Acute Respiratory Failure Secondary to COVID-19 Viral Pneumonia Managed With Hydroxychloroquine/Azithromycin Treatment.

A 74-year-old male was admitted to the Intensive Care Unit (ICU) at State University of New York (SUNY) Downstate Medical Center following acute respiratory failure secondary to coronavirus disease 2019 (COVID-19) viral pneumonia. The patient had significant comorbidities, including a history of lung and esophageal cancer status-post resection, cerebrovascular accident with neurological deficits, diabetes mellitus, hypertension, and peripheral vascular disease. The patient was in septic shock and respiratory failure on admission requiring intubation and mechanical ventilation. Computed tomography (CT) of the chest showed patchy bilateral opacities suspicious for viral pneumonia and the COVID-19 sputum sample sent to the New York Department of Health returned positive. This patient's comorbidities, along with his age, placed him in the highest risk of mortality for COVID-19. The patient was managed pharmacologically with hydroxychloroquine and azithromycin. By Day 5 of his admission, he improved significantly and was extubated and downgraded from the ICU to the medical floor, pending discharge. This case report provides anecdotal evidence for the effectiveness of the hydroxychloroquine and azithromycin combination currently being used across the nation to manage COVID-19, pending development of a definitive vaccine or antiviral treatment.

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.

MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans.

BACKGROUND/OBJECTIVES: Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. METHODS: A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. RESULTS: MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. CONCLUSIONS: These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans.

Perioperative mannan-binding lectin (MBL) patterns in cardiac surgery may correlate with the clinical outcomes in MBL deficient patients.

Previously we reported a case of abrupt change of postoperative mannan-binding-lectin (MBL) in a patient with preexisting MBL deficiency who expired shortly after cardiac surgery. Herein we report additional cases of 3 more patients with preexisting MBL deficiency who underwent cardiac surgery. Analysis of their blood samples from the perioperative period showed their MBL levels were abruptly increased at 24 hours after surgery. However, 2 patients had a subsequent drop of MBL at 48 hours, and both expired. These data indicated that the postoperative decrease of MBL may have been related with an unfavorable outcome after cardiac surgery.

Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia.

Increasing evidence suggests that Mannan-binding lectin (MBL), the initial factor of the lectin pathway of complement, plays a role in cardiovascular diseases, i.e. inversely associated with risk of myocardial infarction (MI). In the present case, a patient with MBL deficiency underwent coronary artery bypass grafting (CABG) after an acute MI with underlining chronic lymphocytic leukemia (CLL). Post-operatively, the patient had a cerebral vascular accident and eventually expired. Analysis of his blood samples from pre-, intra-, and post-operative periods showed that MBL levels abruptly increased post-operatively. We hypothesize that the post-operative increase of MBL in the patient with pre-existing MBL deficiency may contribute to systemic inflammation, causing a detrimental effect after cardiac surgery.

Preoperative blood volume deficit influences blood transfusion requirements in females and males undergoing coronary bypass graft surgery.

STUDY OBJECTIVE: To evaluate whether preoperative blood volume and postoperative blood loss influence blood transfusion in females and males undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective study. SETTING: Anesthesiology department of a teaching hospital. PATIENTS: 57 CABG patients (21 females and 36 males). MEASUREMENTS: Blood volume was determined using the radioactivity dilution method. Preoperatively, each patient received intravenous (IV) injection of 1 mL Albumin I(131) tracer having 25 microcuries of radioactivity. Five-milliliter blood samples were collected at different intervals. From these samples, hematocrit (Hct) value, preoperative total blood volume, red blood cell (RBC) volume, and plasma volume were determined. Postoperatively, some consenting patients received another 1 mL dose of the tracer, and the postoperative blood volumes were determined. If a patient received a blood transfusion, the units of packed red blood cells (PRBCs), platelets, or fresh frozen plasma (FFP) transfused were recorded. For each patient we recorded the gender, age, weight, height, body surface area (BSA), preoperative Hct, duration of surgery, and discharge Hct. RESULTS: Preoperatively, the mean total blood volume, RBC volume, and plasma volume, respectively, were 2095 mL/m(2), 631 mL/m(2), and 1,465 mL/m(2) in females; and 2,580 mL/m(2), 878 mL/m(2), and 1,702 mL/m(2) in males. The preoperative blood volumes were significantly lower (p < 0.01) in females than in males. There was no significant difference between males and females in the extent of blood loss during CABG. Intraoperatively, females received PRBC transfusion of 1.38 units, significantly more (p < 0.01) than the 0.39 units received by males. During the entire hospital stay, females received 4.33 units of PRBC, significantly more than (p < 0.02) the 1.33 units received by males. Significantly more (p < 0.01) females (12 of 21) received intraoperative PRBC transfusion than did males (6 of 36). Multiple logistic regression analysis of the data showed that PRBC transfusion was significantly correlated with the preoperative total blood volume and RBC volume. CONCLUSION: The greater need for blood transfusion in females than in males during CABG is primarily attributable to significantly lower preoperative total blood volume and RBC volume in females.