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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331848

ABSTRACT

Vaccines are the most important means to overcome the SARS–CoV–2 pandemic. They induce specific antibody and T–cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1–nCoV–19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV–2 – including variants of concern such as Delta or Omicron – was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer–lasting humoral immunity than homologous ChAd immunization. T–cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long–term humoral and cellular immune protection.

2.
Emerg Infect Dis ; 28(3): 572-581, 2022 03.
Article in English | MEDLINE | ID: covidwho-1706937

ABSTRACT

Hospital staff are at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease (COVID-19) pandemic. This cross-sectional study aimed to determine the prevalence of SARS-CoV-2 infection in hospital staff at the University Hospital rechts der Isar in Munich, Germany, and identify modulating factors. Overall seroprevalence of SARS-CoV-2-IgG in 4,554 participants was 2.4%. Staff engaged in direct patient care, including those working in COVID-19 units, had a similar probability of being seropositive as non-patient-facing staff. Increased probability of infection was observed in staff reporting interactions with SARS-CoV-2‒infected coworkers or private contacts or exposure to COVID-19 patients without appropriate personal protective equipment. Analysis of spatiotemporal trajectories identified that distinct hotspots for SARS-CoV-2‒positive staff and patients only partially overlap. Patient-facing work in a healthcare facility during the SARS-CoV-2 pandemic might be safe as long as adequate personal protective equipment is used and infection prevention practices are followed inside and outside the hospital.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Germany/epidemiology , Health Personnel , Hospitals, University , Humans , Immunoglobulin G , Infection Control , Personnel, Hospital , Prevalence , Seroepidemiologic Studies
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320926

ABSTRACT

Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. Methods: : IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR+;CT±) and 46 patients with suspected (group B: repetitive PCR-;CT+) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. Results: : Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively;(p<0.01). Compared to hospitalized patients with a non-complicated course, seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p<0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology >14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR >17d after symptom onset. Conclusions: : Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2 nd week following symptom onset.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314315

ABSTRACT

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pandemic in spring 2020, where we identified 91 convalescents from mild SARS-CoV-2 infection among 4554 health care workers. We followed the dynamics and magnitude of spike-specific immunity in convalescents during the spontaneous course over ≥ 9 months, after SARS-CoV-2 re-exposure and after BNT162b2 mRNA vaccination. Virus-neutralizing antibodies and spike-specific T cell responses with predominance of IL-2-secreting polyfunctional CD4 T cells continuously declined over 9 months, but remained detectable at low levels. After a single vaccination, convalescents simultaneously mounted strong antibody and T cell responses against the SARS-CoV-2 spike proteins. In naïve individuals, a prime vaccination induced preferentially IL-2-secreting CD4 T cells that preceded production of spike-specific virus-neutralizing antibodies after boost vaccination. Response to vaccination, however, was not homogenous. Compared to four individuals among 455 naïve vaccinees (0.9%), we identified 5/82 (6.1%) convalescents with a delayed response to vaccination. These convalescents had originally developed dysfunctional spike-specific immune responses after SARS-CoV-2 infection, and required prime and boost vaccination to develop strong spike-specific immunity. Importantly, during the second wave of the COVID-19 pandemic in fall/winter of 2021 and prior to vaccination we detected a surge of virus-neutralizing antibodies consistent with re-exposure to SARS-CoV-2 in 6 out of 82 convalescents. The selective increase in virus-neutralizing antibodies occurred without systemic re-activation of spike-specific T cell immunity, whereas a single BNT162b2 mRNA vaccination sufficed to induce strong spike-specific antibody and systemic T cell responses in the same individuals. These results support the notion that BNT162b2 mRNA vaccination synchronizes spike-specific immunity in all convalescents of mild SARS-CoV-2 infection and may provide additional protection from re-infection by inducing more rigorous stimulation of spike-specific T cell immunity than re-exposure with SARS-CoV-2.

