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1.
Brain Commun ; 5(2): fcad092, 2023.
Article in English | MEDLINE | ID: covidwho-2305799

ABSTRACT

Persistent somatic and neuropsychiatric symptoms have been frequently described in patients after infection with severe acute respiratory syndrome coronavirus 2 even after a benign clinical course of the acute infection during the early phases of the coronavirus severe acute respiratory syndrome coronavirus 2 pandemic and are part of Long COVID. The Omicron variant emerged in November 2021 and has rapidly become predominant due to its high infectivity and suboptimal vaccine cross-protection. The frequency of neuropsychiatric post-acute sequelae after infection with the severe acute respiratory syndrome coronavirus 2 Omicron and adequate vaccination status is not known. Here, we aimed to characterize post-acute symptoms in individuals with asymptomatic or mildly symptomatic breakthrough infection with severe acute respiratory syndrome coronavirus 2. These individuals had either proven infection with the Omicron variant (n = 157) or their infection occurred in 2022 where Omicron was the predominant variant of severe acute respiratory syndrome coronavirus 2 in Germany (n = 107). This monocentric cross-sectional study was conducted at the University Medical Center Hamburg-Eppendorf between 11 February 2022 and 11 April 2022. We employed questionnaires addressing self-reported somatic symptom burden (Somatic Symptom Scale 8) and neuropsychiatric symptoms including mood (Patient Health Questionnaire 2), anxiety (Generalized Anxiety Disorder 7), attention (Mindful Attention Awareness Scale) and fatigue (Fatigue Assessment Scale) in a cohort of hospital workers. Scores were compared between 175 individuals less than 4 weeks after positive testing for severe acute respiratory syndrome coronavirus 2, 88 individuals more than 4 weeks after positive testing and 87 severe acute respiratory syndrome coronavirus 2 uninfected controls. The majority (n = 313; 89.5%) of included individuals were vaccinated at least three times. After recovery from infection, no significant differences in scores assessing neuropsychiatric and somatic symptoms were detected between the three groups (severe acute respiratory syndrome coronavirus 2 uninfected controls, individuals less and more than 4 weeks after positive testing) independent of age, sex, preconditions and vaccination status. In addition, self-reported symptom burden did not significantly correlate with the number of vaccinations against severe acute respiratory syndrome coronavirus 2, time from recovery or the number of infections. Notably, in all three groups, the mean scores for each item of our questionnaire lay below the pathological threshold. Our data show that persistent neuropsychiatric and somatic symptoms after recovery from severe acute respiratory syndrome coronavirus 2 infection in fully vaccinated hospital workers do not occur more frequently than that in uninfected individuals. This will guide healthcare professionals in the clinical management of patients after recovery from breakthrough infections with severe acute respiratory syndrome coronavirus 2.

2.
Microbiol Spectr ; 11(1): e0410322, 2023 02 14.
Article in English | MEDLINE | ID: covidwho-2246385

ABSTRACT

In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June 2022. Out of all 1,254 patients, 185 were treated with sotrovimab: 147 patients received sotrovimab monotherapy, and 38 received combination treatment with sotrovimab and remdesivir. We compared in-hospital mortality for the different treatment regimens for patients treated on regular wards and the intensive care unit separately and performed propensity score matching by age, sex, comorbidities, immunosuppression, and additional dexamethasone treatment to select patients who did not receive antiviral treatment for comparison. No difference in in-hospital mortality was observed between any of the treatment groups and the respective control groups. These findings underline that sotrovimab adds no clinical benefit for hospitalized patients with SARS-CoV-2 Omicron variant infections. IMPORTANCE This study shows that among hospitalized patients with SARS-CoV-2 Omicron variant infection at risk of disease progression, treatment with sotrovimab alone or in combination with remdesivir did not decrease in-hospital mortality. These real-world clinical findings in combination with previous in vitro data about lacking neutralizing activity of sotrovimab against SARS-CoV-2 Omicron variant do not support sotrovimab as a treatment option in these patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Retrospective Studies , Propensity Score , Antibodies, Neutralizing
4.
Viruses ; 15(2)2023 01 20.
Article in English | MEDLINE | ID: covidwho-2200903

ABSTRACT

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.


