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1.
Heliyon ; 8(4): e09230, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1768134

ABSTRACT

SARS-CoV-2 infection causes a wide spectrum of disease severity. Identifying the immunological characteristics of severe disease and the risk factors for their development are important in the management of COVID-19. This study aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19 in order to investigate an immunological signature of severe disease. One hundred and eight patients with positive SARS-CoV-2 PCR were recruited. Routine clinical and laboratory markers were measured, as well as myeloid and lymphoid whole-blood immunophenotyping and measurement of the pro-inflammatory cytokines IL-6 and soluble CD25. All analysis was carried out in a routine hospital diagnostic laboratory. Univariate analysis demonstrated that severe disease was most strongly associated with elevated CRP and IL-6, loss of DLA-DR expression on monocytes and CD10 expression on neutrophils. Unbiased machine learning demonstrated that these four features were strongly associated with severe disease, with an average prediction score for severe disease of 0.925. These results demonstrate that these four markers could be used to identify patients developing severe COVID-19 and allow timely delivery of therapeutics.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330273

ABSTRACT

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.

3.
BMJ Open ; 12(3): e060826, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1731283

ABSTRACT

INTRODUCTION: As the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. Our aims are to: (1) characterise disability experiences among people living with Long COVID in Canada, UK, USA and Ireland; and (2) develop a patient-reported outcome measure to assess the presence, severity and episodic nature of disability with Long COVID. METHODS AND ANALYSIS: In phase 1, we will conduct semistructured interviews with adults living with Long COVID to explore experiences of disability (dimensions, uncertainty, trajectories, influencing contextual factors) and establish an episodic disability (ED) framework in the context of Long COVID (n~10 each country). Using the conceptual framework, we will establish the Long COVID Episodic Disability Questionnaire (EDQ). In phase 2, we will examine the validity (construct, structural) and reliability (internal consistency, test-retest) of the EDQ for use in Long COVID. We will electronically administer the EDQ and four health status criterion measures with adults living with Long COVID, and readminister the EDQ 1 week later (n~170 each country). We will use Rasch analysis to refine the EDQ, and confirm structural and cross-cultural validity. We will calculate Cronbach's alphas (internal consistency reliability), and intraclass correlation coefficients (test-retest reliability), and examine correlations for hypotheses theorising relationships between EDQ and criterion measure scores (construct validity). Using phase 2 data, we will characterise the profile of disability using structural equation modelling techniques to examine relationships between dimensions of disability and the influence of intrinsic and extrinsic contextual factors. This research involves an academic-clinical-community partnership building on foundational work in ED measurement, Long COVID and rehabilitation. ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Research Ethics Board. Knowledge translation will occur with community collaborators in the form of presentations and publications in open access peer-reviewed journals and presentations.


Subject(s)
COVID-19 , HIV Infections , Adult , COVID-19/complications , Concept Formation , Disability Evaluation , HIV Infections/rehabilitation , Humans , Psychometrics/methods , Reproducibility of Results , SARS-CoV-2 , Surveys and Questionnaires
4.
Front Med (Lausanne) ; 8: 758118, 2021.
Article in English | MEDLINE | ID: covidwho-1709387

ABSTRACT

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.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305332

ABSTRACT

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 six 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=9038) 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. ­ Findings: 5085 HCW participated. Seroprevalence increased to 21% and 13% respectively;26% of infections were previously undiagnosed. Black ethnicity, lower level of education, living with other HCW, and direct patient contact were significantly associated with seropositivity (p<.001). Breakthrough infection occurred in 23/4111(0.6%) of fully vaccinated participants;all had anti-S antibodies.Interpretation: 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 versus 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.Funding: This work was supported financially by the Irish Health Service Executive COVID-19budget.Declaration of Interest: None to declare. Ethical Approval: Ethical approval was obtained from the National Research Ethics Committee (NREC) for COVID-19, Study Number 20-NREC. COV-101 (33).

