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5.
Nat Med ; 26(10): 1636-1643, 2020 10.
Article in English | MEDLINE | ID: covidwho-728994

ABSTRACT

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1ß in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.


Subject(s)
Coronavirus Infections/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Interleukin-8/immunology , Pneumonia, Viral/immunology , Tumor Necrosis Factor-alpha/immunology , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Cytokines/immunology , Female , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Severity of Illness Index , Survival Rate
6.
J Hematol Oncol ; 13(1): 94, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-647080

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York. METHODS: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. RESULTS: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19-68) days from initial positive PCR. CONCLUSIONS: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Multiple Myeloma/complications , Pneumonia, Viral/complications , Tertiary Care Centers , Agammaglobulinemia/mortality , Agammaglobulinemia/pathology , Aged , COVID-19 , Cohort Studies , Coronavirus Infections/mortality , Female , Humans , Immunocompromised Host , Inflammation/mortality , Inflammation/pathology , Male , Middle Aged , Multiple Myeloma/immunology , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2
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