthcare workers in a single center in Iran.

Due to the recent coronavirus disease 2019 (COVID-19) pandemic and emergent administration of various vaccines worldwide, comprehensive studies on the different aspects of vaccines are in demand. This study evaluated antibody response after the second dose of the COVID-19 vaccine in the Children's Medical Center personnel. The blood samples of 174 healthcare workers were gathered at least 10 days after vaccination. The administered vaccines included Oxford/AstraZeneca, COVAXIN, Sinopharm, and Sputnik V. This study assessed all antibodies employing ELISA methods, including anti-SARS-CoV-2 neutralizing antibody by DiaZist and Pishtazteb kits, anti-SARS-CoV-2-nucleocapsid by Pishtazteb kit, and anti-SARS-CoV-2-Spike by Razi kit. The cutoff for the tests' results was calculated according to the instructions of each kit. Totally, 174 individuals with an average age of 40 ± 9 years participated in this study, the proportion of men was 31%, and the frequency of past COVID-19 infection was 66 (38%). Sixteen (9%) personnel received Oxford/AstraZeneca, 28 (16%) COVAXIN, 29 (17%) Sinopharm, and 101 (58%) Sputnik V. anti-SARS-CoV-2-nucleocapsid and anti-SARS-CoV-2-Spike were positive in 37 (21%), and 163 (94%) participants and their mean level were more in adenoviral-vectored vaccines (p value < 0.0001). Neutralizing antibody was positive in 74% using Pishtazteb kit while 87% using DiaZist kit. All antibodies' levels were significantly higher in those with a past COVID-19 infection (p value < 0.0001). In conclusion, Oxford/AstraZeneca and Sputnik V had a similar outcome of inducing high levels of anti-SARS-Cov-2-spike and neutralizing antibodies, which were more than Sinopharm and COVAXIN. The titers of Anti-SARS-CoV-2-nucleocapsid antibody were low in all of these four vaccines.

Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan.

INTRODUCTION: Vaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections. METHODS: The subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination. RESULTS: AS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360-896). AS-ab titer had then increased to 22471 U/mL (15761-32622) three weeks after booster vaccination. There were no significant differences among age groups. A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20-29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5-5.6) and those aged 20-49 years (aOR:9.7, 95%CI 1.3-71.2) were risk factors for SARS-CoV-2 infection. CONCLUSIONS: Booster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20-49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection.

Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins.

The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the potential for reemergence, therefore efforts are being made to create a vaccine as a prophylactic strategy for control and prevention. Antibody-dependent enhancement (ADE) is a mechanism through which dengue viruses, feline coronaviruses, and HIV viruses take advantage of anti-viral humoral immune responses to infect host target cells. Here we describe our observations of SARS-CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line. Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV is capable of replication in HL-CZ cells, and of displaying virus-induced cytopathic effects and increased levels of TNF-α, IL-4 and IL-6 two days post-infection. According to flow cytometry data, the HL-CZ cells also expressed angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of the FcγRII receptor. We found that higher concentrations of anti-sera against SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera significantly increased SARS-CoV infection and induced higher levels of apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is primarily mediated by diluted antibodies against envelope spike proteins rather than nucleocapsid proteins. We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis.

Reactogenicity and Peak Anti-RBD-S1 IgG Concentrations in Individuals with No Prior COVID-19 Infection Vaccinated with Different SARS-CoV-2 Vaccines.

OBJECTIVE: To investigate the association of immune response with vaccination adverse effects at peak anti-receptor-binding domain spike subunit 1 (anti-RBDS1) IgG after full vaccination with Comirnaty, Spikevax, or Vaxzevria. METHODS: Anti-RBDS1 IgG concentrations after vaccination were determined in healthy adults vaccinated with the Comirnaty, Spikevax, and Vaxzevria vaccines. The association of reactogenicity and peak antibody response after vaccination was tested. RESULTS: Anti-RBDS1 IgG values were significantly higher in the Comirnaty and Spikevax group, compared with the Vaxzevria group (P < .001). Fever and muscle pain were found to be significant independent predictors of peak anti-RBDS1 IgG in the Comirnaty and Spikevax groups (P = .03 and P = .02, respectively). The multivariate model, adjusted for covariates, showed that no association between reactogenicity and peak antibody concentrations was found in the Comirnaty, Spikevax, and Vaxzevria groups. CONCLUSIONS: No association between reactogenicity and peak anti-RBDS1 IgG after vaccination with the Comirnaty, Spikevax, and Vaxzevria vaccine was found.

