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Aortic Pathology During COVID - 19 Pandemics. Clinical Reports in Literature and Open Questions on the two Co-Occurring Conditions

Published:April 02, 2021DOI:https://doi.org/10.1016/j.avsg.2021.02.037

      Abstract

      Background

      Cardiovascular involvement in SARS-CoV-2 infection has emerged as one of viral major clinical features during actual pandemic; limb arterial ischemic events, venous thrombosis, acute myocardial infection and stroke have occurred in patients.
      Acute aortic conditions have also been described, followed by interesting observations on cases, hypothesis, raised since the emergence of the pandemics.

      Methods

      a review of cases in literature of aortic pathology in patients with clinically suspected/microbiologically confirmed COVID-19 infection has been carried out to analyze anagraphic data, clinical presentation, treatment options and outcome.

      Results

      Seventeen cases have been included. Mean age of patients was 58.6 ± 15.2 years, with a male to female ratio of 12:15 (70.5% vs. 29.5%). Comorbidities were reported in 11 cases (64.7%), but in 5 cases (29.4%) no previous pathology was signaled in history. Hypertension was the most frequently reported comorbidity, in 8 cases, (47%), followed by renal pathology (17.6%), coronary artery disease (17.6%), previous aortic surgery (11.7%) and arrhythmia (11.7%); but also cerebrovascular disease, diabetes, autoimmune conditions, previous neoplasia and arrhythmia were reported once each. Fever and thoracic pain were the most frequently reported findings at presentation (8 cases, 47% each), followed by respiratory symptoms (6, 35.2%), low lymphocyte count (17.6%), features related to aneurysm rupture, ischemic stroke, abdominal pain and acute renal insufficiency. Reported aortic pathology included: type A aortic dissection (11 cases; 64.7%); new pathology of previous aortic graft (2 cases, 11.7%); 2 aortitis, 1 associated with type A aortic dissection; 1 thoraco-abdominal aortic aneurysm, 1 ruptured aortic aneurysm and 1 aortic embolizing thrombosis. Open surgery was carried out in 10 cases (58.8%), endovascular treatment in 3 (17.6%). Three patients (17.6%) died before surgery. Exitus was reported in 4 cases, with a total mortality of 23.5%.

      Conclusions

      Acute aortic events have occurred during pandemic in patients with clinically suspected/microbiologically confirmed COVID-19 infection. Confounding clinical features at presentation, the importance of anamnestic details (as previous vascular graft implant), the observed surgical and postoperatory challenges may suggest the need to consider the implications of the possible link between acute aortic events and SARS-CoV-2 infection, in order to promptly correctly diagnose the patient and respond to specific needs.

      INTRODUCTION

      Many different clinical cardiovascular manifestations in COVID-19 patients have been described since the start of the pandemics, including acute myocardial infarction, acute heart failure,
      • Huet F
      • Prieur C
      • Schurtz G
      • et al.
      One train may hide another: acute cardiovascular diseases could be neglected because of the COVID-19 pandemic.
      ischemic cerebrovascular disease,
      • TunÇ A
      • ÜnlÜbaŞ Y
      • Alemdar M
      • et al.
      Coexistence of COVID-19 and acute ischemic stroke report of four cases.
      acute upper
      • Kaur P
      • Posimreddy S
      • Singh B
      • et al.
      COVID-19 presenting as acute limb ischaemia.
      and lower limb ischemia, associated with acquired hypercoagulability and poorer surgical outcome.
      • Bellosta R
      • Luzzani L
      • Natalini G
      • Pegorer MA
      • Attisani L
      • Cossu LG
      • Ferrandina C
      • Fossati A
      • Conti E
      • Bush RL
      • Piffaretti G
      Acute limb ischemia in patients with COVID-19 pneumonia.
      Angiotensin converting enzyme 2 (ACE-2) has been observed to have a role as a host receptor for SARS-CoV-2, and a prominent overall role in physiopathology of the infection. Present in lungs, gut, kidneys, central nervous system, adipose tissue, ACE-2 is known to be widely expressed in cardiovascular system (cardiomyocytes, cardiac fibroblasts, epicardial adipose tissue, and coronary vascular endothelium).
      • Gheblawi M
      • Wang K
      • Viveiros A
      • et al.
      Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2.
      From a physiopathology point of view, endothelium damage that mimics vasculitis has been observed in patients and pathological autoimmune responses involved in the antivirus immunity are worth to be emphasized.
      • Zhang W
      • Zhao Y
      • Zhang F
      • et al.
      The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China.
      Severe endothelial injury has been described in COVID-19 patients, associated with intracellular SARS-CoV-2 virus; direct viral effects as well as perivascular inflammation may contribute to it. Additionally, a widespread vascular thrombosis with microangiopathy, occlusion of alveolar capillaries and a significant new vessel growth through a mechanism of intussusceptive angiogenesis have been described in histopathology assessment.
      • Ackermann M
      • Verleden SE
      • Kuehnel M
      • Haverich A
      • Welte T
      • Laenger F
      • Vanstapel A
      • Werlein C
      • Stark H
      • Tzankov A
      • Li WW
      • Li VW
      • Mentzer SJ
      • Jonigk D
      Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.
      According to the above reported findings of increased inflammatory burden in patients with a severe clinical presentation, the first vascular sign in early CT scan imaging has been referred to as “vascular thickening,” “vascular enlargement,” or “vascular congestion.”
      • Qanadli SD
      • Beigelman-Aubry C
      • Rotzinger DC.
      Vascular changes detected with thoracic CT in coronavirus disease (COVID-19) might be significant determinants for accurate diagnosis and optimal patient management.
      Many infectious diseases are known to potentially induce lesions involving the aorta, leading to aneurysms (eventually causing its rupture) or dissections.
      • Silvestri V
      • Isernia G.
      Suspected giant cell aortitis: from multiple aortic structural damage to fatal listeria sepsis, a case report.
      • Silvestri V
      • D'Ettorre G
      • Borrazzo C
      • et al.
      Many different patterns under a common flag: aortic pathology in HIV-A review of case reports in literature.
      • De Rango P
      • De Socio GV
      • Silvestri V
      • et al.
      An unusual case of epigastric and back pain: expanding descending thoracic aneurysm resulting from tertiary syphilis diagnosed with positron emission tomography.
      Even though it is early to drive conclusions about aortic pathology and SARS-CoV-2 infection, interesting observations on cases, hypothesis, questions raised since the emergence of the pandemics, are worth to be summarized, which could inspire future investigations.

