IgG Titers Research Articles

Bartonella endocarditis: lessons learnt from an African cohort

Abstract Background Bartonella (B) quintana endocarditis is a preventable, vector-borne, and important cause of blood culture-negative endocarditis (BCNE). The ESC guideline for the management of endocarditis recommends blood serology (IgG titer ≥800) and polymerase chain reaction (PCR) testing on both blood and valvular tissue for diagnosis. Access to these molecular technologies is limited in Africa and there is a paucity of B. quintana endocarditis research on the continent. Purpose Record the clinical picture and explore the risk factors for disease and the diagnostic utility of immunofluorescence (IFA) in PCR-proven cases with B. quintana endocarditis. Methods Data were analysed from a prospective observational cohort study of patients with infective endocarditis managed at our institution. All BCNE cases from October 2019 to January 2024 were evaluated to identify patients with PCR-proven B. quintana on valvular tissue. A commercially available IFA was used for blood serology testing. 16S rRNA PCR testing with sequencing was performed on valvular tissue. Results Thirty five of the 58 cases (60.3%) with BCNE were diagnosed with Bartonella endocarditis. A diagnosis of PCR-proven B. quintana endocarditis was made in 21 cases. Of these, seven patients (33.3%) were either homeless or lived in informal housing. Thirteen patients (61.9%) had an alcohol-use disorder. Four patients (19%) were Human Immunodeficiency (HIV) virus- positive. Eighteen patients (85.7%) reported the onset of symptoms more than two weeks before presentation. Common presenting symptoms were dyspnea (n=21;100%), loss of weight (n=10;47.6%) and fever (n=7;33.3%). Common clinical features were digital clubbing (n=17;80.9%), pallor (n=13; 61.9%), microscopic haematuria (n=12; 57.1%) and severe regurgitant lesions (n=21; 100%). Blood serology was available in 17 patients with an IgG titer (1≥256) in all patients apart from one (1:64). Only one case (5.8%) had an IgG titre ≥800. The most common isolated valve lesion on echocardiography was severe aortic regurgitation (n=10;47.6%). Surgical replacement and repair were performed in 17(80.9%) and 4(19%) patients respectively. The one-, three- and six-month mortality was 14%, 14 % and 14% respectively. No cases of relapse were reported. Discussion B.quintana is the most prevalent cause of BCNE in our centre. The typical clinical and echocardiographic profile was consistent with the reported literature of a destructive endocarditis in a patient with a low socioeconomic background. Despite this, the surgical outcome is fair and comparable to European data. The IFA used in this study is different to the assay referenced in the ESC guideline and may explain the relatively low serology titres observed (despite PCR-proven disease). Further study with the commercial IFA is needed to determine a cut-off titre that will give a comparable sensitivity to the referenced in-house IFA.Destructive aortic valve endocarditisResultant severe aortic regurgitation

Latent cytomegalovirus infection associates with impairments in myocardial reperfusion, left-ventricular function, and quality of life after ST-elevation myocardial infarction

