Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized condition affecting children with recent infection or exposure to coronavirus disease 2019 (COVID-19). MIS-C has symptoms that affect multiple organs systems, with some clinical features resembling Kawasaki disease (KD) and toxic shock syndrome (TSS). OBJECTIVE OF THE REVIEW: Our goal was to review the current literature and describe the evaluation and treatment algorithms for children suspected of having MIS-C who present to the emergency department. DISCUSSION: MIS-C has a wide clinical spectrum and diagnosis is based on a combination of both clinical and laboratory findings. The exact mechanism of immune dysregulation of MIS-C is not well understood. Physical findings may evolve and do not necessarily appear at the same time. Gastrointestinal, cardiac, inflammatory, and coagulopathy manifestations and dysfunction are seen frequently in MIS-C. CONCLUSIONS: The diagnosis of MIS-C is based on clinical presentation and specific laboratory findings. In the emergency setting, a high level of suspicion for MIS-C is required in patients exposed to COVID-19. Early diagnosis and prompt initiation of therapy offer the best chance for optimal outcomes.

Colchicine anti-inflammatory therapy for non-intensive care unit hospitalized COVID-19 patients: results from a pilot open-label, randomized controlled clinical trial.

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.

Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but emerging syndrome related to SARS-CoV-2 infection. While the presentation of MIS-C is generally delayed after exposure to the virus that causes coronavirus 2019, both MIS-C and Kawasaki disease (KD) share similar clinical features. Multisystem inflammatory syndrome in children poses a diagnostic and therapeutic challenge given the lack of definitive diagnostic tests and a paucity of evidence regarding treatment modalities. We review the clinical presentation, diagnostic evaluations, and management of MIS-C and compare its clinical features to those of KD.

Impact of Local and Demographic Factors on Early COVID-19 Vaccine Hesitancy among Health Care Workers in New York City Public Hospitals.

Despite the development of several effective vaccines, SARS-CoV-2 continues to spread, causing serious illness among the unvaccinated. Healthcare professionals are trusted sources of information about vaccination, and therefore understanding the attitudes and beliefs of healthcare professionals regarding the vaccines is of utmost importance. We conducted a survey-based study to understand the factors affecting COVID-19 vaccine attitudes among health care professionals in NYC Health and Hospitals, at a time when the vaccine was new, and received 3759 responses. Machine learning and chi-square analyses were applied to determine the factors most predictive of vaccine hesitancy. Demographic factors, education, role at the hospital, perceptions of the pandemic itself, and location of work and residence were all found to significantly contribute to vaccine attitudes. Location of residence was examined for both borough and neighborhood, and was found to have a significant impact on vaccine receptivity. Interestingly, this borough-level data did not correspond to the number or severity of cases in the respective boroughs, indicating that local social or other influences likely have a substantial impact. Local and demographic factors should be strongly considered when preparing pro-vaccine messages or campaigns.

Experiencing the Unprecedented COVID-19 Lockdown: Abu Dhabi Older Adults' Challenges and Concerns.

This study focused on older adults (60+ years old) of both genders in Abu Dhabi during the COVID-19 pandemic before vaccines were made available (age ranged from 60 years to 75 years). They faced more strict rules of movement restriction and isolation that might have resulted in certain psychological feelings and social reactions. The main objective was to understand Abu Dhabi older adults' psychological feelings during the pandemic and to identify their main concerns and challenges considering the various COVID-19-related policies and restrictions. The psychological feelings focused on fear, loneliness, sadness, irritability, emotional exhaustion, depressive symptoms, sleeping disorders, overeating, and excessive screen use. The objectives also included the changes in the psychological feelings concerning time. Other objectives covered better understanding the differences in (some activities) compared to the other age categories. Data were gathered through an online survey of community members from February to July 2020 as part of government initiatives (Department of Community Development). Responses were collected from 574 older adults in Abu Dhabi (60.1% male and 39.9% female). The analysis mainly used descriptive analysis, t-tests, analysis of variance (ANOVA), and simple trend analysis. For all tests, a p-value less than 0.05 was used for significance. The results pointed to the significant rise in feelings related to excessive screen use, fear, loneliness, and stress. The most significant concerns were related to more restrictions being imposed and not being able to see the grandchildren.The impact of new technologies on their quality of life was significantly reflected by respondents. The influence of the pandemic on older adults' health and weight was also investigated. Analysis of variance, t-tests, and regression analysis with relevant tests were employed. The relevant results showed that some negative psychological feelings were common among older adults during the pandemic. However, the psychological feelings did not portray significant changes with time, except for sleeping disorders and overeating. Overall, older adults scored significantly different from other age groups on many challenges, concerns, and views regarding new technologies during the pandemic. No significant differences were observed regarding gender and marital status for the challenges and concerns. The research summarizes some policy guidance while noting some limitations of this study and future research directions.

Longitudinal humoral antibody response to SARS-CoV-2 infection among healthcare workers in a New York City hospital.

OBJECTIVE: Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs). DESIGN: A prospective longitudinal study. SETTING: This study was conducted in a New York City public hospital in the South Bronx, New York. PARTICIPANTS: HCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study. PRIMARY OUTCOME MEASURE: Evaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay. RESULTS: Anti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177-8812)) than in asymptomatic positive subjects (5803 (2825-11 920)). Marginally higher titres (2382 (1494-3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753-2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001). CONCLUSIONS: Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points.

