Durability of anti-Spike antibodies in the infant after maternal COVID-19 vaccination

COVID-19 vaccination in pregnancy generates functional anti-Spike IgG antibodies that are known to cross the placenta. However, the durability of vaccine-induced maternal anti-S IgG in infant circulation, and how it compares to durability of antibody from maternal natural infection, is unknown. We quantified anti-S IgG in 92 2-month and 6-month-old infants whose mothers were vaccinated in pregnancy, and in 12 6-month-old infants after maternal natural infection with SARS-CoV-2. In the vaccinated group, 94% (58/62) of infants had detectable anti-S IgG at 2 months, and 60% (18/30) had detectable antibody at 6 months. In contrast, 8% (1/12) of infants born to women infected with SARS-CoV-2 in pregnancy had detectable anti-S IgG at the 6-month timepoint. Vaccination resulted in significantly higher maternal and cord titers at delivery and significantly greater antibody persistence in infants at 6 months, compared to natural infection.

Longevity of SARS-CoV-2 immune responses in haemodialysis patients and protection against reinfection

ABSTRACTBackgroundPatients with end stage kidney disease (ESKD) receiving in-centre haemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, ICHD patients frequently develop serological evidence of infection, even with asymptomatic disease. The aim of this study is to investigate the durability and functionality of immune responses to SARS-CoV-2 infection in ICHD patients.MethodsThree hundred and fifty-six ICHD patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies. Patients who became seronegative at 6 months were investigated for SARS-CoV-2 specific T-cell responses.ResultsOne hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at Time 0, of which 127 (98.4%) also had detectable anti-RBD. At 6 months, of 111 patients tested, 71(64.0%) and 97 (87.4%) remained anti-NP and anti-RBD seropositive respectively, p<0.001. For patients who retained antibody, both anti-NP and anti-RBD levels reduced significantly after 6 months. Ten patients who were anti-NP and anti-RBD seropositive at Time 0, had no detectable antibody at 6 months; of which 8 were found to have SARS-CoV-2 antigen specific T cell responses.Independent of antibody status at 6 months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following 6 months.ConclusionsICHD patients mount durable immune responses 6 months post SARS-CoV-2 infection, with <3% of patients showing no evidence of humoral or cellular immunity. These immune responses are associated with a reduced risk of subsequent reinfection.SIGNIFICANCE STATEMENTFollowing infection with SARS-CoV-2, patients with end stage kidney disease (ESKD) frequently develop serological evidence of infection, even with asymptomatic disease. Patients with ESKD receiving in-centre haemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. What is not known is how durable the serological responses in ESKD patients are or whether evidence of prior immune responses protect patients from reinfection. In this study of 356 ICHD patients, at 6 months following the detection of SARS-CoV-2 antibodies, fewer than 3% of patients lacked evidence of either humoral or cellular immunity. Furthermore, patients with serological evidence of infection had a significantly lower risk of being diagnosed with subsequent infection or ‘reinfection’, suggesting functional immune protection.

COVID-19 seroprevalence in primary and secondary healthcare workers (HCWs)

Professional anxiety existed early in the coronavirus disease 2019 (COVID-19) pandemic with challenging infection prevention and control support. The aims of this study were to compare epidemiological features of healthcare workers (HCWs) within primary and secondary care with their serological evidence of infection. A prospective observational cohort of 1,916 HCWs completed a questionnaire, and their sera were assayed for detectable antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein in the first wave of the pandemic. Datasets were compared between the two sub-cohorts in primary and secondary care and between the combined seropositive and seronegative cohorts. Curiosity of antibody status was high. Detectable antibody was 7% in the primary care and 5% in the secondary care workers at a time of 1.7% in the general community. Inappropriate personal protective equipment (PPE) was more common in primary care, and detectable antibody was twice as prevalent in HCWs who felt they did not have appropriate PPE. Contact tracing was perceived to be inadequate although it was more commonly performed in the seropositive cohort suggesting appropriate prioritisation. Both temperature and symptom checking alerts and work exclusion were significantly more prevalent in the seropositive cohort. The seroprevalence data support increased risk for HCWs, the importance of appropriate PPE and the usefulness of the daily temperature and symptom checks, particularly in primary care.

473. Using Serosurveillance for SARS-CoV-2 to Conserve PCR Tests in a Resource Constrained Combat Environment

Background In March 2020, COVID-19 threatened combat operations in Afghanistan. At that time, the NATO Resolute Support mission involved nearly 17,000 troops from 38 partner nations, plus civilians who support the mission, scattered throughout Afghanistan. While Afghanistan did not initially report many confirmed cases, large numbers of cases were reported from neighboring countries with known migration across the borders (sometimes thousands/day). Military medical leaders advised commanders regarding the potential health risks to the force, balancing with risks to the mission. Quarantine and isolation protocols were established. Public health interventions of social distancing, cloth mask wear, enhanced environmental cleaning, active case finding, and emphasis on hand hygiene and cough etiquette were enforced. However, many base locations were unable to alleviate close living quarters. Testing was identified as a means to assess risk to the population. Testing capabilities were limited, particularly PCR. When this testing strategy was established, the utilization and interpretation of antibody tests was quite controversial. With rapid antibody kits, the time to detection of both IgM and IgG are similar; detection of either cannot identify the time since exposure. Methods A novel surveillance plan was established whereby subpopulations at highest risk for exposure to the virus were screened with antibody tests from 17 Apr-1 Jun, 2020. High risk populations included: those leaving quarantine, base defense guards, isolation unit guards, medical personnel, dining facility workers, and those who interact with local populations. Individuals with detectable antibody (either IgM or IgG) were further evaluated with PCR tests. Results In the first six weeks of this testing strategy, 1957 antibody tests were utilized. A total of 37 specimens were identified antibody positives with seroprevalence of 2% (Figure 1). Thirteen were identified to have positive IgG, 22 with IgM, and 2 with both. PCR was performed on those with detectable antibody, 13 (35%) had positive PCR. Conclusion Serosurveillance of populations at high risk for exposure to the virus is a logical way to conserve testing resources in a constrained combat environment. Disclosures Alex M. Case, n/a, United States Air Force (Employee)

Do Immune-Mediated TTP Patients Presenting with No Detectable ADAMTS13 Antibody Represent a Unique Clinical Phenotype?