6.
AIDS Res Ther ; 18(1): 87, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1526645

ABSTRACT

BACKGROUND: Events associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. 'Living strategies' is a concept derived from the perspectives of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. METHODS: Adults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June-August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least 'a few times a week' or 'everyday' during the pandemic. RESULTS: Of the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty [median 30; Interquartile range (IQR): 16, 43] and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p < 0.001), severity (11.4; p < 0.001), and episodic nature (9.3; p < 0.05) of disability. Most participants (> 60%) reported engaging a 'few times a week' or 'everyday' in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. CONCLUSIONS: People living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.


Subject(s)
COVID-19 , HIV Infections , Adult , Cross-Sectional Studies , Disability Evaluation , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Self Care , Surveys and Questionnaires
7.
BMJ Open ; 11(9): e050444, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1443601

ABSTRACT

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.


Subject(s)
COVID-19 , Outpatients , Follow-Up Studies , Health Personnel , Humans , SARS-CoV-2
8.
Microbiol Spectr ; 9(2): e0039121, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1443360

ABSTRACT

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.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Health Personnel/statistics & numerical data , Humans , Immunoglobulin G/blood , Male , Middle Aged , Phosphoproteins/immunology , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
9.
J Thromb Haemost ; 19(10): 2546-2553, 2021 10.
Article in English | MEDLINE | ID: covidwho-1348159

ABSTRACT

BACKGROUND: Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19. OBJECTIVES: To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis. PATIENTS AND METHODS: Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed. RESULTS: Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI -2.57 to -1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15-416 nM/min), and peak thrombin (p < .0001, 95% CI 39-93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09-0.57 IU/ml; p = .009, 95% CI 0.06-0.5 IU/ml; p = .04, 95% CI 0.03-0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01-2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests. CONCLUSIONS: Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.


Subject(s)
COVID-19 , Aged , Biomarkers , COVID-19/complications , Humans , SARS-CoV-2 , von Willebrand Factor
11.
Ir J Med Sci ; 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1321866

ABSTRACT

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.

12.
Viruses ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1314763

ABSTRACT

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.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Serological Testing , Enzyme-Linked Immunosorbent Assay , HEK293 Cells , Humans , Pandemics , SARS-CoV-2/isolation & purification , Seroconversion
13.
JAC Antimicrob Resist ; 2(4): dlaa095, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1288045

ABSTRACT

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

14.
Epidemiol Infect ; 149: e140, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1260913

ABSTRACT

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.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Viral/blood , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/isolation & purification , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Kinetics , Male , Middle Aged , Phosphoproteins/genetics , Phosphoproteins/immunology , Phosphoproteins/isolation & purification , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/isolation & purification
15.
Ann Am Thorac Soc ; 18(6): 997-1003, 2021 06.
Article in English | MEDLINE | ID: covidwho-1256079

ABSTRACT

Rationale: Much is known about the acute infective process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease (COVID-19) pandemic. The marked inflammatory response and coagulopathic state in acute SARS-CoV-2 infection may promote pulmonary fibrosis. However, little is known about the incidence and seriousness of post-COVID-19 pulmonary pathology. Objectives: To describe the respiratory recovery and self-reported health after infection at the time of outpatient attendance. Methods: Infection severity was graded into three groups: 1) not requiring admission, 2) requiring hospital admission, and 3) requiring intensive care unit care. Participants underwent chest radiography and a 6-minute walk test (6MWT). Fatigue and subjective return to health were assessed, and concentrations of CRP (C-reactive protein), IL-6 (interleukin-6), sCD25 (soluble CD25), and D-dimer were measured. The associations between initial illness and abnormal chest X-ray findings, 6MWT distance, and perception of maximal exertion were investigated. Results: A total of 487 patients were offered an outpatient appointment, of whom 153 (31%) attended for assessment at a median of 75 days after diagnosis. A total of 74 (48%) had required hospital admission during acute infection. Persistently abnormal chest X-ray findings were seen in 4%. The median 6MWT distance covered was 460 m. A reduced distance covered was associated with frailty and length of inpatient stay. A total of 95 (62%) patients believed that they had not returned to full health, whereas 47% met the case definition for fatigue. Ongoing ill health and fatigue were associated with an increased perception of exertion. None of the measures of persistent respiratory disease were associated with initial disease severity. Conclusions: This study highlights the rates of objective respiratory disease and subjective respiratory symptoms after COVID-19 and the complex multifactorial nature of post-COVID-19 ill health.


