Anti-spike IgG Research Articles

Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

ObjectivesThe aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. MethodsCOVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. ResultsIn January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. DiscussionIntradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness.

Seroepidemiology of SARS-CoV-2 in a cohort of pregnant women and their infants in Uganda and Malawi.

Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes.

Elevated Serum Levels of SARS-CoV-2 Anti-Spike S1 RBD IgM, IgG, and IgA in Pfizer-BioNTech Vaccinated, COVID-19 Infected, and COVID-19 Infected after Pfizer-BioNTech Vaccinated Individuals after One Month

Background: While protective immunity against some viruses, such as coronaviruses, is relatively short-lived, healing from acute infections of many different viruses, such as those caused by yellow fever, polio, measles, and smallpox, can give cell-mediated and humoral immunity for a lifetime. The main element in the long-term prevention of reinfection by most viruses might be due to the specific antibodies generated by plasma cells. Aim: This study aims to estimate the levels of SARS-CoV-2 Anti-Spike S1 RBD IgM, IgA, and IgG in serum among people in Baghdad after one month of receiving the Pfizer-BioNTech vaccine, infected with the SARS-CoV-2 virus after vaccination and COVID-19 infected patients respectively. Methods: A total of 120 volunteers were enrolled in this study, which was conducted between the 1st of November 2022 and the 13th of January 2023, and they were divided into four groups, each group containing 30 individuals. The study groups were categorized after one month into vaccinated with the Pfizer-BioNTech vaccine (BNT162b2), infected with SARS-CoV-2 after Pfizer vaccination, COVID-19 patients, and control. Results: The study presented a significant difference where (P value < 0.05) in the serum levels of Anti-Spike S1 RBD IgM, IgA, and IgG for all groups compared to the control. Serum levels of S1 RBD IgM Anti-Spike of SARS-CoV-2 in all groups were significantly increased (P value >0.05) compared to each other. For Anti-Spike S1 RBD IgA and IgG, there was no significant difference (P value >0.05) between the COVID-19-infected patients group and those infected by SARS-CoV-2 after the Pfizer vaccination group. Positive correlations were found among Anti-Spike S1 RBD IgM, IgA, and IgG levels in the serum. Conclusions: Natural infection by SARS-CoV-2 or vaccination with Pfizer-BioNTech (BNT162b2) provides significant humoral Immunological protection.

Anti SARS-CoV-2 Monoclonal Antibodies in Pre-Exposure or Post-Exposure in No- or Weak Responder to Vaccine Kidney Transplant Recipients: Is One Strategy Better than Another?

Background: Kidney transplant recipients (KTRs) are likely to develop severe COVID-19 and are less well-protected by vaccines than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) to confer a passive immunity appears attractive in KTRs. Methods: This retrospective monocentric cohort study was conducted between 1 January 2022 and 30 September 2022. All KTRs with a weak antibody response one month after three doses of mRNA vaccine (anti spike IgG < 264 (BAU/mL)) have received tixagevimab-cilgavimab in pre-exposure (group 1), post-exposure (group 2) or no specific treatment (group 3). We compared COVID-19 symptomatic hospitalizations, including intensive care unit hospitalizations, oxygen therapy, and death, between the three groups. Results: A total of 418 KTRs had SARS-CoV-2 infection in 2022. During the study period, we included 112 KTRs in group 1, 40 KTRs in group 2, and 27 KTRs in group 3. The occurrence of intensive care unit hospitalization, oxygen therapy, and COVID-19 death was significantly increased in group 3 compared to group 1 or 2. In group 3, 5 KTRs (18.5%) were admitted to the intensive care unit, 7 KTRs (25.9%) needed oxygen therapy, and 3 KTRs (11.1%) died. Patients who received tixagevimab-cilgavimab pre- or post-exposure had similar outcomes. Conclusions: This retrospective real-life study supports the relative effectiveness of tixagevimab-cilgavimab on COVID-19 infection caused by Omicron, used as a pre- or post-exposure therapy. The continued evolution of Omicron variants has made tixagevimab-cilgavimab ineffective and reinforces the need for new therapeutic monoclonal antibodies for COVID-19 active on new variants.

