Response by Zhang et al to Letter Regarding Article, “Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome”
Authors: Li Zhang, Wei Sun, Yanting Zhang, Chun Wu, Yuman Li, Mingxing Xie
Journal: Circulation (2021)

HomeCirculationVol. 143, No. 5Response by Zhang et al to Letter Regarding Article, "Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Zhang et al to Letter Regarding Article, "Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome" Li Zhang, Wei Sun, Yanting Zhang, Chun Wu, Yuman Li and Mingxing Xie Li ZhangLi Zhang Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). , Wei SunWei Sun Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). , Yanting ZhangYanting Zhang https://orcid.org/0000-0003-2706-9959 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). , Chun WuChun Wu Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). , Yuman LiYuman Li https://orcid.org/0000-0002-4388-8199 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). and Mingxing XieMingxing Xie https://orcid.org/0000-0003-4984-1567 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Clinical Research Center for Medical Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China (L.Z., W.S., Y.Z., C.W., Y.L., M.X.). Originally published1 Feb 2021https://doi.org/10.1161/CIRCULATIONAHA.120.051629Circulation. 2021;143:e33–e34In Response:We feel honored that Drs Albiero and Seresini showed interest in our research of "Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome"1 and offered their valuable feedback. Their view is interesting and worth further exploration. We fully agree that the prevalence of a right-to-left shunt through a patent foramen ovale (PFO) in patients with coronavirus disease 2019 (COVID-19) is a worthy research topic and could have been insightful if incorporated in our study. Unfortunately, because of the dire situation during the epidemic outbreak, we were unable to include this aspect in the research. Of the 143 patients with COVID-19 in our study, only 79 patients had a cardiac ultrasound ordered based on their clinical indication. We elucidated the related echocardiographic data of the 79 patients with COVID-19 in our study. Given the high risk of exposure and contagion to health care workers in the isolation wards, we did not carry out the systematic screening of PFO for patients with COVID-19, which should be diagnosed by the reference standard imaging technology – contrast, transesophageal echocardiography. Thus, cardiac ultrasound in the isolation ward was a targeted examination, and we did not perform the contrast transesophageal echocardiography in these patients with COVID-19, which led to the fact that the incidence of PFO was hard to assess.We value Drs Albiero and Seresini's hypothesis that in patients with severe COVID-19, acute respiratory distress syndrome, deep vein thrombosis (DVT), and a concomitant PFO, reversal of the normal interatrial pressure gradient may occur because of the increase in pulmonary artery pressure. It can further result in an increased PFO right-to-left shunt, leading to an increased risk of paradoxical embolism with adverse outcomes and death. However, to the best of our knowledge, studies about the association between acute respiratory distress syndrome and PFO were still inadequate and inconsistent. Furthermore, the studies about the association among DVT, PFO, and cryptogenic stroke yielded conflicting results. In the study by Cramer et al,2 a higher proportion of DVT was observed in cryptogenic stroke patients than those with noncryptogenic stroke (P=0.025). In contrast, there was no significant difference between cryptogenic stroke and noncryptogenic stroke in the frequency of DVT (P=0.30) in the subgroup of patients with PFO. In another study by Liberman et al,3 of 131 patients with PFO, there was no significant difference in the prevalence of DVT (7.2% versus 9.1%, P=0.71) between the subtypes with cryptogenic stroke (n=98) and with noncryptogenic stroke (n=33). Therefore, further research is needed on the relation among DVT, PFO, and cryptogenic stroke. Moreover, there is no direct evidence on how much increase in right atrial pressure can cause the foramen ovale to reopen.In addition, when it comes to the relation between PFO and a concomitant ischemic stroke in patients with COVID-19, Masi et al4 reported that 10% (6 of 60) of critically ill patients with COVID-19 had PFO that was diagnosed by contrast-enhanced transthoracic echocardiogram. However, the incidence of PFO may be