      MATERIALS AND METHODS

      Aim of our report is to describe aortic pathology occurring in patients with reported positivity to SARS-CoV-2, through the analysis of case reports and case series published in literature since the start of the pandemic.
      Literature was reviewed using as key words for research COVID-19 OR SARS-CoV-2 AND aortic aneurysm OR aortic dissection OR aortic pathology. The following databases were searched for relevant studies: MEDLINE (PubMed) and EMBASE (Embase.com). A filter for language was applied and only papers written in English were included.
      Anagraphic data and details regarding comorbidities, clinical presentation (including fever, respiratory symptoms or pain or signs of ischemia), kind of aortic involvement (extension of lesion, presence of rupture), treatment (conservative, open surgery or endovascular) and patient's outcome were extrapolated from text and registered in an electronic record. Descriptive analysis was carried out. The low number of patients and heterogeneity of reports was not suitable for analytic comparison.

      RESULTS

      A total of 13 papers and 17 cases were finally included (Table 1). Mean age of patients was 58.6 ± 15.2 years; the majority were male (12 males, 5 females, respectively 70.5% and 29.5 % of the total number of patients).
      Table 1Summary of case reports of aortic pathology in patients with clinically suspected or microbiologically confirmed covid-19 infection
      AuthorAgeSexComorbiditiesClinical presentationAortic involvementSurgical managementOutcomeCOVID +
      Fukuhara
      • Fukuhara S
      • Rosati CM
      • El-Dalati S.
      Acute type A aortic dissection during COVID-19 outbreak.
      52MNoneSevere chest + abdominal pain; Low grade fever 37.6 C; No cough or dyspneaType A Aortic dissectionAscending + hemiarch aortic repairEXITUS 11th postop progressive respiratory failure + acute renal failure-> multi-organ failureTested and positive on sixth day p.o, but not tested on admission
      Giacomelli
      • Giacomelli E
      • Dorigo W
      • Fargion A
      • et al.
      Acute thrombosis of an aortic prosthetic graft in a patient with severe COVID-19-related Pneumonia.
      67MChronic hypertension 2014: aorto-bi-iliac Dacron open repair for 60 mm abdominal aortic aneurysm patent on follow up (2019)Eighth day hospitalization for COVID-19 ARDS: pallor + bilateral lower limb hypothermia mottled skin from umbilical line absence of femoral and peripheral pulsesAbdominal aortic graft complete thrombosisExitus before surgeryEXITUS cardiac arrest before surgery planningTested positive on admission
      He
      • He H
      • Zhao S
      • Han L
      • et al.
      Anesthetic management of patients undergoing aortic dissection repair with suspected severe acute respiratory syndrome COVID-19 infection.
      51MHypertensionFever 37.6°C; RX pulmonary inflammatory changes; No respiratory symptoms; Low lymphocyte countType A Aortic dissectionSurgical aortic substitutionALIVE Successful surgery no post operatory follow upClinically suspected on admission
      51MHypertensionFever 37.6°C; RX pulmonary inflammatory changes; No respiratory symptoms; Low lymphocyte countType A Aortic dissectionSurgical aortic substitutionALIVE Successful surgery no post operatory follow upClinically suspected on admission
      62MNoneRX pulmonary inflammatory changes; No respiratory symptoms; Low lymphocyte countType A Aortic dissectionSurgical aortic substitutionALIVE Successful surgery no post operatory follow upClinically suspected on admission
      59FHypertensionFever 38.5°C RX pulmonary inflammatory changes No respiratory symptoms low lymphocyte countType A Aortic dissectionSurgical aortic substitutionALIVE Successful surgery no post operatory follow upClinically suspected on admission
      Martens
      • Martens T
      • Vande Weygaerde Y
      • Vermassen J
      • et al.
      Acute type a aortic dissection complicated by COVID-19 infection.
      64MAcute onset chest pain + Right leg ischemiaType A Aortic dissectionSurgical aortic substitutionALIVE But on 6th day post-op low-grade fever, dyspnea+ dry cough desaturation+ bilateral pleural fluid + ground glass opacification lesions + alveolar infiltration + Hemophilus influenzae -> medical treatment. Discharged 14 day p.o.Tested as protocol on 1 st postop
      Resch
      • Resch T
      • Vogt K
      • Eldrup N
      Atypical COVID-19 presentation in a patient undergoing staged thoracoabdominal aortic aneurysm repair.
      65MHypertension; Myocardial infraction + stenting Stroke without residual deficit Renal a. stenting (nephrogenic hypertension); Stable Crohn's disease; Hypothyroidism; gout; Chronic lower back and hip pain at 500 mt; palpable pulses, ankle brachial index 0.86Programmed 2 stage aortic repair for abdominal aortic aneurysmType III Crawford thoracic-abdominal aortic aneurysm (6.3 × 7.3 cm)Stage 1 percutaneous thoracic endovascular repair (TEVAR) -thoracic stent-graft left subclavian a. -> 4 cm proximal to celiac origin. Waiting for planned 2nd stage exclusion of the aneurysm with a fenestrated stent-graftALIVE 2nd day after discharge claudicatio + legs asthenia 25meters. Foot pulses and ABI's were unchanged; no signs of lower limb weakness or sensory loss. No fever on admission->38 AT DAY 2. Diarrhea. Negative for spinal cord or thrombus embolism . well-positioned TEVAR graft, patent visceral and iliac arteries. On day 2 fever 38,1°C. COVID positive needing oxygen supplementation and respiratory therapy. Discharged to home after 9 days in good clinical condition.Tested on day 2 of second hospitali-zation (7 days after symptoms, 10 days after first discharge)
