Anti-nucleocapsid IgG Research Articles

Characteristics of coronavirus disease 19 convalescent plasma donors and donations in the New York metropolitan area

BackgroundConvalescent plasma (CP) is an important initial treatment in pandemics and the New York (NY) metropolitan area is likely to remain a hotspot for collection and distribution of such units. This study reports characteristics of coronavirus disease 19 CP (CCP) donors and their donations to the New York Blood Center (NYBC).Study design and methodsAll CCP data from our first day of collection on March 26th through July 7th, 2020 are included in this retrospective analysis. Donor and donation data were extracted from NYBC electronic databases. SARS‐CoV‐2 antibody testing was initially performed by the NY State Department of Health, and later by NYBC using Ortho and Abbott platforms.ResultsCCP donor age and ABO distributions were consistent with reported lower COVID‐19 susceptibility in O blood types. CCP versus whole blood donors had similar on‐site deferrals, but higher post‐donation deferral rates. CCP versus routine plasmapheresis donations had higher vasovagal reactions but similar product rejection rates. Changes in antibody (Ab) test platforms resulted in significant changes in the percent of donors regarded as antibody positive. Donor correlates with higher anti‐spike total Ig S/CO ratios were Hispanic ethnicity, overweight body mass index, and longer symptom duration; and with higher anti‐nucleocapsid IgG S/CO ratios were male gender, older age, Hispanic ethnicity, and fewer days between symptom onset and first donation.DiscussionWe identify donor characteristics not previously reported to correlate with Ab titer. Our analysis should assist with donor outreach strategies, blood center operating logistics, and recruitment of high titer donors.

Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.

Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK.

Introduction: SARS-CoV-2 antibody detection serves as an important diagnostic marker for past SARS-CoV-2 infection and is essential to determine the spread of COVID-19, monitor potential COVID-19 long-term effects, and to evaluate possible protection from reinfection. A study was conducted across three hospital sites in a large central London NHS Trust in the UK, to evaluate the prevalence and duration of SARS-CoV-2 IgG antibody positivity in healthcare workers.Methods: A matrix equivalence study consisting of 228 participants was undertaken to evaluate the Abbott Panbio™ COVID-19 IgG/IgM rapid test device. Subsequently, 2001 evaluable healthcare workers (HCW), representing a diverse population, were enrolled in a HCW study between June and August 2020. A plasma sample from each HCW was evaluated using the Abbott Panbio™ COVID-19 IgG/IgM rapid test device, with confirmation of IgG-positive results by the Abbott ArchitectTM SARS-CoV-2 IgG assay. 545 participants, of whom 399 were antibody positive at enrolment, were followed up at 3 months.Results: The Panbio™ COVID-19 IgG/IgM rapid test device demonstrated a high concordance with laboratory tests. SARS-CoV-2 antibodies were detected in 506 participants (25.3%) at enrolment, with a higher prevalence in COVID-19 frontline (28.3%) than non-frontline (19.9%) staff. At follow-up, 274/399 antibody positive participants (68.7%) retained antibodies; 4/146 participants negative at enrolment (2.7%) had seroconverted. Non-white ethnicity, older age, hypertension and COVID-19 symptoms were independent predictors of higher antibody levels (OR 1.881, 2.422–3.034, 2.128, and 1.869 respectively), based on Architect™ index quartiles; participants in the first three categories also showed a greater antibody persistence at 3 months.Conclusion: The SARS-CoV-2 anti-nucleocapsid IgG positivity rate among healthcare staff was high, declining by 31.3% during the 3-month follow-up interval. Interestingly, the IgG-positive participants with certain risk factors for severe COVID-19 illness (older age, Black or Asian Ethnicity hypertension) demonstrated greater persistence over time when compared to the IgG-positive participants without these risk factors.

Update Alert 8: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Update Alert 8: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Diagnostic and analytical performance evaluation of ten commercial assays for detecting SARS-CoV-2 humoral immune response