Abstract Introduction Cytomegalovirus (CMV) is a ubiquitous herpesvirus affecting the majority of adults in European countries. CMV influences T-lymphocyte biology throughout life. We have previously associated CMV status with adverse left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) in a single-centre study. In this study, we aimed to assess the external validity of these findings. Methods This study is a retrospective analysis of 354 patients presenting with STEMI, who were recruited to A Trial of Low-Dose Adjunctive Alteplase During Primary PCI (T-TIME) and had blood samples archived. The participants underwent immediate coronary angiography and percutaneous coronary intervention (PCI), serial cardiovascular magnetic resonance (CMR) imaging at 2-7 days and 3 months post-STEMI, and serial assessment of health-related quality of life with the standardised EQ-5D visual analogue scale (VAS). CMV IgG titre was measured in cryopreserved samples from each patient, and patients were categorised as CMV negative, low-positive or high-positive. All analyses were adjusted for infarct location. Results Of 354 patients, 175 (49.4%) were CMV IgG titre negative, 89 (25.1%) were low-positive and 90 (25.4%) were high-positive. CMV+ patients were older (62.5 vs 58.7 years) and more likely to be non-White (6.7% vs 2.3%). CMV+ patients displayed several adverse outcomes. First, myocardial reperfusion was impaired. Thrombolysis in myocardial infarction (TIMI) flow grade 3 after PCI, indicating complete reperfusion, was less common in CMV+ patients (76.0% vs 84.6%; p=0.042). CMV+ patients also had a higher TIMI frame count after PCI (p=0.021), and non-significantly less ST-segment resolution at 60 minutes (38.8% vs 48.4%; p=0.066). Impaired myocardial reperfusion appeared to lead to impaired LV function, with LV ejection fraction (LVEF) measured on early CMR lower in CMV+ patients (42.6% vs 45.3%, p=0.004). At 3 months, LV function remained impaired in CMV+ patients (LVEF: 47.8% vs 49.7%; p=0.035). This was mirrored by CMV+ patients displaying higher NT-pro BNP levels at 2-7 days (1381 vs 1172pg/mL, p=0.097) and 3 months (575 vs 338pg/mL, p=0.021). Finally, impaired LV function appeared to affect quality of life. Over 3 months, in contrast to CMV-negative patients, those with the highest CMV IgG experienced almost no improvement in quality of life, measured by change in the EQ-5D VAS (negative: +9.93; high-positive: +0.70; p=0.0002). Conclusion CMV+ patients with STEMI experience worse outcomes, with impaired reperfusion, persistently reduced LV function and less improvement in health-related quality of life over 3 months. We hypothesise that the effect of CMV is mediated through immune activation. Future research should explore the mechanisms by which CMV-specific lymphocytes interact with myocardial reperfusion and repair post-STEMI.

Seroprevalence of antibodies against diphtheria, tetanus, and pertussis across various age groups during the post-COVID-19 pandemic period in Chonburi Province, Thailand

BackgroundLimited data exists regarding population immunity against diphtheria, tetanus, and pertussis in Thailand during the post-COVID-19 pandemic period. This study aimed to evaluate the age-specific seroprevalence of anti-diphtheria toxoid (anti-DT) IgG, anti-tetanus toxoid (anti-TT) IgG, and anti-pertussis toxin (anti-PT) IgG in individuals across diverse age groups in Chonburi province, Thailand following the COVID-19 pandemic. MethodsBetween October 2022 and January 2023, a total of 657 participants from Chonburi Province, Thailand, were included in this study. The participants were categorized into 9 age groups: <5, 5–10, 11–20, 21–30, 31–40, 41–50, 51–60, 61–70, and >70 years. Analysis of anti-DT, anti-TT, and anti-PT IgG levels was conducted using commercial ELISA kits (EUROIMMUN, Lübeck, Germany). ResultsOverall, 65.4 % of the population had seroprotection against diphtheria (antibody level ≥0.1 IU/mL), while 95.1 % had seroprotection against tetanus (antibody level ≥0.1 IU/mL). The 31–40 years age group exhibited the lowest seroprotection for diphtheria (48.9 %), and the >70 years age group had the lowest seroprotection for tetanus (73.3 %). The <5 years age group showed the highest seropositive rate and highest geometric mean titers for anti-PT IgG. On the contrary, the majority of individuals over 11 years of age displayed anti-PT IgG levels below 40 IU/mL. ConclusionsTo prevent diphtheria and pertussis outbreaks in Chonburi province, implementing catch-up vaccination is necessary. Targeted interventions should be deployed to enhance vaccination coverage among the susceptible population.

The results of vaccination against novel coronavirus infection in adolescents with allergic diseases

