COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)

T. Ratneswaren; N. Chan; J. Aeron-Thomas; S. Sait; O. Adesalu; M. Alhawamdeh; M. Benger; J. Garnham; L. Dixon; F. Tona; C. Mcnamara; E. Taylor; K. Lobotesis; E. Lim; O. Goldberg; N. Asmar; O. Evbuomwan; S. Banerjee; L. Holm-Mercer; J. Senor; Y. Tsitsiou; P. Tantrige; A. Taha; K. Ballal; A. Mattar; A. Daadipour; K. Elfergani; R. Barker; R. Chakravartty; A.g. Murchison; B.j. Kemp; R. Simister; I. Davagnanam; O.y. Wong; D. Werring; A. Banaras; M. Anjari; J.k.c. Mak; A.m. Falzon; J.c.l. Rodrigues; C.a.s. Thompson; I.r. Haines; T.a. Burnett; R.e.y. Zaher; V.l. Reay; M. Banerjee; C.s.l. Sew hee; A.p. Oo; A. Lo; P. Rogers; T. Hughes; A. Marin; S. Mukherjee; H. Jaber; E. Sanders; S. Owen; M. Bhandari; S. Sundayi; A. Bhagat; M. Elsakka; O.h. Hashmi; M. Lymbouris; Y. Gurung-Koney; M. Arshad; I. Hasan; N. Singh; V. Patel; M. Rahiminejad; T.C. Booth

doi:10.1016/j.nicl.2024.103590

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)

T. Ratneswaren, N. Chan, J. Aeron-Thomas, S. Sait, O. Adesalu, M. Alhawamdeh, M. Benger, J. Garnham, L. Dixon, F. Tona, C. Mcnamara, E. Taylor, K. Lobotesis, E. Lim, O. Goldberg, N. Asmar, O. Evbuomwan, S. Banerjee, L. Holm-Mercer, J. SenorY. Tsitsiou, P. Tantrige, A. Taha, K. Ballal, A. Mattar, A. Daadipour, K. Elfergani, R. Barker, R. Chakravartty, A.g. Murchison, B.j. Kemp, R. Simister, I. Davagnanam, O.y. Wong, D. Werring, A. Banaras, M. Anjari, J.k.c. Mak, A.m. Falzon, J.c.l. Rodrigues, C.a.s. Thompson, I.r. Haines, T.a. Burnett, R.e.y. Zaher, V.l. Reay, M. Banerjee, C.s.l. Sew hee, A.p. Oo, A. Lo, P. Rogers, T. Hughes, A. Marin, S. Mukherjee, H. Jaber, E. Sanders, S. Owen, M. Bhandari, S. Sundayi, A. Bhagat, M. Elsakka, O.h. Hashmi, M. Lymbouris, Y. Gurung-Koney, M. Arshad, I. Hasan, N. Singh, V. Patel, M. Rahiminejad, T.C. Booth

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Research output: Contribution to journal › Article › peer-review

Abstract

Background
Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19.

Objective
To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients.

Methods
In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed.

Results
CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8–95.2) and negative predictive value (NPV; 97.8 %, 96.5–98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8–95.5; NPV 99.7 %, 98.3–100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2–40.1), myalgia (8.9, 2.1–38.2) and higher core body temperature (1.9, 1.1–3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality.

Conclusion
Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Original language	English
Article number	103590
Journal	NeuroImage: Clinical
Volume	42
Early online date	20 Mar 2024
DOIs	https://doi.org/10.1016/j.nicl.2024.103590
Publication status	E-pub ahead of print - 20 Mar 2024

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Ratneswaren, T., Chan, N., Aeron-Thomas, J., Sait, S., Adesalu, O., Alhawamdeh, M., Benger, M., Garnham, J., Dixon, L., Tona, F., Mcnamara, C., Taylor, E., Lobotesis, K., Lim, E., Goldberg, O., Asmar, N., Evbuomwan, O., Banerjee, S., Holm-Mercer, L., ... Booth, T. C. (2024). COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2). NeuroImage: Clinical, 42, Article 103590. Advance online publication. https://doi.org/10.1016/j.nicl.2024.103590

@article{f2950b77b73f48ac913dd4c17fafb0f3,

title = "COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)",

abstract = "BackgroundApical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19.ObjectiveTo prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients.MethodsIn this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed.ResultsCTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8–95.2) and negative predictive value (NPV; 97.8 %, 96.5–98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8–95.5; NPV 99.7 %, 98.3–100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2–40.1), myalgia (8.9, 2.1–38.2) and higher core body temperature (1.9, 1.1–3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality.ConclusionApical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.",

author = "T. Ratneswaren and N. Chan and J. Aeron-Thomas and S. Sait and O. Adesalu and M. Alhawamdeh and M. Benger and J. Garnham and L. Dixon and F. Tona and C. Mcnamara and E. Taylor and K. Lobotesis and E. Lim and O. Goldberg and N. Asmar and O. Evbuomwan and S. Banerjee and L. Holm-Mercer and J. Senor and Y. Tsitsiou and P. Tantrige and A. Taha and K. Ballal and A. Mattar and A. Daadipour and K. Elfergani and R. Barker and R. Chakravartty and A.g. Murchison and B.j. Kemp and R. Simister and I. Davagnanam and O.y. Wong and D. Werring and A. Banaras and M. Anjari and J.k.c. Mak and A.m. Falzon and J.c.l. Rodrigues and C.a.s. Thompson and I.r. Haines and T.a. Burnett and R.e.y. Zaher and V.l. Reay and M. Banerjee and {Sew hee}, C.s.l. and A.p. Oo and A. Lo and P. Rogers and T. Hughes and A. Marin and S. Mukherjee and H. Jaber and E. Sanders and S. Owen and M. Bhandari and S. Sundayi and A. Bhagat and M. Elsakka and O.h. Hashmi and M. Lymbouris and Y. Gurung-Koney and M. Arshad and I. Hasan and N. Singh and V. Patel and M. Rahiminejad and T.C. Booth",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = mar,

