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Case Reports
. 2022 Feb 3;386(5):479-485.
doi: 10.1056/NEJMcps2111163.

Calm before the Storm

Manuel B Braga Neto  1 , Andrew D Badley  1 , Sameer A Parikh  1 , Rondell P Graham  1 , Patrick S Kamath  1
Affiliations
Case Reports

Calm before the Storm

Manuel B Braga Neto et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Imaging of the Gallbladder and Abdomen.
An ultrasound image of the gallbladder (Panel A) and a coronal view of the abdomen on computed tomography (Panel B) show a markedly thickened gallbladder wall measuring 14 mm (normal, ≤3 mm) without associated biliary duct dilatation. The gallbladder lumen is highlighted (asterisk).
Figure 2
Figure 2. Findings on Biopsy of Liver and Bone Marrow.
Panel A shows hemophagocytosis, with the macrophages (green arrows) engulfing red cells (yellow arrow). Cholestatic hepatitis evidenced by hepatocytes with cholestasis (bile pigment, blue arrows) and dying hepatocytes (apoptosis, black arrows) is noted. Hemophagocytosis on bone marrow biopsy is shown in Panel B (red arrow).
Figure 3
Figure 3. Pathogenesis and Manifestations of Post–Covid-19 Hyperinflammatory Syndrome.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is followed a week or so later by activation of the immune system, which coincides with the development of other Covid-19 symptoms. When patients have a hyperinflammatory response and escalating oxygen requirements despite monoclonal antibodies or remdesivir with or without dexamethasone, either baricitinib or tocilizumab therapy is usually considered. Viral clearance is most often associated with resolution of symptoms. In a subgroup of patients, despite viral clearance and sometimes after an asymptomatic interval, hyperactivation of both innate and adaptive immune systems persists and there is an excessive release of proinflammatory cytokines leading to the hyperinflammatory syndrome. Hemophagocytic lymphohistiocytosis (HLH) and multisymptom inflammatory syndrome in adults (MIS-A) are examples of the hyperinflammatory syndrome that induces fever and constitutional symptoms and are strongly considered when the patient’s symptoms persist or worsen after viral clearance. HLH usually occurs within 14 days after onset of Covid-19 infection, whereas MIS-A usually occurs after 2 weeks and up to 12 weeks after infection. However, the hyperinflammatory syndrome is most often seen in patients with severe Covid-19, and when prolonged it may overlap with HLH. Some patients who receive a diagnosis of prolonged Covid-19 may in fact have HLH. Typical features of HLH include hepatosplenomegaly, cytopenias, coagulopathy, liver dysfunction, and hemophagocytosis in bone marrow or tissue (such as the liver). In MIS-A, cardiac dysfunction, rash with nonpurulent conjunctivitis, and gastrointestinal symptoms are more frequent, although cytopenias and liver dysfunction may also be present. Clinical features of HLH and MIS-A overlap, and the specific diagnosis is made on the basis of diagnostic criteria. ARDS denotes acute respiratory distress syndrome and CRP C-reactive protein.
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References

    1. Henter J-I, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-131. - PubMed
    1. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 2014;66:2613-2620. - PubMed
    1. Ramos-Casals M, Brito-Zerón P, Mariette X. Systemic and organ-specific immune-related manifestations of COVID-19. Nat Rev Rheumatol 2021;17:315-332. - PMC - PubMed
    1. Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep 2020;69:1450-1456. - PMC - PubMed
    1. Multisystem inflammatory syndrome in adults (MIS-A) case definition information for healthcare providers. Centers for Disease Control and Prevention, 2021. (https://www.cdc.gov/mis/mis-a/hcp.html).

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