Subject(s)
COVID-19 , Liver Transplantation , Humans , Female , Breakthrough Infections , Liver Transplantation/adverse effects , SARS-CoV-2 , Antibodies , Disease Progression
5.
Cytokine ; 162: 156109, 2023 02.
Article in English | MEDLINE | ID: covidwho-2158715

ABSTRACT

The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5- counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection.


Subject(s)
COVID-19 , Cytokines , Humans , Cytokines/metabolism , Toll-Like Receptor 7/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , Interferon Regulatory Factors/metabolism , Dendritic Cells
6.
Front Psychol ; 13: 1022203, 2022.
Article in English | MEDLINE | ID: covidwho-2109848

ABSTRACT

Introduction: Little is known about risk factors for both Long COVID and somatic symptoms that develop in individuals without a history of COVID-19 in response to the pandemic. There is reason to assume an interplay between pathophysiological mechanisms and psychosocial factors in the etiology of symptom persistence. Objective: Therefore, this study investigates specific risk factors for somatic symptom deterioration in a cohort of German adults with and without prior SARS-CoV-2 infection. Methods: German healthcare professionals underwent SARS-CoV-2 IgG antibody testing and completed self-rating questionnaires at baseline and 21 months later between April 2020 and February 2022. Differences in variables between the time points were analyzed and a regression analysis was performed to predict somatic symptom deterioration at follow-up. Results: Seven hundred fifty-one adults completed both assessments. Until follow-up, n = 58 had contracted SARS-CoV-2 confirmed by serology. Between baseline and follow-up, signs of mental and physical strain increased significantly in the sample. Symptom expectations associated with COVID-19 and a self-reported history of COVID-19, but not serologically confirmed SARS-CoV-2 infection, significantly predicted somatic symptom deterioration at follow-up. A further predictor was baseline psychological symptom burden. Conclusions: This study supports a disease-overarching biopsychosocial model for the development of burdensome somatic symptoms during the COVID-19 pandemic and supports research findings that symptom burden may be more related to the psychosocial effects of the pandemic than to infection itself. Future studies on Long COVID should include SARS-CoV-2 negative control groups and consider symptom burden prior to infection in order to avoid an overestimation of prevalence rates.

7.
Clin Gastroenterol Hepatol ; 20(11): 2558-2566.e5, 2022 11.
Article in English | MEDLINE | ID: covidwho-1936142

ABSTRACT

BACKGROUND & AIMS: Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations. METHODS: In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders. RESULTS: After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders. CONCLUSIONS: A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.


Subject(s)
COVID-19 , Liver Transplantation , Mice , Animals , Humans , COVID-19 Vaccines , Prospective Studies , Mice, Inbred BALB C , SARS-CoV-2 , COVID-19/prevention & control , Immunity, Cellular , Vaccination , RNA, Messenger , Transplant Recipients , Antibodies, Viral
8.
Euro Surveill ; 27(19)2022 05.
Article in English | MEDLINE | ID: covidwho-1917174

ABSTRACT

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3-5, 0-2 and 3-5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0-8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise.


Subject(s)
Hepatitis , Liver Failure, Acute , Liver Transplantation , Acute Disease , Child , Humans , Israel/epidemiology , Liver Failure, Acute/diagnosis , Liver Failure, Acute/epidemiology , Liver Failure, Acute/etiology , Surveys and Questionnaires
9.
Vaccines (Basel) ; 10(7)2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1917889

ABSTRACT

BACKGROUND: The immunogenicity of different COVID-19 vaccine regimens and combinations in naïve and convalescent individuals has not been formally tested in controlled studies, and real-life observational studies are scarce. METHODS: 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 17 and 31 January 2022. RESULTS: 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. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/mL [IQR]: 13,891 [8505-23,543]), indicating strong protection against severe COVID-19. Individuals who received three COVID-19 vaccine doses (median AU/mL [IQR]: 13,856 [8635-22,705]) and those who resolved a prior SARS-CoV-2 infection and had received two COVID-19 vaccine doses (median AU/mL [IQR] 13,409 [6934-25,000]) exhibited the strongest humoral immune responses. CONCLUSIONS: The current study 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.