5.
Nat Med ; 28(3): 496-503, 2022 03.
Article in English | MEDLINE | ID: covidwho-1655606

ABSTRACT

Infection-neutralizing antibody responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 vaccination are an essential component of antiviral immunity. Antibody-mediated protection is challenged by the emergence of SARS-CoV-2 variants of concern (VoCs) with immune escape properties, such as omicron (B.1.1.529), which is rapidly spreading worldwide. Here we report neutralizing antibody dynamics in a longitudinal cohort of coronavirus disease 2019 convalescent and infection-naive individuals vaccinated with mRNA BNT162b2 by quantifying SARS-CoV-2 spike protein antibodies and determining their avidity and neutralization capacity in serum. Using live-virus neutralization assays, we show that a superior infection-neutralizing capacity against all VoCs, including omicron, developed after either two vaccinations in convalescents or a third vaccination or breakthrough infection of twice-vaccinated, naive individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. We conclude that an infection-plus-vaccination-induced hybrid immunity or a triple immunization can induce high-quality antibodies with superior neutralization capacity against VoCs, including omicron.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , Humans , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
6.
Nat Commun ; 13(1): 153, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616980

ABSTRACT

Anti-viral immunity continuously declines over time after SARS-CoV-2 infection. Here, we characterize the dynamics of anti-viral immunity during long-term follow-up and after BNT162b2 mRNA-vaccination in convalescents after asymptomatic or mild SARS-CoV-2 infection. Virus-specific and virus-neutralizing antibody titers rapidly declined in convalescents over 9 months after infection, whereas virus-specific cytokine-producing polyfunctional T cells persisted, among which IL-2-producing T cells correlated with virus-neutralizing antibody titers. Among convalescents, 5% of individuals failed to mount long-lasting immunity after infection and showed a delayed response to vaccination compared to 1% of naïve vaccinees, but successfully responded to prime/boost vaccination. During the follow-up period, 8% of convalescents showed a selective increase in virus-neutralizing antibody titers without accompanying increased frequencies of circulating SARS-CoV-2-specific T cells. The same convalescents, however, responded to vaccination with simultaneous increase in antibody and T cell immunity revealing the strength of mRNA-vaccination to increase virus-specific immunity in convalescents.


Subject(s)
/immunology , COVID-19/immunology , Convalescence , Nucleocapsid/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Cytokines/immunology , Cytokines/metabolism , Flow Cytometry/methods , Follow-Up Studies , Humans , Immunoglobulin G/immunology , Interleukin-2/immunology , Interleukin-2/metabolism , Kinetics , SARS-CoV-2/physiology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/virology , Time Factors , Vaccination/methods
7.
Cell Rep ; 38(2): 110214, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588141

ABSTRACT

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs-classic features of protective immunity-are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Adult , Cells, Cultured , Cross Reactions/immunology , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immunodominant Epitopes/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology , Male , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Cytotoxic/immunology
8.
J Clin Med ; 10(23)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1538417

ABSTRACT

Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were prospectively followed-up at a median of 36, 75.5, 122 and 222 days after discharge. The health-related quality of life (HrQoL) (36-item Short Form Health Survey and St. George's Respiratory Questionnaire, SGRQ), cardiopulmonary function, laboratory parameters and chest imaging were assessed longitudinally. The HrQoL assessment revealed a reduced physical functioning, as well as increased SGRQ impact and symptoms scores that all improved over time but remained markedly impaired compared to the reference groups. The median radiological severity scores significantly declined; persistent abnormalities were found in 33.3% of the patients on follow-up. A reduced diffusion capacity was the most common abnormal pulmonary function parameter. The length of hospitalization correlated with role limitations due to physical problems, the SGRQ symptom and the impact score. In conclusion, in survivors of severe COVID-19, the pulmonary function and symptoms improve over time, but impairments in their physical function and diffusion capacity can persist over months. Longer follow-up studies with larger cohorts will be necessary to comprehensively characterize long-term sequelae upon severe COVID-19 and to identify patients at risk.

