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1.
Front Immunol ; 13: 907343, 2022.
Article in English | MEDLINE | ID: covidwho-1933692

ABSTRACT

Background: Despite the high level of protection against severe COVID-19 provided by the currently available vaccines some breakthrough infections occur. Until now, there is no information whether a potential risk of a breakthrough infection can be inferred from the level of antibodies after booster vaccination. Methods: Levels of binding antibodies and neutralization capacity after the first, one and six month after the second, and one month after the third (booster) vaccination against COVID-19 were measured in serum samples from 1391 healthcare workers at the University Hospital Essen. Demographics, vaccination scheme, pre-infection antibody titers and neutralization capacity were compared between individuals with and without breakthrough infections. Results: The risk of developing an Omicron breakthrough infection was independent of vaccination scheme, sex, body mass index, smoking status or pre-existing conditions. In participants with low pre-infection anti-spike antibodies (≤ 2641.0 BAU/ml) and weaker neutralization capacity (≤ 65.9%) against Omicron one month after the booster vaccination the risk for developing an Omicron infection was 10-fold increased (P = 0.001; 95% confidence interval, 2.36 - 47.55). Conclusion: Routine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying "non"-, "low" and "high"-responders may be used as an indication for re-vaccination.


Subject(s)
Antibody Formation , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunization, Secondary , SARS-CoV-2
3.
Vaccines (Basel) ; 10(2)2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1732265

ABSTRACT

This study analyzed binding and neutralizing antibody titers up to 6 months after standard vaccination with BNT162b2 (two doses of 30 µg each) in SARS-CoV-2 naïve patients (n = 59) on hemodialysis. Humoral vaccine responses were measured before and 6, 12, and 24 weeks after the first vaccination. A chemiluminescent immunoassay (CLIA) was used to quantify SARS-CoV-2 IgG against the spike glycoprotein. SARS-CoV-2 neutralizing activity was tested against the wild-type virus. A multivariable binary regression model was used to identify risk factors for the absence of humoral immune responses at 6 months. At week 6, vaccine-specific seroconversion was detected in 96.6% of all patients with median anti-SARS-CoV-2 IgGs of 918 BAU/mL. At weeks 12 and 24, seroconversion rates decreased to 91.5% and 79.7%, and corresponding median binding antibody titers declined to 298 BAU/mL and 89 BAU/mL, respectively. Neutralizing antibodies showed a decay from 79.6% at week 6 to 32.8% at week 24. The risk factor with the strongest association for vanishing immune responses was low serum albumin (p = 0.018). Regarding vaccine-specific humoral responses 6 months after the standard BNT162b2 vaccination schedule, SARS-CoV-2 naïve patients receiving hemodialysis must be considered at risk of becoming infected with SARS-CoV-2 and being infectious.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315379

ABSTRACT

Background: While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines under real-world conditions. Methods: Venous blood was collected from 126 adults, before and/or after inactivated COVID-19 vaccine inoculation. SARS-CoV-2 neutralizing antibody (NAb) and S-receptor binding domain IgG in the serum were detected. The isolated peripheral blood mononuclear cells were stimulated by three pools of lyophilized peptides covering the spike, nucleocapsid, and membrane protein of SARS-CoV-2 for evaluating antigen-specific T cell responses against the virus. Findings: The seroconversion rate for S-RBD IgG and NAb after two doses of vaccination was 87.06% (74/85) and 78.82% (67/85), respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein increased significantly after a single vaccination dose, and continued to increase after the second administration. S, N, or M-specific CD4+ and CD8+ T cell responses became detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Interpretation: Both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100048837).Funding Fundamental Research Funds for the Central Universities, National Natural Science Foundation of China, National Science and Technology Major Project, Deutsche Forschungsgemeinschaft, Medical Faculty of the University of Duisburg-Essen and Stiftung Universiätsmedizin, University Hospital Essen, Germany, and the Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology.Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the local medical ethics committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (2021-0570)

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311943

ABSTRACT

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokines profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.

6.
Front Immunol ; 13: 816220, 2022.
Article in English | MEDLINE | ID: covidwho-1686484

ABSTRACT

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.


Subject(s)
/immunology , Antibodies, Neutralizing/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibody Affinity/immunology , COVID-19/mortality , Coronavirus M Proteins/immunology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
7.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Article in English | MEDLINE | ID: covidwho-1671749

ABSTRACT

Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies, and have been successfully employed for the treatment of viral diseases. Humans express 12 IFN-alpha (α) subtypes, which activate downstream signaling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in IFN-I immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19; therefore, early administration of IFN-I may be protective against life-threatening disease. Here we comprehensively analyzed the antiviral activity of all IFNα subtypes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate, and low antiviral IFNs. In particular, IFNα5 showed superior antiviral activity against SARS-CoV-2 infection in vitro and in SARS-CoV-2-infected mice in vivo. Dose dependency studies further displayed additive effects upon coadministration with the broad antiviral drug remdesivir in cell culture. Transcriptomic analysis of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting, and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in IFN-I signaling pathways, negative regulation of viral processes, and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multimodular definition of antiviral host responses mediated by defined IFN-I. This knowledge will support the development of novel therapeutic approaches against SARS-CoV-2.


