Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19.

Objectives: To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period. Methods: Serum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay. Results: Children with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease. Conclusion: Even if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which is currently a worldwide pandemic. There are limited available treatments for severe COVID-19 patients. However, some evidence suggests that intravenous immunoglobulin (IVIg) provides clinical benefits for these patients. METHODS: We administered IVIg to 23 severe COVID-19 patients, and all of them survived. Four related coronaviruses can cause the common cold. We speculated that cross-reactivity of SARS-CoV-2 and other common coronaviruses might partially explain the clinical efficacy of IVIg therapy. Thus, we performed multiple alignment analysis of the spike (S), membrane (M), and nucleotide (N) proteins from SARS-CoV-2 and the common coronaviruses to identify conserved regions. Next, we synthesized 25 peptides that were conserved regions and tested their IVIg seropositivity. RESULTS: The results indicated four peptides had significant or nearly significant seropositivity, and all of them were associated with the S and M proteins. Examination of the immune responses of healthy volunteers to each synthetic peptide indicated high seropositivity to the two peptides from S protein. Blood samples from healthy individuals may have pre-existing anti-SARS-CoV-2 IgGs, and IVIg is a potentially effective therapy for severe COVID-19. CONCLUSION: In conclusion, blood samples from many healthy individuals have pre-existing anti-SARS-CoV-2 IgGs, and IVIg may be an effective therapy for severe COVID-19.

Pediatric Respiratory Virus Infections During the COVID-19 Pandemic in a Region Without Active Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Circulation.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were not prevalent in Yonago and its vicinity during autumn 2020, and the relative frequencies of pathogen-induced respiratory infections during this period are unclear. Methods: We collected 109 nasopharyngeal swabs from 93 pediatric patients who visited Tottori University Hospital between October 1, 2020, and March 31, 2021. These samples were comprehensively tested for 18 pathogens with the FilmArray® respiratory panel test (v2.1) using nested real-time polymerase chain reaction, and the frequency of pathogens detected per month was calculated. In addition, we compared the duration of fever and the blood test results of patients infected with each pathogen or multiple pathogens. Results: Of the 109 samples, 42 were obtained from female patients and 67 from male patients (median age, 3 years; range, 0-15 years). Overall, 62 patients (56.9%) had a fever ≥ 38 °C at the time of examination, and the median duration of fever ≥ 38 °C was 2 days (1-12). During the study period, the highest number of samples (22) were collected in November 2020. Among samples that tested positive, the most common pathogens were rhino/enteroviruses (52 samples; 76.5%), followed by adenoviruses (7 samples; 10.3%), coronavirus NL63 (6 samples; 8.8%), coronavirus OC43, parainfluenza virus type 1, and parainfluenza virus type 2 (1 sample each; 1.5% each). The duration of fever was significantly longer in adenovirus-infected patients than in patients infected with other viruses (P < 0.05). Hemoglobin and sodium levels were also significantly lower among the adenovirus-infected patients. However, these variations were mostly within the normal range. No clinically meaningful differences were found between rhino/enterovirus-infected and non-rhino/enterovirus-infected cases, between coronavirus NL63-infected and non-coronavirus NL63-infected cases, and between cases with multiple- and single-pathogen infections. Conclusion: Rhino/enteroviruses were the most common viruses causing respiratory tract infections in areas without endemic SARS-CoV-2.

Comparing Clinical Characteristics of Influenza and Common Coronavirus Infections Using Electronic Health Records.

BACKGROUND: We compared outcomes in inpatients and outpatients, pre-COVID-19, who were infected with either coronavirus or influenza. METHODS: Using deidentified electronic health records data from the Geisinger-Regeneron partnership, we compared patients with RT-PCR-positive tests for the 4 common coronaviruses (229E, HKU1, NL63, OC43) or influenza (A and B) from June 2016 to February 2019. RESULTS: Overall, 52 833 patients were tested for coronaviruses and influenza. For patients ≥21 years old, 1555 and 3991 patient encounters had confirmed positive coronavirus and influenza tests, respectively. Both groups had similar intensive care unit (ICU) admission rates (7.2% vs 6.1%, P = .12), although patients with coronavirus had significantly more pneumonia (15% vs 7.4%, P < .001) and higher death rate within 30 days (4.9% vs 3.0%, P < .001). After controlling for other covariates, coronavirus infection still had a higher risk of death and pneumonia than influenza (odds ratio, 1.64 and 2.05, P < .001), with no significant difference in ICU admission rates. CONCLUSIONS: Common coronaviruses cause significant morbidity, with potentially worse outcomes than influenza. Identifying a subset of patients who are more susceptible to poor outcomes from common coronavirus infections may help plan clinical interventions in patients with suspected infections.