Study protocol for the St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19.

Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited.  Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points  evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.

Prevalence of Antibodies to SARS-CoV-2 Following Natural Infection and Vaccination in Irish Hospital Healthcare Workers: Changing Epidemiology as the Pandemic Progresses.

BACKGROUND: In October 2020 SARS-CoV-2 seroprevalence among hospital healthcare workers (HCW) of two Irish hospitals was 15 and 4. 1%, respectively. We compare seroprevalence in the same HCW population 6 months later, assess changes in risk factors for seropositivity with progression of the pandemic and serological response to vaccination. METHODS: All staff of both hospitals (N = 9,038) were invited to participate in an online questionnaire and SARS-CoV-2 antibody testing in April 2021. We measured anti-nucleocapsid and anti-spike antibodies. Frequencies and percentages for positive SARS-CoV-2 antibodies were calculated and adjusted relative risks for participant characteristics were calculated using multivariable regression analysis. RESULTS: Five thousand and eighty-five HCW participated. Seroprevalence increased to 21 and 13%, respectively; 26% of infections were previously undiagnosed. Black ethnicity (aRR 1.7, 95% CI 1.3-2.2, p < 0.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1-1.8, p = 0.002), living with other HCW (aRR 1.2, 95% CI 1.0-1.4, p = 0.007) were significantly associated with seropositivity. Having direct patient contact also carried a significant risk being a healthcare assistant (aRR 1.8, 95% CI 1.3-2.3, p < 0.001), being a nurse (aRR 1.4, 95% CI 1.0-1.8, p = 0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1-1.7, p = 0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1-1.5, p = 0.013). Breakthrough infection occurred in 23/4,111(0.6%) of fully vaccinated participants; all had anti-S antibodies. CONCLUSION: The increase in seroprevalence reflects the magnitude of the third wave of the pandemic in Ireland. Genomic sequencing is needed to apportion risk to the workplace vs. the household/community. Concerted efforts are needed to mitigate risk factors due to ethnicity and lower level of education, even at this stage of the pandemic. The undiagnosed and breakthrough infections call for ongoing infection prevention and control measures and testing of HCW in the setting of close contact. Vaccinated HCW with confirmed infection should be actively assessed, including SARS-CoV-2 whole genome sequencing (WGS), serology testing and assessment of host determinants, to advance understanding of the reasons for breakthrough infection.

Zoster meningitis in an immunocompetent young patient post first dose of BNT162b2 mRNA COVID-19 vaccine, a case report.

Recently published observational data suggests an increased risk of herpes zoster infection post-vaccination with the BNT162b2 mRNA vaccine. We describe the case of VZV meningitis post BNT162b2 mRNA vaccination in a young immunocompetent patient. A 39-year-old patient with no medical history presented with a vesicular rash, headache, nausea and fever, days after receiving BNT162b2 mRNA vaccination. CSF analysis revealed a pleocytosis, and VZV DNA was confirmed by PCR testing. The patient received intravenous aciclovir with resolution of symptoms within 48 h. He was discharged after 14 days of treatment. Case reports of herpes zoster reactivation post vaccination and details of subsequent successful vaccination course completion have allowed us to recommend the patient receive his second dose of the BNT162b2 mRNA vaccine. At the time of writing, however, the patient has declined to receive further vaccination due to fears of an adverse event. To the best of our knowledge, this is the first reported case in a young patient of herpes zoster meningitis following COVID-19 mRNA vaccination. The sharing of clinical experiences and reporting of suspected side effects, particularly for vaccines that employ novel technology, increases knowledge of the safety profile of these vaccines and allows clinicians to better aid patients make informed decisions with regard to commencing and completing vaccination.

Acceptability of and symptom findings from an online symptom check-in tool for COVID-19 outpatient follow-up among a predominantly healthcare worker population.

INTRODUCTION: Health systems worldwide have had to prepare for a surge in volume in both the outpatient and inpatient settings since the emergence of COVID-19. Early international healthcare experiences showed approximately 80% of patients with COVID-19 had mild disease and therfore could be managed as outpatients. However, SARS-CoV-2 can cause a biphasic illness with those affected experiencing a clinical deterioration usually seen after day 4 of illness. OBJECTIVE: We created an online tool with the primary objective of allowing for virtual disease triage among the increasing number of outpatients diagnosed with COVID-19 at our hospital. Secondary aims included COVID-19 education and the promotion of official COVID-19 information among these outpatients, and analysis of reported symptomatology. METHODS: Outpatients with acute COVID-19 disease received text messages from the hospital containing a link to an online symptom check-in tool which they were invited to complete. RESULTS: 296 unique participants (72%) from 413 contacted by text completed the online check-in tool at least once, generating 831 responses from 1324 texts sent. 83% of text recipients and 91% of unique participants were healthcare workers. 7% of responses to the tool were from participants who admitted to a slight worsening of their symptoms during follow-up. Fatigue was the most commonly reported symptom overall (79%), followed by headache (72%). Fatigue, headache and myalgia were the most frequently reported symptoms in the first 3 days of illness. 8% of responses generated in the first 7 days of illness did not report any of the cardinal symptoms (fever, cough, dyspnoea, taste/smell disturbance) of COVID-19. Participants found the tool to be useful and easy to use, describing it as 'helpful' and 'reassuring' in a follow-up feedback survey (n=140). 93% said they would use such a tool in the future. 39% reported ongoing fatigue, 16% reported ongoing smell disturbance and 14% reported ongoing dyspnoea after 6 months. CONCLUSION: The online symptom check-in tool was found to be acceptable to participants and saw high levels of engagement and satisfaction. Symptomatology findings highlight the variety and persistence of symptoms experienced by those with confirmed COVID-19 disease.