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterised by antibody mediated activity against ADAMTS13. Prompt diagnosis and treatment is critical in this rare condition which has an untreated mortality of around 90%. An ADAMTS13 activity level of <10% is consistent with a diagnosis of TTP and for a significant proportion of patients, ADAMTS13 antibodies can also be demonstrated, confirming iTTP. Recent literature suggests that the sub-group of patients with low ADAMTS13 antigen levels and high ADAMTS13 antibody have the highest mortality (Ferras et al., Blood 2017.); however, the sub-group of patients who have never had a detectable inhibitor remain poorly defined. With therapies becoming increasingly available as adjuvants to plasma exchange, in addition to elective agents for suspected relapsing disease, there is a need to better risk stratify this heterogeneous patient group and identify which patients may benefit most from additional therapies. In most literature to date, patients with low ADAMTS13 inhibitor levels have been excluded from further data analysis and therefore remain an under-represented population. Aim: To define the characteristics of the iTTP patient sub-group where an ADAMTS13 inhibitor has never been demonstrated throughout their clinical course Methods: This was retrospective study of data from a single UK TTP tertiary referral centre from 2011 to 2018. Inclusion criteria for patients with iTTP included ADAMTS13 activity ≤10% at acute presentation. Patients with congenital TTP were excluded from data analysis. A positive ADAMTS13 antibody was defined as >12 U/ml using the Technoclone ADAMTS13 inhibitor ELISA assay. Data collected included patient demographics, presenting symptoms, laboratory markers at first presentation, ADAMTS13 activity and antibody and number of relapses. Clinical relapse was defined as reappearance of clinical manifestations or laboratory parameters consistent with acute TTP and serological relapse was defined as ADAMTS13 activity of <15%. Patients with no detectable antibody were compared with a like group of TTP patients with a detectable ADAMTS13 antibody. Results: A total of 61 patients and 72 acute patient episodes were analysed, of which 7 patients had never demonstrated an ADAMTS13 inhibitor in 10 acute episodes. This sub-group was subsequently compared to an equal sample size of patients with a detectable ADAMTS13 antibody and similar demographics. The average antibody level for the antibody negative group was 5.8 U/ml (range 3 - 10 U/ml) compared to 98.7 U/ml (range 37 - 147U/ml) in the antibody positive group. The respective average ADAMTS13 activity was 4.5% (0-10%), compared with 0.3% (0-1%). 100% of the patients in the antibody positive group had neurological symptoms at presentation compared with 43% of the patients with no detectable antibody. The average presenting platelet count and Troponin T for the antibody negative cohort was 27 x 109/L and 21 ng/L respectively; compared with 10 x 109/L and 206 ng/L in the antibody positive group. 43% of patients in the antibody negative group had multiple acute clinical relapses (1-3) compared with 0% patients presenting with a detectable antibody. 14% of the antibody positive group had a serological relapse treated with elective Rituximab compared with 43% of the patients in the antibody negative group. Conclusion: This data specifically reports the apparent characteristics of patients with ADAMTS13 antibody negative iTTP. Up to 10% of patients may never demonstrate an inhibitor against ADAMTS13 and appear to have a less severe clinical presentation with fewer neurological and cardiac manifestations. This study further suggests that this sub-group may represent a more 'grumbling'/ relapsing phenotype with a tendency for more frequent clinical or serological relapse of TTP. Although TTP is rare, further study of this sub-population of iTTP patients is important in risk stratification, and to support treatment decisions, in particular towards preventing future relapse. Disclosures No relevant conflicts of interest to declare.

Human Antibodies to Bacterial Superantigens and Their Ability To Inhibit T-Cell Activation and Lethality

ABSTRACT Bacterial superantigens (BSAgs) cause massive stimulation of the immune system and are associated with various pathologies and diseases. To address the role of antibodies in protection against BSAgs, we screened the sera of 29 human volunteers for antibodies to the SAgs staphylococcal enterotoxin A (SEA), SEB, SEC1, and toxic shock syndrome toxin 1 (TSST-1). Although all volunteers had detectable levels of antibodies against SEB and SEC1, many (9 out of 29 volunteers) lacked detectable antibody to SEA or had minimal titers. Antibody titers to TSST-1 were well below those to SEB and SEC1, and three volunteers lacked detectable antibody to this BSAg. In addition, pooled immunoglobulin preparations obtained from different companies had antibody titers against SEs and TSST-1. There was a good correlation between antibody titers and inhibition of superantigenic effects of these toxins. Transfer of SEB-specific antibodies, obtained from pooled sera, suppressed in vitro T-cell proliferation and totally protected mice against SEB. These data suggest that the inhibitory activity of human sera was specific to antibodies directed against the toxins. Thus, it may be possible to counteract with specific antibodies BSAg-associated pathologies caused by stimulation of the immune system.