Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO 2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.
Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Unlike other respiratory viruses, little is known about the clinical significance of human coronavirus infection (HCoV) in this population. We retrospectively identified all HSCT recipients who were transplanted between May 2013 and June 2017 at our institution and characterized the cumulative incidence of post-transplant HCoV infection. Of 678 patients who underwent HSCT during the study period, 112 (17%) developed HCoV infection, making HCoV the fourth most common respiratory viral infection. Thirty-four (30%) HCoV-infected patients progressed to proven or probable lower respiratory tract infection (LRTI). Age ≥50, graft-versus-host disease, corticosteroids, hypoalbuminemia, and inpatient status at the time of infection were independently associated with progression to LRTI. Twenty-seven (59%) patients who underwent repeat NP swab had persistent viral shedding for ≥21 days, with a median duration of 4 weeks of viral shedding. We conclude that HCoV is common and clinically significant in HSCT recipients, with nearly one-third of patients progressing to proven or probable LRTI. Evaluating for LRTI risk factors found in this study may identify patients who require closer surveillance and aggressive supportive care when infected with HCoV.
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