10.
Trials ; 23(1): 302, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1789128

ABSTRACT

BACKGROUND: Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication. METHODS: The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021. DISCUSSION: The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis. TRIAL REGISTRATION: EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). CLINICALTRIALS: gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Multicenter Studies as Topic , Prospective Studies , Proton Pump Inhibitors/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
11.
Nat Metab ; 4(3): 310-319, 2022 03.
Article in English | MEDLINE | ID: covidwho-1764213

ABSTRACT

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Liver , Proteomics , Tropism
12.
United European Gastroenterol J ; 10(3): 319-329, 2022 04.
Article in English | MEDLINE | ID: covidwho-1739241

ABSTRACT

BACKGROUND/AIMS: In this observational study, we explored the humoral and cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune hepatitis (AIH) and patients with cholestatic autoimmune liver disease (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]). METHODS: Anti-SARS-CoV-2 antibody titers were determined using the DiaSorin LIAISON and Roche immunoassays in 103 AIH, 64 PSC, and 61 PBC patients and 95 healthy controls >14 days after the second COVID-19 vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of individuals. RESULTS: Previous SARS-CoV-2 infection was frequently detected in AIH but not in PBC/PSC (10/112 (9%), versus 4/144 (2.7%), p = 0.03). In the remaining patients, seroconversion was measurable in 97% of AIH and 99% of PBC/PSC patients, respectively. However, in 13/94 AIH patients antibody levels were lower than in any healthy control, which contributed to lower antibody levels of the total AIH cohort when compared to PBC/PSC or controls (641 vs. 1020 vs. 1200 BAU/ml, respectively). Notably, antibody levels were comparably low in AIH patients with (n = 85) and without immunosuppression (n = 9). Also, antibody titers significantly declined within 7 months after the second vaccination. In the AIM assay of 20 AIH patients, a spike-specific T-cell response was undetectable in 45% despite a positive serology, while 87% (13/15) of the PBC/PSC demonstrated a spike-specific T-cell response. CONCLUSION: Patients with AIH show an increased SARS-CoV-2 infection rate as well as an impaired B- and T-cell response to SARS-CoV-2 vaccine compared to PBC and PSC patients, even in the absence of immunosuppression. Thus, antibody responses to vaccination in AIH patients need to be monitored and early booster immunizations considered in low responders.


Subject(s)
COVID-19 , Cholangitis, Sclerosing , Cholestasis , Hepatitis, Autoimmune , Liver Cirrhosis, Biliary , COVID-19/prevention & control , COVID-19 Vaccines , Cholangitis, Sclerosing/complications , Hepatitis, Autoimmune/complications , Humans , SARS-CoV-2 , Vaccination
13.
Psychother Psychosom Med Psychol ; 72(8): 382-385, 2022 Aug.
Article in German | MEDLINE | ID: covidwho-1721689

ABSTRACT

This cross-sectional study compared hospital staff who had received influenza or COVID-19 vaccination or who had refused COVID-19 vaccination in terms of attitudes towards each vaccination, uptake of influenza vaccination and reasons for refusing COVID-19 vaccination. COVID-19 vaccine refusers rated the risk of infection for themselves and in general and the effectiveness of the vaccination lowest and the vaccination risk highest compared to the other two groups. They also reported the lowest past uptake of influenza vaccination. Perceived pressure to vaccinate proved to be a relevant barrier. Future vaccination campaigns should maintain a balance between information on vaccines, the need for vaccination, and voluntary uptake.


Subject(s)
COVID-19 , Influenza, Human , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Humans , Influenza, Human/prevention & control , Personnel, Hospital , Vaccination
15.
Int J Hyg Environ Health ; 238: 113851, 2021 09.
Article in English | MEDLINE | ID: covidwho-1479610

ABSTRACT

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 indicate 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 , Vaccines , Antibodies, Viral , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Female , Health Personnel , Humans , Longitudinal Studies , Male , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies
17.
Clin Gastroenterol Hepatol ; 20(1): 162-172.e9, 2022 01.
Article in English | MEDLINE | ID: covidwho-1401300

ABSTRACT

BACKGROUND & AIMS: Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups. METHODS: In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10 to 84 days after second vaccination. The spike-specific T-cell response was assessed using an interferon-gamma release assay (EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response. RESULTS: After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared with cirrhotic patients and controls (P < .001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age >65 years (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.48-14.05) and arterial hypertension (OR, 2.50; 95% CI, 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR, 0.36; 95% CI, 0.13-0.99). CONCLUSION: Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.


