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1.
Gut ; 2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1962335

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. DESIGN: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study. RESULTS: Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and were predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups. CONCLUSIONS: Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337281

ABSTRACT

Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn’s disease, 12 ulcerative colitis, 1 IBD-unclassified;26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.021). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R 2 X 0.25, R 2 Y 0.26, Q 2 0.15;CV-ANOVA p = 0.038). Trimethylamine was associated with better response, while succinate, phenylalanine and the bile acids taurolithocholate and taurodeoxycholate were associated with poorer response. Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response.

7.
Nat Commun ; 13(1): 1379, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1747222

ABSTRACT

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Viral Vaccines , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Vaccines , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2 , T-Lymphocytes , Tumor Necrosis Factor Inhibitors
8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308139

ABSTRACT

Background: During the first wave of the coronavirus (COVID-19) pandemic, restrictive public health measures including prolonged shielding, were recommended by the United Kingdom government for many patients with immune-mediated inflammatory disorders treated with immunosuppressive and biologic drugs. Low-volume intracapillary blood sampling can be undertaken by patients at home and returned by post and may ensure access to therapeutic drug monitoring (TDM) for all patients irrespective of shielding status.Methods: We undertook a cross-sectional blood sampling methods comparison study to assess the clinical validity and acceptability to patients of low volume intracapillary testing for serum TDM enzyme-linked immunosorbent assays (ELISA) compared to conventional venepuncture. Sample types were compared using linear regression and fit-for-purpose equivalence was defined using total allowable error (TEa) rates derived using interassay coefficient of variations from routine clinical practice. Acceptability was assessed using a purpose-designed questionnaire.Findings: The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130-210). We showed drug level equivalence (slope [95% CI]: TEa vs observed mean % difference) between intracapillary sampling and conventional venepuncture for adalimumab (1·02 [0·90-1·14]: 11·7% vs 2·1%), infliximab (1·08 [0·98-1·18]: 18·3% vs 1·2%), vedolizumab (0·91 [0·85-0·96]: 17·6% vs 4·1%), and ustekinumab (0·92 [0·90-0·94]: 19·4% vs 3·3%). Anti-drug antibody equivalence was observed for anti-adalimumab (0·96 [0·95-0·98]: 24·5% vs 2·1%) and anti-infliximab (0·89 [0·81-0·97]: 17·3% vs 1·3%) antibody levels. Most patients reported that intracapillary testing was easy, convenient, and that they preferred it to conventional venepuncture.Interpretation: Low-volume intracapillary blood sampling was equivalent to conventional venepuncture for the measurement of biologic drug and anti-drug antibodies. Patients preferred intra-capillary testing to conventional venepuncture. Irrespective of future COVID-19 surges, patient-led intracapillary blood sampling is likely to become a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.Funding: Novo Nordisk Foundation. NIHR Exeter Clinical Research Facility. The Academic Department of Blood Sciences, RDE NHS Trust.Declaration of Interests: All authors have completed the ICMJE Form for Disclosure of Potential Conflicts of Interest and declare: D.C received honoraria from Ferring and Pfizer outside of this work;N.A.K has consulted for Falk and received honoraria from Falk, Allergan, Pharmacosmos and Takeda for unrelated topics and is a deputy editor of Alimentary Pharmacology & Therapeutics Journal;T.A has received unrestricted research grants, advisory board fees, speaker honorariums and support to attend international meetings from AbbVie, Merck, Janssen, Takeda, Ferring, Tillotts, Ferring, Pfizer, NAPP, Celltrion, Hospira for unrelated topics, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years;no other relationships or activities that could appear to have influenced the submitted work. R.N, B.H, E.J, S.H, C.R, V.C, K.P, J.R.G and T.J.M have no conflicts of interest to declare.Ethics Approval Statement: The sponsor was the Royal Devon and Exeter NHS Foundation Trust and the South West Research Ethics Committee approved the study (IRAS Reference Number: 286396;July 2020).

