· More transparency is needed for emergency use authorizations (EUA), including drugs and vaccines for COVID-19, according to a journalist writing for the Journal of the American Medical Association reporting on a recent US Government Accountability Office (GAO) report. The report calls on the Food and Drug Administration (FDA) to publicly share safety and efficacy data related to EUAs to improve public confidence during this unprecedented time.
· Persistence of SARS-CoV-2 in a first trimester placenta may have led to transplacental transmission and fetal demise from an asymptomatic mother. An interdisciplinary group of researchers at Model Hospital in Mumbai, India describe a case of hydrops fetalis detected at 13 weeks gestation in an asymptomatic carrier of the SARS-CoV-2 virus. The patient tested posted for COVID-19 at 7.6 weeks of gestation and then was subsequently found to have detectable SARS-CoV2 in the amniotic fluid and placental cells at 13 weeks gestation. These findings suggest possible transplacental SARS-CoV-2 transmission and viral replication within the placenta. While there was evidence of robust placental inflammation, fetal tissue was unavailable for biopsy and therefore infection of the fetus itself is unable to be determined.
Understanding the Pathology
· Immunometabolism may be useful for inflammaging, immunosenescence, and autoimmunity in COVID-19. In this review, an interdisciplinary group of French researchers propose that inflammaging, which is chronic low-grade inflammation that occurs with aging, may be the common factor predisposing individuals with certain comorbidities to more severe COVID-19. They discuss how the underlying mechanisms of immunosenescence and chronic inflammation seen in diseases such as diabetes, hypertension, metabolic syndrome, systemic lupus erythematosus, and rheumatoid arthritis seem to predispose COVID-19 patients to the immune dysfunction and cytokine storm observed in severe disease. Thus, authors propose an immunometabolism-mediated treatment paradigm that includes metformin, rapamycin, and dimethyl fumarate.
· Muscle biopsy findings in a case sheds light into SARS-CoV-2-associated muscle injury. Researchers at Johns Hopkins and the University of Minnesota describe the muscle biopsy of a patient who died from complications of COVID-19. These findings demonstrate cellular damage within skeletal muscle that is consistent with "primary vascular origin." Since skeletal myocytes have minimal expression of ACE-2 receptors, the authors speculate that damage to skeletal muscles likely results from secondary inflammatory and coagulopathic changes, rather than direct viral damage. They theorize that these findings seen on electron microscopy may correlate with the myalgias and elevated CK enzymes seen in SARS-CoV-2 infection.
Transmission & Prevention
· Intrauterine transmission of SARS-CoV-2 from COVID-19 infected pregnant women is a potential complication according to one review. Members of the Pakistan Health Research Council reviewed 16 articles (498 COVID-19 infected pregnant women) on vertical transmission of SARS-CoV-2 and found vertical transmission occurred in 4.883% of SARs-CoV-2 infected mothers (23/471), and in the 17 cases where outcomes were reported, 4 infants developed COVID-19 pneumonia, 8 required care in the neonatal intensive care unit, 4 received mechanical ventilation, and none died. Authors suggest vertical transmission is possible and that because severe neonatal complications can occur, recommend neonatal screening for infants born to mothers with SARS-CoV-2.
· Do care bundles improve outcomes in patients with COVID-19 or related conditions in intensive care? A systematic review by authors from Ireland and Australia examined the literature on ICU care bundles used in the management of COVID-19 and other acute respiratory pathogens and identified 21 studies encompassing 8 countries, with care bundles most commonly including guidance on ventilator setting, restrictive fluid management, sedation, and prone positioning. The authors ultimately found significant variation in the protocol used for these care bundles, and low-quality evidence to support them. Given that care bundles are a cornerstone of ICU care, there is great need for RCTs in this critical aspect of caring for COVID-19 patients.
· What has been found regarding arterial and venous thrombosis in COVID-19 thus far? A literature review conducted by cardiologists from Harvard Medical School (U.S.) analyzes current data on the incidence and treatment of thrombotic complications in COVID-19 patients. Previous studies have found thrombotic complications in 2.6% of non-critically ill hospitalized patients and in 35% of critically ill hospitalized patients. Laboratory markers of hypercoagulability are also commonly elevated in these patients, such as D-dimer (100%), Fibrinogen (74%), and Factor VIII (100%). Current guidelines agree that prophylactic anticoagulation with low-molecular-weight-heparin (LMWH) is recommended in critically and non-critically ill hospitalized patients, however there is no consensus on anticoagulation of these patients after discharge. While further research is needed on the ideal management of COVID-19-induced coagulopathy, most societies agree that extended prophylaxis in non-hospitalized patients is not recommended.
Adjusting Practice During COVID-19
· Clarithromycin can be used for adjunct surgical prophylaxis before non-elective cesarean deliveries to adapt to azithromycin shortages in the COVID-19 pandemic. A multicenter prospective cohort study of 240 pregnant patients undergoing non-elective cesarean deliveries, found that use of clarithromycin as surgical prophylaxis resulted in significantly lower rates of of postpartum endometritis compared to the control group (4.5% vs 11.2%, p = 0.025). These results are important because there has been pandemic-induced shortages of azithromycin (the macrolide typically used for C-section prophylaxis). Notably, all women were SARS-CoV-2 negative and subgroup analysis revealed a significantly decreased risk for Black women ages 18-29. Therefore, use of clarithromycin for C-section prophylaxis may help improve outcomes in both of these vulnerable populations during the COVID-19 pandemic.