Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12–20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12–20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC.MethodsWe investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC’s health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC’s Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination.FindingsWe identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12–20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12–20 years had received ≥1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1·0 case per million persons receiving ≥1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated persons.InterpretationIn our case series, we describe a small number of persons with MIS-C who had received ≥1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.FundingThis work was supported by the Centers for Disease Control and Prevention Clinical Immunization Safety Assessment (CISA] Project contracts 200-2012-50430-0005 to Vanderbilt University Medical Center and 200-2012-53661 to Cincinnati Children’s Hospital Medical Center.Research in context panelEvidence before this studyMultisystem inflammatory syndrome in children (MIS-C), also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is an uncommon, but serious, complication described after SARS-CoV-2 infection that is characterized by a generalized hyperinflammatory response. A review of the literature using PubMed identified reports of six persons aged 12–20 years who developed MIS-C following COVID-19 vaccination. Search terms used to identify these reports were: “multisystem inflammatory syndrome in children”, “MIS-C”, “MISC”, “multisystem inflammatory syndrome in adults”, “MIS-A”, “MISA”, “paediatric inflammatory multisystem syndrome”, and “PIMS-TS” each with any COVID-19 vaccine type. There were no exclusion criteria (i.e., all ages and languages).Added value of this studyWe conducted integrated surveillance for MIS-C after COVID-19 vaccination using two passive surveillance systems, CDC’s MIS-C national surveillance and the Vaccine Adverse Event Reporting System (VAERS), and clinician or health department outreach to CDC, including through Clinical Immunization Safety Assessment (CISA) Project consultations. We investigated reports of potential MIS-C occurring from December 14, 2020, to August 31, 2021, in persons aged 12–20 years any time after receipt of COVID-19 vaccine to identify those that met the CDC MIS-C case definition. Any positive serology test was accepted as meeting the CDC MIS-C case definition, although anti- nucleocapsid antibody is indicative of SARS-CoV-2 infection, while anti-spike protein antibody may be induced either by SARS-CoV-2 infection or by COVID-19 vaccination. We investigated 47 reports and identified 21 persons with MIS-C after receipt of COVID-19 vaccine. Of the 21 persons with MIS-C, median age was 16 years (range 12–20 years), and 13 (62%) were male. Fifteen (71%) had laboratory evidence of past or recent SARS-CoV-2 infection (positive SARS-CoV-2 nucleic acid amplification test [NAAT], viral antigen, or serology test before or during MIS-C illness evaluation), and 5 (33%) of those 15 had illness onset after their second vaccine dose. Six (29%) of 21 persons had no laboratory evidence of past or recent SARS-CoV-2 infection, and five of those six (83%) had onset of MIS-C after the second vaccine dose.Implications of all the available evidenceDuring the first nine months of the COVID-19 vaccination program in the United States, >21 million persons aged 12 to 20 years received ≥1 dose of COVID-19 vaccine as of August 31, 2021. This case series describes MIS-C in 21 persons following vaccine receipt during this time period; the majority of persons reported also had evidence of SARS-CoV-2 infection. The surveillance has limitations, but our findings suggest that MIS-C as identified in this report following COVID-19 vaccination is rare. In evaluating persons with a clinical presentation consistent with MIS-C after COVID-19 vaccination it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands. Providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS.

A novel assessment method for COVID-19 humoral immunity duration using serial measurements in naturally-infected and vaccinated subjects.

Background: It is crucial for medical decision-making and vaccination strategies to collect information on sustainability of immune responses after infection or vaccination, and how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity, preventing reinfection with SARS-CoV-2 or its variants. The aim of this study is to present a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time. Methods: Two collections of serum samples were used in this study: A collection from 20 naturally-infected subjects (follow-ups to 1 year) and a collection from 83 subjects vaccinated with one or two doses of Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (follow-ups to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test, developed for the serological confirmation of past-infections was used to determine the reactivity of six different SARS-CoV-2 antigens. For each patient sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges, allowing accurate quantitation of the corresponding six specific antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody. Results: Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was respectively 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies. Respectively, 90% of the antibody concentration wanes after 158 vs 398 days for RBD, 171 vs 420 days for S1, and 225 vs 620 days for S2 after the second vaccine shot. Conclusion: The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.

