Saliva and Plasma Antibody Levels in Children and Adolescents After Primary Infection With Omicron Variants of SARS-CoV-2 Infection in Germany.

This cross-sectional study evaluates IgG antibody levels in children and adolescents in Germany following SARS-CoV-2 infection.

Antibody binding and ACE2 binding inhibition is significantly reduced for both the BA1 and BA2 omicron variants.

BACKGROUND: The rapid emergence of the omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the WHO. Subsequently, omicron evolved into distinct sublineages (e.g. BA1 and BA2), which currently represent the majority of global infections. Initial studies of the neutralizing response towards BA1 in convalescent and vaccinated individuals showed a substantial reduction. METHODS: We assessed antibody (IgG) binding, ACE2 (Angiotensin-Converting Enzyme 2) binding inhibition, and IgG binding dynamics for the omicron BA1 and BA2 variants compared to a panel of VOC/VOIs, in a large cohort (n = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. RESULTS: While omicron was capable efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to WT. Whereas BA1 exhibited less IgG binding compared to BA2, BA2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to omicron only improved after administration of a third dose. CONCLUSION: omicron BA1 and BA2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind omicron. The extent of the mutations within both variants prevent a strong inhibitory binding response. As a result, both omicron variants are able to evade control by pre-existing antibodies.

The IgG glycome of SARS-CoV-2 infected individuals reflects disease course and severity.

Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc region, the structure and possible function of the IgG N-glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19.

Stroke care during the COVID-19 pandemic: Case numbers, treatments, and mortality in two large German stroke registries.

Background and purpose: At the beginning of the SARS-CoV-2 pandemic, an alarming decline in hospitalizations for stroke was reported in several countries, including Germany. We assessed hospitalization numbers and indicators of the quality of stroke care in 2020 during the pandemic containment measures. Materials and methods: The analysis was based on data of two large stroke quality assurance registries in the north and the south of Germany (Qualitätssicherung Schlaganfall Nordwestdeutschland and Bayerische Arbeitsgemeinschaft für Qualitätssicherung in der stationären Versorgung). We included 395 hospitals with 467,931 documented cases in 2018-2020. The time interval between admission and thrombolysis, frequency of systemic thrombolysis and intra-arterial therapy (IAT), National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital mortality were assessed. Changes in the second (Q2) and fourth (Q4) quarters of 2020 were compared to corresponding quarters in 2019 by chi-squared tests. Results: Hospitalization numbers decreased in the two stroke registries by 8% and 10% in Q2 of 2020 and by 5% and 15% in Q4 of 2020 compared to the same quarters in 2019, respectively. The decline was particularly seen in women and patients with transient ischemic attacks. In cases with cerebral infarction, no increase in NIHSS scores on admission was observed, and the proportion of patients with a time interval between admission and thrombolysis of ≤60 min was unchanged. No clear pattern was found in the frequency of systemic thrombolysis and IAT. In one of the registries, in-hospital mortality of patients with cerebral infarction increased in Q2 of 2020 compared to Q2 of 2019. Conclusion: Case numbers slightly decreased under pandemic conditions, while our quarterly analysis indicated that the quality of stroke care was largely unchanged throughout the year 2020.

Stroke care during the COVID-19 pandemic: Case numbers, treatments, and mortality in two large German stroke registries

Background and purpose At the beginning of the SARS-CoV-2 pandemic, an alarming decline in hospitalizations for stroke was reported in several countries, including Germany. We assessed hospitalization numbers and indicators of the quality of stroke care in 2020 during the pandemic containment measures. Materials and methods The analysis was based on data of two large stroke quality assurance registries in the north and the south of Germany (Qualitätssicherung Schlaganfall Nordwestdeutschland and Bayerische Arbeitsgemeinschaft für Qualitätssicherung in der stationären Versorgung). We included 395 hospitals with 467,931 documented cases in 2018–2020. The time interval between admission and thrombolysis, frequency of systemic thrombolysis and intra-arterial therapy (IAT), National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital mortality were assessed. Changes in the second (Q2) and fourth (Q4) quarters of 2020 were compared to corresponding quarters in 2019 by chi-squared tests. Results Hospitalization numbers decreased in the two stroke registries by 8% and 10% in Q2 of 2020 and by 5% and 15% in Q4 of 2020 compared to the same quarters in 2019, respectively. The decline was particularly seen in women and patients with transient ischemic attacks. In cases with cerebral infarction, no increase in NIHSS scores on admission was observed, and the proportion of patients with a time interval between admission and thrombolysis of ≤60 min was unchanged. No clear pattern was found in the frequency of systemic thrombolysis and IAT. In one of the registries, in-hospital mortality of patients with cerebral infarction increased in Q2 of 2020 compared to Q2 of 2019. Conclusion Case numbers slightly decreased under pandemic conditions, while our quarterly analysis indicated that the quality of stroke care was largely unchanged throughout the year 2020.

SARS-CoV-2 Antibodies Are Persisting in Saliva for More Than 15 Months After Infection and Become Strongly Boosted After Vaccination.

SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.

Non-Invasive Antibody Assessment in Saliva to Determine SARS-CoV-2 Exposure in Young Children.