      Rinaldi
      • Rinaldi LF
      • Marazzi G
      • Marone EM.
      Endovascular treatment of a ruptured pararenal abdominal aortic aneurysm in a patient with coronavirus disease-2019: suggestions and case report.
      80MEVAR abdominal aortic aneurysm (2013); Rectal cancer- Hartman + colostomy; Chronic kidney failure+ left kidney shrinkageFree rupture of the para-renal abdominal aorta above previous endo-graft (renal a. level); Massive intraperitoneal hematomaRuptured pararenal abdominal aorta above previous endograftMonolateral renal a. stenting + aortic cuff below origin of superior mesenteric a. Postoperative day 2, type IA endoleak - caudal aortic cuff migration ->new endograft aortic cuff below coeliac trunkALIVE constant recovery during the post-operative course of COVID pneumoniaPositive on admission
      Shihi
      • Azouz E.
      • Yang S.
      • Monnier-Cholley L.
      • et al.
      Systemic arterial thrombosis and acute mesenteric ischemia in a patient with COVID-19.
      54MHypertension; Coronary a. disease; Coronary stenting; Wolff-Parkinson-White syndrome; left nephrectomyAbdominal pain for 1 day + Fever, cough, dyspnea 5 daysRuptured Abdominal aortic aneurysm 5.8 cmBifurcated EVARALIVE at 2 weeks follow up stable endograft sac size (5.8 cm) + small type II endoleak. Patent limbs with no mural thrombus. Resolving retroperitoneal hematoma and ground glass opacities in the lungs.Tested negative on admission, but positive during hospital-ization (3 days)
      Akgul
      • Kumar K
      • Vogt JC
      • Divanji PH
      • Cigarroa JE
      Spontaneous coronary artery dissection of the left anterior descending artery in a patient with COVID-19 infection.
      68FDiabetes HypertensionPulseless right femoral a. Pulmonary hypertension. Lung bilateral ground-glass opacitiesType A aortic dissectionAortic transection above commissures and distally before the innominate a. +28mm Dacron graft + distal anastomosis sutured with pledgets in order to affix dissection flap to aortic wallALIVE discharged on 14th postoperative day with antiaggregantOn admission(test not specified)
      Azouz
      • Shih M
      • Swearingen B
      • Rhee R.
      Ruptured abdominal aortic aneurysm treated with endovascular repair in a patient with active COVID-19 infection during the pandemic.
      56FNot reportedAcute ischemic stroke (right middle cerebral a. occlusion); On 2nd day abdominal pain + vomitingfree-floating aortic arch thrombous + superior mesenteric a. occlusionEndovascular thrombectomy + open resection small bowelNOT SPECIFIEDPositive on admission
      Mori
      • Mori M
      • Geirsson A
      • Vallabhajosyula P
      • et al.
      Surgical management of thoracic aortic emergency with pre- and postoperative COVID-19 disease.
      54MFamily history for aortic aneurysm and dissectionSudden onset chest pain, no respiratory symptoms52 mm dilated Aortic root and arch intramural hematoma + ground‐glass opacities in the lungValve‐sparing root+ hemiarch replacement (dacron) + coronary bypassALIVE discharged on 6 po dayPositive on admission (PCR)
      82FAtrial fibrillation, sick sinus syndrome, diastolic heart failure, pacemaker, COPDsudden onset chest pain and facial weakness, anuria and acute kidney injury, no COVID symptoms on admissionType A aortic dissectionAscending aorta and hemiarch replacement + coronary sinus reconstructionALIVE (renal failure requiring dialysis, COVID-19 pos 66 p.o.day)Positive 66 days p.o (respiratory symptoms)
      Mamishi
      • Mamishi S
      • Navaeian A
      • Shabanian R.
      Acute aortic dissection in a patient with Williams syndrome infected by COVID-19.
      14MWilliams Syndrome supravalvular aortic stenosis, coronary involvementFever, shortness of breath and coughType A aortic dissectionExitus before surgeryEXITUS (acute dissection after 3 weeks steroid therapy for COVID treatment)Positive on admission
      Tabaghi
      • Tabaghi S
      • Akbarzadeh MA.
      Acute type A aortic dissection in a patient with COVID-19.
      47FNoneFever, dry cough and bloody diarrheaType A aortic dissectionExitus before surgeryEXITUS cardiac arrest before surgeryPositive on admission
      Shergill
      • Shergill S
      • Davies J
      • Bloomfield J.
      Florid aortitis following SARS-CoV-2 infection.
      71MNoneFever, dry cough, diarrhea 2 weeks. Acute Chest pain (left side)Circumferential aortitisPrednisolone 40mgALIVE (discharged after 2 weeks)Positive on admission
      Details on author, age and sex of patients, comorbidities, aortic pathology, surgical management, outcome and timing of positive testin relation to hospitalization have been reported in column.