9.
J Clin Med ; 10(22)2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1512415

ABSTRACT

Deficiencies in smell and taste are common symptoms of COVID-19. Quantitative losses are well surveyed. This study focuses on qualitative changes such as phantosmia (hallucination of smell), parosmia (alteration of smell), and dysgeusia (alteration of taste) and possible connections with the adaptive immune system. Subjective experience of deficiency in taste and smell was assessed by two different questionnaires after a median of 100 and 244 days after first positive RT-PCR test. SARS-CoV-2-specific antibody levels were measured with the iFlash-SARS-CoV-2 assay. After 100 days a psychophysical screening test for olfactory and gustatory dysfunction was administered. 30 of 44 (68.2%) participants reported a chemosensory dysfunction (14 quantitative, 6 qualitative, 10 quantitative, and qualitative) during COVID-19, eleven (25.0%) participants (1 quantitative, 7 qualitative, 3 quantitative, and quantity) after 100 days, and 14 (31.8%) participants (1 quantitative, 10 qualitative, 3 quantitative and qualitative) after 244 days. Four (9.1%) participants, who were symptom-free after 100 days reported now recently arisen qualitative changes. Serological and T-cell analysis showed no correlation with impairment of taste and smell. In conclusion, qualitative changes can persist for several months and occur as late-onset symptoms months after full recovery from COVID-19-induced quantitative losses in taste and smell.

10.
Transfus Apher Sci ; 60(6): 103278, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415810

ABSTRACT

OBJECTIVE: To investigate the effect of convalescent plasma therapy (CPT) on clinical courses of B-cell-sufficient and B-cell-depleted patients with life-threatening COVID-19. PATIENTS AND METHODS: In this case series, we retrospectively analysed clinical, laboratory and cardiopulmonary parameters of six patients with life-threatening COVID-19 receiving convalescent plasma (CP) as rescue therapy between April 11, 2020 to October 10, 2020. Clinical and laboratory parameters before and after transfusion were compared in two B-cell-depleted patients and four B-cell sufficient patients (control group). RESULTS: Both B-cell-depleted patients cleared SARS-CoV-2 virus and survived, while all other patients died within 14 days from intervention despite maximal therapeutic efforts. D-dimer levels increased in both cohorts subsequent to CPT. In control patients, mean Interleukin-6 increased and platelet levels decreased as opposed to decreasing and stable levels in B-cell-depleted patients, respectively. Control patients required increased doses of vasopressor compared to decreasing doses in B-cell depleted patients subsequent to CPT. PO2/FiO2 decrease was more pronounced and respiratory deterioration required postinterventional extracorporeal membrane oxygenation in two control patients. Transpulmonary thermodilution revealed a further increase of the Extravascular Lung Water Index upon CPT in control patients. CONCLUSION: Use of CP in late stages of life-threatening COVID-19 should be used with caution but may be beneficial in B-cell-depleted patients. Further studies are necessary to assess factors predicting potential therapeutic benefits as well as possible hazards.


Subject(s)
B-Lymphocytes , COVID-19/mortality , COVID-19/therapy , Lymphocyte Depletion , SARS-CoV-2 , Adult , Aged , COVID-19/blood , Disease-Free Survival , Female , Humans , Immunization, Passive , Male , Middle Aged , Retrospective Studies , Survival Rate
12.
Respir Res ; 22(1): 119, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1202183

ABSTRACT

BACKGROUND: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. METHODS: IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic's first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. RESULTS: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p < 0.01). Compared to hospitalized patients with a non-complicated course (non-ICU patients), seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p < 0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology > 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset. CONCLUSIONS: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2nd week following symptom onset.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Critical Care/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Middle Aged , Pandemics , Polymerase Chain Reaction , Retrospective Studies , Seroconversion , Serologic Tests , Tomography, X-Ray Computed , Young Adult
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