Novel coronavirus infection requires analyzing its course in patients with allergic diseases. Patients with atopic allergic diseases remain insufficiently studied with regard to the peculiarities of the course of both the underlying allergic disease and infectious processes caused by viruses and bacteria. Epithelial cells in bronchial asthma do not respond sufficiently to interferons, suggesting that SARS-CoV-2 infection may suppress spontaneous upregulation of angiotensin-converting enzyme expression, which ultimately reduces disease severity, but at the same time makes patients with allergic atopic diseases susceptible to other viral infections. The results obtained indicate statistically significant differences in the formation of anti-RBD IgG antibodies to SARS-CoV-2 between the group of adolescents with bronchial asthma vaccinated against a new coronavirus infection and those not vaccinated against it. During the follow-up period after 6 months, a statistically significant increase in anti-RBD IgG titer to SARS-CoV-2 due to novel coronavirus infection was observed among the unimmunized children. Clinical parameters indicated a favorable course of atopic process and control of bronchial asthma exacerbations in adolescents who received vaccination against both new coronavirus infection and influenza, while those who did not receive vaccination against these viral infections had bronchial asthma exacerbations due to respiratory infection. Also among patients with bronchial asthma who received influenza vaccination, there were no cases of influenza A and bronchial asthma exacerbations due to respiratory infections. In this regard, influenza vaccination is an important intervention to maintain control of asthma exacerbations. It is noteworthy that no new coronavirus infection was reported among vaccinated adolescents within a year after immunization. At the same time, 6 months after vaccination against a new coronavirus infection, we observed a statistically significant increase in antibody levels in unvaccinated adolescents, indicating the presence of high viral neutralizing activity. Vaccination against novel coronavirus infection in patients with bronchial asthma may be considered a possibility.

Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors.

Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

Venom immunization: IgG/IgE titers, safety, risk, and methods of the VIPRBITEM cohort

Background: This is the first study to examine a cohort that engages in the practice of immunization with snake venoms. In this practice, either fresh wet venom or venom reconstituted from freeze-dried form is used in vaccination protocols to produce hyper-immunity to venom. Methods: This is a retrospective community-initiated collaborative research (CICR) project that collated the records of venom immunization. Records of schedules, formulations, photographs, medical records, and diaries were collated from existing practitioners and evaluated by inspection and interviews. One accidental bite was observed over 3 days, with vital signs, and photographic records of swelling taken to verify reality of the bite. Over 74 snake-genera man-years, and 24 man-years of injection data from 8 participants, for 22 species of venomous snakes from Elapidae and Viperidae are represented. Six of those participants had detailed records of date, dose and effects. Results: IgG titers to 6 venoms for 4 cohort members tested of 8 included 2 with clear hyper-immune status. IgE titers were elevated for some. In 861 injections, records showed a rate of atopy/anaphylaxis of 4.3% , an infection rate of 0.58% and an abscess rate of 1.51% . Serious adverse reactions were rare and these appeared to be linked to overly aggressive immunization schedules and formulation accidents. We note that greater cross-immunity of IgE over IgG is suggested. Two basic protocols were followed, one was an approximate one month interval, the other was one or more injection(s) per week. In 176 envenomations, 175 were without antivenom treatment, two hospitalizations occurred, and one received full antivenom treatment. Dry bites were not included in our dataset. Envenomations showed a 1.14% rate of atopy/anaphylaxis, a 0.57% rate of infection and a 1.7% rate of abscess. Conclusions: Immunization of humans to snakebite is effective, and reasonably safe with care. Injection records suggest immune cross-reactivity between ophidians within the same family, and better cross-reactivity within the same genera. A cohort participant was pronounced dead based on EEG, and then recovered without treatment. A neurotoxin case with &amp;ldquo;brain death&amp;rdquo; EEG should stay on life support for 6 weeks to allow time for the immune system to clear venom.

Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa.

To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent to which the currently used messenger RNA (mRNA)-based COVID-19 vaccines induce mucosal immunity remains poorly characterized. We evaluated mucosal neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector-based or mRNA-based COVID-19 vaccination and after mRNA-based booster vaccinations. Our findings revealed that repeated vaccination with mRNA boosters promoted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies in nasal secretions. Nasal and serum neutralizing antibody titers of both IgG and IgA isotypes correlated to one another. We investigated the source of these mucosal antibodies in a mouse model wherein mice received repeated mRNA vaccines for SARS-CoV-2. These experiments indicated that neutralizing antibody-producing cells reside in the spleen and bone marrow, whereas no proof of tissue homing to the respiratory mucosa was observed, despite the detection of mucosal antibodies. Serum transfer experiments confirmed that circulating antibodies were able to migrate to the respiratory mucosa. Collectively, these results demonstrate that, especially upon repeated vaccination, the currently used COVID-19 mRNA vaccines can elicit mucosal neutralizing antibodies and that vaccination might also stimulate mucosal immunity induced by previous SARS-CoV-2 infection. Moreover, migration of circulating antibodies to the respiratory mucosa might be a main mechanism. These findings advance our understanding of mRNA vaccine-induced immunity and have implications for the design of vaccine strategies to combat respiratory infections.