SARS-CoV-2 Antibody Testing in Health Care Workers: A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5,788 health care worker (HCW) serum samples by using two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) and Roche anti-SARS-CoV-2 anti-nucleocapsid total antibody) and a subset of samples (all Abbott assay positive or grayzone, n = 485) on Wantai SARS-CoV-2 anti-spike antibody enzyme-linked immunosorbent assay (ELISA). For 367 samples from HCW with a previous PCR-confirmed SARS-CoV-2 infection, we correlated the timing of infection with assay results. Overall, seroprevalence was 4.2% on Abbott and 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche, respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P ≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (odds ratio [OR], 0.30 male ; 95% confidence interval [CI], 0.15 to 0.60), symptom severity (OR 0.19 severe symptoms; 95% CI, 0.05 to 0.61), ethnicity (OR, 0.28 Asian ethnicity; 95% CI, 0.12 to 0.60), and time since PCR diagnosis (OR, 2.06 for infection 6 months previously; 95% CI, 1.01 to 4.30). Wantai detected all previously confirmed infections. In our population, Roche detected antibodies up to at least 7 months after natural infection with SARS-CoV-2. This finding indicates that the Roche total antibody assay is better suited than Abbott IgG assay to population-based studies. Wantai demonstrated high sensitivity, but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated. IMPORTANCE As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. There is a relative paucity of published literature in this field to help guide public health specialists when planning seroprevalence studies. In this study, we compared results of 5,788 health care worker blood samples tested by using two assays (Roche and Elecsys, anti-nucleocapsid antibody) and by testing a subset on a third assay (Wantai enzyme-linked immunosorbent assay [ELISA] anti-spike antibody). We found significant differences in the performance of these assays, especially with distance in time from PCR-confirmed COVID-19 infection, and we feel these results may significantly impact the choice of assay for others conducting similar studies.

SARS-CoV-2 anti-nucleocapsid assay performance in healthcare workers at baseline and 6 months.

INTRODUCTION: Serological SARS-CoV-2 assays have an important role in guiding the pandemic response. This research aimed to compare the performance of 2 antinucleocapsid assays. METHODS: Serum from 49 HCWs was analysed at baseline and 6 months using the Abbott diagnostics SARS-CoV-2 IgG assay and the Roche Diagnostics Elecsys Anti-SARS-CoV-2 total antibody assay. RESULTS: At baseline, 14/49 participants (29%) demonstrated antibody reactivity using the Abbott assay. At 6 months, 4/14 participants (29%) continued to demonstrate reactivity. A total of 14/49 (29%) participants had detectable antibodies at baseline using the Roche assay. In total, 13/14 (93%) of participants demonstrated antibody reactivity at 6 months. The Abbott assay showed a statistically significant difference in the signal-to-threshold values of baseline reactive samples when repeated at 6 months (p = 0.001). This was not seen with the Roche assay (p = 0.51). CONCLUSION: In this small study, the Roche Diagnostics Elecsys Anti-SARS-CoV-2 total antibody assay appears superior in performance to the Abbott diagnostics SARS-CoV-2 IgG assay in accurately detecting participants with a history of confirmed COVID-19 disease at 6 months follow-up. This finding should be born in mind in the planning of future seroprevalence studies, especially when considering the use of anti-nucleocapsid assays.

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity.

Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within the assay protocol. Furthermore, commercial serology assays have a high buy-in cost that is inaccessible for many research groups. We have replicated the serological enzyme-linked immunosorbent assay for the detection of SARS-CoV-2 antibody isotypes, developed at the Icahn School of Medicine at Mount Sinai, New York. Additionally, we have modified the protocol to include a neutralization assay with only a minor modification to this protocol. We used this assay to screen local COVID-19 patient sera (n = 91) and pre-COVID-19 control sera (n = 103), and obtained approximate parity with approved commercial anti-nucleoprotein-based assays with these sera. Furthermore, data from our neutralization assay closely aligns with that generated using a spike-based pseudovirus infection model when a subset of patient sera was analyzed.