Immunophenotypes of Newborns From SARS-CoV-2-infected Mothers.

Little is known about the neonatal immunologic response to a maternal SARS-CoV-2 infection present during childbirth. Here we analyze a cohort of 75 neonates from SARS-CoV-2-infected mothers. The SARS-CoV-2 infection status was laboratory assessed by real-time reverse transcription polymerase chain reaction on nasopharyngeal swabs (NPS) in both mothers during childbirth and neonates within 24 hours of life. Immunophenotypes of peripheral blood mononucleated cells and SARS-CoV-2 antispike IgA, IgM and IgG of the newborns were recorded. Ten (13.3%) of 75 neonates had positive NPS for SARS-CoV-2; 17 of 75 (23%) were SARS-CoV-2-IgG seropositive, of which one with positive NPS. All the newborns resulted seronegative for SARS-CoV-2 IgA and IgM and were asymptomatic. Our cohort of newborns was divided into groups according to IgG seropositivity (IgG+/-) and NPS results (NPS+/-). The count and proportion of lymphocyte subsets (evaluated measuring CD3, CD4, CD8 and CD19 markers) and of natural killer cells (evaluated by measuring the CD3-/CD16+/CD56+ subset) were all in the normal range, with no statistical differences among groups. We found a significant expansion of the T cell (CD3+) subset in the IgG+ group interpreted as the result of immune effects triggered by trained immunity in these newborns, but a decrease in CD4+ T cells for NPS+ neonates. It is therefore difficult to conclude that the decrease in CD4 can certainly be caused by an infection. A maternal SARS-CoV-2 infection resulted in an expansive effect of CD3+ T cells in IgG+ newborns; nonetheless, it seems not to affect structural and functional development of the newborn immune system.

An epidemiological survey of COVID-19 serology and its association with clinical infection among older adults– does antibody titer matter?

BackgroundOlder adults are at increased risk of severe SARS-CoV-2 infection. In this study we assessed the response to COVID-19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents.MethodsThe study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID-19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates.ResultsTwo-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4 ± 8 versus 82.6 ± 8 and 83.6 ± 5, respectively, p = 0.01), and had more comorbidities (p = 0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/91 (38.4%) versus 11/100 (11%), p < 0.001]. Antibody level was lower among those infected [2113 (1271–3512) Au/ml versus 4113 (3364–5029) Au/ml, p < 0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection.ConclusionAmong older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection.

Investigating the Seroconversion Patterns of Specific Antibodies Against Various Antigens of SARS-CoV-2 in Hospitalized COVID-19 Patients and Vaccinated Individuals

Background: Inducing a humoral response to SARS-CoV-2 may partially control virus dissemination. However, there is a lack of consistency in the reported kinetics of IgM and IgG responses to SARS-CoV-2. Additionally, the humoral response to SARS-CoV-2 may differ from that elicited by vaccination. Therefore, we were motivated to evaluate the kinetics of antibodies against SARS-CoV-2 in both infected and vaccinated individuals. Objectives: This study aimed to investigate the seroconversion patterns of specific antibodies against various antigens of SARS-CoV-2 in hospitalized COVID-19 patients and vaccinated individuals, focusing specifically on comparing the humoral responses elicited by infection and vaccination. Methods: Serial blood and swab samples were collected from 134 COVID-19 patients at six time points following admission. Real-time RT-PCR specific for SARS-CoV-2, as well as anti-SARS-CoV-2 IgM and IgG, were tested using ELISA. Additionally, 141 serum samples were obtained from vaccinated individuals. Anti-SARS-CoV-2 spike and RBD IgGs, along with neutralizing antibodies (NAs), were assessed using ELISA in both the vaccinated group and 96 COVID-19 patients. Results: Anti-SARS-CoV-2 IgM was found positive in 23.3% of patients at 0 - 7 days after symptom onset, with seropositivity increasing to 71.7% at 15 - 21 days. Subsequently, IgM positivity gradually decreased to 62.7% at &gt; 28 days post-symptom onset. Meanwhile, anti-SARS-CoV-2 IgG was positive in 28.3% of patients at 0 -7 days, rising to 83.7% at 22 - 28 days after symptom onset, and remained constant thereafter. Anti-spike and RBD IgGs, along with NAs, were detected in 89.7%, 87.4%, and 87.9% of vaccinated individuals, respectively, and in 37.5%, 32.3%, and 32.3% of COVID-19 patients, respectively. There was a significant correlation between anti-spike IgG and anti-RBD IgG levels and NAs in both COVID-19-infected and vaccinated individuals. The mean concentrations of anti-spike and RBD IgGs were higher in vaccinated individuals with a history of COVID-19 infection compared to those without prior infection. Conclusions: The antibody profile for IgM and IgG against SARS-CoV-2 suggests that as time passes after the onset of disease symptoms, the seropositivity in COVID-19 patients increases. Furthermore, antibodies against SARS-CoV-2 are produced more efficiently through COVID-19 vaccination than natural infection.

