The #Outcome of #COVID19 in Patients with #Hematological #Malignancy (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

The Outcome of COVID‐19 in Patients with Hematological Malignancy

Tugce Nur Yigenoglu MD,  Naim Ata Associated Professor,  Fevzi Altuntas Professor, Semih Bascı MD,  Mehmet Sinan Dal Associated Professor,  Serdal Korkmaz Associated Professor,  Sinem Namdaroglu Associated Professor,  Abdulkadir Basturk Associated Professor,  Tuba Hacıbekiroglu Associated Professor,  Mehmet Hilmi Dogu Associated Professor,  İlhami Berber Associated Professor,  Kursat Dal Associated Professor, Mehmet Ali Erkurt Professor,  Burhan Turgut Professor,  Mahir Ilgu,  Osman Celik MD,  Ersan Imrat,  Suayip Birinci MD

First published: 10 August 2020 | DOI:  https://doi.org/10.1002/jmv.26404

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26404

 

Abstract

Introduction

In this study, we aim to report the outcome of COVID‐19 in patients with hematological malignancy in Turkey.

Method

The data of laboratory‐confirmed 188,897 COVID‐19 patients diagnosed between March 11, 2020 and June 22, 2020 included in the Republic of Turkey, Ministry of Health database were analyzed retrospectively. All of the COVID‐19 patients with hematological malignancy (n=740) were included in the study and an age, gender and comorbidity matched COVID‐19 patients without cancer (n=740) at 1:1 ratio was used for comparison.

Results

Non Hodgkin lymphoma (30.1%), myelodysplastic syndrome (19.7%), myeloproliferative neoplasm (15.7%), were the most common hematological malignancies. The rates of severe and critical disease were significantly higher in patients with hematological malignancy compared to the patients without cancer (p=0.001). The rates of hospital and intensive care unit (ICU) admission were higher in patients with hematological malignancy compared to the patients without cancer (p=0.023, p=0.001, respectively). The length of hospital stay and ICU stay were similar between groups (p=0.7, p=0.3; retrospectively). The rate of mechanical ventilation (MV) support was higher in patients with hematological malignancy compared to the control group (p=0.001). The case fatality rate (CFR) was 13.8% in patients with hematological malignancy, and it was 6.8% in the control group (p=0.001).

Conclusion

This study reveals that there is an increased risk of COVID‐19 related serious events (ICU admission, MV support or death) in patients with hematological malignancy compared to COVID‐19 patients without cancer and supports high vulnerability of patients with hematological malignancy in the current pandemic.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Cancer; Hematology.

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Changes in the #Number of #US #Patients With Newly Identified #Cancer Before and During the #Coronavirus Disease 2019 (#COVID19) Pandemic (JAMA Netw Open, summary)

[Source: JAMA Network Open, full page: (LINK). Summary, edited.]

Changes in the Number of US Patients With Newly Identified Cancer Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic

Harvey W. Kaufman, MD1; Zhen Chen, MS1; Justin Niles, MA1; Yuri Fesko, MD1

Author Affiliations: 1 Quest Diagnostics, Secaucus, New Jersey

JAMA Netw Open. 2020;3(8):e2017267. doi:10.1001/jamanetworkopen.2020.17267

___

Introduction: In response to the coronavirus disease (COVID-19) pandemic, the American Society of Clinical Oncology recommends, “to conserve health system resources and reduce patient contact with health care facilities,… that cancer screening procedures that require clinic/center visits, such as screening mammograms and colonoscopy, be postponed for the time being.”1 A Washington Post headline reported, “Patients with heart attacks, strokes, and even appendicitis vanish from hospitals.”2 A study from 9 high-volume US cardiac catheterization laboratories3 found a 38% decrease in patients treated for ST-elevation myocardial infarction, considered a life-threatening condition. In this study, we analyzed weekly changes in the number of patients with newly identified cancer before and during the COVID-19 pandemic.

(…)

Keywords: SARS-CoV-2; COVID-19; Cancer; USA.

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A #COVID19 patient with repeatedly #undetectable #SARS-CoV-2 #antibodies (J Appl Lab Med., summary)

[Source: Journal of Applied Laboratory Medicine, full page: (LINK). Summary, edited.]

A COVID-19 patient with repeatedly undetectable SARS-CoV-2 antibodies

Lianna Goetz1, Jianbo Yang1, Wallace Greene1, Yusheng Zhu, PhD1*

1 Department of Pathology and Laboratory Medicine, Pennsylvania State University  College of Medicine

* Corresponding author: Yusheng Zhu, PhD, DABCC, FAACC, Department of Pathology &  Laboratory Medicine, Mail Code H160, Pennsylvania State University College of Medicine, 500 University Drivem Hershey, PA 17033 – Tel: (717) 531-5123; Fax: (717) 531-  3803 – E-mail: yzhu@pennstatehealth.psu.edu

© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Downloaded from https://academic.oup.com/jalm/article-abstract/doi/10.1093/jalm/jfaa137/5879990 by guest on 03 August 2020

___

Case Description: A 49-year-old male presented to the emergency department with 7  days of subjective fevers, headaches, muscle aches, increasing shortness-of-breath and  nonproductive cough. One of his family members had been tested positive for SARS-CoV- 2 three days ago. A review of the patient’s past medical history revealed he had chronic  lymphocytic leukemia (CLL) Rai stage IV, Binet stage C, with complex cytogenetics on  daily venetoclax of an obinutuzumab/venetoclax regimen. His past medical history was  also notable for uncontrolled insulin dependent diabetes mellitus type 2 for which he  had recently stopped taking his insulin medication.

