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1.
Eur J Immunol ; 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1782587

ABSTRACT

COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID-19 remains less well understood. Here we characterized NK cell-mediated SARS-CoV-2 antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 spike-1 (S1) and nucleocapsid (NC) protein. Serum samples from SARS-CoV-2 resolvers induced significant CD107a-expression by NK cells in response to S1 and NC, while serum samples from SARS-CoV-2-negative individuals did not. Furthermore, serum samples from individuals that received the BNT162b2 vaccine induced strong CD107a-expression by NK cells that increased with the second vaccination and was significantly higher than observed in infected individuals. As expected, vaccine-induced responses were only directed against S1 and not against NC protein. S1-specific CD107a responses by NK cells were significantly correlated to NK cell-mediated killing of S1-expressing cells. Interestingly, screening of serum samples collected prior to the COVID-19 pandemic identified two individuals with cross-reactive antibodies against SARS-CoV-2 S1, which also induced degranulation of NK cells. Taken together, these data demonstrate that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can trigger significant NK cell-mediated ADCC activity, and identify some cross-reactive ADCC-activity against SARS-CoV-2 by endemic coronavirus-specific antibodies. This article is protected by copyright. All rights reserved.

2.
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
3.
United European Gastroenterol J ; 10(3): 319-329, 2022 Apr.
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
6.
Front Immunol ; 12: 798276, 2021.
Article in English | MEDLINE | ID: covidwho-1606542

ABSTRACT

Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to suspected pneumonitis. After improvement and SARS-CoV-2 clearance, anti-cancer treatment was resumed without pembrolizumab. Immunological analyses with comparison to otherwise healthy SARS-CoV-2-infected ambulatory patients revealed a strong humoral immune response with higher levels of SARS-CoV-2-reactive IgG and neutralizing serum activity. Additionally, sustained increase of Tfh as well as activated CD4+ and CD8+ T cells was observed. Sequential CT scans showed regression of tumor lesions and marked improvement of the pulmonary situation, with no signs of pneumonitis after pembrolizumab re-challenge as maintenance. At the latest follow-up, the patient is ambulatory and in ongoing partial remission on pembrolizumab. In conclusion, anti-PD1 initiation during active COVID-19 pneumonia was feasible and cellular and humoral immune responses to SARS-CoV-2 appeared enhanced in our hospitalized patient. However, distinguishing COVID-19-associated changes from anti-PD1-associated immune-related pneumonitis posed a considerable clinical, radiographic, and immunologic challenge.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , SARS-CoV-2/drug effects , Adult , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/complications , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/immunology , Humans , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Lung Neoplasms/complications , Lung Neoplasms/immunology , Male , Neoplasm Metastasis , Pneumonia/immunology , Pneumonia/prevention & control , Pneumonia/virology , SARS-CoV-2/immunology
7.
Clin Infect Dis ; 73(11): e4020-e4024, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560662

ABSTRACT

We provide detailed clinical, virological, and immunological data of a B-cell-depleted patient treated with obinutuzumab for follicular lymphoma with protracted coronavirus disease 2019 (COVID-19) and viremia. A sustained response was achieved after 2 courses of remdesivir and subsequent convalescent plasma therapy. Immunocompromised patients might require combined and prolonged antiviral treatment regimens.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , COVID-19/therapy , Humans , Immunization, Passive , SARS-CoV-2
8.
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 , Female , Health Personnel , Humans , Longitudinal Studies , Male , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies
9.
Mol Ther Methods Clin Dev ; 23: 418-423, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1466817

ABSTRACT

Vaccination with the adenoviral-vector-based AstraZeneca ChAdOx1 nCov-19 (Vaxzevria) vaccine is efficient and safe. However, in rare cases vaccinated individuals developed life-threatening thrombotic complications, including thrombosis in cerebral sinus and splanchnic veins. Monitoring of the applied vector in vivo represents an important precondition to study the molecular mechanisms underlying vaccine-driven adverse effects now referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). We previously have shown that digital PCR (dPCR) is an excellent tool to quantify transgene copies in vivo. Here, we present a highly sensitive dPCR for in situ quantification of ChAdOx1 nCoV-19 copies. Using this method, we quantified vector copies in human plasma 24, 72, and 168 h post vaccination and in a variety of murine tissues in an experimental vaccination model 30 min post injection. We describe a method for high-sensitivity quantitative detection of ChAdOx1 nCoV-19 with possible implications to elucidate the mechanisms of severe ChAdOx1 nCov-19 vaccine complications.

11.
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 , COVID-19 Vaccines , Humans , Immunity , Liver Cirrhosis , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Vaccination
12.
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
13.
J Clin Med ; 10(14)2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1308366

ABSTRACT

In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) "low", (2) "intermediate" or (3) "high", depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

14.
iScience ; 24(7): 102752, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1275407

ABSTRACT

COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory, and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients.

15.
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.

