scholarly journals COVID-19 in Patients with Hematological Malignancies: High False Negative Rate with High Mortality

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Alex Niu ◽  
Bo Ning ◽  
Francisco Socola ◽  
Hana Safah ◽  
Tim Reynolds ◽  
...  
Keyword(s):  
High Mortality ◽  
Hematological Malignancies ◽  
False Negative ◽  
False Negative Rate ◽  
Respiratory Illness ◽  
Advisory Board ◽  
Rt Pcr ◽  
Negative Rate ◽  
Asymptomatic Patients ◽  
High False Negative Rate

Introduction Patients with hematological malignancies (HM) are uniquely immunocompromised and considered at high risk for COVID-19. However, data regarding the diagnosis, clinical course, treatment, and outcomes of these patients is sparse. In particular, the ability to successfully detect SARS-CoV-2 in patients with HM remains unknown. We have previously reported 2 cases of allogeneic stem cell transplant (SCT) diagnosed with COVID-19 using clustered regularly interspaced short palindromic repeats (CRISPR) technique, following multiple negative nasopharyngeal RT-PCR testing (Niu et al. Bone Marrow Transplantation - Nature). Here we examine 29 patients with a variety of HM with high suspicion for COVID-19 based on clinical presentation, lab results, and imaging, whom were tested with CRISPR and/or RT-PCR based techniques. From 3/31/20 to 7/17/20, 29 patients (age 24 to 82) with a variety of HM (20 lymphoid, 9 myeloid; Table 1), 24 of which presented with an undiagnosed respiratory illness and 5 presented while asymptomatic for testing prior to chemotherapy, were evaluated for COVID-19. While 16 patients tested positive for COVID-19 with guideline-directed nasopharyngeal RT-PCR testing (including the 5 asymptomatic patients), 13 patients tested negative with the same technique. However, based on their clinical history, imaging, and disease course, concern for COVID-19 infection remained in these 13 patients. We then used CRISPR technology available at our institution (Huang et al. Biosensors and Bioelectronics) to test 8 patients who initially tested negative by RT-PCR. Surprisingly, 7 of the 8 patients tested positive for COVID-19 with either a blood sample and/or nasal swab for the SARS-CoV-2 specific N gene and ORF1ab gene. Excluding the patients who were negative by RT-PCR and not tested by CRISPR, the rate of false negativity with RT-PCR testing is significantly elevated at 29% (7/24) in our cohort of HM, which compares unfavorably with the expected false negative rates of RT-PCR techniques. A very high fatality rate was observed with 9 out of the 29 patients (31%) ultimately dying. Fifteen patients were undergoing active chemotherapy, 4 had received an autologous SCT, 6 had received an allogeneic SCT, and 4 were on surveillance. Of the 23 COVID-19 positive patients (by RT-PCR or CRISPR), 8 patients received COVID-19-directed therapy with either hydroxychloroquine/azithromycin, remdesivir, and/or Covid-19 convalescent plasma (CCP) depending on their clinical status, and 4 patients expired. Of the 8 treated patients, 7 improved while 1 patient expired. For the 5 patients who were negative for RT-PCR with no CRISPR completed, 1 patient received hydroxychloroquine/azithromycin proactively due to symptoms and imaging and recovered, while 3 patients expired at outside facilities due to unknown causes. Breakdown of testing and treatment is shown in Fig. 1. The majority of our patients had undergone SCT or were actively on chemotherapy, notably lymphodepleting chemotherapy. Associated with the fact that COVID-19 is known to worsen lymphopenia, our patient's symptoms and immune response to COVID-19 is likely to differ from immunocompetent hosts. This translated into an overall worse outcome as seen by the high mortality with our patients. In our limited dataset, patients presented with a variety of symptoms ranging from asymptomatic to acute respiratory failure. Intriguingly, the 5 asymptomatic patients had lymphoid malignancies and were on chemotherapy. It is thus imperative to establish the diagnosis of COVID-19 quickly, as faster initiation of treatment has been associated with better outcomes. The 8 patients who were diagnosed and treated improved substantially. However, as seen by our dataset, a strikingly high false negative rate was observed. Thus, a high clinical suspicion must guide further workup and therapy in patients with HM who present with an undiagnosed respiratory illness consistent with COVID-19. Patients with HM can have a wide variety of presentations when infected with COVID-19. For this select patient population we must establish an algorithm to diagnose COVID-19 efficiently as we reported a high number of initial false negative COVID-19 tests before the more sensitive CRISPR revealed a positive test. In addition, treatment pathways need to be instituted to not only treat COVID-19 infection, but also provide the best treatment for these patient's underlying HM. Disclosures Safah: Amgen: Honoraria; Verastem: Honoraria; Janssen: Speakers Bureau; Astellas: Speakers Bureau. Saba:Kite: Other: Advisory Board; Pharmacyclics: Other: Advisory Board, Speakers Bureau; AbbVie: Consultancy, Other: Advisory Board, Speakers Bureau; Janssen: Other: Advisory Board, Speakers Bureau; Kyowa Kirin: Other: Advisory Board.