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315494

ABSTRACT

To inform healthcare policy for immunosuppressed patients there is a need to define SARS-CoV-2 vaccine responses. Here we report SARS-CoV-2 vaccine-induced antibody and T cell responses in patients treated with anti-tumour necrosis factor (anti-TNF), a commonly used biologic in inflammatory diseases, compared to patients treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impair systemic immunity. In anti-TNF recipients, the magnitude of anti-SARS-CoV2 antibodies was reduced five-fold, and rapidly decayed towards the seroconversion threshold by 14 weeks after second dose of vaccine. In contrast, anti-SARS-CoV-2 antibodies were sustained up to 16 weeks in vedolizumab-treated patients. Anti-SARS-CoV2 antibody decay was not observed in vaccinated patients previously infected with SARS-CoV-2. T cell responses were absent in one-fifth of anti-TNF and vedolizumab-treated patients after a second dose of either vaccine. Our data have important implications for anti-TNF recipients, including the need for vaccine prioritization, booster doses, and social distancing strategies.

10.
Lancet Gastroenterol Hepatol ; 7(4): 342-352, 2022 04.
Article in English | MEDLINE | ID: covidwho-1665600

ABSTRACT

BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations. INTERPRETATION: For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised. FUNDING: Pfizer.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Adolescent , Adult , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Humans , Inflammatory Bowel Diseases/drug therapy , Prospective Studies , SARS-CoV-2
11.
Eur Heart J Case Rep ; 5(12): ytab470, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1598027

ABSTRACT

BACKGROUND: During the Coronavirus disease 2019 (COVID-19) pandemic, reports have emerged of a multisystem inflammatory syndrome in adults (MIS-A). Multisystem inflammatory syndrome in adults can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems without significant respiratory involvement. CASE SUMMARY: A previously healthy 43-year-old man presented with fevers and abdominal pain then rapidly deteriorated into cardiogenic shock. His constellation of symptoms along with elevated inflammatory markers in the setting of a recent SARS-CoV-2 infection was consistent with the diagnosis of MIS-A. He also had a comprehensive infectious workup that was unremarkable, ruling out other potential infectious aetiologies for his presentation. He subsequently improved through supportive measures and after administration of intravenous immunoglobulin (IVIG). He later demonstrated recovery of cardiac function and cardiac magnetic resonance imaging (MRI) showed signs consistent with myocarditis. DISCUSSION: As the COVID-19 pandemic continues to be an ongoing issue, it is important to recognize MIS-A, a rare and potentially deadly clinical syndrome that can lead to profound cardiovascular complications. Non-invasive imaging modalities such as cardiac MRI can play a role in the identification of myocarditis. In addition to supportive management, adjunctive therapies such as IVIG may be efficacious in MIS-A and should be further investigated.

12.
Research in International Business and Finance ; 60:101579, 2022.
Article in English | ScienceDirect | ID: covidwho-1525937

ABSTRACT

This paper investigates how capital requirements and bank competition affect banks' financial soundness in the Middle East and North Africa (MENA) region. We test the hypothesis that regulatory capital positively impacts the risk-taking behavior of Islamic and conventional banks in the MENA region. The analysis indicates that the capital adequacy ratio has no significant influence on the credit risk of Islamic banks;however, market competition does play a significant role in shaping the risk behavior of these institutions. We report the opposite result for conventional banks – an increase in the minimum capital requirements is associated with an increase in their risk level. We also find that Islamic and conventional banks experience a non-linear relationship between market concentration and bank risk. Our findings inform regulatory authorities concerned with improving banking sector’s stability in the MENA region to strengthen their policies to force banks to better align with capital requirements which is highly important during the COVID-19 pandemic.

13.
Gut ; 70(Suppl 4):A3-A4, 2021.
Article in English | ProQuest Central | ID: covidwho-1506204

ABSTRACT

OFR-8 Figure 1ConclusionsInfliximab is associated with attenuated immunogenicity to a single-dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.

14.
J Crohns Colitis ; 16(3): 389-397, 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1393233

ABSTRACT

BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94-9.96] vs 5.02 [2.18-18.70], p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39-68.10, p < 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels [<0.8 mg/L] were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were treated with anti-TNF. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% [12/152] of patients after a median time of 183.5 days [129.8-235.3], without differences between drugs. CONCLUSION: Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels support a causal relationship, although confounding factors, such as combination therapy with a immunomodulator, may have influenced the results.


