On December 31, 2019, a novel corona virus (SARS-CoV-2) disease (COVID- 19) was first reported in Wuhan City, Hubei Province, China and it has rapidly spread worldwide [1]. On January 19, 2020, the first case of COVID-19 was confirmed in Snohomish Country, Washington, USA [2] . As of May 27, 2020, approximately 5,500,000 cases and 350,000 deaths Acute type A aortic dissection is considered as one of the most lethal conditions, requiring urgent surgical intervention. In contrast, there is a universal concern regarding compromised surgical outcomes in the setting of substantially affected cardiac surgery care.
Furthermore, the optimal management of patients with dual diagnoses of type A aortic dissection and COVID-19 is unknown. This study was undertaken to review and share our experience with type A aortic dissection at major aortic centers located in significantly affected geographic regions by COVID-19 in the United States and China in order to ultimately help guide the management of type A aortic dissection during this world-wide outbreak, which is expected to persist for the foreseeable future. Supplemental Video 1 summarizing the present study is available.
This is a retrospective multicenter study conducted at University of Michigan, Tongji This study was approved by the institutional review boards (IRB) of the three institutions.
The approval included a waiver of informed consent, and investigators analyzed only deidentified data.
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The diagnosis of acute type A aortic dissection was established radiographically by computed tomography (CT) angiography in all patients. CT findings of the lungs were also simultaneously evaluated ( Figure 1A-D) . All patients were considered for surgical repair except for 5 (9.6%) medically managed patients with various clinical reasons. In selected patients with malperfusion syndrome of other vital organs, the most compromised organ system was treated by upfront endovascular reperfusion therapy followed by surgery at resolution of organ failure.
Details describing the endovascular reperfusion procedure have been previously published [6] .
Nasopharyngeal swab samples were immediately collected and sent for COVID-19 detection except for 5 (9.6%) non-suspected patients at the very start of the pandemic period.
A confirmed case of COVID-19 was defined by a positive result on a reversetranscriptase-polymerase-chain-reaction (RT-PCR) assay. Clinically suspected COVID-19 was defined as a condition meeting at least one of the following criteria at presentation; fever ≥ 38°C, cough and/or dyspnea without a clear alternative cause, recent domestic/international travel, employment as a healthcare worker or contact with a known COVID-19 patient or positive CT pulmonary findings. Positive CT was defined as presence of any pulmonary lesions, which include typical, indeterminate and atypical findings for COVID-19 (ground-glass opacity, consolidation, reticulation/thickened interlobular septa, nodules), which are often times nonspecific findings [7] .
Immediate surgical repair was defined as a repair conducted within 24 hours after arrival.
Prolonged ventilation was defined as mechanical ventilation for > 48 hours, which included time 9 from exit from the operating room to extubation.
All surgical repairs were through sternotomy with cardiopulmonary bypass and hypothermic circulatory arrest with antegrade and/or retrograde cerebral perfusion.
Cardiopulmonary bypass was established with direct aortic, right subclavian, innominate artery, or femoral arterial cannulation depending on the aortic pathology at the discretion of the operating surgeon. Myocardial protection was achieved through cold blood cardioplegia delivered antegrade and/or retrograde. Cerebral oximetry as well as bladder and nasopharyngeal temperatures were routinely monitored. The extent of the proximal or distal aortic repair with or without frozen elephant trunk was individualized based on the aortic pathology.
Continuous variables are expressed as mean ± standard deviation for normally distributed variables and median with interquartile range (IQR) for non-normally distributed variables.
Normality was tested with the Shapiro-Wilk test. Categorical variables are presented as proportion and absolute number. Differences between groups were detected using the χ 2 test or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney U test for continuous variables. All p-values were results of 2-tailed tests. The statistical analysis was performed using SPSS 25.0 (IBM, Armonk, NY).
Patient demographic data are shown in Due to the pandemic situation, 24 (46.2%) patients were considered clinically suspicious for COVID-19 based on the aforementioned criteria. Of note, there were two patients (3.9%) who sustained a recent COVID-19 infection prior to the occurrence of the aortic dissection. Both patients were categorized in the suspected group due to the presence of symptoms (fever, dyspnea, cough, positive CT ( Figure 1A) ) and the possibility of persistent or recurrent COVID- 19 . There was no significant difference regarding the clinical characteristics between nonsuspicious and suspicious groups.
Relevant clinical data related to COVID-19 and patient management are shown in Table   2 . Among suspected patients, the leading reason for suspected COVID-19 was the presence of lung lesions on CT scan (70.8%) followed by dyspnea (25.0%), cough (12.5%) and fever ≥ 38.0 °C (12.5%). Representative CT lung findings are demonstrated in Figure 1A -D.