Clinical and immunological responses to COVID-19 vaccination in rheumatoid arthritis patients on disease modifying antirheumatic drugs: a cross-sectional study.

Objective: This study was conducted to investigate the immunological and clinical response to COVID-19 vaccination in rheumatoid arthritis (RA) patients receiving disease modifying antirheumatic drugs (DMARDs). Methods: A cross-sectional study was conducted among RA patients who received two doses of COVID-19 vaccine within 6 months to one year. Demographic information, comorbidities, vaccination details, and past COVID-19 infection details were collected. Hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were estimated. Disease Activity Score-28 (DAS-28) was calculated for RA patients. Anti-spike antibody (ASA) concentrations were measured, and compared with a healthy control population. Correlations of ASA with age, sex, disease parameters, medication use, and comorbidities were assessed. Results: A total of 103 RA patients and 185 controls were included in the study. RA patients had higher mean age, lower mean Hb, higher ESR, and elevated IL-6 levels. Both groups showed positive results for anti-spike antibodies, with a higher percentage in controls. Among RA patients majority had low DAS-28 score. The number of DMARDs used showed a negative correlation with antibody levels. There was a slight positive correlation between ASA concentration and DAS-28 score. Comorbidities did not significantly influence antibody concentration. No significant differences were found in antibody levels based on the type of COVID-19 vaccine or previous COVID-19 infection or booster dose vaccination among RA patients. Conclusion: The study revealed that RA patients showed a reduced antibody response following COVID-19 vaccination compared to the control group and potentially influenced by immunosuppressive treatments and disease-related factors.

Modeling of anti-spike IgG and neutralizing antibody waning after anti-SARS-CoV-2 mRNA vaccination.

At present, mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being administered on a global scale. While the efficacy of mRNA vaccines has been demonstrated, several unknowns remains. For example, as the number of booster vaccinations increases, there are uncertainties regarding how long effects of a vaccine will last and how much individual variability exists. In this study, to predict the duration of vaccine efficacy, we modeled the kinetics of antibody levels for each SARS-CoV-2 vaccination dose, incorporating predictive intervals to estimate the duration of vaccine efficacy and to account for variability among individuals. A total of 3,059 serum samples from 1,346 participants were assayed to quantify IgG antibodies specific for the S1 subunit of the S protein (anti-S1 IgG) and neutralizing antibody activities against SARS-CoV-2. A power law model was used to simulate the decay of antibody titers following vaccination, and models were constructed to assess antibody level kinetics after the second, third, fourth, and fifth vaccinations. The models assumed that booster vaccinations would significantly reduce the decline in anti-S antibody and neutralizing antibody levels, resulting in levels being maintained for a longer period. No significant differences in the decay rate of antibody levels were observed among age groups, yet the peak titers of antibody levels were significantly higher in the ≤ 39 age group than in the ≥ 60 age group following the second vaccination; these differences were not observed after the third and fourth vaccinations. The modeling of antibody level kinetics after vaccination is considered to be useful for understanding the immune status of mRNA vaccine recipients.

Immunogenicity of Abdala COVID-19 vaccine in Vietnamese people after primary and booster vaccinations: a prospective observational study in Vietnam.

OBJECTIVES: We studied the immunogenicity after primary and booster vaccinations of Abdala COVID-19 vaccine, a receptor binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants, and SARS-CoV-1. METHODS: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks post booster dose. We measured anti-nucleocapsid, anti-spike and neutralizing antibodies against SARS-CoV-2, and assessed the cross-neutralization against 14 SARS-CoV-2 variants, and SARS-CoV-1. Complementary antibody data came from Vietnamese healthcare workers fully vaccinated with ChAdOx1-S. RESULTS: After primary vaccination, anti-spike antibody and neutralizing antibodies were detectable in 98.4% and 87% of 251 study participants, respectively, with neutralizing antibody titers similar to that induced by ChAdOx1-S vaccine. Antibody responses after a homologous (Abdala COVID-19) or heterologous (mRNA BNT162b2) booster could neutralize 14 SARS-CoV-2 variants (including Omicron), and SARS-CoV-1. CONCLUSIONS: Abdala COVID-19 vaccine is immunogenic in Vietnamese people. Enhanced antibody response after a booster dose could cross-neutralize 14 SARS-CoV-2 variants and SARS-CoV-1. Our results have added to the growing body of knowledge about the contribution of protein subunit vaccine platforms to pandemic control.

Comparison of SARS-CoV-2 seroprevalence estimates between commercial lab serum specimens and blood donor specimens, United States, September-December 2021.

