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1.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522216

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

2.
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
3.
World Allergy Organ J ; 14(10): 100587, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1433888

ABSTRACT

Efforts to reduce non-urgent hospital attendances during the COVID-19 pandemic have been the focus of much attention from healthcare professionals worldwide. In Ireland, due to funding constraints omalizumab is only available for hospital-based administration. Fifty-eight patients with chronic spontaneous urticaria and angioedema (CSU) receiving omalizumab in our centre were rapidly transitioned to home self-administration at the start of the pandemic. We conducted an anonymised patient survey after 3 months of home therapy with the aim of characterizing the patient experience throughout this period. 41 patients participated in our questionnaire (71% response rate). 93% of patients favored self-injection of omalizumab from home, with respondents citing cost savings, time savings, improved flexibility, fewer hospital visits, and less risk of exposure to COVID-19 infection as particular benefits. Concerns regarding home administration including injecting incorrectly, forgetting a dose, or having a reaction were reported very infrequently. Eighty-three percent (83%) of patients wished to continue with home therapy long-term. This survey highlights broadly positive experiences for patients rapidly transitioning to home omalizumab administration. This data will be useful to inform healthcare funders in decisions regarding patient-centred care in CSU. Facilitating home omalizumab therapy in suitable CSU patients should be strongly considered in the post-pandemic setting.

5.
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.

6.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1317919

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

7.
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
8.
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
9.
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
10.
Journal of Clinical Pharmacology ; 61(6):832-835, 2021.
Article in English | ProQuest Central | ID: covidwho-1209714

ABSTRACT

Polyethylene glycol (PEG), also known as macrogol, is an excipient in numerous medications, health care products, cosmetics, and foods. It acts as an inert bulking, or stabilizing, agent. Despite its ubiquity, including in 2 of the newly launched vaccines against SARS‐CoV‐2, awareness of PEG allergy remains low. We present 6 cases of acute hypersensitivity to PEG. Accurate diagnoses in these cases posed a challenge, and although the triggering agents differed, PEG was demonstrated as the common culprit. All cases were female, with a mean age of 36.4 years. Four patients were originally suspected to have nonsteroid anti‐inflammatory drug allergy, and 2 had a history of chronic spontaneous urticaria and angioedema. Biphasic allergic reactions featured prominently in this case series. Diagnosis relies on a high index of suspicion leading to a focused clinical history, supported by skin tests with PEG solutions to demonstrate sensitization. This case series highlights important clinical features of this rare, potentially serious, and increasingly recognized excipient allergy.

11.
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
12.
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
13.
Ann Am Thorac Soc ; 18(6): 997-1003, 2021 06.
Article in English | MEDLINE | ID: covidwho-1015968

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
14.
Allergy ; 76(3): 816-830, 2021 03.
Article in English | MEDLINE | ID: covidwho-960768

ABSTRACT

INTRODUCTION: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. AIM: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. MATERIALS AND METHODS: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. RESULTS: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. CONCLUSIONS: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.


Subject(s)
COVID-19/epidemiology , Chronic Urticaria/therapy , SARS-CoV-2 , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Internet , Male , Middle Aged , Patient Reported Outcome Measures , Young Adult
15.
PLoS One ; 15(11): e0240784, 2020.
Article in English | MEDLINE | ID: covidwho-917987

ABSTRACT

Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.


Subject(s)
Coronavirus Infections/pathology , Fatigue/etiology , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Fatigue/epidemiology , Female , Humans , Interleukin-2 Receptor alpha Subunit/blood , Interleukin-6/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Prevalence , SARS-CoV-2 , Severity of Illness Index
16.
Br J Haematol ; 189(6): 1044-1049, 2020 06.
Article in English | MEDLINE | ID: covidwho-629751

ABSTRACT

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung-centric coagulopathy may play an important role. Elevated D-dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3-4-fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African-Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late-stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary-specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.


Subject(s)
Betacoronavirus , Blood Coagulation Disorders/etiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Blood Coagulation Disorders/ethnology , Blood Coagulation Disorders/pathology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/ethnology , Disseminated Intravascular Coagulation/prevention & control , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Lung/blood supply , Male , Middle Aged , Pandemics , Pneumonia/blood , Pneumonia/pathology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/ethnology , SARS-CoV-2 , Thrombosis/prevention & control
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