All patients in the suspected COVID group underwent RT-PCR at arrival, while 82.1% in the non-suspected COVID group (p=0.054). There were no positive RT-PCRs at arrival. Overall, 47 (90.4%) underwent a surgical repair. Among operated patients, 59.6% were immediate and 40.4% were delayed. The leading reason for the delayed operation was the waiting time ruling out COVID-19 (68.4%), which was applicable to all suspected COVID patients who underwent a delayed operation (100%), whereas 33.3% in non-suspected COVID patients (p=0.003). Some patients had more than one reasons for the delay. One non-suspected patient with hemodynamic instability went into cardiac arrest in the emergency room and underwent a controlled pericardiocentesis, yielding 40 ml bloody effusion drained. This patient was stabilized afterwards and safely underwent a definitive surgical repair after confirming the negative COVID-19 test.
In contrast, 5 (9.6%) were managed non-operatively. The reasons for non-operative management comprised patient refusal for surgical intervention (40.0%), resolved intramural hematoma (20.0%) and advanced age (89-year-old) without suitable endovascular aortic repair anatomy (20.0%). No patients were managed non-operatively because of COVID-19 related reasons.
Operative data are shown in Supplemental Table 1 . The median time between the arrival to the operating room was 20.5 hours (IQR 7.0-44.0) and 23.8 hours (IQR 13.1-75.3) in the suspected and non-suspected COVID groups, respectively (p=0.89). There was no difference with respect to the cerebral protection strategy, extent of aortic repair or cardiopulmonary bypass/aortic cross-clamp/circulatory arrest times between groups. The majority of patients received blood transfusions.
In-hospital outcomes are shown in Table 3 . The mortality was 7.8% and 6.4% in the entire cohort and surgically managed cohort, respectively. One (1.9%) suspected patient for COVID-19 died of aortic rupture while waiting for the RT-PCR results. A total of 8 (17.0%) underwent a COVID-19 testing postoperatively and 1 (12.5%) came back positive. Among the three deaths in the surgically managed cohort, 1 (33.3%) died of COVID-19 related respiratory failure and 2 (66.6%) died of severe neurological sequela.
In contrast, 80% (4 out of 5) of non-operative managed patients survived to hospital discharge and are alive to date. The composite mortality of non-operatively managed patients (n=5; 9.6%) and patients whose surgical intervention was delayed more than 24 hours (n=19; 36.5%) was 4.2%, suggesting the safety of delayed surgical intervention or non-operative management in selected patients. These 4 non-operatively managed survivors remain alive as of 2 months following the hospital discharge.
13 A total of 3 (5.8%) surgically managed patients had a positive COVID-19 test at various timings. The clinical course of these patients are summarized in Table 4 As for pulmonary CT findings, it is noteworthy to mention that Case 1 did not demonstrate any pulmonary lesions at arrival despite the preoperative COVID-19 acquirement ( Figure 1D ). In contrast, Case 2-3 demonstrated pulmonary infiltrates on the CT scan ( Figure   1A ). However, preoperative RT-PCRs at arrival were both negative.
This study represents the first investigation describing the management and outcomes of type A aortic dissection during the pandemic. In the context of the persistent pandemic situation or possible second surge, a thoughtful discussion regarding optimized management is of paramount importance. lockdown is currently underway.
There has been a perception that patients with certain cardiovascular conditions have been observed less frequently than usual during the pandemic. Reports from US, Spain and Italy demonstrated a similar reduction pattern in the activity of cardiac catheterization laboratory [10] [11] [12] . Another data from 11 major New York City hospitals demonstrated a significant drop in the monthly surgical case volume of type A aortic dissection from 12.8 cases/month to 3.0 cases/month, representing a 76.5% decrease in volume during the pandemic [9] .
While a number of theories that could drive the incidence of urgent cardiac pathologies down, type A aortic dissection, at least at the regional aortic centers located in one of epicenters in the United States and China in the present report, did not appear to be in line with these reported observations. For instance, the number of cases at University of Michigan was the highest (n=16) and its occurrence was constant during the present study period (March 10-May 15 in 2020) compared with the same calendar months in the 5 previous years (2015-2019) (Supplemental Figure 2) . Indeed, our case volume alone was 2.7 times higher than the total volume of 11 New York City hospitals during the pandemic. This higher-than-usual case volume despite the heavy COVID burden (As of May 16th, 50,504 cases and 4,880 deaths related to COVID-19 in the State of Michigan [8]), may be explained by the limited capacity for emergency surgery at other local institutions.
Based on our experience, the following management algorithm has been formulated ( Figure 3 ). While maintaining superb surgical outcomes, protecting healthcare providers and other patients from COVID-19 is an important priority.
Although consensus for general COVID-19 management has been changing day by day due to the rapidly changing circumstances, we strongly advocate for mandatory testing, regardless of the presence of symptoms suspicious for COVID-19 or hemodynamic instability.
There are clearly patients with mild symptoms or even asymptomatic patients who are infected with COVID-19 [13] that will not be detected by the current screening process such as Case 1 in Table 4 . Moreover, patients with type A aortic dissection typically present with severe chest/back pain and sometimes in an unconscious state or already intubated due to cardiogenic shock and/or cerebral malperfusion, raising a concern for masked COVID-19 symptoms. Such patients can then be placed in the appropriate isolation precautions and pre-emptive COVID treatment and providers can wear the appropriate personal protective equipment.