Subject(s)
COVID-19/drug therapy , Interferon-alpha/pharmacology , SARS-CoV-2/drug effects , Transcriptome , Virus Replication/drug effects , Animals , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Cloning, Molecular , Disease Models, Animal , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression Profiling , Gene Expression Regulation , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Humans , Interferon-alpha/genetics , Interferon-alpha/immunology , Mice , Protein Isoforms/classification , Protein Isoforms/genetics , Protein Isoforms/immunology , Protein Isoforms/pharmacology , Recombinant Proteins/classification , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/pharmacology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Signal Transduction , Vero Cells
8.
Frontiers in immunology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1602189

ABSTRACT

While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines in 126 individuals under real-world conditions. After two doses of vaccination, S-receptor binding domain IgG (S-RBD IgG) and neutralizing antibody (NAb) were detected in 87.06% (74/85) and 78.82% (67/85) of individuals, respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein were significantly higher in individuals received two doses of vaccine than those received one dose of vaccine and unvaccinated individuals. S, N, or M-specific CD4+ and CD8+ T cell responses were detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Overall, we provide a comprehensive characterization of immune responses induced by inactivated COVID-19 vaccines in real-world settings, suggesting that both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines.

9.
Notf Rett Med ; : 1-9, 2021 Oct 12.
Article in German | MEDLINE | ID: covidwho-1471832

ABSTRACT

BACKGROUND AND OBJECTIVES: The SARS-CoV­2 pandemic and the different manifestations of the coronavirus disease 2019 (COVID-19) are a major challenge for health systems worldwide. Medical personnel have a special role in containing the pandemic. The aim of the study was to investigate the SARS-CoV­2 IgG antibody prevalence in extraclinical personnel depending on their operational area in the fight against the COVID-19 pandemic. METHODS: On May 28 and 29, 2020, serum samples were taken from 732 of 1183 employees (61.9%) of the professional fire brigade and aid organizations in the city area and tested for SARS-CoV­2 IgG antibodies. The employees were divided into four categories according to their type of participation. category 1: decentralized PCR sampling teams, category 2: rescue service, category 3: fire protection, category 4: situation center. Some employees participated in more than one operational area. RESULTS: SARS-CoV­2 IgG antibodies were detected in 8 of 732 serum samples. This corresponds to a prevalence of 1.1%. A previous COVID-19 infection was known in 3 employees. In order to make a separate assessment of the other employees possible and to diagnose unknown infections, a corrected collective of 729 employees with 6 SARS-CoV­2 antibody detection was considered separately. The prevalence in the corrected collective is 0.82%. After subdividing the collective into areas of activity, the prevalence was low (1: 0.77%, 2: 0.9%, 3: 1.00%, 4: 1.58%). CONCLUSIONS: The seroprevalence of SARS-CoV­2 in the study collective is low at 1.1% and 0.82%, respectively. There is an increased seroprevalence in operational areas with a lower risk of virus exposure in comparison to operational areas with a higher risk.

10.
J Clin Med ; 10(19)2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1463725

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients' humoral immune responses to Spike (S) protein over the long-term, whereas the patients' age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.

11.
iScience ; 24(10): 103194, 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1446743

ABSTRACT

The COVID-19 pandemic poses enormous challenges to global healthcare sectors. To prevent the overburden of medical systems, it is crucial to distinguish individuals approaching the most infectious early phase from those in the declining non-infectious phase. However, a large fraction of transmission events occur during pre- or asymptomatic phases. Especially in the absence of symptoms, it is difficult to distinguish prodromal from late phases of infection just by RT-PCR since both phases are characterized by low viral loads and corresponding high Ct values (>30). We evaluated a new rapid test detecting IgG antibodies recognizing SARS-CoV-2 nucleocapsid protein using two commercial antibody assays and an in-house neutralization test before determining suitability for testing clinical swab material. Our analyses revealed the combination of the well-known RT-PCR and the new rapid antibody test using one single clinical nasopharyngeal swab specimen as a fast, cost-effective, and reliable way to discriminate prodromal from subsiding phases of COVID-19.

12.
Viruses ; 13(10)2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438743

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products.