ObjectiveAnalytical validation of newly released SARS-CoV-2 antibody assays in the clinical laboratory is crucial to ensure sufficient performance in respect to its intended use. We aimed to assess analytical and diagnostic performance of 8 (semi-)quantitative assays detecting anti-nucleocapsid IgG (Euroimmun, Id-Vet) or total Ig (Roche), anti-spike protein IgG (Euroimmun, Theradiag, DiaSorin, Thermo Fisher) or both (Theradiag) and 2 rapid lateral flow assays (LFA) (AAZ-LMB and Theradiag). MethodsSpecificity was evaluated using a cross-reactivity panel of 85 pre-pandemic serum samples. Sensitivity was determined at both the manufacturer's and a 95% specificity cut-off level, using 81 serum samples of patients with a positive rRT-PCR. Sensitivity was determined in function of time post symptoms onset. ResultsSpecificity for all assays ranged from 92.9% to 100% (Roche and Thermo Fisher) with the exception of the Theradiag IgM LFA (82.4%). Sensitivity in asymptomatic patients ranged between 41.7% and 58.3%. Sensitivity on samples taken <10 days since symptom onset was low (23.3%–66.7%) and increased on samples taken between 10 and 20 days and > 20 days since symptom onset (80%–96% and 92.9%–100%, respectively). From 20 days after symptom onset, the Roche, Id-vet and Thermo Fisher assays all met the sensitivity (>95%) and specificity (>97%) targets determined by the WHO. Antibody signal response was significantly higher in the critically ill patient group. ConclusionAntibody detection can complement rRT-PCR for the diagnosis of COVID-19, especially in the later stage, or in asymptomatic patients for epidemiological purposes. Addition of IgM in LFAs did not improve sensitivity.

Sensitivity of serology assay in Covid-19 diagnosis: does the antigen matter?

Since the spreading of Sar-CoV-2 in March 2020, many serologic tests have been developed to identify antibody responses. Indeed, different commercial kits are directed against different antigens and could utilise different methods thereby triggering confusion and criticism. Here, we compared two Food and Drug Administration (FDA)-approved automatized assays that detect IgG responses against spike or nucleocapsid protein of Sars-Cov-2 virus in 127 subjects among healthcare workers of IRCCS Policlinico San Donato (MI), Italy. We observed different kinetics of IgG responses, demonstrating the importance of timing of sampling to correctly interpret the results both for infection diagnosis and for epidemiologic studies. We observed that Anti-N response starts earlier than Anti-S1/S2 response but also decreases earlier, affecting the sensitivity of the tests at different time points. Combining two different assays, designed against different antigens, could reduce false negative results. Finally, we observed a patient who produced anti-nucleocapsid IgG, but not anti-spike IgG. In conclusion, we investigated antibody responses in Covid-19 disease, aiming to direct clinicians and laboratory scientists to correctly interpret serologic results by always paying attention to clinical history correlation, timing of sampling, methods and antigens used, to avoid false negative results and obtain relevant epidemiologic data.

Analysis of viral load in different specimen types and serum antibody levels of COVID-19 patients

BackgroundCOVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load.MethodsNasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA.ResultsThe positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load.ConclusionsOther specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.

SARS-COV-2 vaccine: first-month results of a six-month follow-up study.

Various COVID-19 vaccines are being developed around the world. Important questions to be answered regarding vaccines are efficacy, safety, and whether antibodies are protective when used in different communities. This study aimed to determine seroconversion rates of the inactivated SARS-CoV-2 vaccine in healthcare workers in a hospital and short-term adverse events due to the vaccine. The study carried out in Çukurova University, Turkey, comprised of 282 healthcare workers who received two doses of the inactivated SARS-CoV-2 vaccine administered in two 3 µg doses, 28 days apart. On day 28, after the second dose, antiS-RBD IgG and total anti-spike and anti-nucleocapsid IgM and IgG antibodies against SARS-CoV-2 were detected by using in vitro chemiluminescence immunoassay method. The mean age of participants was 39.06±10.65 (min=21, max=65) with 43.6% males and 56.4% females. On day 28, after the second dose, the seroconversion rates were found to be 92.9% for total anti-spike and anti-nucleocapsid IgG and 15.2% for IgM and 98.2% for anti-S-RBD IgG antibodies and having natural COVID-19 prior to vaccination, age and comorbidity were found to be significant factors for immunogenicity. The incidence of at least one adverse event was found as 29.8% after the first dose and 24.1% after the second dose, with the most common adverse events of having pain at the injection site, weakness, fatigue, and headache.

Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors.

ObjectivesCharacterisation of the human antibody response to SARS‐CoV‐2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT‐PCR‐positive SARS‐CoV‐2 convalescent adults during the first 250 days after onset of symptoms.MethodsWe measured antibody responses to the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT‐PCR‐positive SARS‐CoV‐2 convalescent adults. With a median of 5 (range 2–18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed‐effects modelling.ResultsAll donors were seropositive at the first sampling moment, and only one donor seroreverted during follow‐up analysis. Anti‐RBD IgG and anti‐nucleocapsid IgG levels declined with median half‐lives of 62 and 59 days, respectively, 2–5 months after symptom onset, and several‐fold variation in half‐lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow‐up, which points towards long‐term immunological memory. The magnitude of the anti‐RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in‐house developed competitive assay.ConclusionThe result of this study gives valuable insight into the long‐term longitudinal response of antibodies to SARS‐CoV‐2.

T-cell response after first dose of BNT162b2 SARS-CoV-2 vaccine among healthcare workers with previous infection or cross-reactive immunity.

