Immunodeficient Individuals Research Articles

Anamnestic expansion of Omicron-reactive CD8 +T cells after booster SARS-CoV-2 mRNA vaccination across different immunocompromised states

Abstract Restricted immune responses to SARS-CoV-2 mRNA vaccination have been observed frequently in individuals suffering from various immunodeficiencies. With increased antibody evasion properties of rising Omicron subvariants, there is a need to assess if other components of adaptive immunity generate resilient responses against SARS-CoV-2 across immunodeficient states. Here we assessed T cell responses of n=279 individuals covering five different immunodeficiencies and healthy controls before and after booster vaccination and - in a subset of patients - additional Omicron infection. We observed significantly increased Omicron-reactive T cell responses upon booster vaccination, particularly in initial poor responders, across all patient groups. Overall T cell composition shifted towards an increased CD8/CD4-ratio, which was accompanied by a more pronounced cytotoxic profile. Moreover, Omicron-reactive T cell responses showed signs of longevity represented by a novel T EMRAsubpopulation with stem-cell-like characteristics and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals were protected against severe disease and exhibited ameliorated and diversified T cell responses directed explicitly against Omicron, despite a solid immunological imprint of multiple wildtype Wuhan-based vaccine doses. Supported by grants from SciLifeLab National COVID-19 Research Program and financed by the Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm (Clinical research position-, ALF-, and CIMEDgrants). TRM is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, project: 496946670).

Immunomodulatory Effects of the Pea Defensin Psd1 in the Caco-2/Immune Cells Co-Culture upon Candida albicans Infection.

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.

A case report of brainstem hemorrhage due to Rhizopus delemar-induced encephalitis diagnosed by metagenomic next-generation sequencing (mNGS)

BackgroundRhizopus delemar is an invasive fungal pathogen that can cause fatal mucormycosis in immunodeficient individuals. Encephalitis caused by R. delemar is rare and difficult to diagnose early. Clinical detection methods for R. delemar include blood fungal culture, direct microscopic examination, and histopathological examination, but the detection is often inadequate for clinical diagnosis and can easily lead to missed diagnosis with delayed treatment.Case presentationWe report a case of a 47-year-old male with brainstem hemorrhage caused by encephalitis due to R. delemar. The patient had a history of hypertension, type 2 diabetes, and irregular medication. No pathogens were detected in cerebrospinal fluid (CSF) and nasopharyngeal secretion cultures. R. delemar was identified by metagenomic next-generation sequencing (mNGS) in CSF, and in combination with the patient’s clinical characteristics, encephalitis caused by R. delemar was diagnosed. Antibiotic treatment using amphotericin B liposome in combination with posaconazole was given immediately. However, due to progressive aggravation of the patient’s symptoms, he later died due to brainstem hemorrhage after giving up treatment.ConclusionsmNGS technique is a potential approach for the early diagnosis of infections, which can help clinicians provide appropriate antibiotic treatments, thus reducing the mortality and disability rate of patients.

Pathogen regulatory RNA usage enables chronic infections, T-cell exhaustion and accelerated T-cell exhaustion.

Pathogens evade or disable cellular immune defenses using regulatory ribonucleic acids (RNAs), including microRNAs and long non-coding RNAs. Pathogenic usage of regulatory RNA enables chronic infections. Chronic infections, using host regulatory RNAs and/or creating pathogenic regulatory RNAs against cellular defenses, can cause T-cell exhaustion and latent pathogen reactivations. Concurrent pathogen infections of cells enable several possibilities. A first pathogen can cause an accelerated T-cell exhaustion for a second pathogen cellular infection. Accelerated T-cell exhaustion for the second pathogen weakens T-cell targeting of the second pathogen and enables a first-time infection by the second pathogen to replicate quickly and extensively. This can induce a large antibody population, which may be inadequately targeted against the second pathogen. Accelerated T-cell exhaustion can explain the relatively short median and average times from diagnosis to mortality in some viral epidemics, e.g., COVID-19, where the second pathogen can lethally overwhelm individuals' immune defenses. Alternatively, if an individual survives, the second pathogen could induce a very high titer of antigen-antibody immune complexes. If the antigen-antibody immune complex titer quickly becomes very high, it can exceed the immune system's phagocytic capability in immuno-deficient individuals, resulting in a Type III hypersensitivity immune reaction. Accelerated T-cell exhaustion in immuno-deficient individuals can be a fundamental cause of several hyperinflammatory diseases and autoimmune diseases. This would be possible when impaired follicular helper CD4+ T-cell assistance to germinal center B-cell somatic hypermutation, affinity maturation and isotype switching of antibodies results in high titers of inadequate antibodies, and this initiates a Type III hypersensitivity immune reaction with proteinase releases which express or expose autoantigens.