Saliva is a body fluid with hitherto unused potential for the assessment of SARS-CoV-2 antibodies. Specific antibodies can indicate a past SARS-CoV-2 infection and allow to estimate the proportion of individuals with a potential protective immunity. First, we carefully characterized plasma samples obtained from adult control groups with and without prior SARS-CoV-2 infection using certified reference ELISAs. Simultaneously collected saliva samples of confirmed convalescent and negative individuals where then used to validate the herein newly developed ELISA for the detection of SARS-CoV-2 IgG antibodies in saliva. The saliva ELISA was applied to assess SARS-CoV-2 exposure in young children (N = 837) in the age between 1 and 10 years in Tübingen, Germany, towards the end of the first pandemic year 2020. Sensitivity and specificity of the new saliva ELISA was 87% and 100%, respectively. With 12% of all Tübingen children sampled via their respective educational institutions, estimates of SARS-CoV-2 antibody prevalence was 1.6%. Interestingly, only 0.4% preschool kids were positive compared to 3.0% of primary school children. Less than 20% of positive children self-reported symptoms within two months prior to saliva sampling that could be associated - but not exclusively - with a SARS-CoV-2 infection. The saliva ELISA is a valid and suitable protocol to enable population-based surveys for SARS-CoV-2 antibodies. Using non-invasive sampling and saliva ELISA testing, we found that prevalence of SARS-CoV-2 antibodies was significantly lower in young children than in primary school children.

Prevalence of SARS-CoV-2 Infection in Children by Antibody Detection in Saliva: Protocol for a Prospective Longitudinal Study (Coro-Buddy).

BACKGROUND: The world has been confronted with the COVID-19 pandemic for more than one year. Severe disease is more often found among elderly people, whereas most young children and adolescents show mild symptoms or even remain asymptomatic, so that infection might be undiagnosed. Therefore, only limited epidemiological data on SARS-CoV-2 infection in children and young adults are available. OBJECTIVE: This study aims to determine the prevalence of SARS-CoV-2 antibodies in children from the city of Tübingen, Germany, and to measure the incidence of new cases over 12 months. METHODS: SARS-CoV-2 antibodies will be measured in saliva as a surrogate for a previous SARS-CoV-2 infection. Children will be sampled at their preschools, primary schools, and secondary schools at three time points: July 2020, October to December 2020, and April to July 2021. An adult cohort will be sampled at the same time points (ie, adult comparator group). The saliva-based SARS-CoV-2-antibody enzyme-linked immunosorbent assay will be validated using blood and saliva samples from adults with confirmed previous SARS-CoV-2 infections (ie, adult validation group). RESULTS: The first study participant was enrolled in July 2020, and recruitment and enrollment continued until July 2021. We have recruited and enrolled 1850 children, 560 adults for the comparator group, and 83 adults for the validation group. We have collected samples from the children and the adults for the comparator group at the three time points. We followed up with participants in the adult validation group every 2 months and, as of the writing of this paper, we were at time point 7. We will conduct data analysis after the data collection period. CONCLUSIONS: Infection rates in children are commonly underreported due to a lack of polymerase chain reaction testing. This study will report on the prevalence of SARS-CoV-2 infections in infants, school children, and adolescents as well as the incidence change over 12 months in the city of Tübingen, Germany. The saliva sampling approach for SARS-CoV-2-antibody measurement allows for a unique, representative, population-based sample collection process. TRIAL REGISTRATION: ClinicalTrials.gov NCT04581889; https://clinicaltrials.gov/ct2/show/NCT04581889. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27739.

Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients.

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.

Drug Repurposing: A Review of Old and New Antibiotics for the Treatment of Malaria: Identifying Antibiotics with a Fast Onset of Antiplasmodial Action.

Malaria is one of the most life-threatening infectious diseases and constitutes a major health problem, especially in Africa. Although artemisinin combination therapies remain efficacious to treat malaria, the emergence of resistant parasites emphasizes the urgent need of new alternative chemotherapies. One strategy is the repurposing of existing drugs. Herein, we reviewed the antimalarial effects of marketed antibiotics, and described in detail the fast-acting antibiotics that showed activity in nanomolar concentrations. Antibiotics have been used for prophylaxis and treatment of malaria for many years and are of particular interest because they might exert a different mode of action than current antimalarials, and can be used simultaneously to treat concomitant bacterial infections.

Complementary methods for SARS-CoV-2 diagnosis in times of material shortage.

The pandemic caused by SARS-CoV-2 resulted in increasing demands for diagnostic tests, leading to a shortage of recommended testing materials and reagents. This study reports on the performance of self-sampled alternative swabbing material (ordinary Q-tips tested against flocked swab and rayon swab), of reagents for classical RNA extraction (phenol/guanidine-based protocol against a commercial kit), and of intercalating dye-based one-step quantitative reverse transcription real-time PCRs (RT-qPCR) compared against the gold standard hydrolysis probe-based assays for SARS-CoV-2 detection. The study found sampling with Q-tips, RNA extraction with classical protocol and intercalating dye-based RT-qPCR as a reliable and comparably sensitive strategy for detection of SARS-CoV-2-particularly valuable in the current period with a resurgent and dramatic increase in SARS-CoV-2 infections and growing shortage of diagnostic materials especially for regions limited in resources.

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals.

SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.