Syncope and COVID-19 disease – A systematic review

      Abstract

      Background

      Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19.

      Methods

      A systematic review across PubMed, ISI Web of Knowledge and SCOPUS was performed, according to PRISMA guidelines, in order to identify all relevant articles regarding both COVID-19 and syncope.

      Results

      We identified 136 publications, of which 99 were excluded. The frequency of syncope and pre-syncope across the selected studies was 4.2% (604/14,437). Unexplained syncope was the most common type (87.9% of the episodes), followed by reflex syncope (7.8% of the cases). Orthostatic hypotension was responsible for 2.2% of the cases and syncope of presumable cardiac cause also accounted for 2.2% of cases. Arterial hypertension was present in 52.0% of syncope patients. The use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors were not associated with an increased incidence of syncope (chi-square test 1.07, p 0.30), unlike the use of beta-blockers (chi-square test 12.48, p < 0.01).

      Conclusion

      Syncope, although not considered a typical symptom of COVID-19, can be associated with it, particularly in early stages. Different causes of syncope were seen in this context. A reevaluation of blood pressure in patients with COVID-19 is suggested, including reassessment of antihypertensive therapy, especially in the case of beta-blockers.

      Keywords

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      References

        • Aoi S.
        • Kakkar A.M.
        • Golowa Y.
        • Grushko M.
        • Coyle C.M.
        • Elrafei T.
        • et al.
        Saddle pulmonary embolism and clot in transit in COVID-19 infection: a case report of catastrophic venous thromboembolism.
        Eur. Heart J. 2020;
        • Argenziano M.G.
        • Bruce S.L.
        • Slater C.L.
        • Tiao J.R.
        • Baldwin M.R.
        • Barr R.G.
        • et al.
        Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series.
        BMJ. 2020; : 369
        • Birlutiu V.
        • Birlutiu R.M.
        • Feiereisz A.I.
        SARS-CoV-2 infection associated with micturition syncope: our experience with 4 case reports.
        Medicine. 2020; 99
        • Brignole M.
        • Moya A.
        • de Lange F.J.
        • Deharo J.-C.
        • Elliott P.M.
        • Fanciulli A.
        • et al.
        2018 ESC guidelines for the diagnosis and management of syncope.
        Eur. Heart J. 2018; 39: 1883-1948
        • Canetta C.
        • Accordino S.
        • Buscarini E.
        • Benelli G.
        • La Piana G.
        • Scartabellati A.
        • et al.
        Syncope at SARS-CoV-2 onset.
        Auton. Neurosci. 2020; 229102734
        • Cardiology ESo
        ESC guidelines for the diagnosis and management of syncope.
        Eur. Heart J. 2018; https://doi.org/10.1093/eurheartj/ehy037
        • Chachkhiani D.
        • Soliman M.Y.
        • Barua D.
        • Isakadze M.
        • Villemarette-Pittman N.R.
        • Devier D.J.
        • et al.
        Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization.
        Clin. Neurol. Neurosurg. 2020; 197106173
        • Chalela R.
        • Caguana O.
        • Zuccarino F.
        • Khilzi K.
        • Rodríguez-Chiaradía D.A.
        Case report on a patient with Steinert disease complicated by COVID-19.
        Vasc. Health Risk Manag. 2020; 16: 463
        • Chang D.
        • Saleh M.
        • Garcia-Bengo Y.
        • Choi E.
        • Epstein L.
        • Willner J.
        COVID-19 infection unmasking brugada syndrome.
        HeartRhythm Case Reports. 2020; 6: 237-240
        • Chen T.
        • Hanna J.
        • Walsh E.E.
        • Falsey A.R.
        • Laguio-Vila M.
        • Lesho E.
        Syncope, near-syncope, or non-mechanical falls as a presenting feature of COVID-19.
        Ann. Emerg. Med. 2020;
        • Chibane S.
        • Gibeau G.
        • Poulin F.
        • Tessier P.
        • Goulet M.
        • Carrier M.
        • et al.
        Hyperacute multi-organ thromboembolic storm in COVID-19: a case report.
        J. Thromb. Thrombolysis. 2020; 1–4
        • Chou S.H.-Y.
        • Beghi E.
        • Helbok R.
        • Moro E.
        • Sampson J.
        • Altamirano V.
        • et al.
        Global prevalence of neurological manifestations among patients hospitalized with COVID-19: a report of the global consortium study of neurologic dysfunction in COVID-19 (GCS-NeuroCOVID) and the European Academy of Neurology [ENERGY].
