key: cord-0762402-zenbyjtb authors: Williams, KM; Wilson, PT; Silva-Palacios, F; Kebbe, J; LaBeaud, AD; Agudelo, Higuita N; Sidonio, RF; Stowell, SR; Josephson, C; Beth, A. Tarini; Holter, Chakrabarty J; Agwu, AL title: COVID-19 Cliff Notes–A COVID-19 Multi-disciplinary Care Compendium: COVID-19 Cliff Notes date: 2021-03-03 journal: Transplant Cell Ther DOI: 10.1016/j.jtct.2021.02.036 sha: 50bd64757c1556891d226afddc43bc508d196cfd doc_id: 762402 cord_uid: zenbyjtb As we pass the nearly 9 month mark of the coronavirus virus disease 2019 (COVID-19) pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise (Figure 1). Abstract: As we pass the nearly 9 month mark of the coronavirus virus disease 2019 pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise ( Figure 1 ). Pulmonary and supportive care: Progressive COVID-19 requires critical care. Priorities include: appropriate personal protective equipment, negative pressure rooms and minimization of particle aerosolization: regular or high flow nasal cannula (limited to ≤30 liters/minute), oxygen mask, and in very select cases a trial of non-invasive ventilation. 1 Progressive failure necessitates safe endotracheal intubation by experienced providers and lung-protective mechanical ventilation (high positive end expiratory pressure and low tidal volumes), with adjunct therapies including: proning, inhaled pulmonary vasodilators, Extracorporeal Membrane Oxygenation, vasopressors, nutrition, and renal replacement therapy. Safe and expedient extubation must be prioritized in patients with successful spontaneous breathing trials 1 . Adult Respiratory Distress Syndrome (ARDS) is a life-threatening complication, with data suggesting low dose, short term, dexamethasone may have a critical role. 2 Cardiac complications are increasingly recognized in COVID-19, including myocarditis, heart failure, arrhythmia; thus, cardiac evaluation is recommended in children and adults with severe disease. Additional risks of ulcers, thrombi, and fluid overload should be minimized. Evaluation for co-infections is warranted, as data have shown that bacterial and fungal pathogens contribute to mortality, and some suggest empiric anti-microbials. 1 COVID-19 Treatments: Two therapies continue to show promise for primary treatment of COVID-19. Convalescent plasma, i.e., plasma containing antibodies to SARS-CoV-2, obtained from individuals who have recovered from COVID-19, has a good safety record, data to suggest efficacy in severe disease, and was recently given emergency use authorization (EUA) by the FDA for use in COVID-19. 3 Studies in children and adults are ongoing, with best results anticipated in patients who receive products with high neutralization titers. To date, the most encouraging antiviral agent is remdesivir, with some data showing it decreases time to recovery in adults. 4 Antiviral treatment is likely most effective earlier in the illness (day 0-7) when there is active viral replication. It has been given emergency use authorization for the treatment of SARS-Co-V-2 in hospitalized adult and pediatric patients with severe disease. Emerging data suggests that monoclonal antibody therapy to SARS-COV2 may mitigate severe disease in outpatients early in the disease process, with either casirivimab and imdevimab or bamlanivimab (under EUA). 5, 6 Coagulopathy and bleeding diathesis: SARS-CoV-2 infection predisposes patients to venous and arterial thrombosis, due to excessive inflammation, platelet activation, endothelial dysfunction and stasis. 7 Venous thromboembolism incidence risk is associated with disease severity, ≤70% in intensive care patients. 7 Bleeding diatheses also occur in up to 5% of patients with COVID-19 and can be accompanied by hypofibrinogemia. 7 To risk stratify, follow coagulation and hematology labs daily. Intermediate dose prophylaxis should be considered in ill patients, using anti-FXa to evaluate resistance and adjust dosage, including those on therapeutic dosing. 7 Careful consideration of changing renal function, thrombocytopenia, and impact of BMI on dosing of anticoagulation. Consider a very low threshold for chest computer tomography angiography, venous ultrasound. In ill adults, post-discharge thromboembolism prophylaxis could be considered for up to 4-5 weeks. Inflammation/ cytokine storm: Severe COVID-19 may present with life-threatening, uncompensated shock similar to cytokine release or macrophage activation syndromes with elevated ferritin, c-reactive protein, and d-dimers. Hallmarks include lymphopenia, elevated interleukin-6 (IL-6), and tumor necrosis factor alpha. Tociluzumab, an IL-6 antagonist, has shown survival benefit in the treatment of COVID-19 8 without affecting viral clearance. This may be especially important for immunocompromised patients e.g. after cellular transplantation. 9 In contrast, the risks of secondary infections have cautioned against systemic steroids in patients who do not have ARDS. For those refractory to tocilizumab, a method for in-line cytokine removal, CytoSorb, has received EUA for adults, though limited data exists. Post-infectious syndromes such as a Guillain-Barré and a severe multisystem disease inflammatory syndrome in children (MIS-C) (also called pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) are emerging. MIS-C, is characterized by fever with one of the following: hypotension or shock, severe cardiac illness, severe end-organ involvement; or two or more of the following: maculopapular rash, bilateral non-purulent conjunctivitis, mucocutaneous inflammatory signs, acute gastrointestinal symptoms; and not explained by another diagnosis. 10 Echocardiogram should be performed at presentation and repeated in 1-2 weeks. Treatment includes supportive care alongside consideration of immunomodulation, e.g. steroids, intravenous immunoglobulin, with uncommon use of inhibitors to IL-1 or Il-6, and anticoagulation. 10 This perspective is not a guideline, but provides a brief summary of current considerations for the care of patients with COVID-19, including details of: pulmonary and intensive care management, specific treatments for severe disease, coagulopathy, dysregulated inflammation, and post-infectious syndromes. The care of COVID-19 patients is a rapidly evolving field, which will require continued collaborations across disciplines and age groups to best care for these patients and improve outcomes as is highlighted by the patient synopsis. Author statement: All authors contributed to the generation of the manuscript, editing, and final review. Dr. Williams initially crafted the outline of the manuscript and the panel of individuals to be included, which was further broadened by those individuals' subsequent invitations. Management of Critically Ill Adults With COVID-19 Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial Remdesivir for the Treatment of Covid-19 -Preliminary Report Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA 2021 REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19 COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study Multisystem Inflammatory Syndrome in U.S. Children and Adolescents