Cellular and humoral immunity and IgG subclass distribution after omicron XBB.1.5 monovalent vaccination in Japan

BackgroundUp to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7. ObjectiveAlthough the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world. Study designTwenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed. ResultsWe found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups. ConclusionsThe study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance.

C1q Binding Ability for Prior Risk Assessment of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

In ABO blood group incompatible kidney transplantation (ABO-I), potential issues on acute antibody-mediated rejection (ABMR) remain to be solved. This study aimed to assess the risk factors of acute ABMR using recipient- or donor-derived specimens. Quantitative analysis of A/B antigen expression was conducted in 104 donor kidney tissues (Kt), platelets (Plt), and red blood cells (RBC) by immunohistochemical staining or flow cytometry (FCM). ABO-I pre-transplant recipient serum samples (ABMR = 12, non-ABMR = 27) were extracted by propensity score matching. Anti-A antibody titers of IgM, IgG and IgG subclasses, and C1q binding ability (%) on antibody were measured using RBC-FCM. No association was observed between ABMR and A/B antigen expression levels in donor's Plt, RBC, or Kt. In recipient's sample, C1q-IgG binding ability was significantly higher in the ABMR group than in the non-ABMR group (C1q-IgG: 9.04% vs. 5.93% p = 0.049). Neither the A/B antigen expression level in donors (grafts) nor anti-blood group IgG/IgM antibodies in recipient sera before desensitization seemed to influence ABMR incidence in ABO-I. In contrast, C1q-IgG binding ability could be a potential predictor for ABMR in ABO-I.

Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts.

Systemic administration of nanomedicines results in the activation of the complement cascade, promoting phagocytic uptake and triggering proinflammatory responses. Identifying the biomarkers that can predict the "risk" of abnormally high complement responders can improve the safety and efficacy of nanomedicines. Polyethylene glycol (PEG) and dextran are two types of clinically approved polymer coatings that trigger complement activation. We performed a multifaceted analysis of the factors affecting the complement activation by PEGylated liposomal doxorubicin (PLD) and dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs) in plasma from patients with different inflammatory disease conditions and healthy donors. The complement activation (measured as deposition of the complement protein C3) varied greatly, with 29-fold and 26-fold differences for PLD and SPIO NWs, respectively. Chronic inflammation, acute infection, use of steroids, and sex had minor effects on the variable complement activation, whereas age inversely correlated with the complement activation. C-reactive protein level was not predictive of high (top 20th percentile) complement responses. Plasma concentrations of the main complement factors, as well as total IgG and IgM, showed no correlation with the activation by either nanoparticle. On the other hand, plasma concentrations of anti-PEG IgG and IgM showed a strong positive correlation with the activation by PLD. Particularly, titers of anti-PEG IgM showed the best predictive value for the "risk" of high complement activation by PLD. Titers of antidextran IgG and IgM showed a lower correlation with the activation by SPIO NWs and poor predictive value of the top 20% complement responses. Nanoparticle-bound immunoglobulins showed the best correlation with complement activation and a strong predictive value, supporting the critical role of immunoglobulins in inciting complement. The opsonization of PLD with C3 in plasma with high anti-PEG antibodies was predominantly via the alternative pathway. Characterizing the nature of nanoparticle-binding antibodies has important implications in mitigating and stratifying nanomedicine safety.

Factors Associated with IgG/IgM Levels after SARS-CoV-2 Vaccination in Patients with Head and Neck Cancer.

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient's demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time.

Symptomatology and IgG Levels before and after SARS-CoV-2 Omicron Breakthrough Infections in Vaccinated Individuals.

(1) Background: After the COVID-19 pandemic, there is concern regarding the immunity of the population to SARS-CoV-2 variants, particularly the Omicron variant and its sub-lineages. (2) Methods: The study involved analyzing the immune response and symptomatology of 27 vaccinated individuals who were subsequently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. The levels of anti-Spike IgG found prior to infection did not correlate with symptom intensity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlated with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in symptom intensity. (4) Conclusions: In line with previous studies, the high levels of IgG anti-Spike resulting from vaccination did not provide complete protection against infection by the Omicron variant. Additionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections.

Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation.

Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

Sex, vaccination status, and comorbidities influence long COVID persistence

BackgroundThere is interest in the public health impact of Long COVID, defined as symptoms that persist or begin after SARS-CoV-2 infection. We aimed to identify demographic and clinical risk factors associated with Long COVID over time in an Upper Middle-Income Country (UMIC) and potential biomarkers predictive of symptom trajectory. MethodsProspective cohort study of adults with mild SARS-COV-2 during the Omicron period. We tracked symptom persistence and IgG antibody titers against the spike S1 subunit. ResultsOf 383 participants, 276 had confirmed SARS-CoV-2 infection. Long COVID persisted for ≥ two months in 21 % and ≥ 12 months in 5 %. The most common symptoms were fatigue, upper respiratory symptoms, and myalgia/arthralgia: 15 % had fatigue for ≥ one month, 10 % for ≥ two months, and 5 % ≥ three months. Upper respiratory symptoms lasted ≥ one month in 17 %, ≥ two months in 7 %, and ≥ three months in 3 %. Fully 9 % reported myalgia/arthralgia lasting ≥ one month, 6 % ≥ two months, and 4 % ≥ three months. Risk factors for symptom persistence included female sex, not being fully vaccinated, and comorbidities. Participants experiencing persistent fatigue had lower anti-S1 IgG titers. ConclusionsIn this population, symptom persistence declined after the acute phase, but 5 % of participants did not fully recover. Even in a population that was almost fully vaccinated, women, individuals with comorbidities, and the few remaining people who were unvaccinated were at greater risk for Long COVID. Immunoglobulins may have utility as a biomarker of Long COVID fatigue in this population.

The Influence of Initial Immunosuppression on the Kinetics of Humoral Response after SARS-CoV-2 Vaccination in Patients Undergoing Kidney Transplantation.

Background: The effect of initial immunosuppressive therapy on the kinetics of the SARS-CoV-2 vaccine-induced humoral response is unknown. Here, we compared the kinetics of SARS-CoV-2 vaccine-induced humoral response in chronic kidney disease patients undergoing kidney transplantation (KTRs) and compared to patients remaining on dialysis during the Omicron circulation. Methods: This prospective, non-randomized, real-world study included 113 KTRs and 108 patients on dialysis. Those with previous COVID-19 or negative IgG at screening were excluded. Blood samples were collected to assess SARS-CoV-2 IgG titers and neutralizing antibodies at months (M) 1, 3, 6, and 12. Results: Seroreversion occurred in one KTR and in three patients on dialysis. KTRs had lower IgG titers over time (M1: 10,809.3 ± 12,621.7 vs. 15,267.8 ± 16,096.2 AU/mL; M3: 12,215.5 ± 12,885.8 vs. 15,016.2 ± 15,346.1 AU/mL; M6: 12,540.4 ± 13,010.7 vs. 18,503.5 ± 14,581.0 AU/mL; p = 0.005), but neutralizing antibodies were similar (M1: 94.0 vs. 90.3%; M3: 92.9 vs. 90.5%; M6: 99.0 vs. 95.5%; M12: 98.9 vs. 97.5%; p = 0.812). During follow-up, KTRs received more vaccines (141 vs. 73; p < 0.001) and contracted more COVID-19 (32.7% vs. 14.8%; p = 0.002). Conclusions: Compared to patients on dialysis, KTRs had lower SARS-CoV-2 IgG titers and similar rates of seroreversion and neutralizing antibodies over time. Although KTRs received more boosters, they had a higher incidence of COVID-19.

Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors

INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.