        in: Registry Collaborative. 2021
        • Chuang D.T.
        • Aydemir S.
        • Magda P.
        • Thomas C.
        • Zarnegar R.
        Neurological manifestations as primary presentation of COVID-19 in hospitalized patients.
        Acta Neurol. Scand. 2021;
        • Doodnauth A.V.
        • Jallad A.
        • Rizk D.
        • Valery E.
        • McFarlane S.I.
        Syncope associated with sinus nodal dysfunction in a COVID-19 patient: a case report and review of the literature.
        Am. J. Med. Case Rep. 2021; 9: 263
        • Ebrille E.
        • Lucciola M.T.
        • Amellone C.
        • Ballocca F.
        • Orlando F.
        • Giammaria M.
        Syncope as the presenting symptom of COVID-19 infection.
        in: HeartRhythm Case Reports. 2020
        • Espinoza D.
        • Jasti M.
        • Malwi U.H.
        • Junia C.
        Cardiovascular disease risk and outcomes in patients infected with SARS-CoV-2.
        Cureus. 2021; 13
        • Favas T.
        • Dev P.
        • Chaurasia R.N.
        • Chakravarty K.
        • Mishra R.
        • Joshi D.
        • et al.
        Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions.
        Neurol. Sci. 2020; 1–34
        • García-Moncó J.C.
        • Cabrera-Muras A.
        • Collía-Fernández A.
        • Erburu-Iriarte M.
        • Rodrigo-Armenteros P.
        • Oyarzun-Irazu I.
        • et al.
        Neurological reasons for consultation and hospitalization during the COVID-19 pandemic.
        Neurol. Sci. 2020; 41: 3031-3038
        • Gaze D.C.
        Clinical utility of cardiac troponin measurement in COVID-19 infection.
        Ann. Clin. Biochem. 2020; 57: 202-205
        • Gonfiotti A.
        • Gatteschi L.
        • Salvicchi A.
        • Bongiolatti S.
        • Lavorini F.
        • Voltolini L.
        Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by severe acute respiratory syndrome coronavirus 2.
        Eur. J. Cardiothorac. Surg. 2020; 58: 598-604
        • Huang Y.H.
        • Jiang D.
        • Huang J.T.
        A case of COVID-19 encephalitis.
        Brain Behav. Immun. 2020;
        • Kanjwal K.
        • Jamal S.
        • Kichloo A.
        • Grubb B.P.
        New-onset postural orthostatic tachycardia syndrome following coronavirus disease 2019 infection.
        J. Innov. Cardiac Rhythm Manag. 2020; 11: 4302
        • Khan H.M.W.
        • Khan M.R.
        • Munir A.
        • Moughrabieh A.
        • Changezi H.U.
        A Giant right-heart thrombus-in-transit in a patient with COVID-19 pneumonia.
        Am. J. Case Rep. 2020; 21: e927380-e927381
        • Lam K.
        • McClelland S.
        • Dallo M.J.
        ECG: essential in care of patients with COVID-19.
        Med. J. Aust. 2020; 213 (e1): 476
        • Logmin K.
        • Karam M.
        • Schichel T.
        • Harmel J.
        • Wojtecki L.
        Non-epileptic seizures in autonomic dysfunction as the initial symptom of COVID-19.
        J. Neurol. 2020; 1
        • Luetkens J.A.
        • Isaak A.
        • Zimmer S.
        • Nattermann J.
        • Sprinkart A.M.
        • Boesecke C.
        • et al.
        Diffuse myocardial inflammation in COVID-19 associated myocarditis detected by multiparametric cardiac magnetic resonance imaging.
        Circ. Cardiovasc. Imaging. 2020; 13e010897
        • Martín-Sánchez F.J.
        • Del Toro E.
        • Cardassay E.
        • Carbó A.V.
        • Cuesta F.
        • Vigara M.
        • et al.
        Clinical presentation and outcome across age categories among patients with COVID-19 admitted to a Spanish emergency department.
        Euro. Geriatr. Med. 2020; 11: 829-841
        • Miglis M.G.
        • Prieto T.
        • Shaik R.
        • Muppidi S.
        • Sinn D.-I.
        • Jaradeh S.
        A case report of postural tachycardia syndrome after COVID-19.
        Clin. Auton. Res. 2020; 30: 449-451
        • Mizrahi B.
        • Shilo S.
        • Rossman H.
        • Kalkstein N.
        • Marcus K.
        • Barer Y.
        • et al.
        Longitudinal symptom dynamics of COVID-19 infection.
        Nat. Commun. 2020; 11: 1-10
        • National Heart LaBI
        Study Quality Assessment Tools.
        (Available from:)
        • Oates C.P.
        • Turagam M.K.
        • Musikantow D.
        • Chu E.