Subject(s)
Biological Products , COVID-19 , Inflammatory Bowel Diseases , Adalimumab , Adult , Antibody Formation , Biological Products/therapeutic use , Drug Monitoring , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab , Male , SARS-CoV-2 , Seroepidemiologic Studies , Tumor Necrosis Factor Inhibitors/therapeutic use
15.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
16.
Am J Trop Med Hyg ; 105(5): 1137-1140, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1380037

ABSTRACT

A country's preparedness for a prompt and successful implementation of vaccination programs plays a pivotal role in disease control and prevention. As it stands now, Afghanistan seems to be ill-prepared to embrace a successful implementation of the COVID-19 vaccination program because of a spate of challenges. These include, but are not limited to, the insufficient number of vaccinators, a dearth of fully integrated functioning cold chain, challenging geographical barriers, cultural issues, insecurity, and protracted conflict. The COVID-19 infodemic along with vaccine mistrust in the country will lead to a pervasive public vaccine hesitancy in Afghanistan, which will present serious obstacles to the COVID-19 immunization efforts. The politicization of the Ministry of Public Health (MoPH) and the complaints of embezzlement and misuse of the pandemic aid have already eroded public trust during the pandemic. To ensure a large-scale and equitable distribution of COVID-19 vaccines, the cold chain infrastructure should be strengthened, and the immunization personnel trained. Antivaccination propaganda and misinformation should be tackled with effective communication approaches and effective community engagement, which consider culturally relevant messages appropriate to the culture and people. The allegations of corruption should be addressed to revive public trust in public health interventions, including COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Programs , Public Health/methods , Afghanistan/epidemiology , COVID-19/epidemiology , COVID-19 Vaccines/economics , Communication , Female , Geography , Humans , Immunization Programs/methods , Immunization Programs/standards , Public Health/economics , Public Health/standards , Trust , Vaccination
17.
Diabetes ; 70, 2021.
Article in English | ProQuest Central | ID: covidwho-1362238

ABSTRACT

Background: The impact of SARS-COV-2 on islet cell function and immune dysregulation is unclear. Though adults with diabetes suffer higher rates of morbidity and mortality from COVID-19, pediatric data is limited. We aimed to study the number and characteristics of new onset type 1 (T1D) and type 2 (T2D) diabetes pre- and during the pandemic. Method: This was a retrospective study using inpatient data at UCSF Benioff Children's Hospital Oakland. We examined newly diagnosed T1D and T2D, aged < 18 years old, from May 2019 to Jan 2021. COVID-19 pandemic was defined from Mar 2020 onward. Results: Respectively, there were 59 and 64 new T1D, and 25 and 34 new T2D pre- and during COVID-19 pandemic. No difference was observed in time-adjusted incidence rate in T1D, but a rising trend in T2D was seen. A higher infection rate (PCR or IgG) was shown in T2D than T1D (11.8% vs. 3.1%, p = 0.05). During COVID-19, individuals with T1D had higher BMI z-scores (0.4 vs. -0.2, p = 0.03) and c-peptide levels (0.8 ng/ml vs. 0.5 ng/ml, p <0.01), and more Hispanics were diagnosed (46.9% vs. 27.1%, p = 0.02). Individuals with T2D were younger (mean age 12.8 yr vs. 14.5 yr, p = 0.02) and had more DKA on presentation (35.3% vs. 12.0%, p = 0.04) during the pandemic. Insurance and income were not associated with T1D nor T2D. No differences in patient demographics were observed in relation to COVID-19. Conclusion: We observed a rising trend of new onset T2D in the pediatric population during COVID-19, who were younger and sicker at presentation, and had a higher COVID-19 positivity rate than T1D. T1D incidence was similar, but individuals were more obese, had greater beta cell reserve at presentation, and a higher proportion were Hispanic compared to pre-pandemic. The roles of COVID-19, stress, and/or lifestyle changes associated with shelter-in-place orders, contributing to increased BMI and c-peptide levels in T1D, or increasing the risk for new onset diabetes and DKA in youths with T2D needs to be elucidated further and studied.

18.
J Crohns Colitis ; 16(2): 190-198, 2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1319160

ABSTRACT

BACKGROUND AND AIMS: Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.


Subject(s)
Drug Monitoring , Inflammatory Bowel Diseases , Self-Testing , Adalimumab/therapeutic use , COVID-19 , Cross-Sectional Studies , Drug Monitoring/methods , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Pandemics , SARS-CoV-2 , United Kingdom
20.
Gut ; 70(10): 1884-1893, 2021 10.
Article in English | MEDLINE | ID: covidwho-1203979

ABSTRACT

OBJECTIVE: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. DESIGN: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4ß7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. CONCLUSION: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Gastrointestinal Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Serologic Tests
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