16.
Immun Inflamm Dis ; 9(3): 905-917, 2021 09.
Article in English | MEDLINE | ID: covidwho-1224967

ABSTRACT

BACKGROUND: Hamburg is a city state of approximately 1.9 Mio inhabitants in Northern Germany. Currently, the COVID-19 epidemic that had largely subsided during last summer is resurging in Hamburg and in other parts of the world, underlining the need for additional tools to monitor SARS-CoV-2 antibody responses. AIM: We aimed to develop and validate a simple, low-cost assay for detecting antibodies against the native coronavirus 2 spike protein (CoV-2 S) that does not require recombinant protein or virus. METHOD: We transiently co-transfected HEK cells or CHO cells with expression vectors encoding CoV-2 S and nuclear GFP. Spike protein-specific antibodies in human serum samples bound to transfected cells were detected with fluorochrome conjugated secondary antibodies by flow cytometry orimmunofluorescence microscopy. We applied this assay to monitor antibody development in COVID-19 patients, household contacts, and hospital personnel during the ongoing epidemic in the city state of Hamburg. RESULTS: All recovered COVID-19 patients showed high levels of CoV-2 S-specific antibodies. With one exception, all household members that did not develop symptoms also did not develop detectable antibodies. Similarly, lab personnel that worked during the epidemic and followed social distancing guidelines remained antibody-negative. CONCLUSION: We conclude that high-titer CoV-2 S-specific antibodies are found in most recovered COVID-19 patients and in symptomatic contacts, but only rarely in asymptomatic contacts. The assay may help health care providers to monitor disease progression and antibody responses in vaccination trials, to identify health care personnel that likely are resistant to re-infection, and recovered individuals with high antibody titers that may be suitable asplasma and/or antibody donors.


Subject(s)
Antibodies, Viral/analysis , COVID-19 , Spike Glycoprotein, Coronavirus , Adult , Aged , Aged, 80 and over , Animals , COVID-19/immunology , Cricetinae , Cricetulus , Flow Cytometry , HEK293 Cells , Humans , Middle Aged , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
17.
Adv Exp Med Biol ; 1318: 549-573, 2021.
Article in English | MEDLINE | ID: covidwho-1222734

ABSTRACT

The history of vaccine development spans centuries. At first, whole pathogens were used as vaccine agents, either inactivated or attenuated, to reduce virulence in humans. Safety and tolerability were increased by including only specific proteins as antigens and using cell culture methods, while novel vaccine strategies, like nucleic acid- or vector-based vaccines, hold high promise for the future. Vaccines have generally not been employed as the primary tools in outbreak response, but this might change since advances in medical technology in the last decades have made the concept of developing vaccines against novel pathogens a realistic strategy. Wandering the uncharted territory of a novel pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we can learn from other human Betacoronaviridae that emerged in the last decades, SARS-CoV-1 and MERS-CoV. We can identify the most likely target structures of immunity, establish animal models that emulate human disease and immunity as closely as possible, and learn about complex mechanisms of immune interaction such as cross-reactivity or antibody-dependent enhancement (ADE). However, significant knowledge gaps remain. What are the correlates of protection? How do we best induce immunity in vulnerable populations like the elderly? Will the immunity induced by vaccination (or by natural infection) wane over time? To date, at least 149 vaccine candidates against SARS-CoV-2 are under development. At the time of writing, at least 17 candidates have already progressed past preclinical studies (in vitro models and in vivo animal experiments) into clinical development. This chapter will provide an overview of this rapidly developing field.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Vaccines , Viral Vaccines , Aged , Animals , COVID-19 Vaccines , Humans , SARS-CoV-2
18.
J Leukoc Biol ; 109(1): 77-90, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188012

ABSTRACT

B cells play a central role in antiviral and antiparasitic immunity, not only as producers of antibodies, but also as APCs and mediators of inflammation. In this study, we used 16-color flow cytometry analysis to investigate the frequency, differentiation, and activation status of peripheral B cells of patients with SARS-CoV-2 infection or acute Plasmodium falciparum malaria compared with the healthy individuals. As a main result, we observed an increase of the frequency of (CD27-, CD21-) atypical memory B cells and (CD19+, CD27+, CD38+) plasmablasts in malaria and COVID-19 patients. Additionally, CD86, PD-1, CXCR3, and CD39 expression was up-regulated, whereas CD73 was down-regulated on plasmablasts of COVID-19 and malaria patients compared with the bulk B cell population. In particular, there was a more pronounced loss of CD73+ B cells in malaria. The frequency of plasmablasts positively correlated with serum levels of CRP, IL-6, and LDH of COVID-19 patients. In the longitudinal course of COVID-19, a rapid normalization of the frequency of atypical memory B cells was observed. The role and function of plasmablasts and atypical memory B cells in COVID-19 and other acute infections remain to be further investigated. The role of B cells as either "driver or passenger" of hyperinflammation during COVID-19 needs to be clarified.


Subject(s)
COVID-19/immunology , Immunologic Memory , Malaria, Falciparum/immunology , Plasma Cells/immunology , Plasmodium falciparum/immunology , SARS-CoV-2/immunology , Adult , Aged , Antigens, CD/immunology , COVID-19/pathology , Female , Humans , Malaria, Falciparum/pathology , Male , Middle Aged , Plasma Cells/pathology
19.
Viruses ; 13(4)2021 04 12.
Article in English | MEDLINE | ID: covidwho-1178437

ABSTRACT

So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Health Personnel , Reinfection/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Immunity , SARS-CoV-2/genetics , Virus Shedding , Whole Genome Sequencing
20.
Pathogens ; 10(4)2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1178372

ABSTRACT

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (#1) and mild disease (#2 and #3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals #1 and #2, whereas #3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient #1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases #2 and #3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics.

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