Furthermore, many surgeons might think a negative CT for typical radiographic features suffices as a screening for COVID-19 infection rather than waiting for RT-PCR results.
Compared to RT-PCR, CT imaging may be a more reliable and practical method to diagnose COVID-19, especially in the epidemic area [7] . However, it did not seem to be helpful in the presence of type A aortic dissection and its positive predictive value for detecting COVID was very low. Those typical COVID-19 pneumonia findings appeared surprisingly common in type A dissection patients. At arrival, 33% demonstrated simultaneous pulmonary lesions on the CT scan. More importantly, among these 3 cases with confirmed perioperative COVID-19, Case 1 who was initially not suspected for, but later diagnosed with COVID-19, presented with normal CT findings ( Figure 1D ). Cases 2 and 3 demonstrated obvious pulmonary lesions ( Figure 1A) , while the preoperative RT-PCR tests were negative. CT pulmonary findings, some of which mimic COVID-19 CT features, are known to accompany acute aortic dissection [14] . Lungs can be affected due to compressive effect of dissecting aneurysm, hematoma spread along with the pulmonary artery ( Figure 1B) , perfusion defect in the corresponding lung, pleural effusion, and thickening of the peribronchovascular interstitium [14, 15] .
Timely surgical intervention is imperative in the management of type A aortic dissection.
On the contrary, the delay associated with upfront COVID-19 testing did not affect the outcomes 18 in the present study. The only mortality was an aortic rupture in a suspected patient during the wait time for the RT-PCR result. This fatality occurred at the very beginning of the pandemic when the processing time for RT-PCR was significantly longer (> 24 hours). The current turnaround time at many institutions including our own is < 2 hours. While waiting strategy in type A aortic dissection is controversial, this fact in combination of aggressive medical management assures safety. Critical tamponade can be safely temporized by controlled pericardial drainage procedures. There has been another historic myth that pericardial drainage might induce cardiac rupture by abruptly elevating blood pressure and dislodging of already formed thrombus from the pericardial space [16] based on a series of 10 patients back in 90's.
However, more recent reports support controlled pericardial drainage procedures in unstable patients with tamponade with more favorable results [17] . In our practice, as performed in one patient in the present study, controlled pericardial drainage procedure is routinely performed in the emergency room or ICU setting for critical tamponade with hemodynamic collapse. Many patients with type A aortic dissection can be safely managed non-operatively short-term at experienced aortic centers.
Surgical repair in patients with confirmed COVID-19 may result in fatal outcomes based on this report and unpublished personal communication data from Wuhan and New York City.
Martens et al. reported an otherwise healthy asymptomatic 64-year-old patient with type A dissection in whom COVID-19 was incidentally detected via RT-PCR on the 1st postoperative day from their postoperative mandatory screening process [18] . No preoperative testing was performed. Despite respiratory complications and prolonged hospital course, this patient survived to hospital discharge. We speculate early recognition of COVID-19 and immediate aggressive treatment in Case 1 might have diverted the outcome despite the concurrent COVID-19. In contrast, fatal outcomes may be inevitable in patients with advanced age and/or severe medical comorbidities. Such operation is not only being futile but also risking the provider team for COVID-19 exposure. In such circumstance, optimal medical treatment, rather than surgical repair, may be preferred. Operation may be considered only for those achieved convalescence from COVID-19. The definition of convalescence in patients needing open heart surgery is unknown. However, we propose acquisition of negative RT-PCR results to be one indicator for the readiness of surgical repair in this unique setting. The fact that two very sick patients (Cases 2 and 3 in Table 4 ) who had a recent COVID-19 prior to the aortic dissection survived to hospital discharge also supports this management, although postoperative severe coagulopathy was noted in both patients. Alternatively, ascending aortic endovascular repair may be considered if anatomically suitable.
This study has several limitations inherent to its retrospective nature with small sample size. The difference in surgical and medical management of type A aortic dissection among the 3 institutions may be significant. In view of the ongoing and future COVID-19 burden to the global healthcare system, further investigation involving other institutions using standardized methodology and diagnostic criteria is highly warranted to validate our results.
In summary, in light of the potential high mortality associated with dual diagnoses of type A aortic dissection and COVID-19, the higher-than-expected number of asymptomatic COVID-19 carriers, masked symptoms in type A dissection and unreliability of CT scan as a screening tool, we strongly advocate testing all comers for COVID-19 immediately after arrival and confirming a negative result before performing any surgical repair to avoid fatal outcomes and spread of COVID-19 to caregivers and other patients. Surgical intervention in patients with positive COVID-19 may be considered for low risk patients with minimal symptoms. Otherwise our recommendation is non-operative management until full convalescence, which may be a negative RT-PCR result. We believe lessons learned from this series remains critically important for the management of type A aortic dissection for the upcoming persistent COVID-19 pandemic or second major surge in the post-lockdown era. 