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1.
Open Forum Infectious Diseases ; 8(SUPPL 1):S22-S23, 2021.
Article in English | EMBASE | ID: covidwho-1746807

ABSTRACT

Background. Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods. Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results. Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2;p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature's area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77;p = 0.033) and CRP (AUC 0.78;p < 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p < 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001;Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p < 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion. The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation.

2.
International Journal of Qualitative Methods ; 20:3-3, 2021.
Article in English | Web of Science | ID: covidwho-1558223
3.
International Journal of Qualitative Methods ; 20:6-6, 2021.
Article in English | Web of Science | ID: covidwho-1558128
4.
International Journal of Qualitative Methods ; 20:9-10, 2021.
Article in English | Web of Science | ID: covidwho-1558127
5.
Blood ; 136(Supplement 1):41-42, 2020.
Article in English | PMC | ID: covidwho-1338982

ABSTRACT

Background: Patients (pts) with hematologic disease are at increased risk of severe SARS-CoV-2 infection. Recent observations reported poor outcomes of COVID-19 in pts with various cancer types and higher mortality rates compared with the general population. However, currently available data on COVID-19 in pts with hematologic disease are limited.Methods: CHRONOS19 registry is an observational prospective cohort study with the primary objective to evaluate the treatment outcomes in adult pts (age 18 or older) with hematologic disease and COVID-19. Secondary objectives are to describe severity and complications of COVID-19 and course of hematologic disease in SARS-CoV-2 infected pts, and to explore importance of various factors for disease severity and mortality. Pts with laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 were eligible for enrollment. Data were collected on a web platform and managed in a de-identified manner. Physicians from 8 hematology clinical centers and hospitals from all over Russia (Moscow, Ulan-Ude, Saransk, Vladimir, Nizhniy Novgorod, Kazan) participate in this study. Pts are followed for 30 days (ds) after COVID-19 diagnosis and up to 6 months (mos) for hematologic disease outcomes and overall survival assessment. The results of the first follow-up are presented in this interim analysis.Results: As of July 30, 2020, 184 pts were enrolled (females/males [n(%)]: 80(44%)/104 (56%);median [range] age: 55 [18-83] years. Disease type (malignant/non-malignant [n(%)]): 164(89%)/20(11%), including AML 36(20%), ALL 16(9%), MDS 5(2%), APL 5(2%), MM 38(21%), HL 4(2%), NHL 38(21%), MPN 9(5%), CLL 13(7%), others 20(11%). Concomitant diseases were in 95(52%) pts: cardiovascular 56(59%), pulmonary 6(6%), hepatic 6(6%) or renal 5(5%), diabetes 17(18%), obesity 4(4%), other 16(17%). 176 patients were evaluable for the primary outcome assessment with a median follow-up of 41(1-125) ds. Thirty-day all-cause mortality was 23% (41 pts died). Death due to COVID-19 complications occurred in 34 (83%) pts, 7(17%) pts died due to progression of hematologic disease. Fifty (28%) pts experienced COVID-19 complications, the most common were pneumonia in 125 (71%) pts, respiratory failure in 82(47%) pts, ARDS in 11(6%) pts, cytokine release syndrome in 15(9%) pts, multiple organ failure in 10(6%) pts, sepsis in 6(3%) pts, and pulmonary bleeding in 1(0,6%). Specific anti-COVID-19 treatment was given to 117 pts(67%) pts: most common first-line treatment was hydroxichloroquine+azithromycin in 84(72%) pts, azithromycin monotherapy in 27(23%) pts, other drugs in 6(5%) pts;second-line treatment comprised lopinavir+ritonavir in 38 pts, tocilizumab in 29 pts, umifenovir in 5 pts, baricitinib in 5 pts, canakinumab in 1pt, sarilumab in 1 pt. The rate of ICU admissions was 27%(47 pts), among them only 11(23%) pts survived, 36(20%) pts required mechanical ventilation, only 2(5.5%) pts survived. Eighty-eight(50%) pts received anticoagulants. With regard to the blood disease, treatment delays occurred in 101(57%) pts with a median 4 weeks, 6(3%) pts required change of treatment. At the first follow-up (30 ds) the rate of relapse / progression of hematologic disease was 16 of 151 evaluable pts (10.6%). Thirty-day overall survival was 75%. At the data cutoff, median overall survival was not reached. Antibody detection was performed in 70 pts: 53(76%) pts had IgG SARS-CoV-2 antibodies. Among factors possibly associated with poor survival were: stage of COVID-19 1(n=41) - 91,8%/ 2(n=75) - 90%/ 3(n=36) - 56,5%/ 4(n=22) - 13,6% (p<0,0001), concomitant diseases (n=93/81): 59,5% vs. 87% (p=0,0001), transfusion dependence (n=65/104): 58,1% vs. 81,8% (p=0,0007), prior steroid therapy (n=73/90): 64,6% vs. 82% (p=0,019), older age (<60 (n=108)/≥60 (n=68) years): 80% vs. 60% (p=0,048). Sex, disease type, myelotoxic agranulocytosis, and prior hematopoietic stem cell transplantation were not associated with worse outcomes. Data on the longer follow-up (90 and 180 ds) will be presented.Conclusions: Patients w th hematologic disease and SARS-CoV-2 infection have high 30-day all-cause mortality predominantly due to COVID-19 complications. Stage of COVID-19, concomitant diseases, transfusion dependence, prior steroid therapy, and older age were associated with poor outcomes.