higher in the scenario of diagnosing PFO by contrast transesophageal echocardiography. We have not found any direct data about the incidence of PFO in the patients with COVID-19 and ischemic stroke so far. In the study of 3556 patients hospitalized with COVID-19 infection by Yaghi et al,5 patients with COVID-19 had a higher proportion of cryptogenic stroke subtype (65.6% versus 30.4%) but a similar proportion of cardioembolic stroke (21.9% versus 21.7%) compared with contemporary controls, without depiction of the incidence of PFO. Furthermore, intrapulmonary shunt is common in patients with COVID-19 pneumonia and was speculated by some researchers to be another mechanism to facilitate ischemic cerebrovascular events. Further studies on a more representative population sample are needed to investigate the prevalence of right-to-left shunt and to assess the association between right-to-left shunt and cryptogenic stroke.We totally agree with Drs Albiero and Seresini's comment that the prevalence of PFO and paradoxical embolism in patients with severe COVID-19 and DVT should be evaluated in future studies. Because of the inconsistency in the literature, the topic merits more attention. We appreciate this chance for an exchange of ideas. We welcome and are available for follow-up and further discussions.Disclosures None.Footnotes*Drs L. Zhang, Sun, Y. Zhang, Wu, Y. Li, and M. Xie contributed equally.https://www.ahajournals.org/journal/circReferences1. Zhang L, Feng X, Zhang D, Jiang C, Mei H, Wang J, Zhang C, Li H, Xia X, Kong S, et al. Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome.Circulation. 2020; 142:114–128. doi: 10.1161/CIRCULATIONAHA.120.046702LinkGoogle Scholar2. Cramer SC, Rordorf G, Maki JH, Kramer LA, Grotta JC, Burgin WS, Hinchey JA, Benesch C, Furie KL, Lutsep HL, et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study.Stroke. 2004; 35:46–50. doi: 10.1161/01.STR.0000106137.42649.ABLinkGoogle Scholar3. Liberman AL, Daruwalla VJ, Collins JD, Maas MB, Botelho MP, Ayache JB, Carr J, Ruff I, Bernstein RA, Alberts MJ, et al. Diagnostic yield of pelvic magnetic resonance venography in patients with cryptogenic stroke and patent foramen ovale.Stroke. 2014; 45:2324–2329. doi: 10.1161/STROKEAHA.114.005539LinkGoogle Scholar4. Masi P, Bagate F, d'Humières T, Al-Assaad L, Abou Chakra L, Derumeaux G, Mekontso Dessap A. Is hypoxemia explained by intracardiac or intrapulmonary shunt in COVID-19-related acute respiratory distress syndrome?Ann Intensive Care. 2020; 10:108. doi: 10.1186/s13613-020-00726-zCrossrefMedlineGoogle Scholar5. Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, Henninger N, Trivedi T, Lillemoe K, Alam S, et al. SARS-CoV-2 and stroke in a New York healthcare system.Stroke. 2020; 51:2002–2011. doi: 10.1161/STROKEAHA.120.030335LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Mahmood M (2022) COVID-19 and Blood Clots: Is it only The Virus to be Blamed? What are new Updates? A Systematic Review, Journal of Cardiology and Cardiovascular Research, 10.37191/Mapsci-JCCR-3(2)-055 Jaligidad K and P C (2022) STUDY OF HEMATOLOGICAL MANIFESTATIONS IN COVID-19 INFECTED PATIENTS AND THEIR OUTCOME-OBSERVATIONAL RETROSPECTIVE LONGITUDANAL STUDY, GLOBAL JOURNAL FOR RESEARCH ANALYSIS, 10.36106/gjra/7906525, (47-49), Online publication date: 15-Apr-2022. Xiong X, Chi J and Gao Q (2021) Prevalence and risk factors of thrombotic events on patients with COVID-19: a systematic review and meta‐analysis, Thrombosis Journal, 10.1186/s12959-021-00284-9, 19:1, Online publication date: 1-Dec-2021. Demir K, Simard C, Lipes J and Yang S (2021) Life and Limb: a Case of COVID-19-Associated Multisystem Thrombosis and Review of the Literature, Journal of General Internal Medicine, 10.1007/s11606-020-06496-5, 36:3, (802-806), Online publication date: 1-Mar-2021. Ruiz Camacho D, Acuña Aguas D, Ojeda Maldonado D and Herrera Lema C (2021) Flegmasia cerúlea dolens and venous gangrena associated with infection by SARS-CoV-2: case report and literature review, Angiología, 10.20960/angiologia.00222, . Mondal S, Quintili A, Karamchandani K and Bose S (2020) Thromboembolic disease in COVID-19 patients: A brief narrative review, Journal of Intensive Care, 10.1186/s40560-020-00483-y, 8:1, Online publication date: 1-Dec-2020. February 2, 2021Vol 143, Issue 5 Advertisement Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.120.051629PMID: 33523724 Originally publishedFebruary 1, 2021 PDF download Advertisement SubjectsBlood PressureEthics and PolicyThrombosis