Clinical Features of Pediatric Age Herpes Simplex Virus Keratitis.

The objective of this study is to evaluate the clinical features of pediatric herpes simplex virus keratitis, its recurrence rates, and its effects on visual acuity. In this retrospective case series, records of pediatric patients (0-16 years) who presented with herpes simplex virus keratitis between January 2012 and September 2021 were evaluated. Data including age, gender, additional systemic diseases, the number of recurrences, recurrence time, treatment protocol, follow-up period, and presence of amblyopia were reviewed. Twenty-four patients (16 females and 8 males) with a mean age of 6.6 ± 4 (1.1-15) years were included in the study. The mean follow-up time was 21 ± 19.9 (7-94) months. Four patients (16.6%) had bilateral keratitis. Including all 4 patients with bilateral involvement, a total of 10 (41.6%) patients had additional systemic diseases that cause immunodeficiency. After prophylactic antiviral treatment for at least 6 months (except for isolated epithelial keratitis), recurrence was detected in 5 (22.7%) patients, who were all immunodeficient. Among immunodeficient individuals, the recurrence rate was found to be 50%. Keratitis recurrence was significantly associated with immunodeficiency ( P = 0.03). However, type of keratitis ( P = 0.42), gender ( P = 0.47), and bilaterality ( P = 0.54) were not related with recurrence. 66.7% of the patients younger than 10 years developed amblyopia during follow-up. In childhood, the most frequent corneal manifestation of herpes simplex virus is stromal keratitis that mostly progresses with corneal scarring, residual astigmatism, and amblyopia. The recurrence rate increases in the presence of immunosuppression. Close follow-up, rapid diagnosis, and treatment are critical for battling against amblyopia and achieving good visual prognosis.

Immune globulin usage trends in commercially insured and Medicare populations, 2009-2019.

Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life-saving/health-preserving therapy. The study describes US IG utilization patterns from 2009 to 2019. Using IBM MarketScan commercial and Medicare claims data, we examined four metrics overall and by condition-specific categories during 2009-2019: (1) IG administrations per 100,000 person-years, (2) IG recipients per 100,000 enrollees, (3) average annual administrations per recipient, and (4) average annual dose per recipient. In the commercial and Medicare populations respectively: IG administrations per 100,000 person-years increased by 120% (213-470) and 144% (692-1693); IG recipients per 100,000 enrollees grew by 71% (24-42) and 102% (89-179); average annual administrations per recipient rose by 28% (8-10) and 19% (8-9); and average annual dose (grams) per recipient increased by 29% (384-497) and 34% (317-426). IG administrations associated with immunodeficiency (per 100,000 person-years) increased by 154% (from 127 to 321) and 176% (from 365 to 1007). Autoimmune and neurologic conditions were associated with higher annual average administrations and dose than other conditions. IG use increased, coinciding with a growth in the IG recipient population in the United States. Several conditions contributed to the trend, with the largest increase observed among immunodeficient individuals. Future investigations should assess changes in the demand for IVIG by disease state or indication and consider treatment effectiveness.

Conjoint Citizen Participation of Pro-vaxxers and Vaccine Deniers to Eradicate Vaccination Conflicts: Illuminating a Novel Win-Win Pathway

