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

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.

Lipid nanoparticle formulations for optimal RNA-based topical delivery to murine airways.

INTRODUCTION: Lipid nanoparticles (LNP) have been successfully used as a platform technology for delivering nucleic acids to the liver. To broaden the application of LNPs in targeting non-hepatic tissues, we developed LNP-based RNA therapies (siRNA or mRNA) for the respiratory tract. Such optimized LNP systems could offer an early treatment strategy for viral respiratory tract infections such as COVID-19. METHODS: We generated a small library of six LNP formulations with varying helper lipid compositions and characterized their hydrodynamic diameter, size distribution and cargo entrapment properties. Next, we screened these LNP formulations for particle uptake and evaluated their potential for transfecting mRNA encoding green fluorescence protein (GFP) or SARS-CoV2 nucleocapsid-GFP fusion reporter gene in a human airway epithelial cell line in vitro. Following LNP-siGFP delivery, GFP protein knockdown efficiency was assessed by flow cytometry to determine %GFP+ cells and median fluorescence intensity (MFI) for GFP. Finally, lead LNP candidates were validated in Friend leukemia virus B (FVB) male mice via intranasal delivery of an mRNA encoding luciferase, using in vivo bioluminescence imaging. RESULTS: Dynamic light scattering revealed that all LNP formulations contained particles with an average diameter of <100 nm and a polydispersity index of <0.2. Human airway epithelial cell lines in culture internalized LNPs with differential GFP transfection efficiencies (73-97%). The lead formulation LNP6 entrapping GFP or Nuc-GFP mRNA demonstrated the highest transfection efficiency (97%). Administration of LNP-GFP siRNA resulted in a significant reduction of GFP protein expression. For in vivo studies, intranasal delivery of LNPs containing helper lipids (DSPC, DOPC, ESM or DOPS) with luciferase mRNA showed significant increase in luminescence expression in nasal cavity and lungs by at least 10 times above baseline control. CONCLUSION: LNP formulations enable the delivery of RNA payloads into human airway epithelial cells, and in the murine respiratory system; they can be delivered to nasal mucosa and lower respiratory tract via intranasal delivery. The composition of helper lipids in LNPs crucially modulates transfection efficiencies in airway epithelia, highlighting their importance in effective delivery of therapeutic products for airways diseases.

Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel Real-time reverse transcription-PCR assay validated in vitro and with clinical specimens

On 31 December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated coronavirus disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time reverse transcription-PCR (RT-PCR) assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay, which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 50% tissue culture infective doses [TCID50]/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19- RdRp/Hel assay was positive for an additional 42 RdRp-P2-negative specimens (119/273 [43.6%] versus 77/273 [28.2%];P 0.001), including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21 x 104 RNA copies/ml (range, 2.21 x 102 to 4.71 x 105 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of 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.

Cardiovascular sequalae in uncomplicated COVID-19 survivors

Background: A high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.

The “super green pathway’’;what have we learned so far? The experience and outcomes of elective urgent and cancer surgery in a district general hospital in the united kingdom during covid-19 pandemic

Background The coronavirus disease (COVID-19) had so far claimed more than 600 000 lives worldwide. Many urgent and elective surgeries were postponed to cope with the pandemic, with the latest data found a substantial postoperative mortality risk (25.6%, 18.9%) after an emergency and elective surgery, respectively. Our institution was one of the first few in the country to offer essential elective surgery using a “COVID-free” designated site during the start of the pandemic. This study aims to analyze the clinical outcomes of patients who underwent essential elective procedures during the virus outbreak in the UK. Methods Retrospective analysis of outcomes of all patients who had undergone urgent elective and cancer surgery, from 30th March 2020 to 21st May 2020, using an implemented “Super Green Pathway.” The primary endpoints were 30 days mortality and COVID-related morbidities, and the secondary end-points were surgically related complications and oncological outcomes. Results A total of 92 patients (Male: 45%;Female: 55%) across 5 surgical specialties were identified. There was no record of mortality in our cohort. Only 1 patient was tested positive for SARS-CoV-2, 18 days after the initial operation without any pulmonary complications. There were 7 postoperative surgical complications managed at the acute hospital site. The waiting time for surgery ranges from 6 to 191 days, mean of 30 days, and a median of 23 days. Conclusion It is possible to mitigate the high mortality risk of post-operative complications associated with COVID-19, with no delay to essential surgeries for cancer patients, thus delivering safe practice during the pandemic.