Evaluation Of The Impact Of Covid-19 Vaccines On Thyroid Function And Autoimmunity And The Potential Influence Of Pre-existing Thyroid Autoimmunity On Neutralizing Antibody Responses

Objectives: There are concerns for COVID-19 vaccination in causing thyroid dysfunction and triggering thyroid autoimmunity. Also, data on the impact of pre-existing thyroid autoimmunity on COVID-19 vaccination efficacy are limited. We evaluated the impact of COVID-19 vaccination on thyroid function and antibodies, and the influence of pre-existing thyroid autoimmunity on neutralizing antibody (NAb) responses. Methods: Adults without history of COVID-19 or thyroid disorders who received COVID-19 vaccination between 14 June 2021 and 8 August 2021 at three vaccination centers were recruited. All participants received two doses of vaccines. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks after the first dose of vaccination. Post-vaccination NAb against SARS-CoV-2 receptor-binding domain was measured. Results: In total, 215 individuals were included (129 BNT162b2 [60%] and 86 CoronaVac [40%] recipients): mean age 49.6 years, 37.2% men, and 12.1% positive for anti-TPO/anti-Tg at baseline. After vaccination, TSH levels did not change (p=0.225), but fT4 slightly increased (from 12. 0±1.1 to 12.2±1.2 pmol/L, p<0. 001) and fT3 slightly decreased (from 4.1±0.4 to 4. 0±0.4 pmol/L, p<0. 001). Only 3 patients (1.4%) had abnormal thyroid function after vaccination: two occurred among BNT162b2 recipients - both were subclinical thyrotoxicosis (TSH 0.32mIU/L, fT4 11.51pmol/L and fT3 4.40pmol/L;TSH 0.34mIU/L, fT4 12.67pmol/L and fT3 4.22pmol/L;both were anti-TPO and anti-Tg negative before and after vaccination);one occurred among CoronaVac recipients - isolated mild low fT3 (TSH 0.90mIU/L, fT4 9.94pmol/L and fT3 2.33pmol/L;anti-TPO/Tg negative before and after vaccination). All three recipients were asymptomatic. Both anti-TPO and anti-Tg titers increased modestly after vaccination (anti-TPO: from 7.50 [IQR: 5.90-11.2] to 9.80 IU/mL [IQR: 7.80-13.1], p<0. 001;anti-Tg: from 12.4 [IQR: 11.1-14.9] to 15.7 IU/mL [IQR: 14.2-18.2], p<0. 001), without significant changes in anti-TPO/Tg positivity. Changes in thyroid function and anti-thyroid antibodies were generally consistent between BNT162b2 and CoronaVac recipients, although anti-TPO titer rise was greater after BNT162b2 (p<0. 001). NAb responses were similar between individuals with and without pre-existing thyroid autoimmunity (p=0.855). Conclusion: COVID-19 vaccination was associated with a modest increase in anti-thyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction 8 weeks post-vaccination. NAb responses were not influenced by pre-existing thyroid autoimmunity. Our results provided important reassurance to people to proceed to COVID-19 vaccination.Presentation: No date and time listed

Safety of Inactivated and mRNA COVID-19 Vaccination among Patients Treated for Hypothyroidism: a Population-based Cohort Study

Background: Thyroiditis and Graves’ disease have been reported after COVID-19 vaccination. Patients with hypothyroidism due to various etiologies may be at risk of thyroid-specific outcomes. We aimed to evaluate the risks of thyroid-specific outcomes and adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this population-based cohort from Hong Kong Hospital Authority electronic health records with Department of Health vaccination records linkage, levothyroxine users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine) or CoronaVac (inactivated vaccine) between 23 February and 9 September 2021. Propensity score (PS) weighting with inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics among the three groups, which included age, sex, history of COVID-19, health care utilization, comorbidities, baseline thyroid-stimulating hormone (TSH) level (within the 6 months before the index date), and recent use of medications including anti-hypertensive, anti-diabetic and lipid-lowering agents. Study outcomes were dosage reduction or escalation in levothyroxine, emergency department visit, unscheduled hospitalization, adverse events of special interest (AESI) according to World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Results: In total, 47,086 levothyroxine users were identified (BNT162b2: n=12,310;CoronaVac: n=11,353;unvaccinated: n=23,423). After PS weighting, all baseline characteristics had standardised differences of less than 0.2, implying a balance of covariates among the three groups. COVID-19 vaccination was not associated with increased risks of levothyroxine dosage reduction (BNT162b2: HR=0.971, 95% CI 0.892–1. 058;CoronaVac: HR=0.968, 95% CI 0.904–1. 037) or escalation (BNT162b2: HR=0.779, 95% CI 0.519–1.169;CoronaVac: HR=0.715, 95% CI 0.481–1. 062). Besides, COVID-19 vaccination was not associated with a higher risk of emergency department visits (BNT162b2: HR=0.944, 95% CI 0.700-1.273;CoronaVac: HR=0.851, 95% CI 0.647-1.120) or unscheduled hospitalization (BNT162b2: HR=0.905, 95% CI 0.539-1.520;CoronaVac: HR=0.735, 95% CI 0.448-1.207). There were two (0. 016%) deaths and six (0. 062%) AESI recorded for BNT162b2 recipients, and one (0. 009%) and three (0. 035%) for CoronaVac recipients, respectively. Sensitivity analyses were performed by stratifying the groups according to age, sex and pre-vaccination thyroid status. The results were largely consistent with the main analysis. Conclusion: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.Presentation: No date and time listed