      Among anamnestic comorbidities, hypertension was the most frequently reported (7 cases, 58.3%), followed by renal pathology (3 cases, 25%), coronary artery disease (2 cases, 16.7%), and previous aortic surgery (2 cases, 16.7%). Furthermore, previous cerebrovascular disease, diabetes, autoimmune conditions, specifically Crohn disease, COPD, previous neoplastic condition and arrhythmia were also reported once each. In 4 patients (33.3%) no comorbidity was reported in previous clinical history.
      COVID diagnosis was suspected after clinical assessment in 4 cases (23.5%), carried out by laboratory investigations at hospitalization in 9 cases (52.5%) and during the hospital stay in the remaining 4 patients.
      Fever was the most frequent symptom (8 cases, 47%), followed by thoracic pain (8 cases, 47%), respiratory symptoms (6 cases 35.2%) and low lymphocyte count (3 cases, 17.6%%). Thoracic pain was the most frequent vascular related symptom; in other cases, clinical presentation was characterized by ruptured aneurysm (2 cases; 11.7%), ischemic stroke and abdominal pain (2 cases each). Acute renal insufficiency was present in 1 case.
      Aorta was found to be involved by the following acute aortic conditions: Type A aortic dissection (11 cases; 64.7%); aortitis in 2 cases, 1 associated to aortic dissection; new pathology on previous aortic graft in 2 cases (specifically 1 bilateral branch thrombosis; 1 embolizing aortic thrombosis; 1 recurrent aneurysm rupture on the proximal end point of an infrarenal abdominal aortic graft); 1 ruptured abdominal aortic aneurysm; 1 thoracoabdominal aortic aneurysm. Rupture, as reported above, occurred in 2 cases, the abdominal aortic aneurysm and the recurrent aneurysm on previous abdominal aortic graft.
      As for treatment, exitus before surgery has been reported in 3 cases, 17.6% (in 1 case because of acute thrombosis on previously implanted endovascular aortic bifurcated graft; in 1 because of acute type A dissection on enlarged ascending aorta; the third because of acute type A aortic dissection on aortitis after prolonged COVID steroidal treatment in a patient with William syndrome). Open surgery was the most frequently reported surgical option (10 cases, 58.8%) consisting in 9 open surgical procedures for type A aortic dissection and 1 embolectomy of a free floating aortic arch thrombus, associated with bowl resection for mesenteric ischemia. Endovascular treatment was carried out in 3 cases (17.6%), including 1 EVAR procedure planned in 2 steps for an unbroken thoraco-abdominal aortic aneurysm, 1 EVAR for ruptured abdominal aortic aneurysm and 1 endovascular embolectomy for aortic acute embolic thrombosis.
      Exitus was reported in 4 cases, with a total mortality of 23.5%. Specifically, death was due to multiorgan a failure occurred on the 11th day postaortic arch repair for type A dissection; to cardiac arrest while waiting for surgery, in a patient diagnosed with previous abdominal aortic endo-graft thrombosis; to acute aortic type A dissection in 2 patients hospitalized for COVID, during treatment for the infectious disease condition. Results have been summarized in Table 2.
      Table 2Summary of data from case reports
      n (N tot = 17)%
      Anagraphic data
      Age58.6 ± 15.2
      M/F12/570.5%/29.5%
      Days of COVID symptoms/diagnosis prior to vascular event6.1 ± 15.4
      Diagnosed through clinical presentation423.5%
      COVID+ on admission/first day952.5%
      COVID+ during hospitalization423.5%
      ComorbiditiesN tot available 16
      Comorbidities present1164.7%
      None529.4%
      Hypertension847.0%
      Renal pathology317.6%
      Previous coronary artery disease317.6%
      Previous aortic surgery211.7%
      Arrhythmia211.7%
      Previous cerebrovascular disease15.8%
      Diabetes15.8%
      Autoimmune disease (Crohn disease)15.8%
      Previous neoplastic condition15.8%
      BPCO15.8%
      Heart failure15.8%
      Clinical presentation
      Fever847.0%
      Thoracic pain847.0%
      Respiratory symptoms635.2%
      Low lymphocyte count317.6%
      Ruptured aneurysm211.7%
      Ischemic stroke211.7%
      Abdominal pain211.7%
      Acute renal insufficiency15.8%
      Aortic pathology
      Type A aortic dissection1164.7%
      New pathology of previous aortic graft (1 bilateral branch thrombosis; 1 aneurysm rupture proximal end point)211.7%
      Aortitis (associated to dissection in 1 case)211.7%
      thoracoabdominal aortic aneurysm15.8%
      Abdominal aortic aneurysm with rupture15.8%
      Embolizing aortic thrombosis15.8%
      Management
      Open surgery1058.8%
      Endovascular317.6%
      Exitus before treatment317.6%
      Conservative15.8%
      Outcome
      Total mortality423.5%
      • multi-organ failure 11th day postaortic arch repair for type A dissection15.8%
      • waiting for surgery previous endo-graft thrombosis15.8%
      • aortitis and acute aortic dissection after steroidal therapy for COVID15.8%
      • Acute aortic dissection on aortic root enlargement after 1 week hospitalization for COVID symptoms15.8%
      Anagraphic data, details on coomorbidities, aortic pathology clinical presentation, management and outcome have been analyzed.