The impact of ABO blood types on humoral immunity responses and antibody persistency after different COVID-19 vaccine regimens.

This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022. Anti-Spike IgG and neutralizing Ab rise were tracked on Day 21 as well as the humoral immune persistency assessment 180 after booster shots. Late adverse events up to 6 months after the booster dose were collected. The results showed that blood type A, led to a significantly higher anti-Spike Ab rise in AstraZeneca primed recipients in comparison with Sinopharm primed ones in heterologous regimens (p: 0.019). Furthermore, blood type O was a great co-effector in homologous AstraZeneca recipients regarding neutralizing Ab rise (0.013). In addition, blood type O led to a better anti-Spike Ab persistency in the Sinopharm homologous group whereas type A had the best effect on neutralizing Ab durability in the same vaccine group. What is more, Rh-positive individuals in AstraZeneca + PastoCovac Plus group had a higher rate of anti-Spike Ab rise (p = 0.001). Neutralizing Ab rise was also induced in AstraZeneca homologous and heterologous regimens of Rh-positive individuals significantly higher than Sinopharm primed cases. The present study showed the potential impact of blood types A/O and Rh-positive on a better humoral immune responses and Ab persistency. It is proposed that blood type A and Rh-positive could increase the Ab rise in AstraZeneca vaccinated individuals. Moreover, blood type O might be a better co-effector of anti-Spike Ab persistency in Sinopharm recipients.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV

BackgroundReal-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). MethodsPWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. ResultsOf 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04–0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). ConclusionsPWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

EXPLORING FACTORS ASSOCIATED WITH SEROLOGICAL RESPONSE TO SARS-COV-2 VACCINES IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE: INTERACTIVE VISUALIZATION METHODS FOR MULTIDIMENSIONAL DATA

