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1.
Clin Infect Dis ; 2022 Jul 07.
Article in English | MEDLINE | ID: covidwho-1985051

ABSTRACT

BACKGROUND: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls. METHODS: 152 participants with CKD stages G4/5 (eGFR <30  mL/min/1.73m2), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay. RESULTS: At 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days. CONCLUSIONS: Although seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.

2.
Sci Rep ; 12(1): 8991, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1947470

ABSTRACT

Knowledge about contagiousness is key to accurate management of hospitalized COVID-19 patients. Epidemiological studies suggest that in addition to transmission through droplets, aerogenic SARS-CoV-2 transmission contributes to the spread of infection. However, the presence of virus in exhaled air has not yet been sufficiently demonstrated. In pandemic situations low tech disposable and user-friendly bedside devices are required, while commercially available samplers are unsuitable for application in patients with respiratory distress. We included 49 hospitalized COVID-19 patients and used a disposable modular breath sampler to measure SARS-CoV-2 RNA load in exhaled air samples and compared these to SARS-CoV-2 RNA load of combined nasopharyngeal throat swabs and saliva. Exhaled air sampling using the modular breath sampler has proven feasible in a clinical COVID-19 setting and demonstrated viral detection in 25% of the patients.


Subject(s)
COVID-19 , RNA, Viral , COVID-19/diagnosis , Humans , Nasopharynx , Pharynx , RNA, Viral/genetics , SARS-CoV-2/genetics
3.
Front Immunol ; 13: 838132, 2022.
Article in English | MEDLINE | ID: covidwho-1809394

ABSTRACT

The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.


Subject(s)
COVID-19 , Convalescence , Disease Progression , Humans , Leukocytes, Mononuclear , SARS-CoV-2
4.
RMD Open ; 8(1)2022 04.
Article in English | MEDLINE | ID: covidwho-1788979

ABSTRACT

OBJECTIVES: To evaluate humoral and cellular immune responses and adverse events (AEs) after COVID-19 vaccination in patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC), and disease activity following vaccination in patients with pSS. METHODS: 67 patients with pSS and 33 HC (ratio 2:1) received COVID-19 vaccinations following the Dutch vaccination programme. Patients with pSS did not use immunomodulatory drugs, except hydroxychloroquine. Anti-spike 1 receptor binding domain IgG serum antibody levels were measured 28 days after complete vaccination. AEs were collected 7 days after vaccination. In a subgroup, salivary anti-SARS-CoV-2 antibodies and T-cell response by interferon-γ enzyme-linked immune absorbent spot was measured. RESULTS: 47 patients with pSS (70%) and 14 HC (42%) received BNT162b2 (Pfizer-BioNtech), 13 (19%) and 5 (15%) received ChAdOx1 nCoV-19 (AstraZeneca), 6 (9%) and 8 (24%) received mRNA-1273 (Moderna), and 1 (1%) and 6 (18%) received Ad.26.COV2.S (Janssen). All participants had positive anti-SARS-CoV-2 antibody levels (>2500 AU/mL) postvaccination. No differences in anti-SARS-CoV-2 antibody levels were observed between patients with pSS and HC, for each vaccine type. Salivary anti-SARS-CoV-2 IgG antibodies also increased, and a T-cell response was observed in patients with pSS and HC. Frequencies of systemic AEs were comparable between patients with pSS and HC (first vaccination: 34/67 (51%) vs 16/33 (48%), p=0.83; second: 41/66 (62%) vs 14/25 (56%), p=0.59). No significant worsening was observed in patient-reported and systemic disease activity, including auto-antibodies. CONCLUSIONS: Patients with pSS had similar humoral and cellular immune responses as HC, suggesting COVID-19 vaccination is effective in patients with pSS. AEs were also comparable, and no increase in disease activity was seen in patients with pSS.


Subject(s)
COVID-19 , Sjogren's Syndrome , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunoglobulin G , SARS-CoV-2 , Sjogren's Syndrome/complications , Vaccination/adverse effects
5.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-331736

ABSTRACT

Background: The i mmune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls. Methods: 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73m 2 ), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay. Findings: At 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days. Interpretation: Although seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.