      DISCUSSION

      Many matters of concern have been raised when analyzing the occurrence and managing of acute aortic syndromes during COVID-19 pandemic, from organizational level of vascular emergencies, challenged by lockdown provisions, to the hypothesis of a likely direct link of the infectious agent as a cause of major acute aortic events.

      Challenges in Aortic Patients Access to Emergency Assessment and Diagnostic Issue

      COVID-19 pandemic has initially forced health care systems to delay elective operations, including abdominal aortic aneurysm (AAA) repair, because of shortage of resources and high patients’ comorbidities related to acute vascular disease in this specific infectious setting.
      A report by El-Hamamsy on the experience on acute aortic dissections occurring since the pandemic outbreak in New York has observed a 76.5% drop in the monthly surgical case volume of acute type A aortic dissection and an 8- to 10-fold increase of at-home deaths compared to the same time period in 2019, causing delayed or missed diagnoses.
      • El-Hamamsy I
      • Brinster DR
      • DeRose JJ
      • et al.
      The COVID-19 pandemic and acute aortic dissections in New York: a matter of public health [published online ahead of print, 2020 May 14].
      Similar findings of a dramatic drop in the number of cardiovascular admissions after the establishment of containment have been reported from a French group.
      • Huet F
      • Prieur C
      • Schurtz G
      • et al.
      One train may hide another: acute cardiovascular diseases could be neglected because of the COVID-19 pandemic.
      Observations from the Cleveland Clinic comparing baseline to pandemic data on cardiovascular daily transfers for aortic emergencies presented a relative reduction of 21%, even though not statistically significant.
      • Khot UN
      • Reimer AP
      • Brown A
      • et al.
      Impact of COVID-19 pandemic on critical care transfers for ST-segment-elevation myocardial infarction, stroke, and aortic emergencies.
      However, new data have forced to reconsider delay in cardiovascular disease management during pandemics at a level of benefit-risk assessment of procrastinating treatment.
      Mori et al., who reported 2 cases of surgical thoracic aortic emergencies, 1 undergoing an operation with known COVID‐19 positive status and another who contracted COVID‐19 in the postoperative period, suggested the possibility of favorable recovery from the combination of the highly morbid vascular pathology undergoing high‐risk operations in the setting of highly virulent respiratory illness.
      • Mori M
      • Geirsson A
      • Vallabhajosyula P
      • et al.
      Surgical management of thoracic aortic emergency with pre- and postoperative COVID-19 disease.
      Recent probabilistic sensitivity analyses suggest that the decision to delay operative repair of AAA should consider both patient age and local COVID-19 prevalence in addition to aneurysm size. Patients with large aneurysms (>7 cm) faced a 5.4% to 7.7% absolute increase in the probability of mortality with a delay of repair of 3 months, but demonstrated a higher probability of survival when treated with immediate endovascular repair or open surgery. Immediate endovascular repair had a higher probability of survival for smaller aneurysms (5.5–6.9 cm) except in settings with a high probability of COVID-19 infection (10–30%) and advanced age (70–85 years).
      • McGuinness B
      • Troncone M
      • James LP
      • Bisch SP
      • Iyer V
      Reassessing the operative threshold for abdominal aortic aneurysm repair in the context of COVID-19.

      Patients’ Clinical Presentation: Special Considerations

      Analyzing the reported clinical/microbiological positivity for SARS-CoV-2 infection in relation to timing of hospitalization for aortic event, we can observe that the majority of patients were either positive or highly clinically suspected on admission in 52.5% of the cases. Along with symptoms due to the aortic condition, clinical features that may be referred to the associated COVID-19 infection were also present on presentation, including fever, respiratory symptoms, low white cell blood count, in some cases associated to positivity for radiological pulmonary imaging confirming the co-occurrence of vascular aortic involvement and SARS-CoV-2 infection (Table 1).
      Because vascular acute complications have occurred in known COVID-19 patient during hospitalization due to the infectious condition, there is a need to assess any concomitant clinical condition (including vascular acute syndromes) that may occur in COVID-19 patients and not merely viewing them as purely infectious patients.
      • Tabaghi S
      • Akbarzadeh MA.
      Acute type A aortic dissection in a patient with COVID-19.
      At this purpose, vasculitic sequelae of SARS-CoV-2 have been well documented in the pediatric population,
      • Silvestri V
      Clinical and surgical features of non-coronary arterial aneurysms in Kawasaki Disease: a review of the literature.
      and have involved also the aorta, as in the 14 years old patient with William syndrome who presented acute type A aortic dissection complicating a prolonged steroidal therapy for COVID-19 infection,
      • Mamishi S
      • Navaeian A
      • Shabanian R.
      Acute aortic dissection in a patient with Williams syndrome infected by COVID-19.
      which was included in our review. Adult aortitis has also been described.
      • Shergill S
      • Davies J
      • Bloomfield J.
      Florid aortitis following SARS-CoV-2 infection.
      Features that include both acute vascular syndromes due to wall damage, such as aneurysm or dissections, or major vessels thrombosis, which may present in variable clinical scenarios, such as acute abdomen, intestinal or peripheral ischemia should raise a clinical suspect of COVID-19 infection also in patients otherwise free of classical presenting symptoms, given the specific anatomopathological features attributed to virion damage which specifically targets the arterial wall. These features have been analyzed in detail in a recent paper by Manenti et.al, findings that we summarize in a dedicated section of this paper.
      • Manenti A
      • Farinetti A
      • Manco G
      • et al.
      Vasculitis and aortitis: COVID-19 challenging complications.
      If it's true that vascular conditions need to be considered as a complicating feature in COVID-19 patients, we should also keep in mind that vascular pathology may mimic in some cases COVID-19 symptoms in COVID-19 negative patients, thus challenging differential diagnosis. Differential diagnosis of acute aortic conditions in pregnancy, for example, is usually challenging due to confounding overlapping features of labor and vascular conditions,
      • Silvestri V
      • Mazzesi G
      • Mele R.
      Postpartum aortic dissection. A case report and review of literature.
      but has been reported to be additionally challenged by similarity of COVID-19 infection features and acute aortic symptoms, in a patient actually negative to the disease, finally diagnosed with pregnancy related aortic dissection.
      • Bogaert K
      • Christensen K
      • Cagliostro M
      • et al.
      Contained aortic rupture in a term pregnant patient during the COVID-19 pandemic.