Subject(s)
COVID-19/drug therapy , Curcumin/therapeutic use , SARS-CoV-2/drug effects , Animals , Antiviral Agents/therapeutic use , Cell Line , Chlorocebus aethiops , Curcuma/metabolism , Curcumin/metabolism , Dietary Supplements , Humans , Medicine, Traditional/methods , Plant Extracts/metabolism , Plant Extracts/therapeutic use , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Vero Cells
13.
Nat Commun ; 12(1): 5376, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1402068

ABSTRACT

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.


Subject(s)
Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Retroviridae Infections/immunology , Animals , Bone Marrow , COVID-19 , Cytokines , HIV , HIV Infections , Large Neutral Amino Acid-Transporter 1/genetics , Large Neutral Amino Acid-Transporter 1/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria , Retroviridae , Retroviridae Infections/virology , SARS-CoV-2 , Viral Load
14.
Front Immunol ; 12: 722027, 2021.
Article in English | MEDLINE | ID: covidwho-1399138

ABSTRACT

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibody Formation , COVID-19/epidemiology , China , Epidemiological Monitoring , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/pathogenicity , Young Adult
15.
Anal Chem ; 93(36): 12391-12399, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1380888

ABSTRACT

As an immune response to COVID-19 infection, patients develop SARS-CoV-2-specific IgM/IgG antibodies. Here, we compare the performance of a conventional lateral flow assay (LFA) with a surface-enhanced Raman scattering (SERS)-based LFA test for the detection of SARS-CoV-2-specific IgM/IgG in sera of COVID-19 patients. Sensitive detection of IgM might enable early serological diagnosis of acute infections. Rapid detection in serum using a custom-built SERS reader is at least an order of magnitude more sensitive than the conventional LFAs with naked-eye detection. For absolute quantification and the determination of the limit of detection (LOD), a set of reference measurements using purified (total) IgM in buffer was performed. In this purified system, the sensitivity of SERS detection is even 7 orders of magnitude higher: the LOD for SERS was ca. 100 fg/mL compared to ca. 1 µg/mL for the naked-eye detection. This outlines the high potential of SERS-based LFAs in point-of-care testing once the interference of serum components with the gold conjugates and the nitrocellulose membrane is minimized.


Subject(s)
COVID-19 , RNA, Viral , Antibodies, Viral , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Sensitivity and Specificity
16.
Front Immunol ; 12: 708523, 2021.
Article in English | MEDLINE | ID: covidwho-1295646

ABSTRACT

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Aged , Antibody Formation/immunology , COVID-19/therapy , Convalescence , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Male , Middle Aged , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Time Factors
17.
Pathogens ; 10(6)2021 May 26.
Article in English | MEDLINE | ID: covidwho-1244093

ABSTRACT

We aimed to evaluate the LIAISON® SARS-CoV-2 antigen assay (DiaSorin), comparing its performance to real-time polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2 RNA. 182 (110 PCR-positive and 72 PCR-negative) nasopharyngeal swab samples were taken for the detection of SARS-CoV-2. RT-PCR and antigen assay were performed using the same material. The sensitivity and specificity of the antigen assay were calculated for different cut-offs, with RT-PCR serving as the reference method. Stored clinical samples that were positive for other respiratory viruses were tested to evaluate cross-reactivity. One third (33/110, 30%) were falsely classified as negative, while no false positives were found using the 200 TCID50/mL cut-off for the SARS-CoV-2 antigen as proposed by the manufacturer. This corresponded to a sensitivity of 70% (60-78%) and a specificity of 100% (94-100%). Lowering the cut-off for positivity of the antigen assay to 22.79 or 57.68 TCID50/mL increased the sensitivity of the method, reaching a sensitivity of 92% (85-96%) vs. 79% (70-86%) and a specificity of 81% (69-89%) vs. 99% (91-100%), respectively. The antigen assay reliably detected samples with high SARS-CoV-2 viral loads (≥106 copies SARS-CoV-2/mL), while it cannot differentiate between negative and low positive samples. Cross-reactivity toward other respiratory viruses was not detected.

19.
Pharmacogenet Genomics ; 31(8): 165-171, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1232235

ABSTRACT

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Genetic Predisposition to Disease , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , Severity of Illness Index , Young Adult
20.
J Infect Dis ; 224(3): 420-424, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1228502

ABSTRACT

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern with increased transmission dynamics has raised questions regarding stability and disinfection of these viruses. We analyzed surface stability and disinfection of the currently circulating SARS-CoV-2 variants B.1.1.7 and B.1.351 compared to wild type. Treatment with heat, soap, and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper, and face masks. Overall, our data support the application of currently recommended hygiene measures to minimize the risk of B.1.1.7 and B.1.351 transmission.


Subject(s)
Disinfection , SARS-CoV-2/physiology , COVID-19/virology , Disinfectants/pharmacology , Hot Temperature , Humans , SARS-CoV-2/drug effects , Soaps/pharmacology
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