Conflicts among pro-vaxxers and vaccine deniers will remain endless if both these groups fail to view vaccination through an unusual lens agreeable to both. Citizen participation encourages people to get involved in decision-making processes to build a better society or nation. Pro-vaxxers and vaccine deniers might be correct from their health activism and citizen participation standpoint but lack effective basis towards scientific precision. Under such circumstances, it is important to scrutinize if any aspect of the science remains neglected to facilitate resolving persistent conflicts. Lack of immunological tests to objectively measure the natural and adaptive immunity could have been instrumental in vaccination disputes. Epidemiological findings and publications should not be solely trusted to devise public health strategies. Affordable and precise immunological tests to prove the necessity and efficacy of vaccination on an individual level should be discovered to equally benefit pro-vaxxers and vaccine deniers. Perhaps, such immunological tests should be made disease-specific and vaccine-specific, and also enable development of an immunological classification system with gradations for immunocompetent and immunodeficient individuals. If disease-specific immunological tests are unavailable or cannot be discovered, tests based on homeostasis could be the best alternative but the relationship between homeostasis and immunity is surprisingly neither well established nor widely discussed, thus, immunity may be often seen as an ‘isolated’, ‘vaccine-dependent’ department in the human body. Any prophylactic intervention or treatment should upbring measurable changes in homeostasis of an individual to prove its scientific credibility. Ideally, both pro-vaxxers and vaccine deniers should be labeled as ‘defeated’ in their meaningless tug-of-war for being ignorant about “objective immunoassays”. As citizens, the pro-vaxxers and vaccine deniers have important onus to eradicate vaccination disputes by exploring what is equally relevant and beneficial to both of them to evaluate and regulate their immunity to ensure satisfactory personal health and community health, without any obligation to be sacrificial to justify the authenticity of their citizen participation. A scope for pro-vaxxers and vaccine deniers to work together (conjoint citizen participation) to eradicate vaccination conflicts is possible only based on ‘affordable and reliable immunological test’ to clinically examine themselves and clearly interpret if they are genuinely contributing to herd immunity or sabotaging herd immunity through their personal immune status. Even a single individual could contribute to massive scientific transformations through his or her discoveries, or just through critically questioning established scientific practices, and this is how naturally science evolves as a marvelous product of intellectual humility. Pseudoscience evolves as a malevolent product of intellectual arrogance. Keywords: Citizen Participation, Vaccination, Immunology, Pro-vaxxers, Vaccine deniers, Herd immunity, Antibodies, Innate immunity, Adaptive immunity, Immunological memory

Early immune and host cell responses to Cryptosporidium infection.

Cryptosporidium spp. are opportunistic protozoan parasites that infect epithelial cells of the small intestine and cause diarrheal illness in both immunocompetent and immunodeficient individuals. These infections may be more severe in immunocompromised individuals and young children, especially in children under 2 in developing countries. The parasite has a global distribution and is an important cause of childhood diarrhea where it may result in cognitive impairment and growth deficits. Current therapies are limited with nitazoxanide being the only FDA-approved drug. However, it is not efficacious in immunocompromised patients. Additionally, there are no vaccines for cryptosporidiosis available. While acquired immunity is needed to clear Cryptosporidium parasites completely, innate immunity and early responses to infection are important in keeping the infection in check so that adaptive responses have time to develop. Infection is localized to the epithelial cells of the gut. Therefore, host cell defenses are important in the early response to infection and may be triggered through toll receptors or inflammasomes which induce a number of signal pathways, interferons, cytokines, and other immune mediators. Chemokines and chemokine receptors are upregulated which recruit immune cells such neutrophils, NK cells, and macrophages to the infection site to help in host cell defense as well as dendritic cells that are an important bridge between innate and adaptive responses. This review will focus on the host cell responses and the immune responses that are important in the early stages of infection.

Immunological Indicators of Pink Salmon Oncorhynchus during the Marine Phase of their Life Cycles

A comparative study of some parameters of nonspecific immunity in sexually mature individuals of pink salmon and chum salmon caught on June 6–July 1, 2018 by an epipelagic trawl in the open waters of the northwestern part of the Pacific Ocean was carried out. The level of antimicrobial properties of blood serum and nonspecific immune complexes in the tissues of the kidney, spleen and liver and the proportion of immunodeficient individuals were studied. Significant differences in the antimicrobial properties of blood serum and immunodeficient individuals were found. These differences are probably due to species characteristics, as well as the pre-spawning period of the annual cycle in pink salmon.

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients.

Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination. Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.

Relation of salivary MMP-8 with oral submucous fibrosis and oral squamous cell carcinoma: a cross sectional analytical study

ObjectivesWe aim to evaluate salivary matrix metalloproteinases (MMP-8) levels in oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) for the purpose of diagnosis at the early stage via...

Malaria an opportunistic infection in HIV/AIDS patients? - A Nigerian experience.