      Physiopathology Hypothesis and Observations: Direct Arterial Damage and Thromboembolic Conditions

      Because of its supposed direct viral effect on endothelium (inducing endothelial dysfunction) and because of the effect of viral induced late inflammatory burden, COVID-19 has been suggested to be involved in both venous and arterial thromboembolic diseases, as occurred in the thoracic aortic thromboembolic conditions described in the case reported by Azouz et al. and included in our review,
      • Azouz E
      • Yang S
      • Monnier-Cholley L
      • et al.
      Systemic arterial thrombosis and acute mesenteric ischemia in a patient with COVID-19.
      or in native arterial wall damage, as in the case of otherwise rare lesions such as coronary artery dissections.
      • Fernandez Gasso L
      • Maneiro Melon NM
      • Sarnago Cebada F
      • Solis J
      • Garcia Tejada J
      Multivessel spontaneous coronary artery dissection presenting in a patient with severe acute SARS-CoV-2 respiratory infection.
      Two cases of coronary dissection have been reported in literature, 1 in a 39 years old male patient without cardiovascular risk factors, which was additionally complicated by a coronary/ pulmonary fistula, successfully treated conservatively
      • Fernandez Gasso L
      • Maneiro Melon NM
      • Sarnago Cebada F
      • Solis J
      • Garcia Tejada J
      Multivessel spontaneous coronary artery dissection presenting in a patient with severe acute SARS-CoV-2 respiratory infection.
      and the other in a 48 years old female patient with dyslipidemia, also conservatively treated because of absence of suitable coronary outflow.
      • Kumar K
      • Vogt JC
      • Divanji PH
      • Cigarroa JE
      Spontaneous coronary artery dissection of the left anterior descending artery in a patient with COVID-19 infection.
      Even though coronary complications are not the direct object of this paper, we think it is important to consider these lesions while speculating on the likeliness of a link between aortic pathology and COVID-19. Given that the association between otherwise rare coronary artery dissection events and COVID-19 induced inflammatory endothelial damage seem to be straightforward, we could speculate a possible link between COVID-19 and other vessel wall pathology, including aortic dissection.
      Thickening of the wall (as seen in inflammatory aortopathies) has been observed during surgical treatment of aortic type A dissection in a COVID-19 positive patient reported by Akgul et al., which appeared to be “pronounced” when compared to the authors monocentric experience of previous aortic dissections. In the same report, the possibility of “similarity” of virulence and therapy between HIV and SARS CoV- 2 and their infections has been interestingly suggested by the authors.
      • Akgul A
      • Turkyilmaz S
      • Turkyilmaz G
      • Toz H
      Acute aortic dissection surgery in patient with COVID-19.
      This hypothesis becomes more interesting as the authors add considerations on the complications occurring at distal anastomotic site of the aortic repair performed through aortic synthetic graft implant in their patient: as occurs in aortic conditions related to other infectious or autoimmune disease,
      • Silvestri V
      • Isernia G.
      Suspected giant cell aortitis: from multiple aortic structural damage to fatal listeria sepsis, a case report.
      ,
      • Silvestri V
      • Simonte G.
      Aortic pathology in systemic lupus erythematosus: a case report and review of literature.
      the authors have observed the occurrence of bleeding in the suture line (usually due to aortic wall loss of elastic structure and strength). These complications may be frequent in inflammatory aortopathy in its acute phase, which may later evolve, in a chronic phase, to formation of aneurysms. It has been suggested that SARS-CoV-2 viremia may have had a role in the observed aortic wall inflammation and in the surgical complications induced by it, as preoperative measurement of C-reactive protein and erythrocyte sedimentation rate were high, requiring immunosuppressive therapy after surgery.
      • Kumar K
      • Vogt JC
      • Divanji PH
      • Cigarroa JE
      Spontaneous coronary artery dissection of the left anterior descending artery in a patient with COVID-19 infection.
      Interesting consideration on physiopathology mechanisms underlining aortitis in COVID-19 patients has been summarized by Manenti et. Al, that have described 2 main processes leading to arterial damage. The first is an acute endothelitis, due to endothelial infiltration by virions and, by neutrophils and mononuclear elements involved in an inflammatory/prothrombotic response. Acute endothelitis may be followed by peri/panarteritis and leukocytoclastic vasculitis with deposition of polyclonal antigen-antibody immune complexes (IgG, IgA IgM, C3 complement fraction proteins), featuring a type III hypersensitive acute vasculitis, which predisposes to thrombosis. According to this model, aortic endothelium, provided of angiotensin-converting enzyme-2 receptors, is directly attacked by virions, leading to an endotheliitis that could later by complicated by a hypersensitive vasculitis. This process can be favored by a pre-existing pathology, like atherosclerotic plaques or by facilitating hemodynamic conditions, such as a turbulent flow and a reduced parietal elasticity, common in elderly patients or after endovascular procedures.
      • Manenti A
      • Farinetti A
      • Manco G
      • et al.
      Vasculitis and aortitis: COVID-19 challenging complications.

      Challenges for Patients With Previous Vascular Graft Implant

      Not only the native arteries seem to be at risk. Specifically referring to patients with positive history for previous vascular surgery, it has been suggested that thrombotic risk related to Sars-CoV-2 infection might be much higher in a patient with a vascular prosthesis. As observed in the report by Giacomelli et al., while aortic graft thrombosis is an uncommon event (occurring in less than 1% of all aortic reconstructions) this complication may occur in COVID -19 patients also in the absence of structural abnormalities involving the graft or its inflow or outflow, or of proximal and distal anastomosis stenosis or severe occlusive disease of distal vessels, thus suggesting to consider these patients as candidates to an aggressive treatment with heparin at therapeutic dosage, given the high mortality linked to acute aortic thrombosis.
      • Giacomelli E
      • Dorigo W
      • Fargion A
      • et al.
      Acute thrombosis of an aortic prosthetic graft in a patient with severe COVID-19-related Pneumonia.
      Additionally, free rupture of the para-renal abdominal aorta, above a previous abdominal aortic endo-graft implanted for aneurysm in an 80 years old patient, was reported by Rinaldi et. Even though the timing of proximal aortic aneurysm formation can't be determined, recurrent complicated aortic pathology has previously been described in patients with inflammatory conditions, such as autoimmune disease, due to histological changes leading to weakening of aortic wall.
      • Silvestri V
      • Simonte G.
      Aortic pathology in systemic lupus erythematosus: a case report and review of literature.