Abstract BACKGROUND SARS-CoV-2 vaccine response may be reduced in seniors (age 65+) with inflammatory bowel disease (IBD) and those on anti-TNF therapy. A challenge of the COVID-19 era has been conveying rapid-evolving health information, especially for groups with higher risk of poor outcomes of COVID-19 such as seniors and immunocompromised individuals. AIM To develop sharable, interactive 3D models of the relationship of age and days from vaccine dose on serological responses to SARS-CoV-2 vaccines in people with IBD who are either on or not on anti-TNF therapy. METHODS A prospective cohort study of individuals with IBD (n=528) who received 1–4 doses of a COVID-19 vaccine were assessed for serological responses 1–8 weeks and 8–16 weeks following each dose using the SARS-CoV-2 IgG II Quant assay. The cohort was stratified into those on and not on anti-TNF therapy at vaccination. We created 3D models with the plotly R package. Data were plotted as days from vaccine dose on the x-axis, age at the time of serology on the y-axis, and spike-protein antibody levels on the z-axis. Linear regressions were run with Anti-Spike IgG levels (AU/mL) as the outcome, and days from vaccine and age at serology as continuous exposures. Results were visualized as regression planes in 3D models. To share our visualizations, we built an open-access, online, interactive dashboard (https://covid19-sero.shinyapps.io/dashboard/). RESULTS The dashboard allows knowledge users to make selections based on desired data stratifications, and then zoom, pan, and rotate the plot to inspect the data or download an image of the plot they generate. Post-2nd dose samples comprised the largest dose subset in our study (n=658). Our model for post-2nd dose data shows that antibody levels significantly decrease by 20.9 (AU/mL) per day from a dose (p&amp;lt;0.001) and by 116.6 (AU/mL) per year increase in age (p=0.002) (Figure 1). As age increases, antibody levels significantly decrease by 107.5 (AU/mL) for those on anti-TNFs (p=0.026) and by 124.8 (AU/mL) for those not on anti-TNFs (p=0.002) (Figure 2). Those not on anti-TNFs experienced a decrease of 31.1 (AU/mL) (p&amp;lt;0.001) per day after 2nd vaccine dose; we did not find a significant decrease over time for those on anti-TNFs (p=0.927) (Figure 2). DISCUSSION In people with IBD, advancing age is associated with lower antibody responses to SARS-CoV-2 vaccines; however, antibody response does not significantly decrease over time for those on anti-TNF therapy. Integrating visualizations of quantitative data with participant demographics and medical therapy in open-access, interactive web applications promotes rapid release of research findings in a format that is accessible by a maximum number of knowledge users, which is of continued importance for those with a high risk of complications resulting from COVID-19. Figure 1 A scatterplot with post-2nd dose data for all possible data stratifications, downloaded from our online dashboard. The plot depicts decreasing trends in Anti-Spike IgG levels (AU/mL) as days from dose and participant age increase. Figure 2 Scatterplots with post-2nd dose data comparing Anti-Spike IgG levels (AU/mL) for participants either on or not on anti-TNF therapy. Plots depict lower antibody levels for individuals with IBD on anti-TNF therapy. Panel A shows no change in antibody levels for those on anti-TNF therapy as days from vaccine dose increase and Panel B shows that antibody levels in those not on anti-TNF therapy decrease as both days from vaccine dose and age increase.

Efficacy and safety of antiviral plus anti-spike monoclonal antibody combination therapy vs. monotherapy for high-risk immunocompromised patients with mild-to-moderate SARS-CoV2 infection during the Omicron era: A prospective cohort study

Antivirals and monoclonal antibodies lower the risk of progression in immunocompromised patients. However, combination therapy with both types of agents has not been studied. This was a single-centre, prospective, cohort study. All immunocompromised patients who received treatment for mild-to-moderate COVID-19 from 1 January 2022 to 30 October 2022 were enrolled. The primary endpoint was COVID-19 progression at 90 days, defined as hospital admission or death due to COVID-19 and/or seronegative persistent COVID-19. A total of 304 patients were included: 43 patients (14.1%) received sotrovimab plus a direct-acting antiviral, and 261 (85.9%) received monotherapy. Primary outcome occurred more frequently after monotherapy (4.6% vs. 0%, P=0.154). Among patients with anti-spike immunoglobulin G (anti-S IgG) titre <750 BAU/mL, COVID-19 progression was more common after monotherapy (23.9% vs. 0%, P=0.001), including more frequent COVID-related admission (15.2% vs. 0%, P=0.014) and seronegative persistent COVID-19 (10.9% vs. 0%, P=0.044). Combination therapy was associated with lower risk of progression (odds ratio [OR] 0.08, 95% confidence interval [95% CI] 0.01-0.64). Anti-S IgG titre <750 BAU/mL and previous anti-CD20 were associated with higher risk of progression (OR 13.70, 95% CI 2.77-67.68; and OR 3.05, 95% CI 1.20-10.94, respectively). In immunocompromised patients, combination therapy with sotrovimab plus an antiviral may be more effective than monotherapy for SARS-CoV2.

Serological responses and clinical outcomes following a three-dose primary COVID-19 vaccine schedule in kidney transplant recipients and people on dialysis.

Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection. Plasma from 30 KTRs and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination. After three doses, KTRs achieved lower anti-Spike RBD IgG levels (P < 0.001) and NAb titres than people receiving dialysis (P = 0.002). Seropositive cross-reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral-vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B-cell counts predicted poor serological responses in KTRs. ChAdOx-1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation (R = 0.9, P < 0.001). More KTRs contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti-Spike RBD IgG and ancestral NAb titres. Serological responses to COVID-19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.

