ABSTRACT
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we show that SARS-CoV-2 is detectable in postmortem vagus nerve specimen together with inflammatory cell infiltration derived primarily from monocytes. This is associated with a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction.
Subject(s)
COVID-19 , Inflammation , Vagus Nerve Diseases , Primary DysautonomiasABSTRACT
As part of our ongoing prospective seroprevalence study, we assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between January 17 and 31, 2022. The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.8% (n=68) and thus lower than the seroprevalence in the general population in Hamburg. At the current study visit, 99.3% (n=692) had received at least one vaccine dose and 93.1% (n=649) had received at least three vaccine doses. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/ml [IQR]: 13.891 [8.505 to 23.543]), indicating strong protection against severe COVID-19. In addition, we show that individuals who received three COVID-19 vaccine doses (median AU/ml [IQR]: 13.856 [8.635 to 22.705]), and those who resolved a prior SARS-CoV-2 infection and received two COVID-19 vaccine doses (median AU/ml [IQR] 13.409 [6.934 to 25.000]) exhibited the strongest humoral immune responses. The low prevalence of anti-NC-SARS-CoV-2 antibodies indicates persistent effectiveness of established infection control interventions in preventing nosocomial SARS-CoV-2 transmission with the delta and omicron viral variants as predominant strains. Our study further indicates that three exposures to the viral spike protein by either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses, which supports current vaccination recommendations.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN- γ and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.
Subject(s)
COVID-19ABSTRACT
In a cross-sectional analysis, we have identified a high prevalence of respiratory muscle dysfunction in persistently symptomatic patients after COVID-19 (‘Long COVID’). Respiratory muscle impairment in these patients was associated with exercise-induced deoxygenation, impaired exercise tolerance, activity and functional outcomes after COVID-19.
Subject(s)
COVID-19 , Respiratory ParalysisABSTRACT
In this longitudinal cohort study, we assessed the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) seroconversion rates and analyzed the coronavirus disease 2019 (COVID-19) vaccine-induced immunity of 872 hospital workers at the University Medical Center Hamburg-Eppendorf between May 11 and May 31, 2021. The overall seroprevalence of anti-NC-SARS-CoV-2 antibodies was 4.7% (n=41), indicating low SARS-CoV-2 infection rates and persistent effectiveness of hospital-wide infection control interventions during the second and third wave of the pandemic. In total, 92.7% (n=808) out of the entire study cohort, 98.2% (n=325) of those who had been vaccinated once and all 393 individuals who had been vaccinated twice had detectable anti-S1-RBD-SARS-CoV-2 antibody titers and no significant differences in vaccine-induced immune response were detected between male and female individuals and between different age groups. Vaccinated study participants with detectable anti-NC-SARS-CoV-2 antibody titers (n=30) developed generally higher anti-S1-RBD-SARS-CoV-2 antibody titers compared to anti-NC-SARS-CoV-2 negative individuals (n=694) (median titer: 7812 vs. 345 BAU/ml, p<0.0001). Furthermore, study participants who received heterologous vaccination with AZD1222 followed by an mRNA vaccine showed markedly higher anti-S1-RBD-SARS-CoV-2 antibody titers than individuals who received two doses of an mRNA vaccine or two doses of AZD1222 (median titer: AZD1222 / AZD1222: 1069 BAU/ml, mRNA / mRNA: 1388 BAU/ml, AZD1222/mRNA: 9450 BAU/ml; p<0.0001). Our results demonstrate that infection control interventions were generally effective in preventing nosocomial transmission of SARS-CoV-2 and that COVID-19 vaccines can elicit strong humoral responses in the majority of a real-world cohort of hospital workers.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
BackgroundSARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand. ObjectiveWe evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens). Methods100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire. ResultsThe median duration from symptom onset to sampling was 6 days (IQR 2-12 days). The overall relative sensitivity was 49.4%, 44.6%, 45.8% and 54.9 % for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106 copies of SARS-CoV-2 /swab, n=26), AgPOCTs reached sensitivities of 92.3% or more (range 92.3%-100%). Specificity was 100% for tests I, II and IV and 97% for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills. DiscussionBesides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.
ABSTRACT
Objective: To assess the effectiveness of multimodal infection control interventions in the prevention of SARS-CoV-2 infections in healthcare professionals. Design: Sequential follow-up study. Setting: Largest tertiary care centre in northern Germany. Participants: 1253 employees of the University Medical Center Hamburg-Eppendorf were sequentially assessed for the presence of SARS-CoV-2 IgG antibodies at the beginning of the covid-19 epidemic (20 March - 9 April), one month (20 April - 8 May), and another two months later (22 June - 24 July). Of those, 1026 were healthcare workers (HCWs) of whom 292 were directly involved in the care of covid-19 patients. During the study period, infection control interventions were deployed, those included i) strict barrier nursing of all known covid-19 patients including FFP2 (N95) masks, goggles, gloves, hoods and protective gowns, ii) visitor restrictions with access control at all hospital entries, iii) mandatory wearing of disposable face masks in all clinical settings, and iv) universal RT-PCR admission screening of patients. Main Outcome Measures: SARS-CoV-2 IgG seroconversion rate. Results: At the initial screening, ten participants displayed significant IgG antibody ratios. Another ten individuals showed seroconversion at the second time point one month later, only two further participants seroconverted during the subsequent two months. The overall SARS-CoV-2 seroprevalence in the study cohort at the last follow-up was 1.8%, the seroconversion rate dropped from 0.81% to 0.08% per month despite a longer observation period. Amongst HCWs seropositivity was increased in those directly involved in the care of patients with SARS-CoV-2 infections (3.8%, n=11) compared to other HCWs (1.4%, n=10, P=0.025). However, after the adoption of all multimodal infection control interventions seroconversions were observed in only two more HCWs, neither of whom were involved in inpatient care. Conclusion: Multimodal infection control and prevention interventions are highly effective in mitigating SARS-CoV-2 infections of healthcare professionals.