Transplant clinicians should exercise vigilance in surveillance for Chagas disease in both organ donors and recipients. Although Chagas disease may seem uncommon, it is pervasive in endemic and several nonendemic countries, including the United States and Spain.
Background
Preliminary data from SARS-CoV-2 pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is FDA-approved for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia.
Methods
We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment.
Results
Twenty seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. IL-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, four patients did not show rapid CRP declines, of whom three had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but two deaths (7.4%) occurred that were felt unrelated to tocilizumab.
Conclusions
Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.
Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.
Five homosexual men dying at UCLA Center for the Health Sciences, Los Angeles, with acquired immunodeficiency and Pneumocystis pneumonia, Kaposi's sarcoma, or cryptosporidiosis since May 1981 have all had mycobacteria of the Mycobacterium avium-intracellulare complex cultured from tissues taken just before death or at postmortem examination. Each man had histological evidence of disseminated mycobacterial infection. Acid-fast organisms were seen in macrophages in the lung, spleen, and lymph nodes in all cases and in a variety of additional organs in two cases. Other severe infections were always found at postmortem examination--cytomegalovirus, cryptosporidiosis, and Pneumocystis. Disseminated M avium-intracellulare infection has been so striking in homosexual males dying with acquired immunodeficiency at our institution that we believe a vigorous search for mycobacteria should be made in all such patients. Empiric therapy for mycobacterial infection may be justified in selected cases of immunodeficiency before a specific microbiological diagnosis.
In February 1982, a four-year-old Nevada girl with acute lymphoblastic leukemia in remission was hospitalized with fulminant pneumonia and died eight days later at a hospital in California. An influenza virus was the only pathogen detected, and was present in both antemortem and postmortem specimens. The virus was closely related antigenically to A/New Jersey/8/76 (H1N1) and had a genome very similar to a contemporary enzootic swine influenza virus. The patient had had no known contact with swine, and the source of infection could not be determined. Only five possible secondary cases could be detected by retrospective investigation of 62 contacts, and there was no evidence of spread to the general community. Swine influenza viruses circulate among pigs in the United States annually, and it is likely that sporadic transmissions to humans will continue to be detected. Nevertheless, person-to-person spread under these circumstances appears to be limited.
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