Microfluidic particle counter visualizing mucosal antibodies against SARS-CoV-2 in the upper respiratory tract for rapid evaluation of immune protection.

Mucosal antibodies in the upper respiratory tract are the earliest and most critical responders to prevent respiratory infections, providing an indication for the rapid evaluation of immune protection. Here, we report a microfluidic particle counter that directly visualizes mucosal antibody levels in nasal mucus. The mucosal anti-SARS-CoV-2 spike receptor binding domain (RBD) antibodies in nasal secretions first react with magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) that are surface-modified to form a "MMPs-anti-spike RBD IgG-PMPs" complex when RBD is present. After magnetic separation and loading into the microfluidic particle counter, the free PMPs, which are reduced with increasing anti-spike RBD IgG antibody levels, are trapped by a microfluidic particle dam and accumulate in the trapping channel. A sensitive mode [limit of detection (LOD): 14.0 ng mL-1; sample-to-answer time: 70 min] and an equipment-free rapid mode (LOD: 37.4 ng mL-1; sample-to-answer time: 20 min) were achieved. Eighty-seven nasal secretion (NS) samples from vaccinees were analyzed using our microfluidic particle counter, and the results closely resemble those of the gold-standard enzyme-linked immunosorbent assay (ELISA). The analysis shows that higher antibody levels were found in convalescent volunteers compared to noninfected volunteers. Together, we demonstrate a rapid kit that directly indicates immune status, which can guide vaccine strategy for individuals and the government.

High prevalence of long COVID in anti-TPO positive euthyroid individuals with strongly elevated SARS-CoV-2-specific T cell responses and moderately raised anti-spike IgG levels 23 months post-infection.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), causes post-acute infection syndrome in a surprisingly large number of cases worldwide. This condition, also known as long COVID or post-acute sequelae of COVID-19, is characterized by extremely complex symptoms and pathology. There is a growing consensus that this condition is a consequence of virus-induced immune activation and the inflammatory cascade, with its prolonged duration caused by a persistent virus reservoir. In this cross-sectional study, we analyzed the SARS-CoV-2-specific T cell response against the spike, nucleocapsid, and membrane proteins, as well as the levels of spike-specific IgG antibodies in 51 healthcare workers, categorized into long COVID or convalescent control groups based on the presence or absence of post-acute symptoms. Additionally, we compared the levels of autoantibodies previously identified during acute or critical COVID-19, including anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-neutrophil cytoplasmic antibodies, and anti-thyroid peroxidase (anti-TPO). Furthermore, we analyzed the antibody levels targeting six nuclear antigens within the ENA-6 S panel, as positivity for certain anti-nuclear antibodies has recently been shown to associate not only with acute COVID-19 but also with long COVID. Finally, we examined the frequency of diabetes in both groups. Our investigations were conducted at an average of 18.2 months (convalescent control group) and 23.1 months (long COVID group) after confirmed acute COVID-19 infection, and an average of 21 months after booster vaccination. Our results showed significant differences between the two groups regarding the occurrence of acute infection relative to administering the individual vaccine doses, the frequency of acute symptoms, and the T cell response against all structural SARS-CoV-2 proteins. A statistical association was observed between the incidence of long COVID symptoms and highly elevated anti-TPO antibodies based on Pearson's chi-squared test. Although patients with long COVID showed moderately elevated anti-SARS-CoV-2 spike IgG serum antibody levels compared to control participants, and further differences were found regarding the positivity for anti-nuclear antibodies, anti-dsDNA, and HbA1c levels between the two groups, these differences were not statistically significant. This study highlights the need for close monitoring of long COVID development in patients with elevated anti-TPO titers, which can be indicated by strongly elevated SARS-CoV-2-specific T cell response and moderately raised anti-spike IgG levels even long after the acute infection. However, our results do not exclude the possibility of new-onset thyroid autoimmunity after COVID-19, and further investigations are required to clarify the etiological link between highly elevated anti-TPO titers and long COVID.