        • Shivamurthy P.
        • Lampert J.
        • et al.
        Syncope and presyncope in patients with COVID-19.
        Pacing Clin. Electrophysiol. 2020;
        • Omotosho Y.B.
        • Ying G.W.
        • Stolar M.
        • Mallari A.J.P.
        COVID-19-induced diabetic ketoacidosis in an adult with latent autoimmune diabetes.
        Cureus. 2021; 13
        • Organization
        WH. WHO Coronavirus (COVID-19) Dashboard.
        ([July 1, 2021]. Available from:)
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • Boutron I.
        • Hoffmann T.C.
        • Mulrow C.D.
        • et al.
        Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement.
        J. Clin. Epidemiol. 2021; 134: 103-112
        • Pasquetto G.
        • Conti G.B.
        • Susana A.
        • Leone L.A.
        • Bertaglia E.
        Syncope, Brugada syndrome, and COVID-19 lung disease.
        J. Arrhythmia. 2020; 36: 768-770
        • Pendower L.
        • Benedetti G.
        • Breen K.
        • Karunanithy N.
        Catheter-directed thrombolysis to treat acute pulmonary thrombosis in a patient with COVID-19 pneumonia.
        BMJ Case Rep. CP. 2020; 13e237046
        • Pérez I.H.
        • de la Esperanza B.T.
        • Peñacoba G.V.
        • Azorin D.G.
        Isolated syncope as a form of presentation of COVID-19 infection.
        Neurología (English Edition). 2020;
        • Radmanesh A.
        • Raz E.
        • Zan E.
        • Derman A.
        • Kaminetzky M.
        Brain imaging use and findings in COVID-19: a single academic center experience in the epicenter of disease in the United States.
        Am. J. Neuroradiol. 2020; 41: 1179-1183
        • Romero-Sánchez C.M.
        • Díaz-Maroto I.
        • Fernández-Díaz E.
        • Sánchez-Larsen Á.
        • Layos-Romero A.
        • García-García J.
        • et al.
        Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry.
        Neurology. 2020;
        • Sang C.J.
        • Heindl B.
        • Von Mering G.
        • Rajapreyar I.
        Massive pulmonary embolism in a COVID-19 patient: a case report.
        European Heart Journal-Case Reports. 2020;
        • Santacroce L.
        • Charitos I.A.
        • Carretta D.M.
        • De Nitto E.
        • Lovero R.
        The human coronaviruses (HCoVs) and the molecular mechanisms of SARS-CoV-2 infection.
        J. Mol. Med. 2020; 1–14
        • Shafi A.M.
        • Shaikh S.A.
        • Shirke M.M.
        • Iddawela S.
        • Harky A.
        Cardiac manifestations in COVID-19 patients—a systematic review.
        J. Card. Surg. 2020; 35: 1988-2008
        • Singhania N.
        • Bansal S.
        • Singhania G.
        An atypical presentation of novel coronavirus disease 2019 (COVID-19).
        Am. J. Med. 2020;
        • Tadic M.
        • Cuspidi C.
        • Grassi G.
        • Mancia G.
        COVID-19 and arterial hypertension: hypothesis or evidence?.
        J. Clin. Hypertens. 2020; 22: 1120-1126
        • Tapé C.
        • Byrd K.M.
        • Aung S.
        • Lonks J.R.
        • Flanigan T.P.
        • Rybak N.R.
        COVID-19 in a patient presenting with syncope and a normal chest X-ray.
        Rhode Island Med. J. 2013; 103 (2020): 50
        • Terpos E.
        • Ntanasis-Stathopoulos I.
        • Elalamy I.
        • Kastritis E.
        • Sergentanis T.N.
        • Politou M.
        • et al.
        Hematological findings and complications of COVID-19.
        Am. J. Hematol. 2020;
        • Travi G.
        • Rossotti R.
        • Merli M.
        • D'Amico F.
        • Chiappetta S.
        • Panariello A.
        • et al.
        Neurological Manifestations in Patients Hospitalized With COVID-19: A Retrospective Analysis From a Large Cohort in Northern Italy.
        2020
        • Wang M.-Y.
        • Zhao R.
        • Gao L.-J.
        • Gao X.-F.
        • Wang D.-P.
        • Cao J.-M.
        SARS-CoV-2: structure, biology, and structure-based therapeutics development.
        Front. Cell. Infect. Microbiol. 2020; : 10
        • Xia H.
        • Lazartigues E.
        Angiotensin-converting enzyme 2: central regulator for cardiovascular function.
        Curr. Hypertens. Rep. 2010; 12: 170-175
        • Xiong W.
        • Mu J.
        • Guo J.
        • Lu L.
        • Liu D.
        • Luo J.
        • et al.
        New onset neurologic events in people with COVID-19 in 3 regions in China.
        Neurology. 2020; 95: e1479-e1487