6.
Transplantation ; 106(4): 821-834, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1511132

ABSTRACT

BACKGROUND: In kidney patients COVID-19 is associated with severely increased morbidity and mortality. A comprehensive comparison of the immunogenicity, tolerability, and safety of COVID-19 vaccination in different cohorts of kidney patients and a control cohort is lacking. METHODS: This investigator driven, prospective, controlled multicenter study included 162 participants with chronic kidney disease (CKD) stages G4/5 (eGFR < 30 mL/min/1.73m2), 159 participants on dialysis, 288 kidney transplant recipients, and 191 controls. Participants received 2 doses of the mRNA-1273 COVID-19 vaccine (Moderna). The primary endpoint was seroconversion. RESULTS: Transplant recipients had a significantly lower seroconversion rate when compared with controls (56.9% versus 100%, P < 0.001), with especially mycophenolic acid, but also, higher age, lower lymphocyte concentration, lower eGFR, and shorter time after transplantation being associated with nonresponder state. Transplant recipients also showed significantly lower titers of neutralizing antibodies and T-cell responses when compared with controls. Although a high seroconversion rate was observed for participants with CKD G4/5 (100%) and on dialysis (99.4%), mean antibody concentrations in the CKD G4/5 cohort and dialysis cohort were lower than in controls (2405 [interquartile interval 1287-4524] and 1650 [698-3024] versus 3186 [1896-4911] BAU/mL, P = 0.06 and P < 0.001, respectively). Dialysis patients and especially kidney transplant recipients experienced less systemic vaccination related adverse events. No specific safety issues were noted. CONCLUSIONS: The immune response following vaccination in patients with CKD G4/5 and on dialysis is almost comparable to controls. In contrast, kidney transplant recipients have a poor response. In this latter, patient group development of alternative vaccination strategies are warranted.


Subject(s)
COVID-19 , Kidney Transplantation , Renal Insufficiency, Chronic , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunity , Kidney Transplantation/adverse effects , Prospective Studies , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Vaccination
7.
Nat Commun ; 12(1): 5621, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1437680

ABSTRACT

Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudinal nasal antibody response in index cases with mild COVID-19 and their household contacts. Nasal and serum antibody responses were analysed for up to nine months. Higher nasal receptor binding domain and spike protein-specific antibody levels at study inclusion were associated with lower viral load. Older age was correlated with more frequent COVID-19 related symptoms. Receptor binding domain and spike protein-specific mucosal antibodies were associated with the resolution of systemic, but not respiratory symptoms. Finally, receptor binding domain and spike protein-specific mucosal antibodies remained elevated up to nine months after symptom onset.


Subject(s)
Antibodies, Neutralizing/analysis , Antibodies, Viral/analysis , COVID-19/diagnosis , Nasal Mucosa/metabolism , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , COVID-19/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/statistics & numerical data , Child , Humans , Immunity, Mucosal , Longitudinal Studies , Male , Middle Aged , Nasal Mucosa/immunology , Nasal Mucosa/virology , Severity of Illness Index , Viral Load , Young Adult
9.
Curr Opin Infect Dis ; 34(3): 181-186, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1201884

ABSTRACT

PURPOSE OF REVIEW: Despite its crucial role in protection against viral infections, mucosal immunity has been largely understudied in the context of coronavirus disease 2019 (COVID-19). This review outlines the current evidence about the role of mucosal immune responses in the clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as potential mucosal mechanisms of protection against (re-)infection. RECENT FINDINGS: The angiotensin-converting enzyme 2 cellular entry receptor for SARS-CoV-2 is most highly expressed in the upper respiratory tract and most SARS-CoV-2 shedding occurs from the upper respiratory tract. Viral shedding peaks early during infection around the onset of symptoms, before dropping rapidly in most individuals within 7 days of symptom onset, suggesting mucosal inhibition of viral infection. Serum and mucosal immunoglobulin G and immunoglobulin M responses were found to be strongly correlated in infected patients, whereas correlations were much weaker for immunoglobulin A (IgA). Mucosal IgA responses have been detected in infected cases in the absence of serum antibody responses, with mucosal antibody levels correlating strongly with virus neutralization. Bulk and single-cell RNA sequencing analysis of nasopharyngeal swabs and bronchoalveolar lavage samples of COVID-19 patients revealed the induction of mucosal chemokine and cytokine genes, complement pathways, Janus Kinase/Signal Transducer and Activator of Transcription signaling and cytotoxic T cells. SUMMARY: Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Further studies are needed to understand how the systemic immunological endpoints measured in vaccination studies translate to mucosal protection against SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Mucosal , Immunoglobulin A/immunology , Virus Shedding , COVID-19/prevention & control , Humans , Immunoglobulin A/blood , SARS-CoV-2/immunology , Vaccination
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