Table 1.

Select Summary of Thrombotic and Thromboembolic Events During Viral Outbreaks

Proposed Mechanisms	Event Type	Epidemiological Data
SARS
Inflammatory cytokine release	VTE	Retrospective analysis of 46 critically ill patients with SARS showed 11 DVT and 7 PE events (9). Case series of 8 SARS positive ICU patients. Autopsy identified PE in 4, and DVT in 3 individuals (138).
Critical illness	Arterial thrombotic events	In a prospective series of 75 patients, 2 patients died of acute myocardial infarction (within 3-week period) (139). Case report of an NSTEMI patient who received PCI but subsequently developed STEMI several hours later, concerning for immune-mediated plaque instability (140).
Traditional risk factors (138)	Other	In a case series of 206 patients with SARS, 5 developed large artery ischemic stroke with DIC present in 2 of 5 (141). In a retrospective analysis of 157 patients with SARS, isolated, subclinical elevations in aPTT were noted in 96 patients and DIC developed in 4 patients (142).
MERS
Nonspecific mechanism; potentially similar to SARS. Models suggest elevated inflammatory cytokine levels (143)	Other	In a series of 157 cases of MERS (confirmed and probable), at least 2 were reported to have a consumptive coagulopathy (145).
Transgenic murine models show evidence of microvascular thrombosis (144)
Influenza
Possible de novo pulmonary emboli in certain cases (146)  Acute inflammation and decreased mobility in hospitalized patients (147)  Possible thrombosis owing to rupture of pre-existing high-risk plaques (98)  Platelet aggregation over inflamed atherosclerotic plaques noted in animal models (148)	VTE	Retrospective study of 119 patients showed 4 VTE events in patients receiving prophylactic anticoagulation (147). Case series describes 7 PEs in patients with influenza pneumonia. In 6 of 7, there was no evidence of DVT (146). A multicenter, observational, case-control study (N = 1,454) suggested that lower VTE rates are associated with influenza vaccination (odds ratio: 0.74; 95% confidence interval: 0.57–0.97) (149). This is a representative but not comprehensive list of associated studies.
	Arterial thrombotic events	A self-controlled study of 364 patients hospitalized with acute myocardial infarction found an increased incidence ratio (6.05; 95% confidence interval: 3.86–9.50) for myocardial infarction during periods after influenza compared with controls (97). Similar evidence exists in prior studies (150,151). A retrospective cohort study of 119 patients reports 3 arterial thrombotic events, 2 of which had STEMI (147). This is a representative but not comprehensive list of associated studies.
	Other	DIC has been described with influenza infection in a number of case reports and small case series (152, 153, 154).
COVID-19
Mechanistic understanding continues to evolve	VTE	Two case series of acute pulmonary embolism were described in patients hospitalized with COVID-19 (83). In a study from 3 hospitals from the Netherlands, 31% of 184 critically ill patients with COVID-19 had thrombosis, with most events being VTE.
Factors may include inflammatory cytokine release and critical illness/underlying risk factors	Arterial thrombotic events	Data are continuing to emerge regarding the risk of thrombotic events associated with COVID-19 infection, and an international registry for ACS is planned. Please see text for more detail.
SARS-CoV-2 binds cells expressing angiotensin-converting enzyme 2 (155), and this may mediate further mechanisms of injury (3)	Other	Retrospective analysis of 183 patients found nonsurvivors had significantly higher D-dimer and PT values, compared with survivors. Further, 15 of 21 (71.4%) nonsurvivors met criteria for DIC vs. 1 of 162 (0.6%) survivors (7). Systematic review of literature published prior to February 24, 2020, suggests elevations in PT and D-dimer levels were associated with poor prognosis in patients with COVID-19 (25).

ACS = acute coronary syndrome; aPTT = activated partial thromboplastin time; COVID-19 = coronavirus disease-2019; DIC = disseminated intravascular coagulation; DVT = deep vein thrombosis; ICU = intensive care unit; MERS = Middle East respiratory syndrome; NSTEMI = non–ST-segment elevation myocardial infarction; PCI = percutaneous coronary intervention; PE = pulmonary embolism; PT = prothrombin time; SARS = severe acute respiratory syndrome; SARS-CoV-2 = severe acute respiratory syndrome-coronavirus-2; STEMI = ST-segment elevation myocardial infarction; VTE = venous thromboembolism.