COVID-19 vaccine intentions and uptake in a tertiary care healthcare system: A longitudinal study

Objective Healthcare workers (HCWs) are a high priority group for COVID-19 vaccination and serve as sources for information for the public. This analysis assessed vaccine intentions, factors associated with intentions, and change in uptake over time in HCWs. Methods A prospective cohort study of COVID-19 seroprevalence was conducted with HCWs in a large healthcare system in the Chicago area. Participants completed surveys (November 25, 2020-January 9, 2021 and April 24-July 12, 2021) on COVID-19 exposures, diagnosis and symptoms, demographics, and vaccination status. Results Of 4,180 HCWs who responded to a survey, 77.1% indicated they intended to get the vaccine; in this group, 23.2% had already received at least one dose of the vaccine (23.2%), 17.4% were unsure, and 5.5% reported that they would not get the vaccine. Factors associated with intention or vaccination were being exposed to clinical procedures (vs no procedures) and having a negative serology test for COVID-19 (vs no test) (adjusted odds ratio (AOR)=1.39, 95% Confidence Interval (CI) 1.16-1.65, AOR=1.46, 95% CI 1.24-1.73, respectively). Nurses (vs physicians, AOR=0.24 95% CI 0.17-0.33), non-Hispanic Black (vs Asians, AOR=0.35, 95% CI 0.21-0.59), and women (vs men, AOR=0.38, 95% CI 0.30-0.50) had lower odds of intention to get vaccinated. By 6-months follow-up, over 90% of those who had previously been unsure were vaccinated, while 59.7% of those who previously reported no intention of getting vaccinated, were vaccinated. Conclusions COVID-19 vaccination in HCWs was high, but variability in vaccination intention exists. Targeted messaging coupled with vaccine mandates can support uptake.

Validity of Chemiluminescent Immunoassay Serology Test for Anti-Sars Cov-2 Antibodies IgM and IgG 1

In December 2019, an outbreak of acute pneumonia occurred in Wuhan, China. The disease was transmitted betweenhumans through droplets (coughing or sneezing) of infected patients, causing this outbreak to spread rapidly in variouscountries in the world, including Indonesia. On February 11, 2020, WHO announced the pneumonia was caused byCoronavirus Disease 2019 (COVID-19), which was caused by a new type of Coronavirus, the SARS-CoV-2. A rapid andaccurate diagnosis is critical for the control of the COVID-19 outbreak. The widely used test is a serology-based test thatdetects the presence of SARS-CoV-2 IgM/IgG antibodies in the patient's body. One of the methods used for this test isChemiluminescent Immunoassay (CLIA). This study aimed to determine the reliability of CLIA. The study was conductedfrom August to September 2020. The number of samples was 63 patients' serum. Polymerase chain reaction examination atHusada Utama Hospital, Surabaya, revealed that 21 patients were confirmed positive for COVID-19 with positive PCRresults, and 42 patients were healthy with negative COVID-19 results. The results showed that IgM had a diagnosticsensitivity of 85.7%, diagnostic specificity of 92.8%, a positive predictive value of 85.7%, a negative predictive value of 92.8%,and accuracy of 90.4%. In comparison, IgG had a diagnostic sensitivity of 90.4%, diagnostic specificity of 90.4%, a positivepredictive value of 82.6%, a negative predictive value of 90.5%, and accuracy of 90.4%. In conclusion, IgG has a highersensitivity than IgM, while IgM had higher specificity, positive predictive value, and negative predictive value than IgG.However, the positive, negative predictive value and efficiency values were the same for IgM and IgG.

SARS-CoV2 serology assays: utility and limits of different antigen based tests through the evaluation and the comparison of four commercial tests

Introduction: SARS-CoV2 serology testing is multipurpose provided to choose an efficient test. We evaluated and compared 4 different commercial serology tests, three of them had the Food and Drug Administration (FDA) approval. Our goal was to provide new data to help to guide the interpretation and the choice of the serological tests. Methods: Four commercial tests were evaluated: Cobas®Roche®(total anti-N antibodies), VIDAS®Biomerieux®(IgM and IgG anti-RBD antibodies), Mindray®(IgM and IgG anti-N and anti-RBD antibodies) and Access®Beckman Coulter®(IgG anti-RBD antibodies). Were tested: a positive panel (n=72 sera) obtained from COVID-19 confirmed patients and a negative panel (n=119) of pre-pandemic sera. Were determined the analytical performances and was drawn the ROC curve to assess the manufacturer's threshold. Results: A large range of variability between the tests was found. Mindray®IgG and Cobas® tests showed the best overall sensitivity 79,2%CI95%[67,9-87,8]. Cobas® showed the best sensitivity after D14; 85,4%CI95%[72,2-93,9]. The best specificity was noted for Cobas®, VIDAS®IgG and Access® IgG(100%CI95%[96,9-100]). Access® had the lower sensitivity even after D14 (55,5% CI95%[43,4-67,3]). VIDAS®IgM and Mindray®IgM tests showed the lowest specificity and sensitivity rates. Overall, only 43 out of 72 sera gave concordant results (59,7%). Retained cut-offs for a significantly better sensitivity and accuracy, without altering significantly the specificity, were: 0,87 for Vidas®IgM(p=0,01), 0,55 for Vidas®IgG(p=0,05) and 0,14 for Access®(p<10-4). Conclusion: Although FDA approved, each laboratory should realize its own evaluation for commercial tests. Tests variability may raise some concerns that seroprevalence studies may vary significantly based on the used serology test.