Management of protective lung ventilation in children with a critical course of acute respiratory distress syndrome caused by SARS-CoV-2 coronavirus infection

the pandemic of coronavirus disease COVID-19 has created a serious threat to the public health system worldwide. With the beginning of the pandemic, it became clear that children infected by SARS-CoV-2, for unknown reasons, have a milder course compared to adults. In some cases, children are asymptomatic carriers of the infection. In light of today's scientific discoveries, contrary to initial reports, recent studies have shown that children are just as likely to contract the virus as adults, while vague symptoms and a milder course more often characterize the disease itself. However, it is worth noting that the true prevalence of asymptomatic SARS-CoV-2 infection is most likely underestimated since children are not tested for COVID-19 without obvious clinical symptoms. This fact has been confirmed by multiple blood tests indicating high titers of IgG to SARS-CoV-2. Compared to adults, the typical clinical manifestations of COVID-19 in children are fever, runny nose, cough, and general weakness. The laboratory test results indicate a normal level of leukocytes, lymphopenia, and an increased level of aspartate aminotransferase, alanine aminotransferase, D-dimer, and MB creatine kinase. Currently, there is no sufficient evidence that the etiotropic therapy is 100% successful. Yet a course of action such as respiratory system protection, control of fluids and electrolyte homeostasis, anti-cytokine therapy, preventative measures for thrombosis, and treatment for bacterial superinfection proved to be efficient at preventing the development of possible complications caused by SARS-CoV-2. Therefore, it is important to collect and accumulate new experiences\cases of respiratory system protection management of an acute respiratory syndrome with a critical course of acute respiratory distress syndrome caused by COVID-19 and implement practical treatment plans for healthcare facilities. The results were analyzed using clinical epidemiology methods. Children were admitted to the intensive care unit on an average of 6,6±0,62 days of illness and were more associated with systemic disorders and water-electrolyte imbalance, which required prosthetic respiratory function, correction of hemodynamics and water-electrolyte disorders, which was carried out in the infectious diseases department of anesthesiology and intensive care for an average of 5,2±0,7 days. In children in the clinical group, SARS-CoV-2 was verified by reverse transcription polymerase chain reaction of a nasopharyngeal swab and/or exhaled air condensate based on its positive results. Comprehensive treatment of patients with severe and extremely severe respiratory distress syndrome in coronavirus disease included respiratory and hemodynamic support, antiviral and antibacterial therapy, parenteral glucocorticosteroids and anticoagulants, which was in line with current national regulatory guidelines and local protocols. According to the criteria for choosing a method of respiratory function prosthetics, in more than half of the patients (62,2%) with hemoglobin oxygen saturation of less than 92%, while maintaining active respiratory capacity, respiratory support was provided by supplementing humidified oxygen through a face mask or nasal cannulas. In another 29,7% of patients, non-invasive ventilation was performed by constant positive airway pressure, with an oxygenation index of 0,4-0,5 and a positive end-expiratory pressure of 4-5 cm of water column. Children who had a critical course of acute respiratory syndrome caused by coronavirus infection COVID-19 (8,1%) and in whom non-invasive methods of respiratory support did not bring the desired therapeutic result were on invasive ventilation in the mode of auxiliary controlled ventilation or in the mode of synchronized intermittent forced ventilation. It should be noted that children who received respiratory support in the form of non-invasive ventilation by means of constant positive airway pressure required a lower concentration of oxygen in the inhalation mixture compared to patients on free-flow oxygen supplementation. The need for admission to the intensive care unit of children with COVID-19 is primarily associated with respiratory disorders caused by interstitial pneumonia. Oxygen supplementation was of paramount importance in patient management, primarily through noninvasive ventilation with constant positive airway pressure or free flow. The use of a pulmonary protective strategy in the treatment of acute respiratory distress syndrome caused by coronavirus disease COVID-19 in children requiring invasive ventilation was accompanied by a pronounced positive result, as it was not accompanied by side effects and resulted in a rapid recovery of patients.

Exploratory study of antibody titers against SARS-CoV-2 using an indirect immunoperoxidase assay in COVID-19 patients and vaccinated volunteers