6.
Open Forum Infectious Diseases ; 7(SUPPL 1):S279-S280, 2020.
Article in English | EMBASE | ID: covidwho-1185790

ABSTRACT

Background: It is estimated that up to 10% of SARS-CoV-2 patients progress from early and pulmonary stages to the most severe stage of illness, which manifests as an extra-pulmonary systemic hyperinflammatory syndrome. Interferon gamma-induced protein 10 (IP-10) is an inflammatory marker that plays a role in the dysregulated host response of COVID-19 infected patients. Clinical monitoring of IP-10 has been restricted in the absence of a rapid diagnostic test. MeMed KeyTM is a novel platform recently cleared to provide IP-10 measurements in 15 minutes. We hypothesized that providing physicians with real time IP-10 measurements would support detection and continuous monitoring of patients with a dysregulated immune response and potentially allow personalized immunomodulation to improve patient outcome. IP-10 levels reflect corticosteroid treatment Methods: From 7th April 2020 to 10th May 2020 blood was routinely collected serially from 52 SARS-CoV-2 positive patients hospitalized at a COVID-19 dedicated medical center. A clinical decision support protocol was in place focused on managing viral response, oxygenation and inflammatory state (NCT04389645). Results: The median age of the 52 patients was 69, 69% were male, 21% were ventilated, 4 died, 2 due to non-COVID-19 related complications. The most common comorbidities were Diabetes 40% and Hypertension 46%. IP-10 >1000 pg/ml correlated with ICU admission (p< 0.05) and increased COVID-19 severity score (p< 0.01). 19 of the 52 patients had IP-10 >1000 pg/ml, of these 12 were treated with corticosteroids. Monitoring IP-10 within the clinical decision support protocol assisted with personalized corticosteroid regimens with the aim of reducing IP-10 < 1000 pg/ml. The 10 patients that survived exhibited IP-10 levels >1000 pg/ml for 2.6 days on average. In contrast, the 2 patients that died of COVID-19 related complications displayed an average of 7.5 days with IP-10 >1000 pg/ml (p< 0.05). Conclusion: Providing physicians with real time measurements of IP-10 in COVID-19 patients proved a useful tool as part of the clinical decision support protocol. Timely identification, monitoring and personalized treatment of COVID-19 patients exhibiting a dysregulated immune response may aid in improving patient outcome. Further studies are warranted.

7.
Sci Rep ; 11(1): 3461, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1078603

ABSTRACT

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.


Subject(s)
COVID-19/immunology , Immunoglobulin G/immunology , Interleukin-12/blood , Interleukin-33/blood , Seroconversion/physiology , Antibody Formation , COVID-19/blood , COVID-19/diagnosis , Humans , Severity of Illness Index
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