ObjectivesAntibody response to the first dose of BNT162b2 SARS‐CoV‐2 is greater in COVID‐19‐convalescent than in infection‐naïve individuals. However, there are no data about T‐cell response in individuals with pre‐existing cellular immunity.MethodsWe evaluated T‐cell responses in parallel with SARS‐CoV‐2 antibody level after first dose of BNT162b2 vaccine in 23 infection‐naïve and 27 convalescent healthcare workers (HCWs) previously included in a study about humoral and T‐cell immunity.ResultsOverall, the antibody response was lower in the infection‐naïve group than in convalescent individuals (18 895 vs 662.7 AU mL−1, P < 0.001), and intermediate but significantly lower in convalescent HCWs with previous negative serology (25 174 vs 1793 AU mL−1; P = 0.015). Indeed, anti‐spike IgG titres after the first dose correlated with baseline anti‐nucleocapsid IgG titres (rho = 0.689; P < 0.001). Pre‐existing T‐cell immunity was observed in 78% of convalescent and 65% of the infection‐naïve HCWs. T‐cell response after the first dose of the vaccine was observed in nearly all the cases with pre‐existing T‐cell immunity, reaching 94% in convalescent HCWs and 93% in those with cross‐reactive T cells. It was lower in the infection‐naïve group (50%; P = 0.087) and in convalescent HCWs with negative serology (56%; P = 0.085). Notably, systemic reactogenicity after vaccination was mainly observed in those with pre‐existing T‐cell immunity (P = 0.051).ConclusionHere, we report that the first dose of BTN162b2 elicits a similar S‐specific T‐cell response in cases of either past infection or cross‐reactive T cells, but lower in the rest of infection‐naïve individuals and in convalescent HCWs who have lost detectable specific antibodies during follow‐up.

Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

BackgroundThe relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.MethodsWe investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time.ResultsA total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status.ConclusionsThe presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.)

Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors.

BackgroundConvalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19–susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood.MethodsSARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression.ResultsAntibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19–2.12]), independent of age, sex, and hospitalization.ConclusionsSARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-β) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome.

There are a large number of well recognised syndromes comprising cerebellar ataxia in association with other neurological features. We report three family members who presented with a relapsing, early onset...

Clinical relevance of raised soluble serum interleukin-2 receptor concentrations in cystic fibrosis.

<h3>Abstract</h3> <h3>Objectives</h3> To identify factors that contribute to protection from infection with the Omicron variant of SARS-CoV-2 in older adults in nursing and retirement homes. <h3>Design</h3> Longitudinal cohort study with retrospective analysis of infection risk. <h3>Setting and Participants</h3> 997 residents of nursing and retirement homes from Ontario, Canada, in the COVID-in-LTC study. <h3>Methods</h3> Residents with three mRNA dose vaccinations were included in the study. SARS-CoV-2 infection was determined by positive nasopharyngeal PCR test and/or circulating anti-nucleocapsid IgG antibodies. Cumulative probability of Omicron infection after recent COVID-19 was assessed by log-rank test of Kaplan-Meier curves. Cox regression was used to assess risk of Omicron infection by age, sex, mRNA vaccine combination, whether individuals received a fourth dose, as well as recent COVID-19. <h3>Results</h3> 171 residents (17.2%) had a presumed Omicron variant SARS-CoV-2 infection between December 15, 2021 (local start of the first Omicron wave) and May 3, 2022. Risk of Omicron infection was not different by age [hazard ratio (95% confidence interval): 1.01 (0.99-1.02)], or in women compared to men [0.97 (0.70-1.34)], but infection risk decreased 47% with three vaccine doses of mRNA-1273 (Moderna) compared to BNT162b2 (Pfizer) [0.53 (0.31-0.90)], 81% with any fourth mRNA vaccine dose [0.19 (0.12-0.30)], and 48% with SARS-CoV-2 infection in the 3 months prior to beginning of the Omicron wave [0.52, (0.27-0.99)]. <h3>Conclusions and Implications</h3> Vaccine type (i.e., mRNA-1273/Spikevax vs BNT162b2/Cominarty), any fourth vaccine dose, and hybrid immunity from recent COVID-19, were protective against infection with the Omicron variant. These data emphasize the importance of vaccine type, and number of vaccine doses, in maintenance of protective immunity and reduction of risk of Omicron variant breakthrough infection. These findings promote continued public health efforts to support vaccination programs and monitor vaccine immunogenicity in older adults. <h3>Brief summary</h3> Risk of infection with the SARS-CoV-2 Omicron variant in older adults in early 2022 was reduced with triple mRNA-1273 vaccination, any fourth dose vaccine, and within three months of prior COVID-19.