      Considerations on Treatment

      When it comes to treatment option, it has been underlined that the postoperatory of aortic surgery may be challenged by severe pulmonary associated conditions even in healthy nonsmoker patients after uneventful surgery.
      • Fukuhara S
      • Rosati CM
      • El-Dalati S.
      Acute type A aortic dissection during COVID-19 outbreak.
      Furthermore, the shortage of available places in intensive care unit during pandemic may influence patient's management decisions, such as the preference of open or endovascular option for treatment, wherever they are both potentially feasible. Patients with ruptured abdominal aortic aneurysms are among those who may need the intensive care unit postoperatively. Open repair treatment increases both the intraoperative complexity of treatment and the need for postoperative intensive care. On the other hand, endovascular aneurysm repair (EVAR) can be performed under local anesthesia and a successful outcome is usually accompanied by short recovery and quick turnover.
      • Verikokos C
      • Lazaris AM
      • Geroulakos G.
      Doing the right thing for the right reason when treating ruptured abdominal aortic aneurysms in the COVID-19 era.
      Thus, endovascular repair has been proposed as a preferable option, if anatomically suitable, as the pulmonary burden from cardiopulmonary bypass usage and associated induced inflammatory cascade can be avoided.
      • Fukuhara S
      • Rosati CM
      • El-Dalati S.
      Acute type A aortic dissection during COVID-19 outbreak.
      ,
      • Selway WG
      • Stenson KM
      • Holt PJ
      • et al.
      Willingness of patients to attend abdominal aortic aneurysm surveillance: the implications of COVID-19 on restarting the National Abdominal Aortic Aneurysm Screening Programme.

      Prevention Issues

      Last but not least, the literature has invited to consider the consequences of the fall in aneurysm surveillance and lower screening attendance (from 90% to 59% in United Kingdom) which has been denounced recently, because it could lead to an increase in incidence of aneurysm-related deaths and presentation of ruptured aortic aneurysms.
      • Selway WG
      • Stenson KM
      • Holt PJ
      • et al.
      Willingness of patients to attend abdominal aortic aneurysm surveillance: the implications of COVID-19 on restarting the National Abdominal Aortic Aneurysm Screening Programme.

      CONCLUSIONS

      Acute aortic events have occurred during the actual pandemic in patients with clinically suspected/microbiologically confirmed COVID-19 infection.
      Clinical features at presentation, anamnestic details (as previous vascular graft implant), the observed surgical and postoperatory challenges in these patients may suggest the need for further studies, analyzing the link between acute aortic events and the emerging infectious disease, in order to better define eventual physiopathology links between aortic diseases and SARS-CoV-2 infection and involvement of major vessel in the form of acute aortic events or vascular involvement sequelae.

      Author's contributions

      The authors have contributed equally to the review process, the writing of the manuscript and the approval of the definitive version for submission.