Erratum to: Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

[This corrects the article DOI: 10.1093/jacamr/dlaa071.].

Improved diagnosis of SARS-CoV-2 by using nucleoprotein and spike protein fragment 2 in quantitative dual ELISA tests.

The novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative enzyme-linked immunosorbent assays (ELISAs) that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive coronavirus disease-2019 (COVID-19) cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients who had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

Prevalence of antibodies to SARS-CoV-2 in Irish hospital healthcare workers.

Hospital healthcare workers (HCWs) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HCWs in Ireland. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% and 1.8% of staff respectively by the time of the study (October 2020). All staff of both hospitals (N = 9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. In total, 5788 HCWs participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in hospitals 1 and 2, respectively. Thirty-nine percent of infections were previously undiagnosed. Risk for seropositivity was higher for healthcare assistants (aRR 2.0, 95% confidence interval (CI) 1.4-3.0), nurses (aRR: 1.6, 95% CI 1.1-2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95% CI 1.2-2.1), age 18-29 years (aRR: 1.4, 95% CI 1.1-1.9), living with other HCWs (aRR: 1.3, 95% CI 1.1-1.5), Asian background (aRR: 1.3, 95% CI 1.0-1.6) and male sex (aRR: 1.2, 95% CI 1.0-1.4). The HCW seroprevalence was six times higher than community seroprevalence. Risk was higher for those with close patient contact. The proportion of undiagnosed infections call for robust infection control guidance, easy access to testing and consideration of screening in asymptomatic HCWs. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCWs.

Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

BACKGROUND: Bacterial respiratory coinfection in the setting of SARS-CoV-2 infection remains poorly described. A description of coinfection and antimicrobial usage is needed to guide ongoing antimicrobial stewardship. OBJECTIVES: To assess the rate of empirical antimicrobial treatment in COVID-19 cases, assess the rate and methods of microbiological sampling, assess the rate of bacterial respiratory coinfections and evaluate the factors associated with antimicrobial therapy in this cohort. METHODS: Inpatients with positive SARS-CoV-2 PCR were recruited. Antibiotic prescription, choice and duration were recorded. Taking of microbiological samples (sputum culture, blood culture, urinary antigens) and culture positivity rate was also recorded. Linear regression was performed to determine factors associated with prolonged antimicrobial administration. RESULTS: A total of 117 patients were recruited; 84 (72%) were prescribed antimicrobial therapy for lower respiratory tract infections. Respiratory pathogens were identified in seven (6%) patients. The median duration of antimicrobial therapy was 7 days. C-reactive protein level, oxygen requirement and positive cultures were associated with prolonged duration of therapy. CONCLUSIONS: The rate of bacterial coinfection in SARS-CoV-2 is low. Despite this, prolonged courses of antimicrobial therapy were prescribed in our cohort. We recommend active antimicrobial stewardship in COVID-19 cases to ensure appropriate antimicrobial prescribing.

Prevalence of smell and taste dysfunction in a cohort of CoVID19 outpatients managed through remote consultation from a large urban teaching hospital in Dublin, Ireland.

BACKGROUND: Coronaviruses are known to precipitate disorders of smell and taste function. With the emerging global coronavirus disease (CoVID19) pandemic due to the severe acute respiratory syndrome coronavirus 2, early reports suggested that smell and taste dysfunction were clinical features of CoVID19. Our study aimed to investigate the prevalence of smell and taste disturbances in a cohort of CoVID19 positive patients who were isolated at home and being medically managed through telephone consultation. METHODS: This was a retrospective cross-sectional study conducted at St. James's Hospital Dublin, an urban 850 bed tertiary referral centre. 46 out of 50 CoVID19 positive patients, managed through a telephone clinic from the hospital infectious disease department, were assessed for olfactory and gustatory function loss. RESULTS: The median age of participants was 36.5 years (interquartile range (IQR) 27 - 48) and 19 (41%) were male. The majority (31; 67%) never smoked and 17 (37%) reported co-morbidities. Approximately half of patients reported some degree of smell (22; 48%) or taste (25; 54%) function loss. 13 patients (28%) reported a complete loss of sense of smell, 8 (17%) reported a complete loss of sense of taste and 7 (15%) reported simultaneous total loss of both. The median age of patients with any degree of smell disturbance was significantly lower than patients without (median 30.5 years (IQR 24 - 43.25) versus 41 years (IQR 28.25 - 52.75), p = 0.025). The median age of patients with any degree of taste disturbance was lower than those without, but did not reach statistical significance (median 34 years (IQR 24 - 45) versus 40 years (IQR 27.5 - 52.5) p = 0.174). CONCLUSION: Smell or taste dysfunction were present in our defined subgroup of patients. Further research is required in different population cohorts to build the evidence base for smell and taste dysfunction as clinical indicators of CoVID19 disease and to assess if these symptoms persist after disease resolution.