scholarly journals High mortality with High false negative rate: COVID-19 infection in patients with hematologic malignancies

2021 ◽  
Vol 106 ◽  
pp. 106582
Author(s):  
Alex Niu ◽  
Bo Ning ◽  
Francisco Socola ◽  
Hana Safah ◽  
Tim Reynolds ◽  
...  
Keyword(s):  
High Mortality ◽  
False Negative ◽  
False Negative Rate ◽  
Hematologic Malignancies ◽  
Negative Rate ◽  
High False Negative Rate

scholarly journals False Negative Mitigation in Group Testing for COVID-19 Screening

2021 ◽  
Vol 8 ◽  
Author(s):  
Amir Reza Alizad Rahvar ◽  
Safar Vafadar ◽  
Mehdi Totonchi ◽  
Mehdi Sadeghi
Keyword(s):  
Viral Load ◽  
False Negative ◽  
Group Testing ◽  
False Negative Rate ◽  
Screening Strategy ◽  
Web Interface ◽  
Rt Pcr ◽  
Promising Candidate ◽  
Testing Method ◽  
High False Negative Rate

After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.

scholarly journals Microfluidic Nano-Scale qPCR Enables Ultra-Sensitive and Quantitative Detection of SARS-CoV-2

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1425
Author(s):  
Xin Xie ◽  
Tamara Gjorgjieva ◽  
Zaynoun Attieh ◽  
Mame Massar Dieng ◽  
Marc Arnoux ◽  
...  
Keyword(s):  
Viral Infections ◽  
Limit Of Detection ◽  
False Negative ◽  
False Negative Rate ◽  
Clinical Samples ◽  
Quantitative Detection ◽  
Rt Pcr ◽  
Viral Loads ◽  
Nano Scale ◽  
Negative Rate

A major challenge in controlling the COVID-19 pandemic is the high false-negative rate of the commonly used RT-PCR methods for SARS-CoV-2 detection in clinical samples. Accurate detection is particularly challenging in samples with low viral loads that are below the limit of detection (LoD) of standard one- or two-step RT-PCR methods. In this study, we implemented a three-step approach for SARS-CoV-2 detection and quantification that employs reverse transcription, targeted cDNA preamplification, and nano-scale qPCR based on a commercially available microfluidic chip. Using SARS-CoV-2 synthetic RNA and plasmid controls, we demonstrate that the addition of a preamplification step enhances the LoD of this microfluidic RT-qPCR by 1000-fold, enabling detection below 1 copy/µL. We applied this method to analyze 182 clinical NP swab samples previously diagnosed using a standard RT-qPCR protocol (91 positive, 91 negative) and demonstrate reproducible and quantitative detection of SARS-CoV-2 over five orders of magnitude (<1 to 106 viral copies/µL). Crucially, we detect SARS-CoV-2 with relatively low viral load estimates (<1 to 40 viral copies/µL) in 17 samples with negative clinical diagnosis, indicating a potential false-negative rate of 18.7% by clinical diagnostic procedures. In summary, this three-step nano-scale RT-qPCR method can robustly detect SARS-CoV-2 in samples with relatively low viral loads (<1 viral copy/µL) and has the potential to reduce the false-negative rate of standard RT-PCR-based diagnostic tests for SARS-CoV-2 and other viral infections.

scholarly journals 0587 Convenience vs Accuracy: Negative Predictability of the Home Sleep Test in Clinical Practice

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A225-A225
Author(s):  
C D Morse ◽  
S Meissner ◽  
L Kodali
Keyword(s):  
Clinical Practice ◽  
Sleep Apnea ◽  
False Negative ◽  
False Negative Rate ◽  
True Negative ◽  
Negative Rate ◽  
High False Negative Rate ◽  
Obstructive Sleep ◽  
Respiratory Disturbance ◽  
Lost To Follow Up