      REFERENCES

        • Huet F
        • Prieur C
        • Schurtz G
        • et al.
        One train may hide another: acute cardiovascular diseases could be neglected because of the COVID-19 pandemic.
        Arch Cardiovasc Dis. 2020; 113: 303-307
        • TunÇ A
        • ÜnlÜbaŞ Y
        • Alemdar M
        • et al.
        Coexistence of COVID-19 and acute ischemic stroke report of four cases.
        J Clin Neurosci. 2020; 77: 227-229
        • Kaur P
        • Posimreddy S
        • Singh B
        • et al.
        COVID-19 presenting as acute limb ischaemia.
        Eur J Case Rep Intern Med. 2020; 7 (Published 2020 May 19)001724
        • Bellosta R
        • Luzzani L
        • Natalini G
        • Pegorer MA
        • Attisani L
        • Cossu LG
        • Ferrandina C
        • Fossati A
        • Conti E
        • Bush RL
        • Piffaretti G
        Acute limb ischemia in patients with COVID-19 pneumonia.
        J Vasc Surg. 2020; 72: 1864-1872
        • Gheblawi M
        • Wang K
        • Viveiros A
        • et al.
        Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2.
        Circ Res. 2020; 126: 1456-1474
        • Zhang W
        • Zhao Y
        • Zhang F
        • et al.
        The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China.
        Clin Immunol. 2020; 214108393
        • Ackermann M
        • Verleden SE
        • Kuehnel M
        • Haverich A
        • Welte T
        • Laenger F
        • Vanstapel A
        • Werlein C
        • Stark H
        • Tzankov A
        • Li WW
        • Li VW
        • Mentzer SJ
        • Jonigk D
        Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.
        N Engl J Med. 2020; 383: 120-128
        • Qanadli SD
        • Beigelman-Aubry C
        • Rotzinger DC.
        Vascular changes detected with thoracic CT in coronavirus disease (COVID-19) might be significant determinants for accurate diagnosis and optimal patient management.
        AJR Am J Roentgenol. 2020; 215: W15
        • Silvestri V
        • Isernia G.
        Suspected giant cell aortitis: from multiple aortic structural damage to fatal listeria sepsis, a case report.
        Ann Vasc Surg. 2017; 42 (307.e1-307.e6)
        • Silvestri V
        • D'Ettorre G
        • Borrazzo C
        • et al.
        Many different patterns under a common flag: aortic pathology in HIV-A review of case reports in literature.
        Ann Vasc Surg. 2019; 59: 268-284
        • De Rango P
        • De Socio GV
        • Silvestri V
        • et al.
        An unusual case of epigastric and back pain: expanding descending thoracic aneurysm resulting from tertiary syphilis diagnosed with positron emission tomography.
        Circ Cardiovasc Imaging. 2013; 6: 1120-1121
        • El-Hamamsy I
        • Brinster DR
        • DeRose JJ
        • et al.
        The COVID-19 pandemic and acute aortic dissections in New York: a matter of public health [published online ahead of print, 2020 May 14].
        J Am Coll Cardiol. 2020; 76: 227-229
        • Khot UN
        • Reimer AP
        • Brown A
        • et al.
        Impact of COVID-19 pandemic on critical care transfers for ST-segment-elevation myocardial infarction, stroke, and aortic emergencies.
        Circ Cardiovasc Qual Outcomes. 2020; 13e006938
        • Mori M
        • Geirsson A
        • Vallabhajosyula P
        • et al.
        Surgical management of thoracic aortic emergency with pre- and postoperative COVID-19 disease.
        J Card Surg. 2021; 35: 2832-2834
        • McGuinness B
        • Troncone M
        • James LP
        • Bisch SP
        • Iyer V
        Reassessing the operative threshold for abdominal aortic aneurysm repair in the context of COVID-19.
        J Vasc Surg. 2020; 73: 780-788
        • Tabaghi S
        • Akbarzadeh MA.
        Acute type A aortic dissection in a patient with COVID-19.
        Future cardiology. 2020; https://doi.org/10.2217/fca-2020-0103
        • Silvestri V
        Clinical and surgical features of non-coronary arterial aneurysms in Kawasaki Disease: a review of the literature.
        Prog Pediat Cardiol. 2020; : 101310https://doi.org/10.1016/j.ppedcard.2020.101310
        • Mamishi S
        • Navaeian A
        • Shabanian R.
        Acute aortic dissection in a patient with Williams syndrome infected by COVID-19.
        Cardiol Young. 2021; 31: 132-134
        • Shergill S
        • Davies J
        • Bloomfield J.
        Florid aortitis following SARS-CoV-2 infection.
        Eur Heart J. 2020; 41: 4286
        • Manenti A
        • Farinetti A
        • Manco G
        • et al.
        Vasculitis and aortitis: COVID-19 challenging complications.
        J Vasc Surg. 2021; 73: 347-348
        • Silvestri V
        • Mazzesi G
        • Mele R.
        Postpartum aortic dissection. A case report and review of literature.
        Int J Surg Case Rep. 2019; 56: 101-106
        • Bogaert K
        • Christensen K
        • Cagliostro M
        • et al.
        Contained aortic rupture in a term pregnant patient during the COVID-19 pandemic.
        BMJ Case Rep. 2020; 13e238370
        • Azouz E
        • Yang S
        • Monnier-Cholley L
        • et al.
        Systemic arterial thrombosis and acute mesenteric ischemia in a patient with COVID-19.
        Intensive Care Med. 2020; 46: 1464-1465
        • Fernandez Gasso L
        • Maneiro Melon NM
        • Sarnago Cebada F
        • Solis J
        • Garcia Tejada J
        Multivessel spontaneous coronary artery dissection presenting in a patient with severe acute SARS-CoV-2 respiratory infection.
        Eur Heart J. 2020; 41: 3100-3101
        • Kumar K
        • Vogt JC
        • Divanji PH
        • Cigarroa JE
        Spontaneous coronary artery dissection of the left anterior descending artery in a patient with COVID-19 infection.
        Catheter Cardiovasc Interv. 2021; 97: E249-E252
        • Akgul A
        • Turkyilmaz S
        • Turkyilmaz G
        • Toz H
        Acute aortic dissection surgery in patient with COVID-19.
        Ann Thorac Surg. 2021; 111: e1-e3
        • Silvestri V
        • Simonte G.
        Aortic pathology in systemic lupus erythematosus: a case report and review of literature.
        Ann Vasc Surg. 2017; 43 (312.e5-312.e12): 312
        • Giacomelli E
        • Dorigo W
        • Fargion A
        • et al.
        Acute thrombosis of an aortic prosthetic graft in a patient with severe COVID-19-related Pneumonia.
        Ann Vasc Surg. 2020; 66: 8-10
        • Fukuhara S
        • Rosati CM
        • El-Dalati S.
        Acute type A aortic dissection during COVID-19 outbreak.
        Ann Thorac Surg. 2020; 110: e405-e407
        • Verikokos C
        • Lazaris AM
        • Geroulakos G.
        Doing the right thing for the right reason when treating ruptured abdominal aortic aneurysms in the COVID-19 era.
        J Vasc Surg. 2020; 72: 373-374
        • Selway WG
        • Stenson KM
        • Holt PJ
        • et al.
        Willingness of patients to attend abdominal aortic aneurysm surveillance: the implications of COVID-19 on restarting the National Abdominal Aortic Aneurysm Screening Programme.
        Br J Surg. 2020; 107: e646-e647
        • He H
        • Zhao S
        • Han L
        • et al.
        Anesthetic management of patients undergoing aortic dissection repair with suspected severe acute respiratory syndrome COVID-19 infection.
        J Cardiothorac Vasc Anesth. 2020; 34: 1402-1414
        • Martens T
        • Vande Weygaerde Y
        • Vermassen J
        • et al.
        Acute type a aortic dissection complicated by COVID-19 infection.
        Ann Thorac Surg. 2020; 110: e421-e423
        • Resch T
        • Vogt K
        • Eldrup N
        Atypical COVID-19 presentation in a patient undergoing staged thoracoabdominal aortic aneurysm repair.
        J Vasc Surg Cases Innov Tech. 2020; 6: 337-339
        • Rinaldi LF
        • Marazzi G
        • Marone EM.
        Endovascular treatment of a ruptured pararenal abdominal aortic aneurysm in a patient with coronavirus disease-2019: suggestions and case report.
        Ann Vasc Surg. 2020; 66: 18-23
        • Azouz E.
        • Yang S.
        • Monnier-Cholley L.
        • et al.
        Systemic arterial thrombosis and acute mesenteric ischemia in a patient with COVID-19.
        Intensive Care Med. 2020; 46: 1464-1465
        • Shih M
        • Swearingen B
        • Rhee R.
        Ruptured abdominal aortic aneurysm treated with endovascular repair in a patient with active COVID-19 infection during the pandemic.
        Ann Vasc Surg. 2020; 66: 14-17