Subject(s)
COVID-19 , RNA, Viral , Aged , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , Humans , Immunity , Liver Cirrhosis , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Vaccination
18.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz ; 64(9): 1165-1168, 2021 Sep.
Article in German | MEDLINE | ID: covidwho-1349280

ABSTRACT

BACKGROUND: Healthcare workers are among the most exposed and potentially most threatened populations of the ongoing COVID-19 pandemic. Despite some reports on numbers of infections with SARS-CoV­2 in German healthcare workers, the courses of their clinical presentation when affected by COVID-19 are not well described. OBJECTIVE: In this contribution, characteristics and progressions of infected cases among healthcare workers at the University Medical Center Hamburg-Eppendorf during the first wave of the COVID-19 pandemic will be presented. METHODS: Between 1 July and 28 July 2020, 67 healthcare workers, who previously tested positive for SARS-CoV­2 via PCR, were invited via E­mail to participate in an anonymous online questionnaire; 39 persons participated. RESULTS: Participants (58%) were mostly ≤ 39 years old (64%) and female (70%). Most healthcare workers were involved in direct patient management (85%), including contact with SARS-CoV­2 positive patients (62%). All participants reported acute symptoms with a median duration of 19 days. The most frequent symptoms were fatigue (85%), anosmia (67%), cough (64%), headache (62%), and shortness of breath (51%). The disease course was mostly mild with low admission rates (5%). Ongoing symptoms lasting more than four weeks post-symptom-onset, particularly anosmia, fatigue, and shortness of breath, were reported by 38%. This group more frequently had pre-existing conditions (53% vs. 12%, p = 0.010), specifically hypertension (27% vs. 4%, p = 0.062). DISCUSSION: Healthcare workers reported mostly mild courses of COVID-19 despite increased contact with SARS-CoV-2 patients. However, some reported persistent symptoms months after infection.


Subject(s)
COVID-19 , Health Personnel/statistics & numerical data , Pandemics , Academic Medical Centers , Adult , COVID-19/epidemiology , Female , Germany/epidemiology , Humans , Male , Universities
19.
United European Gastroenterol J ; 9(7): 797-808, 2021 09.
Article in English | MEDLINE | ID: covidwho-1261778

ABSTRACT

BACKGROUND: During the current SARS-CoV-2 pandemic it is important to identify risk factors for COVID-19. Registry studies are providing growing evidence on the elevated risk of mortality from COVID-19 in patients with chronic liver disease, especially in advanced stages. Results may, however, have a selection bias towards severe cases. Limited data is available on COVID-19 in patients with autoimmune liver disease (AILD). AIM: To perform an online survey to capture the prevalence of COVID-19 and the state of medical care of patients with AILD in Europe during the pandemic. METHODS: Data was collected via an anonymous patient-oriented, online survey, which was available on the EUSurvey platform in nine European languages between 24th June 2020 and 14th October 2020. Of 1834 contributions, 51 were excluded because participants did not name an underlying AILD, and four were excluded because of duplicate data entry. RESULTS: Of 1,779 participants, 1,752 resided in 20 different countries of the European Union and the United Kingdom (UK). The five countries with the highest numbers of contributions were France (n = 450), Germany (n = 318), the Netherlands (n = 267), Spain (n = 225), and the UK (n = 183). 2.2% of participants (39/1779) had been diagnosed with COVID-19. There were no differences regarding age, sex, AILD, the status of liver cirrhosis, or status post liver transplantation between COVID-19 and non-COVID-19 cases. Of the 39 COVID-19 cases, five patients were admitted to a regular ward, one patient was admitted to ICU and required ventilation. CONCLUSION: In our Europe-wide, patient-oriented survey on COVID-19 in patients with AILD, we detected a low rate of COVID-19, comparable to the period prevalence of the general population. These results suggest that patients with AILD are not at elevated risk of COVID-19.


Subject(s)
COVID-19/epidemiology , End Stage Liver Disease/epidemiology , Hepatitis, Autoimmune/epidemiology , Liver Cirrhosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , End Stage Liver Disease/surgery , Europe/epidemiology , Female , Hepatitis, Autoimmune/surgery , Humans , Liver Cirrhosis/surgery , Liver Transplantation , Male , Middle Aged , Prevalence , Registries , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires , Young Adult
20.
J Clin Med ; 10(11)2021 May 24.
Article in English | MEDLINE | ID: covidwho-1244046

ABSTRACT

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February-28 July 2020) and second (29 July-31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

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