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Clin Infect Dis ; 71(12): 3168-3173, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-612034


BACKGROUND: Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration 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. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 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 2 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.

COVID-19 , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Compassionate Use Trials , Humans , Male , Middle Aged , Treatment Outcome
Endocr Relat Cancer ; 27(9): R281-R292, 2020 09.
Article in English | MEDLINE | ID: covidwho-577793


The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.

Androgen Antagonists/therapeutic use , Betacoronavirus , Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Prostatic Neoplasms/drug therapy , Androgens/physiology , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/drug therapy , Humans , Hypothalamo-Hypophyseal System/physiology , Male , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Serine Endopeptidases/physiology