Exploring immune response and lab markers across COVID-19 severity levels

&lt;p&gt;This retrospective cohort study investigated antigen-specific antibody responses to SARS-CoV-2 and laboratory markers in coronavirus disease 2019 (COVID-19) patients of varying severities. Serum or plasma samples collected early in the pandemic were analyzed for the presence of IgG antibodies and IgG subclasses which target the recombinant spike (S) and nucleocapsid (N) proteins of SARS-CoV-2. Correlation analyses were conducted to assess the possible relationship between the IgG subclasses to SARS-CoV-2 proteins, inflammatory markers, and the severity of the disease. It was shown that the severity of the disease positively correlated with the C-reactive protein (CRP), but most of all with the neutrophil/lymphocyte ratio (NLR) levels. IgG titers against the S- and N-proteins decreased in the most severe COVID-19 cases, which potentially attributed to a delayed IgG formation compared to milder infections. The presence of anti-spike IgG displayed a medium negative correlation trend (not statistically significant, which might be due to the small sample size in our study) with laboratory markers (such as CRP, Fibrinogen, Degree) which are suggestive of infection severity. anti-S IgG correlated positively but weakly with the serum histamine levels. The presence of anti-N IgG at the time of hospitalization correlated with the subsequent outcome. At the same time, anti-N IgG1 correlated with the detection of the viral RNA in the blood. Thus, seroconversion may occur later in patients with a more severe pneumonia. The summary data suggests correlations between the expression of inflammatory markers and the antibody responses, which can also serve as early clinical markers.&lt;/p&gt;

Effect of previous exposure to COVID-19, occurrence of spikes, and type of vaccine on the humoral immune response of institutionalized older adults

This study evaluated the explanatory factors of humoral immune response in older adults admitted to long-term care institutions in Buenos Aires, Argentina, up to 180 days after vaccination. An open-label, prospective, multicenter cohort study was conducted with volunteers who received two doses of the Sputnik V, Sinopharm, or AZD1222 vaccines. Plasma samples were analyzed at 0 and 21 days after the first dose, 21 days after the second dose, and 120 and 180 days after the first dose. Marginal linear models and generalized additives mixed models were adjusted to determine the behavior of anti-spike IgG antibody concentration over time according to exposure group (naïve/no-naïve) and vaccine. Occurrence of an outbreak of COVID-19 in long-term care institutions and comorbidities were the covariates analyzed. A total of 773 participants were included, with a mean age of 83 years (IQR: 76-89). Results showed that antibody levels in the naïve: Sinopharm group were significantly lower to the other groups (p < 0.05). Antibody levels in the no-naïve: Sinopharm group were similar to those in the naïve group who received AZD1222 (p = 0.945) or Sputnik V (p = 1). Participants exposed to outbreaks in long-term care institutions had significantly higher antibody levels, regardless of exposure group and vaccine (p < 0.001). In conclusion, previous exposure to COVID-19, type of vaccine, and admittance into a long-term care institution with a history of outbreaks are factors to be considered in future epidemic events with transmission dynamics and immunological mechanisms similar to COVID-19, in populations similar to the one analyzed.

Genetic determinants of IgG antibody response to COVID-19 vaccination

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n= 54,066) or the second dose (n= 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF= 4.0%, OR= 0.75, p= 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRβ1 (p= 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

Hybrid Immunity to SARS-CoV-2 During Pregnancy Provides More Durable Infant Antibody Responses Compared to Natural Infection Alone.

Hybrid immunity (infection plus vaccination) may increase maternally derived SARS-CoV-2 antibody responses and durability versus infection alone. Prospective cohort of pregnant participants with prior SARS-CoV-2 infection (anti-nucleocapsid IgG, RT-PCR, or antigen positive) and their infants had blood collected in pregnancy, at delivery/birth, and postpartum tested for anti-spike (anti-S) IgG and neutralizing antibodies (neutAb). Among 107 participants at enrollment, 40% were unvaccinated and 60% were vaccinated (received ≥1 dose); 102 had previous SARS-CoV-2 infection in pregnancy (median, 19 weeks' gestation); 5 were diagnosed just prior to pregnancy (median, 8 weeks). At delivery, fewer unvaccinated participants (87% anti-S IgG+, 86% neutAb) and their infants (86% anti-S IgG+, 75% neutAb) had anti-S IgG+ or neutAb compared to vaccinated participants and their infants (100%, P ≤ .01 for all). By 3-6 months postpartum, 50% of infants of unvaccinated participants were anti-S IgG+ and 14% had neutAb, versus 100% among infants of vaccinated participants (all P < .01), with lower median antibody responses (anti-S IgG log10 1.95 vs 3.84 AU/mL, P < .01; neutAb log10 1:1.34 vs 1:3.20, P = .11). In pregnant people with prior SARS-CoV-2, vaccination before delivery provided more durable maternally derived antibody responses than infection alone in infants through 6 months.