Subject(s)
COVID-19/complications , Fatigue/physiopathology , Frailty/physiopathology , Lung/physiopathology , Recovery of Function , Adult , Aged , Ambulatory Care , COVID-19/diagnostic imaging , COVID-19/physiopathology , Dyspnea/physiopathology , Female , Health Status , Hospitalization , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Physical Exertion , Radiography, Thoracic , SARS-CoV-2 , Severity of Illness Index , Walk Test
16.
J Thromb Haemost ; 19(8): 1914-1921, 2021 08.
Article in English | MEDLINE | ID: covidwho-1247253

ABSTRACT

BACKGROUND: Consistent with fulminant endothelial cell activation, elevated plasma von Willebrand factor (VWF) antigen levels have been reported in patients with COVID-19. The multimeric size and function of VWF are normally regulated through A Disintegrin And Metalloprotease with ThrombSpondin Motif type 1 motif, member 13 (ADAMTS-13)--mediated proteolysis. OBJECTIVES: This study investigated the hypothesis that ADAMTS-13 regulation of VWF multimer distribution may be impaired in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection contributing to the observed microvascular thrombosis. PATIENTS AND METHODS: Patients with COVID-19 (n = 23) were recruited from the Beaumont Hospital Intensive Care Unit (ICU) in Dublin. Plasma VWF antigen, multimer distribution, ADAMTS-13 activity, and known inhibitors thereof were assessed. RESULTS: We observed markedly increased VWF collagen-binding activity in patients with severe COVID-19 compared to controls (median 509.1 versus 94.3 IU/dl). Conversely, plasma ADAMTS-13 activity was significantly reduced (median 68.2 IU/dl). In keeping with an increase in VWF:ADAMTS-13 ratio, abnormalities in VWF multimer distribution were common in patients with COVID-19, with reductions in high molecular weight VWF multimers. Terminal sialylation regulates VWF susceptibility to proteolysis by ADAMTS-13 and other proteases. We observed that both N- and O-linked sialylation were altered in severe COVID-19. Furthermore, plasma levels of the ADAMTS-13 inhibitors interleukin-6, thrombospondin-1, and platelet factor 4 were significantly elevated. CONCLUSIONS: These findings support the hypothesis that SARS-CoV-2 is associated with profound quantitative and qualitative increases in plasma VWF levels, and a multifactorial down-regulation in ADAMTS-13 function. Further studies will be required to determine whether therapeutic interventions to correct ADAMTS-13-VWF multimer dysfunction may be useful in COVID-microvascular thrombosis and angiopathy.


Subject(s)
COVID-19 , von Willebrand Factor , ADAMTS13 Protein , Humans , SARS-CoV-2 , Thrombospondin 1
17.
Front Immunol ; 12: 676932, 2021.
Article in English | MEDLINE | ID: covidwho-1241170

ABSTRACT

Objectives: The immunological and inflammatory changes following acute COVID-19 are hugely variable. Persistent clinical symptoms following resolution of initial infection, termed long COVID, are also hugely variable, but association with immunological changes has not been described. We investigate changing immunological parameters in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms. Methods: We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed as cardinal features of long COVID using the Chalder Fatigue Scale and 6-minute-walk test. The relationships between these clinical outcomes and convalescent immunological results were investigated. Results: We identify persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common in this cohort. These symptoms were not associated with immune cell populations or circulating inflammatory cytokines. Conclusion: We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.


Subject(s)
Aging/physiology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adult , Age Factors , Aged , Cohort Studies , Convalescence , Female , Humans , Immunophenotyping , Longitudinal Studies , Lymphocyte Activation , Male , Middle Aged , Pandemics
18.
Epidemiol Infect ; 149: e157, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1203374

ABSTRACT

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.