Abstract Introduction Sleep apnea is a serious disorder associated with numerous health conditions. In clinical practice, providers order screening home sleep testing (HST) for obstructive sleep apnea (OSA); however, there is limited research about the negative predictive value (NPV) and false negative rate of this test. Providers may not understand HST limitations; therefore, what is the NPV and false negative rate in clinical practice? Methods A retrospective study of non-diagnostic HST is conducted in a Northeastern US rural community sleep clinic. The study population includes adult patients ≥ 18 years old who underwent HST from 2016-2019. The non-diagnostic HST result is compared to the gold standard, the patient’s nocturnal polysomnogram (NPSG). The results provide the NPV (true negative/total) and false negative (true positive/total) for the non-diagnostic HST. Results We identified 211 potential patients with a mean age of 43 years, of which 67% were female. Of those, 85% (n=179) underwent NPSG, with the others declining/delaying testing or lost to follow up. The non-diagnostic HST showed 15.6% NPV for no apnea using AHI&lt;5 and 8.4% NPV using respiratory disturbance index (tRDI)&lt;5. The false negative rate for AHI/tRDI was 84.4% and 91.6%, respectively. The AHI for positive tests ranged from 5-89 per hour (mean AHI 14.9/tRDI 16/hour), of which OSA was identified with an elevated AHI (≥5) ranging from 54.2% mild, 21.8% moderate, and 8.4% severe. Conclusion The high false negative rate of the HST is alarming. Some providers and patients may forgo NPSG after non-diagnostic HST due to a lack of understanding for the HST’s limitations. Knowing that the non-diagnostic HST is a very poor predictor of no sleep apnea will help providers advise patients appropriately for the necessity of the NPSG. The subsequent NPSG provides an accurate diagnosis and, therefore, an informed decision about pursuing or eschewing sleep apnea treatment. Support none

scholarly journals Avoiding COVID-19 Hospital Outbreaks: RT-PCR Swab and Clinical Assessment

2021 ◽  
Author(s):  
Luca Allievi ◽  
Amedeo Bongarzoni ◽  
Guido Tassinario ◽  
Stefano Carugo
Keyword(s):  
Clinical Assessment ◽  
False Negative ◽  
False Negative Rate ◽  
High Specificity ◽  
Diagnostic Process ◽  
Rt Pcr ◽  
Negative Results ◽  
High False Negative Rate ◽  
Degree Of Confidence ◽  
Low Sensitivity

Nasopharyngeal RT-PCR swab test for COVID-19 diagnosis has a high specificity but also a low sensitivity. The high false-negative rate and the overconfidence in negative results sometimes lead to hospital outbreaks. Therefore, we recommend always integrating the clinical assessment in the diagnostic process, mostly after the test, to determine what degree of confidence can be attributed to a negative result.

High False-Negative Rate of HER2 Quantitative Reverse Transcription Polymerase Chain Reaction of the Oncotype DX Test: An Independent Quality Assurance Study

2011 ◽  
Vol 29 (32) ◽  
pp. 4279-4285 ◽  
Author(s):  
David J. Dabbs ◽  
Molly E. Klein ◽  
Syed K. Mohsin ◽  
Raymond R. Tubbs ◽  
Yongli Shuai ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Quality Assurance ◽  
Reverse Transcription ◽  
False Negative ◽  
False Negative Rate ◽  
Oncotype Dx ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Negative Rate ◽  
Polymerase Chain

Purpose HER2 (ERBB2) status is an important prognostic and predictive marker in breast carcinoma. In recent years, Genomic Health (GHI), purveyors of the Oncotype DX test, has been separately reporting HER2 by reverse transcription polymerase chain reaction (RT-PCR) to oncologists. Because of the lack of independent evaluation, this quality assurance study was undertaken to define the concordance rate between immunohistochemistry (IHC)/fluorescent in situ hybridization (FISH) and GHI RT-PCR HER2 assay. Methods All patients at three participating laboratories (Magee-Womens Hospital [Pittsburgh, PA], Cleveland Clinic [Cleveland, OH], and Riverside Methodist Hospital [Columbus, OH]) with available HER2 RT-PCR results from GHI were included in this study. All IHC-positive and equivocal patient cases were further evaluated and classified by FISH at respective laboratories. Results Of the total 843 patient cases, 784 (93%) were classified as negative, 36 (4%) as positive, and 23 (3%) as equivocal at the three institutions using IHC/FISH. Of the 784 negative patient cases, 779 (99%) were also classified as negative by GHI RT-PCR assay. However, all 23 equivocal patient cases were reported as negative by GHI. Of the 36 positive cases, only 10 (28%; 95% CI, 14% to 45%) were reported as positive, 12 (33%) as equivocal, and 14 (39%) as negative. Conclusion There was an unacceptable false-negative rate for HER2 status with GHI HER2 assay in this independent study. This could create confusion in the decision-making process for targeted treatment and potentially lead to mismanagement of patients with breast cancer if only GHI HER2 information is used.

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