Post-COVID-19 and Post-COVID-19 Vaccine Arthritis, Polymyalgia Rheumatica and Horton's Arteritis: A Single-Center Assessment of Clinical, Serological, Genetic, and Ultrasonographic Biomarkers.

The potential role of the COVID-19 vaccine and infection to induce autoimmunity is currently underestimated despite the literature emphasizing arthralgia as a common adverse event. We aimed to study the impact of rheumatological complications post-COVID-19 (PC) and post-COVID-19 vaccine (PCV), comparing undifferentiated arthritis (UA) to Polymyalgia Rheumatica, Horton's Arteritis (PMR-HA) and isolated arthritis to UA with "connective-like" accompanying symptoms. We retrospectively included 109 patients with at least 6 months of follow-up, analyzing serum biomarkers, joint ultrasound (US), lung HRCT, DLCO, and HLA haplotypes. There were 87 UA patients showing increased gastrointestinal and lung involvement (p = 0.021 and p = 0.012), higher anti-spike protein IgG levels (p = 0.003), and anti-SARS-CoV-2 IgG positivity (p = 0.003). Among them, 66 cases progressed to ACR-EULAR 2010 early arthritis after 3 months, whereas PMR-HA patients were more commonly PCV (81.8%, p = 0.008), demonstrating higher CRP (p = 0.007) and ESR (p = 0.006) levels, a lower rate of ANA positivity (p = 0.005), and a higher remission rate after six months (p = 0.050). In UA patients, the prevalent HLA was DRB1*11 and C*07 (36.8% and 42.1%). Serum calprotectin, interleukin-6, and C*07 (p = 0.021, 0.041, 0.018) seemed more specific for isolated UA. Conversely, "connective-like" arthritis showed poorer DLCO (p = 0.041) and more frequent US synovitis (p = 0.041). In conclusion, UA is a frequent common PC and PCV complication and may persist over time when compared to PMR-HA.

Airway and Systemic Immune Responses Following the Third COVID-19 Vaccination in COPD Patients.

Booster vaccinations are required to maintain protection against COVID-19. COPD patients are at higher risk of developing severe illness following SARS-CoV-2 infection. Previous cross-sectional analysis after the second COVID-19 booster showed similar immune responses in COPD patients and controls, but pre-vaccination samples were not available. This longitudinal study evaluated systemic and airway immune responses in COPD patients using samples obtained pre- and post-third COVID-19 vaccination. Twelve COPD patients were recruited, with plasma, nasal and sputum (n = 10) samples collected pre-vaccination and 4- and 14-weeks post vaccination. Samples were analyzed for anti-spike IgA and IgG and cellular immunity. The ability of plasma and nasal samples to block ACE2-spike protein interaction was assessed for Wild type, Delta, and Omicron spike variants. Vaccinations increased anti-spike IgG in plasma (p < 0.001), nasal (IgG p < 0.001) and sputum (p = 0.002) samples, IgA in plasma (p < 0.001) and blood cellular immunity (p = 0.001). Plasma and nasal anti-spike IgA levels correlated (rho: 0.6, p = 0.02), with similar results for IgG (rho: 0.79, p = 0.003). Post-vaccination nasal (p = 0.002) and plasma (p < 0.001) samples were less effective at blocking Omicron spike binding to ACE2 compared to the Wild type spike variant. Airway and systemic immune responses against SARS-CoV-2 increased in COPD patients following a third COVID-19 vaccination. Nasal and systemic responses in COPD patients were less effective against Omicron variant compared to previous variants.