Prevalence and Demographic Risk Factors of Mycobacterium tuberculosis Infections in Captive Asian Elephants (Elephas maximus) Based on Serological Assays

To address putative TB statuses of elephants and to identify and quantify potential demographic risk factors for TB, three ELISAs specific for different mycobacterial antigens (ESAT6, CFP10, MPB83) and the TB Stat-Pak assay were used as surrogate serological markers for TB infection in elephants. In view of the low number of animals of which the infected status could be confirmed (4 out of 708) Latent Class Analyses of TB serology test outcomes was used to predict the putative TB status of each of 708 elephants as positive (17.3%), inconclusive (48.7%), or negative (34%) when assessed on a population basis. Correlation between test performance of the individual assays was high between the ELISAs, but low with that of the TB Stat-Pak assay. Risk factors, assessed based on cut off values for each of the ELISAs determined by ROC analysis, included sex, BCS, age, working time, feed type, management system, camp size and region. Old age elephants were more likely to show a positive TB serology test outcome, than younger ones. Elephants working 7 h per day and the ones in good condition BCS (7–11) were less likely to be positive in TB serology testing. In addition, fewer animals in the large camp size (31–50 elephants) were found to be positive in ELISA tests, compared to elephants in the other camp sizes. In this study, the North region had the lowest percentages of elephants with positive TB test outcome, the West region and to a lesser extend the other regions showed clearly higher percentages of positive animals. Even though assays used in the present study have not been validated yet, results obtained showed promise as diagnostic or screening tests. For the diagnosis of animals suspected to be infected, the ELISA tests, once further optimized for the individual antigens, can be used in parallel. For screening of complete camps for presence or absence of infection, a single optimized ELISA test can be utilized.

Clinical epidemiological characteristics of patients diagnosed with SARS-CoV-2. Hospital I Florencia de Mora EsSalud – La Libertad, 2020

Introduction: the SARS-CoV-2 pandemic affected a large part of the population of La Libertad, among them, the population of Florencia de Mora whose hospital played an important role in the care of patients diagnosed with COVID-19. Objective: to determine the epidemiological clinical characteristics of patients diagnosed with SARS-CoV-2 treated at the care center. Methods: Retrospective observational descriptive study, with a population of 2622 patients treated in the COVID-19 triage, taking into account the molecular test and the rapid serology test for the detection of SARS-CoV-2. Results: SARS-CoV-2 was detected in 74.90% (1155) of patients. The months with the highest number of cases were June and July with 29.4% (340) and 37.4% (432), respectively. The predominant age group was 27- 59 years with 77.9% (900) and males with 57.5% (664). Regarding the clinical profile, the most frequent comorbidity was hypertension with 6.9% (80), obesity and overweight with 3.7% (43) and the most frequent symptoms were cough 62.9% (726) and odynophagia 55.7% (643). Conclusions: 75 out of 100 screened patients had SARS-CoV-2, predominantly males, the age group of 27-59 years, hypertension, obesity and overweight as comorbidity, cough and odynophagia as the most frequent symptoms.

Reactivation of Latent Toxoplasmosis in a Schizophrenia Patient: A Case Report

Schizophrenia is a serious mental disorder characterized by chronic relapsing episodes of psychosis. The disease is multifactorial, where infections, genetic vulnerability and environmental factors are involved in the development of the illness. Toxoplasma gondii is one of the parasites that has long been known associated with schizophrenia in many studies. To date, there is growing evidence of association between T. gondii infections and schizophrenia. Herein we report a rare case of reactivated toxoplasmosis in a schizophrenia individual. This patient was incidentally diagnosed with reactivated T. gondii infection. He denied any symptoms of toxoplasmosis but experienced a mild psychiatric auditory hallucination. Serology test for T. gondii immunoglobulin antibodies measured a high positive IgG titer (135.9 IU/ml) and negative for IgM. Interestingly, nested PCR exhibited a positive result for the type I strain of T. gondii dense granular (GRA) 7 gene (GRA7). This case highlights the detection of probable reactivation of toxoplasmosis in an immunocompetent schizophrenic patient without psychiatric treatment-resistant and remains asymptomatic for toxoplasmosis. Both serology and molecular tools have been a helpful aid in establishing the diagnosis. Nonetheless, early detection as in this case may aid the patient management in the future.

Celiac disease with acute cerebellar stroke as first presentation: A case report

Celiac disease is an immune disorder occurring in response to ingestion of gluten in genetically predisposed individuals. It is a complex multiorgan disease with possible neurological involvement. Thrombotic events can occur but rarely as presenting symptom. We describe the case of a young man admitted to the Stroke Unit for worsening headache, nausea, vomiting, unsteadiness, dysarthria, and dysmetria. Brain CT scan showed an ischemic hypodense lesion of the right cerebellar hemisphere with compression of the adjacent IV ventricle. Studies to determine the etiology of stroke showed positive serology for celiac disease. On follow up he has completely recovered clinically. He is on gluten-free diet and the serology is now negative. Our case demonstrated that in young stroke, even without gastrointestinal symptoms, celiac disease should be considered a possible differential diagnosis and the appropriate serology test performed.