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Preadmission use of DPP4i reduced risk of hyperinflammatory syndrome, in-hospital death or invasive mechanical ventilation in COVID-19 patients with type 2 diabetes: A territory-wide retrospective cohort study

OBJECTIVE: T2DM patients with COVID-19 were associated with increased risk of hyperinflammation and hence poor prognosis. Inconclusive evidence suggested that dipeptidyl peptidase-4 inhibitors (DPP4i) may have anti-inflammatory effect and preventing SARS-CoV-2 viral entry. This territory-wide retrospective cohort study evaluated the clinical outcomes associated with the pre-admission use of DPP4i for T2DM patients with COVID-19. METHODS: Patients with T2DM admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong were observed from date of admission until the date of in-hospital death, hospital discharge or data cut-off date (30th April 2021). Exposure was defined as receiving DPP4i treatment from 90 days prior admission to the day before admission for COVID-19. The primary outcome was the incidence rate of hyperinflammatory syndrome. Multivariable logistic regression models weighted by inverse probability of treatment weighting using the propensity score were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes for exposure versus nonexposure. RESULTS: Out of 1214 eligible patients at a median follow-up of 16 days with 30,035 person-days, 107 patients received DPP4i prior to COVID-19 hospitalization. Preadmission use of DPP4i was associated with a lower risk of hyperinflammatory syndrome (OR = 0.56, 95%CI 0.45 to 0.69, P < 0.001), composite outcome of in-hospital death or the need of invasive mechanical ventilation (OR = 0.71, 95%CI 0.54 to 0.93, P = 0.013) and reduced length of hospital stay among survivors (-4.82 days, 95%CI -6.80 to -2.84, P < 0.001). Moreover, DPP4i users incurred significantly lower cumulative healthcare costs from day-7 (US$7,877 vs US$10,246, P < 0.001) to day-90 (US$26,310 vs US$39,482, P < 0.001) than control. CONCLUSION: Our study may have shed light regarding hyperinflammatory dynamics in mild-to-moderate COVID-19 patients with T2DM, which may be informative to these patient cohorts and associated clinicians. However, prospective studies are necessary to further elucidate the potential role of DPP4i in the pathophysiology of T2DM and COVID-19.

A prospective study of the impact of glycaemic status on clinical outcomes and anti-SARS-CoV-2 antibody responses among patients with predominantly non-severe COVID-19

OBJECTIVE: We aimed to evaluate the impact of glycaemic status on clinical outcomes and anti-SARS-CoV-2 antibody (Ab) response among patients with predominantly non-severe COVID-19, highly relevant to the current COVID-19 vaccination programme. METHODS: We included consecutive adults admitted to Queen Mary Hospital for COVID-19 from July 2020 to May 2021. Glycaemic status was defined by HbA1c on admission: normoglycaemia (<5.7%), prediabetes (5.7-6.4%) and diabetes (≥6.5% or known diabetes). Clinical deterioration was defined by radiological progression, new oxygen requirement, intensive care unit admission, or death. COVID-19 survivors had Ab measurements at 1-month, 2-month, 3- month and 6-month post-discharge, with a live SARS-CoV-2-based microneutralization assay which correlated well with anti-SARS-CoV-2 receptor binding domain IgG (≥1:20 defined as positive). RESULTS: Among 605 patients (age 50.2 - 17.1 years;45.1% men;96.9% non-severe COVID-19), 325 had normoglycaemia, 185 had prediabetes and 95 had diabetes. 74 had clinical deterioration (12.2%): 16 required intensive care and 4 died. Clinical deterioration was more likely with worse glycaemic status (P < 0.001) and higher HbA1c (OR 1.403, P < 0.001). Older age (P < 0.001), higher viral loads (P < 0.001), higher C-reactive protein (CRP) (P < 0.001) and symptomatic presentation (P = 0.008), but not glycaemic status/HbA1c, independently predicted clinical deterioration. 314 patients had Ab measured upon follow-up (1-month: 295;2-month: 227;3-month: 207;6-month: 122). Ab titres were comparable across glycaemic status throughout follow-up period. CRP (P = 0.003), but not glycaemic status/HbA1c, was the only positive independent determinant of Ab levels. Rate of decline of Ab titre was comparable across glycaemic status, and did not correlate with HbA1c. Furthermore, most patients remained Ab-positive throughout follow-up (1-month: 94.9%, 2-month: 93.8%, 3-month: 87.4%, 6-month 80.3%), similar across glycaemic status. CONCLUSION: Worse glycaemic status was associated with a higher chance of clinical deterioration in COVID-19, contributed by older age, more severe inflammation and higher viral loads. Importantly, glycaemic status did not adversely influence the Ab response.