HIV and malaria interact at the level of the host's susceptibility to infection, but little is known about the effect of HIV on malaria infection in Nigeria. This study estimated the prevalence of malaria parasitaemia and its relationship with HIV immunodeficiency. This cross-sectional study was conducted in two hospitals in Abuja, Nigeria between October 2012 and March 2013 among 600 respondents, comprising 200 HIV-negative controls, 200 HIV-positive patients on antiretroviral therapy (ART), and 200 HIV-positive patients not on ART. Malaria parasites, malaria density and absolute CD4 counts were carried out on all three groups. Participants with CD4 counts below 350 cells/mm3 were considered immunocompromised and likely to develop opportunistic infections. Most study participants were aged 21-40 years (65.2%). The mean CD4 counts of HIV-positive patients not on ART (300 ± 211 cells/mm3) and those on ART (354 cells/mm3) were significantly lower than among controls (834 cells/mm3) (p < 0.001). Malaria prevalence was not statistically different between the controls (44.5%), patients on ART (40.5%), and those not on ART (39.5%) (p = 0.562). Compared to 7% immunodeficiency among controls, 56% of patients on ART and 65.5% of those not on ART had a CD4 count < 350 cells/mm3 (p < 0.001). The prevalence of malaria parasitaemia among immunodeficient individuals (42.4%) was similar to prevalence among those with CD4 counts > 350 cells/mm3 (40.8%; p = 0.695). These findings suggest that malaria parasitaemia is not an opportunistic infection among HIV-positive individuals in Nigeria.

The Medawar Prize Acceptance Speech 2022.

The Medawar Prize Acceptance Speech 2022.

Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency.

The rise in nosocomial infections caused by multidrug-resistant pathogens is a major public health concern. Patients taking immunosuppressants or chemotherapeutics are naturally more susceptible to infections. Thus, strategies for protecting immunodeficient individuals from infections are of great importance. Here, we investigate the effectiveness of a biomimetic nanotoxoid vaccine in defending animals with immunodeficiency against Pseudomonas aeruginosa. The nanotoxoids use a macrophage membrane coating to sequester and safely present bacterial virulence factors that would otherwise be too toxic to administer. Vaccination with the nanoformulation results in rapid and long-lasting immunity, protecting against lethal infections despite severe immunodeficiency. The nanovaccine can be administered through multiple routes and is effective in both pneumonia and septicemia models of infection. Mechanistically, protection is mediated by neutrophils and pathogen-specific antibodies. Overall, nanotoxoid vaccination is an attractive strategy to protect vulnerable patients and could help to mitigate the threat posed by antibiotic-resistant superbugs.

Recurrent SARS-CoV-2 mutations in immunodeficient patients.

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

SARS-CoV-2 pre-exposure prophylaxis: A potential COVID-19 preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders.

The unprecedented worldwide spread of SARS-CoV-2 has imposed severe challenges on global health care systems. The roll-out and widespread administration of COVID-19 vaccines has been deemed a major milestone in the race to restrict the severity of the infection. Vaccines have as yet not entirely suppressed the relentless progression of the pandemic, due mainly to the emergence of new virus variants, and also secondary to the waning of protective antibody titers over time. Encouragingly, an increasing number of antiviral drugs, such as remdesivir and the newly developed drug combination, Paxlovid® (nirmatrelvir/ritonavir), as well as molnupiravir, have shown significant benefits for COVID-19 patient outcomes. Pre-exposure prophylaxis (PrEP) has been proven to be an effective preventive strategy in high-risk uninfected people exposed to HIV. Building on knowledge from what is already known about the use of PrEP for HIV disease, and from recently gleaned knowledge of antivirals used against COVID-19, we propose that SARS-CoV-2 PrEP, using specific antiviral and adjuvant drugs against SARS-CoV-2, may represent a novel preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders. Herein, we critically review the risk factors for severe COVID-19 and discuss PrEP strategies against SARS-CoV-2. In addition, we outline details of candidate anti-SARS-CoV-2 PrEP drugs, thus creating a framework with respect to the development of alternative and/or complementary strategies to prevent COVID-19, and contributing to the global armamentarium that has been developed to limit SARS-CoV-2 infection, severity, and transmission.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment

BackgroundCytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity.MethodsThe antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo.ResultsMPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently.ConclusionThe present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.Graphical

Characteristics of COVID-19 Breakthrough Infections among Vaccinated Individuals and Associated Risk Factors: A Systematic Review.