We estimated monthly cross-sectional seroprevalence rates of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies to severe acute respiratory syndrome coronavirus 2 in two U.S. nationwide studies. The nationwide blood donor seroprevalence (NBDS) study included specimens from blood donors, while the nationwide commercial laboratory seroprevalence (NCLS) study included residual serum specimens tested in commercial laboratories for reasons unrelated to the assessment of coronavirus disease 2019 infection. In September-December 2021, specimens collected from both nationwide studies were tested for anti-N antibodies. In September-October 2021, specimens from both studies within a five-state area were tested for anti-S antibodies. We used raking methods to adjust all seroprevalence estimates by the population distribution of key demographics in included states. Seroprevalence estimates of each antibody type were compared across the two studies for specimens drawn in the same U.S. states during the same time period. Our analysis revealed that over a 4-month period, national NCLS monthly anti-N estimates were 0.5-1.9 percentage points higher than NBDS estimates. In contrast, across five states during a 2-month period, NBDS anti-S estimates were 7.6 and 8.2 percentage points higher than NCLS estimates. The observed differences in seroprevalence estimates between the NBDS and NCLS studies may be attributed to variations in the characteristics of the study sample populations, particularly with respect to health status, health behaviors, and vaccination status. These differences should be considered in the interpretation of seroprevalence study results based on blood donors or commercial lab residual specimens. IMPORTANCE: This study was the first systematic comparison between two nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies which estimated seroprevalence, or the proportion of the population with antibodies to the virus, using differing convenience sample populations. One study tested blood donor specimens; the other study tested specimens left over from clinical blood tests. The seroprevalence of anti-nucleocapsid and anti-spike antibodies was compared in the same states during the same months with statistical adjustments based on state demographics. Similar anti-nucleocapsid antibody seroprevalence estimates produced by two independent studies using differing convenience samples build confidence in the generalizability of their anti-nucleocapsid findings. Due to high blood donor vaccine rates, blood donor SARS-CoV-2 anti-spike antibody estimates might overestimate general population seroprevalence, an important consideration for interpreting national seroprevalence study results. Furthermore, because laboratory residuals and blood donations are two common sources of specimens for seroprevalence studies, study findings may be informative for other respiratory virus seroepidemiology studies.

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients.

We investigated humoral and T-cell response to a SARS-CoV-2 mRNA vaccine in solid organ transplant recipients (SOT-Rs) and healthy donors (HDs) before (T0) and after two (T1) and twelve months (T2) since the third dose administration. SOT-Rs were stratified according to the transplanted organ and to the time elapsed since the transplant. In SOT-Rs, detectable levels of anti-S antibodies were observed in 44%, 81% and 88% at T0, T1 and T2, respectively. Conversely, anti-S antibody levels were detected in 100% of HD at all time points. Lower antibody titers were observed in SOT-Rs compared to HDs, even stratifying by transplanted organs and the time elapsed since transplant. Lower percentages of responding and polyfunctional T-cells were observed in SOT-Rs as well as in each subgroup of SOT-Rs compared to HDs. At both T0 and T1, in SOT-Rs, a predominance of one cytokine production shortly was observed. Conversely, at T2, a dynamic change in the T-cells subset distribution was observed, similar to what was observed in HDs. In SOT-Rs, the third dose increased the rate of seroconversion, although anti-S levels remained lower compared to HDs, and a qualitatively inferior T-cell response to vaccination was observed. Vaccine effectiveness in SOT-Rs is still suboptimal and might be improved by booster doses and prophylactic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.

Background: Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied. Objective: We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. Methods: We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes. Results: The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis. Conclusions: In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.

Validation of a SARS-CoV-2 Surrogate Virus Neutralization Test in Recovered and Vaccinated Healthcare Workers.

Vaccination against COVID-19 is the main public health approach to fight against the pandemic. The Spike (S) glycoprotein of SARS-CoV-2 is the principal target of the neutralizing humoral response. We evaluated the analytical and clinical performances of a surrogate virus neutralization test (sVNT) compared to conventional neutralization tests (cVNTs) and anti-S eCLIA assays in recovered and/or vaccinated healthcare workers. Our results indicate that sVNTs displayed high specificity and no cross-reactivity. Both eCLIA and sVNT immunoassays were good at identifying cVNT serum dilutions ≥1:16. The optimal thresholds when identifying cVNT titers ≥1:16, were 74.5 U/mL and 49.4 IU/mL for anti-S eCLIA and sVNT, respectively. Our data show that neutralizing antibody titers (Nab) differ from one individual to another and may diminish over time. Specific assays such as sVNTs could offer a reliable complementary tool to routine anti-S serological assays.

Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses.

Background: The main objective was to evaluate the efficacy of intranasal photodynamic therapy (PDT) in SARS-CoV-2 mildly symptomatic carriers on decreasing the infectivity period. SARS-CoV-2-specific immune-stimulating effects and safety were also analysed. Methods: We performed a randomized, placebo-controlled, clinical trial in a tertiary hospital (NCT05184205). Patients with a positive SARS-CoV-2 PCR in the last 48 hours were recruited and aleatorily assigned to PDT or placebo. Patients with pneumonia were excluded. Participants and investigators were masked to group assignment. The primary outcome was the reduction in in vitro infectivity of nasopharyngeal samples at days 3 and 7. Additional outcomes included safety assessment and quantification of humoral and T-cell immune-responses. Findings: Patients were recruited between December 2021 and February 2022. Most were previously healthy adults vaccinated against COVID-19 and most carried Omicron variant. 38 patients were assigned to placebo and 37 to PDT. Intranasal PDT reduced infectivity at day 3 post-treatment when compared to placebo with a ß-coefficient of -812.2 (CI95%= -478660 - -1.3, p<0.05) infectivity arbitrary units. The probability of becoming PCR negative (ct>34) at day 7 was higher on the PDT-group, with an OR of 0.15 (CI95%=0.04-0.58). There was a decay in anti-Spike titre and specific SARS-CoV-2 T cell immunity in the placebo group 10 and 20 weeks after infection, but not in the PDT-group. No serious adverse events were reported. Interpretation: Intranasal-PDT is safe in pauci-symptomatic COVID-19 patients, it reduces SARS-CoV-2 infectivity and decelerates the decline SARS-CoV-2 specific immune-responses.

Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Immunogenicity among Chimeric Antigen Receptor T Cell Therapy Recipients.

Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least 2 doses of SARS-CoV-2 vaccination with BNT162b2 or mRNA-1273 or 1 dose of Ad26.COV2.S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least 1 month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. The seropositivity rate (assessed by an anti-S assay cutoff of ≥.8 U/mL in the Roche assay) and median anti-S IgG titers were analyzed. Fifty patients were included in the study. The median age was 65 years (interquartile range [IQR], 58 to 70 years), and the majority were male (68%). Thirty-two participants (64%) had a positive antibody response, with a median titer of 138.5 U/mL (IQR, 11.61 to 2541 U/mL). Receipt of ≥3 vaccines was associated with a significantly higher anti-S IgG level. Our study supports current guidelines for SARS-CoV-2 vaccination among recipients of CAR-T therapy and demonstrates that a 3-dose primary series followed by a fourth booster increases antibody levels. However, the relatively low magnitude of titers and low percentage of nonresponders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population.

Distinct features of SARS-CoV-2 humoral immunity against Omicron breakthrough infection.

BACKGROUND: SARS-CoV-2 Omicron breakthrough infection (Omicron-BTI) after vaccination has been frequently observed. A more detailed understanding of the humoral immunity against Omicron-BTI is required. METHODS: We measured strain-specific live-virus based neutralizing activity, anti-spike IgG, and anti-receptor-binding domain (RBD) IgG titers in individuals with Omicron/BA.1-BTI and directly compared them with controls with diverse combinations of wild-type (WT) mRNA vaccination and infection history. RESULTS: Omicron-BTI individuals showed markedly higher neutralizing titers against all the WT, Delta, and Omicron strains in convalescent sera, compared with unvaccinated Omicron-infection individuals with only Omicron neutralizing activity. Similar tendencies were found in strain-specific anti-spike and anti-RBD IgG titers. The Omicron-specificity (BA.1/WT neutralizing ratio), Omicron-neutralizing efficiency per antibody unit, and anti-Omicron RBD-directivity of anti-spike antibodies in Omicron-BTI individuals were all significantly lower than those in unvaccinated Omicron-infection individuals, but they were equivalent to or higher than those in uninfected vaccinees. The induction of Omicron-specific neutralizing activity after Omicron-BTI was not weakened for eight months from the last vaccination. CONCLUSIONS: These findings suggest that cross-reactive vaccine-induced immunity was intensively stimulated following Omicron breakthrough infection, which contributed to Omicron neutralization. Measuring SARS-CoV-2 variant-specific antibody levels as well as neutralizing activity is useful for evaluating humoral immunity after breakthrough infection in the current situation of antigenic gaps between vaccinated and epidemic (Omicron sub-lineages) strains.

SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.