Subject(s)
Antibodies, Viral/blood , COVID-19 , Personnel, Hospital/statistics & numerical data , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/immunology , Cross-Sectional Studies , Female , Humans , Ireland/epidemiology , Male , Middle Aged , SARS-CoV-2/immunology , Seroepidemiologic Studies , Young Adult
19.
PLoS One ; 16(2): e0247280, 2021.
Article in English | MEDLINE | ID: covidwho-1102383

ABSTRACT

BACKGROUND: The long-term clinical and physiological consequences of COVID-19 infection remain unclear. While fatigue has emerged as a common symptom following infection, little is known about its links with autonomic dysfunction. SARS-CoV-2 is known to infect endothelial cells in acute infection, resulting in autonomic dysfunction. Here we set out to test the hypothesis that this results in persistent autonomic dysfunction and is associated with post-COVID fatigue in convalescent patients. METHODS: We recruited 20 fatigued and 20 non-fatigued post-COVID patients (median age 44.5 years, 36/40 (90%) female, median time to follow up 166.5 days). Fatigue was assessed using the Chalder Fatigue Scale. These underwent the Ewing's autonomic function test battery, including deep breathing, active standing, Valsalva manoeuvre and cold-pressor testing, with continuous electrocardiogram and blood pressure monitoring, as well as near-infrared spectroscopy-based cerebral oxygenation. 24-hour ambulatory blood pressure monitoring was also conducted, and patients completed the generalised anxiety disorder-7 questionnaire. We assessed between-group differences in autonomic function test results and used unadjusted and adjusted linear regression to investigate the relationship between fatigue, anxiety, and autonomic test results. RESULTS: We found no pathological differences between fatigued and non-fatigued patients on autonomic testing or on 24-hour blood pressure monitoring. Symptoms of orthostatic intolerance were reported by 70% of the fatigued cohort at the time of active standing, with no associated physiological abnormality detected. Fatigue was strongly associated with increased anxiety (p <0.001), with no patients having a pre-existing diagnosis of anxiety. CONCLUSIONS: These results demonstrate the significant burden of fatigue, symptoms of autonomic dysfunction and anxiety in the aftermath of COVID-19 infection, but reassuringly do not demonstrate pathological findings on autonomic testing.


Subject(s)
COVID-19/pathology , Anxiety/physiopathology , Autonomic Nervous System/pathology , Blood Pressure , COVID-19/physiopathology , COVID-19/psychology , Electrocardiography , Fatigue/physiopathology , Heart Rate , Humans , Middle Aged
20.
J Thromb Haemost ; 19(4): 1064-1070, 2021 04.
Article in English | MEDLINE | ID: covidwho-1084302

ABSTRACT

BACKGROUND: Persistent fatigue, breathlessness, and reduced exercise tolerance have been reported following acute COVID-19 infection. Although immuno-thrombosis has been implicated in acute COVID-19 pathogenesis, the biological mechanisms underpinning long COVID remain unknown. We hypothesized that pulmonary microvascular immuno-thrombosis may be important in this context. METHODS: One hundred fifty COVID-19 patients were reviewed at St James's Hospital Dublin between May and September 2020 at a median of 80.5 (range 44-155) days after initial diagnosis. These included patients hospitalized during initial illness (n = 69) and others managed entirely as out-patients (n = 81). Clinical examination, chest x-ray, and 6-min walk tests were performed. In addition, a range of coagulation and inflammatory markers were assessed. RESULTS: Increased D-dimer levels (>500 ng/ml) were observed in 25.3% patients up to 4 months post-SARS-CoV-2 infection. On univariate analysis, elevated convalescent D-dimers were more common in COVID-19 patients who had required hospital admission and in patients aged more than 50 years (p < .001). Interestingly, we observed that 29% (n = 11) of patients with elevated convalescent D-dimers had been managed exclusively as out-patients during their illness. In contrast, other coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen, platelet count) and inflammation (C-reactive protein, interleukin-6, and sCD25) markers had returned to normal in >90% of convalescent patients. CONCLUSIONS: Elucidating the biological mechanisms responsible for sustained D-dimer increases may be of relevance in long COVID pathogenesis and has implications for clinical management of these patients.


Subject(s)
Acute-Phase Reaction , COVID-19/blood , Fibrin Fibrinogen Degradation Products/analysis , Aged , COVID-19/rehabilitation , Female , Humans , Male , Middle Aged , SARS-CoV-2
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