day = "20",

doi = "10.1016/j.nicl.2024.103590",

language = "English",

volume = "42",

journal = "NeuroImage: Clinical",

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Ratneswaren, T, Chan, N, Aeron-Thomas, J, Sait, S, Adesalu, O, Alhawamdeh, M, Benger, M, Garnham, J, Dixon, L, Tona, F, Mcnamara, C, Taylor, E, Lobotesis, K, Lim, E, Goldberg, O, Asmar, N, Evbuomwan, O, Banerjee, S, Holm-Mercer, L, Senor, J, Tsitsiou, Y, Tantrige, P, Taha, A, Ballal, K, Mattar, A, Daadipour, A, Elfergani, K, Barker, R, Chakravartty, R, Murchison, AG, Kemp, BJ, Simister, R, Davagnanam, I, Wong, OY, Werring, D, Banaras, A, Anjari, M, Mak, JKC, Falzon, AM, Rodrigues, JCL, Thompson, CAS, Haines, IR, Burnett, TA, Zaher, REY, Reay, VL, Banerjee, M, Sew hee, CSL, Oo, AP, Lo, A, Rogers, P, Hughes, T, Marin, A, Mukherjee, S, Jaber, H, Sanders, E, Owen, S, Bhandari, M, Sundayi, S, Bhagat, A, Elsakka, M, Hashmi, OH, Lymbouris, M, Gurung-Koney, Y, Arshad, M, Hasan, I, Singh, N, Patel, V, Rahiminejad, M & Booth, TC 2024, 'COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)', NeuroImage: Clinical, vol. 42, 103590. https://doi.org/10.1016/j.nicl.2024.103590

TY - JOUR

T1 - COVID-19 Stroke Apical Lung Examination Study 2

T2 - a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)

AU - Ratneswaren, T.

AU - Chan, N.

AU - Aeron-Thomas, J.

AU - Sait, S.

AU - Adesalu, O.

AU - Alhawamdeh, M.

AU - Benger, M.

AU - Garnham, J.

AU - Dixon, L.

AU - Tona, F.

AU - Mcnamara, C.

AU - Taylor, E.

AU - Lobotesis, K.

AU - Lim, E.

AU - Goldberg, O.

AU - Asmar, N.

AU - Evbuomwan, O.

AU - Banerjee, S.

AU - Holm-Mercer, L.

AU - Senor, J.

AU - Tsitsiou, Y.

AU - Tantrige, P.

AU - Taha, A.

AU - Ballal, K.

AU - Mattar, A.

AU - Daadipour, A.

AU - Elfergani, K.

AU - Barker, R.

AU - Chakravartty, R.

AU - Murchison, A.g.

AU - Kemp, B.j.

AU - Simister, R.

AU - Davagnanam, I.

AU - Wong, O.y.

AU - Werring, D.

AU - Banaras, A.

AU - Anjari, M.

AU - Mak, J.k.c.

AU - Falzon, A.m.

AU - Rodrigues, J.c.l.

AU - Thompson, C.a.s.

AU - Haines, I.r.

AU - Burnett, T.a.

AU - Zaher, R.e.y.

AU - Reay, V.l.

AU - Banerjee, M.

AU - Sew hee, C.s.l.

AU - Oo, A.p.

AU - Lo, A.

AU - Rogers, P.

AU - Hughes, T.

AU - Marin, A.

AU - Mukherjee, S.

AU - Jaber, H.

AU - Sanders, E.

AU - Owen, S.

AU - Bhandari, M.

AU - Sundayi, S.

AU - Bhagat, A.

AU - Elsakka, M.

AU - Hashmi, O.h.

AU - Lymbouris, M.

AU - Gurung-Koney, Y.

AU - Arshad, M.

AU - Hasan, I.

AU - Singh, N.

AU - Patel, V.

AU - Rahiminejad, M.

AU - Booth, T.C.

PY - 2024/3/20

Y1 - 2024/3/20

N2 - BackgroundApical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19.ObjectiveTo prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients.MethodsIn this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed.ResultsCTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8–95.2) and negative predictive value (NPV; 97.8 %, 96.5–98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8–95.5; NPV 99.7 %, 98.3–100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2–40.1), myalgia (8.9, 2.1–38.2) and higher core body temperature (1.9, 1.1–3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality.ConclusionApical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

AB - BackgroundApical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19.ObjectiveTo prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients.MethodsIn this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed.ResultsCTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8–95.2) and negative predictive value (NPV; 97.8 %, 96.5–98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8–95.5; NPV 99.7 %, 98.3–100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2–40.1), myalgia (8.9, 2.1–38.2) and higher core body temperature (1.9, 1.1–3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality.ConclusionApical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

UR - http://www.scopus.com/inward/record.url?scp=85188451338&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2024.103590

DO - 10.1016/j.nicl.2024.103590

M3 - Article

SN - 2213-1582

VL - 42

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 103590

ER -

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2)

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