Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease.

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.

A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae.

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .

Failure rates of nonoperative management of low-grade splenic injuries with active extravasation: an Eastern Association for the Surgery of Trauma multicenter study.

Objectives: There is little evidence guiding the management of grade I-II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I-II splenic injuries with CB in hemodynamically stable patients. Methods: A multicenter, retrospective cohort study examining all grade I-II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not. Results: A total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I-II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05). Conclusion: NOM of grade I-II splenic injuries with CB fails in 20% of patients. Level of evidence: IV.

Grade 1 Internal Carotid Artery Blunt Cerebrovascular Injury Persistence Risks Stroke With Current Management: An EAST Multicenter Study.

BACKGROUND: Higher blunt cerebrovascular injury (BCVI) grade and lack of medical therapy are associated with stroke. Knowledge of stroke risk factors specific to individual grades may help tailor BCVI therapy to specific injury characteristics. METHODS: A post-hoc analysis of a 16 center, prospective, observational trial (2018-2020) was performed including grade 1 internal carotid artery (ICA) BCVI. Repeat imaging was considered the second imaging occurrence only. RESULTS: From 145 grade 1 ICA BCVI included, 8 (5.5%) suffered a stroke. Grade 1 ICA BCVI with stroke were more commonly treated with mixed anticoagulation and antiplatelet therapy (75.0% vs 9.6%, P <.001) and less commonly antiplatelet therapy (25.0% vs 82.5%, P = .001) compared to injuries without stroke. Of the 8 grade 1 ICA BCVI with stroke, 4 (50.0%) had stroke after medical therapy was started. In comparing injuries with resolution at repeat imaging to those without, stroke occurred in 7 (15.9%) injuries without resolution and 0 (0%) injuries with resolution (P = .005). At repeat imaging in grade 1 ICA BCVI with stroke, grade of injury was grade 1 in 2 injuries, grade 2 in 3 injuries, grade 3 in 1 injury, and grade 5 in one injury. DISCUSSION: While the stroke rate for grade 1 ICA BCVI is low overall, injury persistence appears to heighten stroke risk. Some strokes occurred despite initiation of medical therapy. Repeat imaging is needed in grade 1 ICA BCVI to evaluate for injury progression or resolution.

Patient characteristics and diagnostic tests associated with syncopal falls: A Southwestern surgical congress multicenter study.

BACKGROUND: Patients suspected of syncope frequently undergo laboratory and imaging studies to determine the etiology of the syncope. Variability exists in these workups across institutions. The purpose of this study was to evaluate the utilization and diagnostic yield of these workups and the patient characteristics associated with syncopal falls. METHODS: A multi-institutional retrospective review was performed on adult patients admitted after a fall between 1/2017-12/2018. Syncopal falls were compared to non-syncopal falls. RESULTS: 4478 patients were included. There were 795 (18%) patients with a syncopal fall. Electrocardiogram, troponin, echocardiogram, CT angiography (CTA), and carotid ultrasound were more frequently tested in syncope patients compared to non-syncope patients. Syncope patients had higher rates of positive telemetry/Holter monitoring, CTAs, and electroencephalograms. CONCLUSION: Patients who sustain syncopal falls frequently undergo diagnostic testing without a higher yield to determine the etiology of syncope.

Does treatment delay for blunt cerebrovascular injury affect stroke rate?: An EAST multicenter study.

BACKGROUND: The purpose of this study was to analyze injury characteristics and stroke rates between blunt cerebrovascular injury (BCVI) with delayed vs non-delayed medical therapy. We hypothesized there would be increased stroke formation with delayed medical therapy. METHODS: This is a sub-analysis of a 16 center, prospective, observational trial on BCVI. Delayed medial therapy was defined as initiation >24 hours after admission. BCVI which did not receive medical therapy were excluded. Subgroups for injury presence were created using Abbreviated Injury Scale (AIS) score >0 for AIS categories. RESULTS: 636 BCVI were included. Median time to first medical therapy was 62 hours in the delayed group and 11 hours in the non-delayed group (p < 0.001). The injury severity score (ISS) was greater in the delayed group (24.0 vs the non-delayed group 22.0, p <  0.001) as was the median AIS head score (2.0 vs 1.0, p <  0.001). The overall stroke rate was not different between the delayed vs non-delayed groups respectively (9.7% vs 9.5%, p = 1.00). Further evaluation of carotid vs vertebral artery injury showed no difference in stroke rate, 13.6% and 13.2%, p = 1.00 vs 7.3% and 6.5%, p = 0.84. Additionally, within all AIS categories there was no difference in stroke rate between delayed and non-delayed medical therapy (all N.S.), with AIS head >0 13.8% vs 9.2%, p = 0.20 and AIS spine >0 11.0% vs 9.3%, p = 0.63 respectively. CONCLUSIONS: Modern BCVI therapy is administered early. BCVI with delayed therapy were more severely injured. However, a higher stroke rate was not seen with delayed therapy, even for BCVI with head or spine injuries. This data suggests with competing injuries or other clinical concerns there is not an increased stroke rate with necessary delays of medical treatment for BCVI.

Endovascular Intervention in Internal Carotid Artery Blunt Cerebrovascular Injury: An EAST Multicenter Study.

BACKGROUND: Use of endovascular intervention (EI) for blunt cerebrovascular injury (BCVI) is without consensus guidelines. Rates of EI use and radiographic characteristics of BCVI undergoing EI nationally are unknown. METHODS: A post-hoc analysis of a prospective, observational study at 16 U.S. trauma centers from 2018 to 2020 was conducted. Internal carotid artery (ICA) BCVI was included. The primary outcome was EI use. Multivariable logistic regression was performed for predictors of EI use. RESULTS: From 332 ICA BCVI included, 21 (6.3%) underwent EI. 0/145 (0%) grade 1, 8/101 (7.9%) grade 2, 12/51 (23.5%) grade 3, and 1/20 (5.0%) grade 4 ICA BCVI underwent EI. Stroke occurred in 6/21 (28.6%) ICA BCVI undergoing EI and in 33/311 (10.6%) not undergoing EI (P = .03), with all strokes with EI use occurring prior to or at the same time as EI. Percentage of luminal stenosis (37.75 vs 20.29%, P = .01) and median pseudoaneurysm size (9.00 mm vs 3.00 mm, P = .01) were greater in ICA BCVI undergoing EI. On logistic regression, only pseudoaneurysm size was associated with EI (odds ratio 1.205, 95% CI 1.035-1.404, P = .02). Of the 8 grade 2 ICA BCVI undergoing EI, 3/8 were grade 2 and 5/8 were grade 3 prior to EI. Of the 12 grade 3 ICA BCVI undergoing EI, 11/12 were grade 3 and 1/12 was a grade 2 ICA BCVI prior to EI. DISCUSSION: Pseudoaneurysm size is associated with use of EI for ICA BCVI. Stroke is more common in ICA BCVI with EI but did not occur after EI use.

Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study.

BACKGROUND: Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. METHODS: An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. RESULTS: Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. CONCLUSION: Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level IV.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

BACKGROUND: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock. METHODS: Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group. RESULTS: A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05). CONCLUSION: This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Prehospital end-tidal carbon dioxide is predictive of death and massive transfusion in injured patients: An Eastern Association for Surgery of Trauma multicenter trial.

BACKGROUND: Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients. METHODS: This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as >10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused. RESULTS: A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p < 0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p < 0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%. CONCLUSION: Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock. LEVEL OF EVIDENCE: Diagnostic test, level III.