Longitudinal analysis of severe acute respiratory syndrome coronavirus 2 seroprevalence using multiple serology platforms.

Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests are based on the full-length spike (S), the receptor-binding domain (RBD), or the nucleoprotein (NP) as substrates. Here, we used samples from healthcare workers (HCWs) to perform a longitudinal analysis of the antibody responses using a research-grade RBD and spike-based enzyme-linked immunosorbent assay (ELISA), a commercial RBD and spike-based ELISA, and a commercial NP-based chemiluminescent microparticle immunoassay. Seroprevalence ranged around 28% early during the pandemic and a good correlation was observed between RBD and spike-based ELISAs. Modest correlations were observed between NP and both RBD and spike-based assays. The antibody levels in HCWs declined over time; however, the overall seroprevalence measured by RBD and spike-based assays remained unchanged, while the seroprevalence of NP-reactive antibodies significantly declined. Moreover, RBD and spike-based assays effectively detected seroconversion in vaccinees. Overall, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.

Knowledge, Attitudes and Perceptions of COVID-19 Vaccination among Healthcare Workers of an Inner-City Hospital in New York.

Introduction: New York City is one of the areas most affected by the COVID-19 pandemic in the United States. Healthcare workers are among those at high risk of contracting the virus, and a vital source of information and trust in vaccines to the community. Methods: This study was conducted about attitudes towards COVID-19 vaccination among healthcare workers at a public hospital in New York City during the beginning of COVID-19 vaccination. 428 hospital employees responded. Results: Several factors were significantly associated with vaccine attitudes, including demographics such as gender (p = 0.002), age (p = 0.005), race (p < 0.001) and home location (p < 0.001), role within the hospital (p < 0.001), knowledge about the virus (p < 0.001) and confidence in and expectations about personal protective equipment and behaviors (p < 0.001). Structural equation modeling revealed that the most predictive factors were prior vaccine attitudes and concern with the speed of testing and approval of the vaccines (p < 0.001). Multivariate analysis reinforced these, while also identifying perceived personal risk as significant (p = 0.033). Conclusions: Several modifiable factors that reflect confidence in science, scientific knowledge, personal risk perception, experience and medical authority are correlated with vaccine attitudes, indicating that a holistic educational approach to improve trust in science is likely to be effective in long-term reduction in vaccine hesitancy.

High Initial Titres of Anti-Spike Antibodies following SARS-CoV-2 Infection is Associated with Faster Decay Rates at Four Months Follow-Up (preprint)

Background Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggests an initial decay of antibody followed by subsequent stabilization. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCW). Methods In this cross-sectional longitudinal cohort study done in two phases over four months, HCW underwent serial qualitative serology testing for anti-N antibody, quantitative MSH-ELISA to detect Receptor Binding Domain and full-length S reactive antibodies and completed online surveys about COVID-19 related symptoms and healthcare/community exposure. Results Anti-N antibody positivity was 27% and anti-S positivity was 28% in Phase 1. In Phase 2 anti-S titres were higher in symptomatic than in asymptomatic positive subjects in Phase 1. Marginally higher titers were seen in asymptomatic compared to the symptomatic positive subgroup in Phase 2. A positive correlation was noted between age, number and duration of symptoms, and Phase 1 anti-S antibody titre. A strong correlation was observed between Phase 1 titers and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever, GI symptoms, and total number and duration of COVID-19 symptoms. Conclusions Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as faster decay during the two time points.

Longitudinal analysis of SARS-CoV-2 seroprevalence using multiple serology platforms (preprint)

Serological tests are important tools helping to determine previous infection with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) and to monitor immune responses. The current tests are based on spike (S), the receptor binding domain (RBD), or the nucleoprotein (NP) as substrate. Here, we used samples from a high seroprevalence cohort of health care workers (HCWs) to perform a longitudinal analysis of the antibody responses using three distinct serological assays. 501 serum samples were tested using: a) a research-grade RBD and spike based tandem enzyme-linked immunosorbent assay (MS-RBD ELISA, MS-spike ELISA), b) a commercial RBD and spike based tandem ELISA (Kantaro-RBD, -spike), and c) a commercial NP-based chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). Seroprevalence ranged around 28% during the early stage of the pandemic (a: 28.4% positives; b: 28.1%; c: 27.3%). Good correlation was observed between the MS and Kantaro RBD ELISAs and between the MS and Kantaro spike ELISAs. By contrast, modest correlations were observed between the Abbott Architect and both RBD and spike-based assays. A proportion of HCWs (n=178) were sampled again 3-5 months after the first time point. Although antibody levels declined in most of the positive individuals, the overall seroprevalence measured by RBD-spike based assays remained unchanged. However the seroprevalence of NP-reactive antibodies significantly declined. Lastly, we tested six samples of individuals who received two doses of SARS-CoV-2 mRNA vaccine and found that seroconversion was detected by the RBD-spike assays but, of course as expected, not the NP based assay. In summary, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.