BackgroundA number of antibody test kits for detecting prior SARS-CoV-2 infection and post-immunization status have been commercialized. Indirect immunoperoxidase assay (IIP) is a conventional method to test antibodies. We evaluated the diagnostic accuracy and antibody titer profile of the IIP in COVID-19 and pre- and post-vaccination.MethodsWe conducted a hospital-based observational study in Fukushima prefecture, Japan. We enrolled COVID-19 inpatients who tested positive by PCR. We used serum samples collected > 10 years before the pandemic as the negative control. We also included volunteers vaccinated at the hospital. All participants were tested using an IIP with whole-cell antigen of the six SARS-CoV-2 variants isolated in Japan during the epidemic and an IgG ELISA kit. Negative controls and vaccinated volunteers were also tested using a lateral flow assay (LFA) kit. We conducted receiver operating characteristic (ROC) analysis to evaluate diagnostic accuracy and performed logistic regression analysis to explore factors associated with antibody titer.ResultsWe included 146 COVID-19 inpatients, 38 negative controls, and 36 vaccinated volunteers. Most participants had the highest titer for IgG and IgM in the wild type-A antigen among the six variants. The sensitivity, specificity, and accuracy of the IgG ELISA kit were 60.3%, 100%, and 68.5%; of the IIP for IgG with the cutoff titer at 1:80, 82.2%, 94.7%, and 84.8%, respectively. The ROC curves of the ELISA and IIP for IgG were almost identical. In the IgG tests of the 36 volunteers, 35 were positive for ELISA and IIP and 34 for LFA after two vaccinations. IgM titers in the IIP were < = 1:40 in 114 patients and 32 volunteers after two vaccinations; therefore, the IgM titer is unsuitable for diagnosis. In COVID-19 patients, age, days from disease onset, > = 7 days after the second vaccination, and immunosuppressants for comorbidity were associated with IgG titer of > = 1:640 in the IIP.ConclusionsThe diagnostic accuracy of the IIP for detecting IgG antibodies in COVID-19 or after two vaccinations is equivalent to that of an ELISA. Further investigations are required to address the association between antibody titers in the IIP and their protective or harmful effects against COVID-19.

SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly even though SARS-CoV-2-specific plasma cells can be found in the bone marrow (BM). Here, to explore this paradox, we enrolled 19 healthy adults at 2.5-33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. The ratios of non-LLPC:LLPC for influenza, tetanus and SARS-CoV-2 were 0.61, 0.44 and 29.07, respectively. In five patients with known PCR-proven history of recent infection and vaccination, SARS-CoV-2-specific ASCs were mostly absent from the LLPCs. We show similar results with measurement for secreted antibodies from BM ASC culture supernatant. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within 3-6 months after vaccination, were associated with IgG non-LLPCs. In all, our studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.

Antibody response to SARS-CoV-2 natural and breakthrough infection in patients undergoing maintenance hemodialysis: A prospective cohort study over 4 months

BackgroundPatients undergoing maintenance hemodialysis (MHD) are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the antibody response of these patients to natural and breakthrough infections remains poorly understood. MethodsBetween January 15, 2023, and February 15, 2023, a total of 53 patients undergoing MHD and diagnosed with SARS-CoV-2 infection at The Affiliated Hospital of Hangzhou Normal University were enrolled. They were categorized into the natural (n = 40) and breakthrough infection groups (n = 13) based on their vaccination status before infection. Comprehensive data, including basic clinical information, vaccination status, and routine post-infection blood parameters, were collected from all participants. Blood specimens were drawn monthly after infection, and SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin (Ig) G and IgM tests were conducted. The study included continuous follow-up over 4 months. ResultsDuring the acute phase of infection, the SARS-CoV-2 RBD IgM positivity was 5 % in patients undergoing MHD who were naturally infected and 15.4 % in those with breakthrough infections. Four months after infection, SARS-CoV-2 RBD IgG positivity in patients with natural and breakthrough infection was 77.5 % and 100 %, respectively. Patients undergoing MHD with breakthrough infection exhibited higher SARS-CoV-2 RBD IgG titers (751.21 signal-to cutoff ratio, S/CO [interquartile range, IQR, 30.54–1173.63]) than those with natural infections (3.43 S/CO [IQR, 1.12–15.6]) (p < 0.0001). No significant differences were observed in SARS-CoV-2 RBD IgG between males and females or among those aged <70 and ≥70 years. Patients who received three doses of the inactivated vaccine produced significantly higher SARS-CoV-2 RBD IgG levels after infection than those who received one or two doses; these differences were significant. ConclusionsAlthough patients undergoing MHD exhibit a low rate of SARS-CoV-2 RBD IgM positivity following infection, those vaccinated with inactivated vaccines can generate elevated SARS-CoV-2 RBD IgG levels, particularly those who receive three doses.