We sought to assess breakthrough SARS-CoV-2 infections in vaccinated individuals by variant distribution and to identify the common risk associations. The PubMed, Web of Science, ProQuest, and Embase databases were searched from 2019 to 30 January 2022. The outcome of interest was breakthrough infections (BTIs) in individuals who had completed a primary COVID-19 vaccination series. Thirty-three papers were included in the review. BTIs were more common among variants of concern (VOC) of which Delta accounted for the largest number of BTIs (96%), followed by Alpha (0.94%). In addition, 90% of patients with BTIs recovered, 11.6% were hospitalized with mechanical ventilation, and 0.6% resulted in mortality. BTIs were more common in healthcare workers (HCWs) and immunodeficient individuals with a small percentage found in fully vaccinated healthy individuals. VOC mutations were the primary cause of BTIs. Continued mitigation approaches (e.g., wearing masks and social distancing) are warranted even in fully vaccinated individuals to prevent transmission. Further studies utilizing genomic surveillance and heterologous vaccine regimens to boost the immune response are needed to better understand and control BTIs.

Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant

Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient.

P072 Audit on the uptake of COVID-19 vaccination in biologic patients with autoimmune conditions

Background/AimsCoronavirus-2 (SARS-CoV-2) has become a disastrous pandemic since its first outbreak in December 2019. Until 8th of October, 2021, more than 239 million people were infected by COVID-19 leading to over 4.8 million deaths. While vaccines and drugs are two arms in controlling the pandemic, safe and effective vaccines are one of the most reliable interventions to suppress viral transmission. Patients with specific immunological deficits, such as patients with autoimmune diseases or those receiving immunosuppressive need special attention. Besides, vaccination in these patients is problematic due to the probable suppression or over-activation of the immune system. However, there still remain questions about the efficacy and safety of vaccination in immunocompromised patients. Studies are ongoing into the safety and immunogenicity of approved of SARS-CoV-2 vaccines, with regards to immuno-deficient individuals. The aim of this audit was to check the uptake and side effects of the BNT162b2 and ChAdOx1 vaccines.MethodsWe collected data on 352 patients from routine clinics which included diagnosis, type of vaccine, number of doses, side effects of the vaccines and flare up of arthritis or underlying autoimmune condition. Descriptive statistics were used to analyse the data.ResultsOf the 352,174 (49%) were Males and 178 (51%) Females. Most common diagnosis was Rheumatoid Arthritis 181 (51%), Axial spondyloarthropathy, 80(23%), Psoriatic Arthritis 65 (18%), GCA 10 (3%), Non-Radiographic Axial Spondyloarthropathy 5 (1.4%), JIA 3 (0.9%), Sarcoidosis 1 (0.3%), and overlap 6 (2%). Medications: 227(65%) patients were on Biosimilars, 26 (7%) on Biologics, 28 (8%) Certolizumab pegol, 21 (6%) Secukinumab, 2 (0.6%) Baricitinib, 3 (0.8%) Abatacept, 29 (8%) Tocilizumab and 16 (4.5%) on Tofacitinib. Vaccination uptake: 329 patients received double dose and 8 received single dose. 15 (4.3%) patients didn’t take vaccine. Reasons for not taking vaccine were severe reactions to Arthritis medication and biologics, concerned they may have severe reaction with the vaccine. Some were worried that vaccine may trigger flares, COVID-19 vaccine potentially has tracking chips, didn’t trust the vaccine as not gone through enough clinical trialling, lack of any statistics on side effects of the vaccines in immunocompromised patients. Side effects: 146 patients experienced mild side effects based on CTAE5 criteria. Only 3 (2.1%) had severe side effects Grade 3 or above, this included Pulmonary embolism, Stroke, and symptomatic pleural effusion. 15(10%) reported Arthritis flare. Most common side effects were Headache 50(34%), Fatigue 32(22%, Myalgia 32(22%), Fever 30(21%), Chills 30(21%), Injection site pain 28(19%), Rhinorrhoea 11(7.5%), Lethargy 11(7.5%) and maculopapular rash 5(3.4%).ConclusionThis audit highlights both the ChAdOx1 and BNT162b2 are safe for use in immune-deficient patients. Immunocompromised patients should be encouraged to take vaccines as benefits of the COVID-19 vaccination outweigh the risks and might reduce the risk of developing severe complications due to COVID-19.Disclosure G.M. Koduri: None.