Protecting the vulnerable: SARS-CoV-2 vaccination in immunosuppressed patients with interstitial lung disease.
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ABSTRACT:
SUBMITTER: Mackintosh JA
PROVIDER: S-EPMC8285116 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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Protecting the vulnerable: SARS-CoV-2 vaccination in immunosuppressed patients with interstitial lung disease.
Mackintosh John A JA Lipman Marc M Lowe David M DM Renzoni Elisabetta A EA
The Lancet. Respiratory medicine 20210717 9
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Project description:ObjectivesTo describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19.MethodsWe performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with "COVID-19" and "severe COVID-19".ResultsWe included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946-0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030-0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129-6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004-0.170); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508-19.097); p = 0.018).ConclusionsAround 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.
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Project description:ObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine-immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. There is an urgent need to address the impact of immunosuppression on vaccine immunogenicity.MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n = 13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n = 12), unvaccinated (UNVACC, n = 11) and infection-naïve unvaccinated (HC, n = 3) cohorts.ResultsNo significant different differences in T-cell responses were observed between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n = 3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.
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Project description:IntroductionDespite repeated vaccinations against SARS-CoV-2 virus, patients who are immunocompromised remain at very high risk of catching SARS-CoV-2 virus and becoming unwell. AZD7442 (Evusheld) is a long-acting monoclonal antibody treatment that has been shown in clinical trials to prevent SARS-CoV-2 infection for up to a year after a single dose. Vaccines require a healthy immune system to generate protective immunity. AZD7442 may prevent SARS-CoV-2 infection in immunocompromised individuals that may not have responded to repeated vaccinations against SARS-CoV-2 virus. Unlike vaccinations, AZD7442 reaches effective levels within the body a few hours after a single dose. The RAPID-PROTECTION trial will determine the levels of immune protection that AZD7442 offers patients at the very highest risk of SARS-CoV-2 infection and whether this protection can be further enhanced by repeated vaccination against SARS-CoV-2 virus.MethodsRAPID-PROTECTION is a multicentre, interventional and open-label adaptive platform trial that aims to recruit 350 immunocompromised participants across five UK centres. Participants will be administered AZD7442 on day 0 followed by a SARS-CoV-2 vaccination 28 days later. Participants will be randomised (1:1) to the Moderna vaccine or Pfizer/BioNTech vaccine. Participant samples will be taken at baseline and at multiple timepoints after the administration of AZD7442.AnalysisThe participant samples will be analysed to measure the function and magnitude of SARS-CoV-2 specific antibody and T-cell responses at baseline and at multiple timepoints after the administration of AZD7442. The immunological effect of the study interventions will be determined by comparison of the results of immunological assessments at baseline and subsequent timepoints.Ethics and disseminationThe trial protocol was approved by the research ethics committee of the National Health Service (reference 22/HRA/0359), Health Research Authority and Health and Care Research Wales on 25 July 2022. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.Trial registration numberISRCTN53507177.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2's mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.
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Project description:IntroductionThe COVID-19 pandemic is a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination against COVID-19 is crucial for preventing severe illness and controlling the pandemic. This study aimed to examine how immunosuppressed patients with inflammatory bowel disease (IBD) responded to the third mRNA vaccination against SARS-CoV-2. The patients were undergoing treatments such as anti-TNF (infliximab, adalimumab), anti-α4ß7 integrin (vedolizumab), anti-IL12/23 (ustekinumab) and azathioprine (purine analog). Their responses were compared to those of healthy individuals.MethodsIn this prospective study, 81 IBD patients and 15 healthy controls were enrolled 2-4 months after receiving the third mRNA vaccination. This study measured IgG antibody levels against the SARS-CoV-2 spike protein's receptor binding domain (RBD) and assessed potential neutralization capacity using a surrogate virus neutralization test (sVNT).ResultsOverall, immunosuppressed IBD patients (without SARS-CoV-2 infection) exhibited significantly lower levels of anti-S-IgG (anti-RBD-IgG) and binding inhibition in the sVNT after the third vaccination compared to healthy controls. Patients under anti-TNF therapy showed notably reduced anti-S-IgG levels after the booster vaccination, in contrast to those receiving ustekinumab and azathioprine (p = 0.030, p = 0.031). IBD patients on anti-TNF therapy demonstrated significantly increased anti-S-IgG levels following prior SARS-CoV-2 infection (p = 0.020).ConclusionEven after the third vaccination, immunosuppressed IBD patients exhibited diminished humoral immunity compared to healthy controls, especially those on anti-TNF therapy. Cases of penetrating infections led to considerably higher antibody levels in IBD patients under anti-TNF therapy compared to uninfected patients. Further investigation through prospective studies in immunosuppressed IBD patients is needed to determine whether this effectively safeguards against future infections or severe disease.
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Project description:At a time of need, these organizations fostered trusted relationships with patients through proactive outreach and support, initiated a comprehensive virtual-care program, and provided home-based care services to protect them against the infection and its effects. Summary Older people (?70 years of age) with multiple chronic conditions have the highest risk of being hospitalized and dying from COVID-19. The current pandemic has highlighted how a strong primary-care system can play an important role in protecting this group of people. The ways in which innovative primary-care organizations have adapted their approach to the pandemic may offer important lessons, not only for future health crises but also for redesigning post-pandemic health care. We studied four primary care organizations that specialize in the care of vulnerable older patients (Iora Health, Oak Street Health, ChenMed, and Landmark Health) and assessed their responses to the COVID-19 crisis. Based on our analysis, we identified three key lessons for health-care systems: (1) the importance of fostering trusted relationships with vulnerable older patients to identify and address their clinical and non-clinical needs in a timely fashion, (2) the rapid implementation of a comprehensive virtual care approach to facilitate frequent touchpoints between the patient and the care team, and (3) the delivery of home-based health-care services to ensure health-care access during the pandemic.
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Project description:BackgroundHumoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.MethodsWe performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.Results496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.ConclusionsHumoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.
| S-EPMC9188451 | biostudies-literature
Project description:BackgroundThe continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts.MethodsNasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro.ResultsOur sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry.ConclusionsThese observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.
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Project description:BackgroundPatients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.MethodsWe conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4-6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021.ResultsAll patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207-811] AU/ml vs. 820.75 [IQR, 459-1313] AU/ml; P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25-165] AU/ml vs. 970.1 [IQR, 505-1926] AU/ml; P < 0.001).ConclusionIPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.
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Project description: Not available
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