Clinical outcomes associated with early in-hospital use of metformin, dipeptidyl peptidase-4 inhibitor or insulin in COVID-19 patients with type 2 diabetes: A territory-wide retrospective observational study

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with worse outcomes for patients with COVID-19. Commonly used glucose-lowering medications, metformin, dipeptidyl peptidase-4 inhibitor (DPP4i), or insulin, were found to impact the level of inflammatory and cytokine, therefore potentially influence the clinical outcomes in SARS-CoV-2 infected patients. Concerns remain on the early in-hospital use of these medications. This territory-wide retrospective observational study evaluated clinical improvement, virality, acidosis, hypoglycemia, hyperinflammation status, composite clinical outcomes associated with use of metformin, DPP4i, or insulin for hospitalized T2DM patients with COVID-19 infection. METHODS: Baseline covariate between the two groups were balanced by multiple imputation followed by inverse probability of treatment weighting for propensity score. Multivariable cox proportional hazard models were performed to estimate hazard ratios (HR) and their 95% confidence intervals (CI) of time-to-event outcomes. Exposure was defined as receiving glucose-lowering drug class within 3 days of admission. RESULTS: After propensity-score weighting, baseline characteristics were generally balanced. Metformin users (n = 609) were associated with quicker time to clinical improvement (HR = 1.41, 95%CI 1.19 to 1.65, P < 0.001), hospital discharge (HR = 1.43, 95%CI 1.20 to 1.69, P < 0.001) and recovery (HR = 2.09, 95%CI 1.42 to 3.06, P < 0.001), shorter hospital length of stay among survivors (-6.45 days, 95%CI -8.34 to -4.56, P < 0.001), reduced costs from 30-days onward, lower risk of composite outcome (HR = 0.41, 95%CI 0.23 to 0.74, P = 0.003) and macrophage activation (HR = 0.64, 95%CI 0.47 to 0.87, P < 0.004) when compared to non-metformin users. Shorter hospital length of stay was also observed in DPP4i users (n = 144) compared with non-DPP4i users (-5.32 days, 95%CI to 7.30 to -3.34, P < 0.001). Insulin users (n = 414) have greater risk of hypoglycemia during admission (HR = 2.61, 95%CI 1.23 to 5.53, P = 0.013) when compared to non-insulin users. CONCLUSION: Metformin and DPP4i have exhibited association with improved clinical outcomes while insulin has proved to be associated with increased risk of hypoglycemia for in hospitalized T2DM patients with COVID-19.

Central venous access in ventilated COVID-19 patients: A vascular surgery perspective

Introduction: The number of patients on intensive care units (ICU) increased manifold during the initial COVID-19 surge and medical staff were relocated to help compensate. The need for central venous catheters (CVCs) increased accordingly and comprised a significant workload under challenging circumstances. Several models were proposed to manage the lines. We assigned a vascular team of vascular surgeons and interventional radiologists for CVCs in ICU. We report on the workload outcomes and lessons learned Method: 50 consecutive ventilated COVID-19 patients in ICU (median age 63 years, 80% male) who had a CVC inserted by the vascular team from March to May 2020 were assessed. Median follow up was 18 days (range 14- 29 days) after ICU admission Result: 166 CVCs (80 VasCaths) were inserted. Femoral access was preferred Each patient required a median of 3 lines (IQR 2-4). CVCs were exchanged after median 7 days (IQR 4-9) for thrombosis (35%), infection (24%) or prophylactically (41%). Our learning curve included the establishment of an online referral pathway, CVC teams of two operators extended disposable CVC kits and ICU based ultrasound scanners Additional staffing and retraining were avoided. There were no technical complications Conclusion: Ventilated COVID-19 patients require multiple CVCs which is a challenging workload during a pandemic. Vascular surgeons and interventional radiologists with endovascular skills are well positioned to perform central venous cannulation to alleviate the burden on critical care teams. Our lessons learned can help to provide a safe and efficient model amidst the ongoing national outbreaks Take-home Message: With the postponement of many elective vascular procedures during the pandemic crisis, the involvement of vascular surgeons in a dedicated Lines team is an important way that they can contribute given their proficiency with wires and cannulation equipment as well as familiarity in femoral triangle and jugular anatomy The retraining of staff and additional on-call rotas can then be avoided .