(…)

Keywords: SARS-CoV-2; COVID-19; Cancer; Diabetes; Diagnostic tests.

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#Nosocomial #outbreak of #SARS-CoV-2 infection in a #haematological #unit – high #mortality rate in infected patients with haematologic #malignancies (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology | Available online 1 August 2020, 104574 | In Press, Journal Pre-proof

Nosocomial outbreak of SARS-CoV-2 infection in a haematological unit – high mortality rate in infected patients with haematologic malignancies

Monika M Biernat a, Aleksander Zińczuk b, Paweł Biernat c, Aleksandra Bogucka-Fedorczuk d, Jacek Kwiatkowski e, Elżbieta Kalicińsk a,f, Dominik Marciniak g, Krzysztof Simon h, Tomasz Wróbel i

a Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow  Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; b Department of Forensic Medicine, Wroclaw Medical University, Infectious Diseases Unit, Gromkowski Regional Hospital in Wrocław, Mikulicz-Radecki Street 4, Koszarowa Street 5, 51-149 50-345, Wroclaw, Poland; c Department of Drugs Form Technology, Wroclaw Medical University, Borowska Street 211A, 50-556, Wroclaw, Poland; d Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; e Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; f Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; g Department of Drugs Form Technology, Wroclaw Medical University, Borowska Street 211A, 50-556, Wroclaw, Poland; h Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Koszarowa Street 5, 51-149, Wroclaw, Poland; i Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow  Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Poland

Received 27 July 2020, Accepted 30 July 2020, Available online 1 August 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104574

 

Highlights

  • Higher mortality rate in COVID-19 patients with haematologic diseases.
  • Haematologic patients with COVID-19 have 50% less chance of survival.
  • Probability of death was higher in patients older than 40 yrs of age with AML/MDS.

 

Abstract

Background

Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2.

Methods

The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2.

Results

Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8%. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p < 0.05). Additionally, the probability of death was much higher in patients older than 40 years of age (p = 0.032).

Conclusion

This study showed significantly higher mortality rate in COVID-19 patients with haematologic diseases compared to the non-infected patient group. Haematologic patients with COVID-19 have 50% less chance of survival.

Keywords: SARS-CoV-2; COVID-19; Cancer; Hematology; Poland.

——

#Persistent #COVID19 in an #Immunocompromised Patient Temporarily Responsive to Two Courses of #Remdesivir #Therapy (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy

Marie Helleberg, Carsten Utoft Niemann, Kasper Moestrup, Ole Kirk, Anne-Mette Lebech, Clifford Lane, Jens Lundgren

The Journal of Infectious Diseases, jiaa446, https://doi.org/10.1093/infdis/jiaa446

Published: 23 July 2020

 

Abstract

The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever, and severe viral pneumonia. During two 10-day courses of remdesivir starting days 24 and 45 after fever onset, the pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.

COVID-19, SARS-CoV-2, remdesivir, immunocompromised, case report

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Antivirals; Remdesivir; Cancer.

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The #impact of the #COVID19 pandemic on #cancer #deaths due to #delays in #diagnosis in #England, #UK: a national, population-based, modelling study (Lancet Oncol., abstract)

[Source: Lancet Oncology, full page: (LINK). Abstract, edited.]

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study

Camille Maringe, PhD, Prof James Spicer, PhD, Melanie Morris, PhD, Prof Arnie Purushotham, MD, Prof Ellen Nolte, PhD, Prof Richard Sullivan, PhD, Prof Bernard Rachet, PhD †, Ajay Aggarwal, PhD  †

Open Access | Published: July 20, 2020 | DOI: https://doi.org/10.1016/S1470-2045(20)30388-0

 

Summary

Background

Since a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types.

Methods

In this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15–84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data.

Findings

We collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9–9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266–295) and 344 (329–358) additional deaths. For colorectal cancer, we estimate 1445 (1392–1591) to 1563 (1534–1592) additional deaths, a 15·3–16·6% increase; for lung cancer, 1235 (1220–1254) to 1372 (1343–1401) additional deaths, a 4·8–5·3% increase; and for oesophageal cancer, 330 (324–335) to 342 (336–348) additional deaths, 5·8–6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291–3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204–63 229 years.

Interpretation

Substantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer.

Funding

UK Research and Innovation Economic and Social Research Council.

Keywords: SARS-CoV-2; COVID-19; Cancer; England; UK.

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#Effect of #delays in the 2-week-wait #cancer #referral pathway during the #COVID19 pandemic on cancer #survival in the #UK: a modelling study (Lancet, abstract)

[Source: Lancet Oncology, full page: (LINK). Abstract, edited.]

Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: a modelling study

Amit Sud, PhD †, Bethany Torr, MSc †, Michael E Jones, PhD, John Broggio, MSci, Stephen Scott, BSc, Chey Loveday, PhD, Alice Garrett, MSc, Firza Gronthoud, MD, David L Nicol, FRACS, Shaman Jhanji, PhD, Stephen A Boyce, PhD, Matthew Williams, PhD, Prof Elio Riboli, MD, David C Muller, PhD, Emma Kipps, PhD, Prof James Larkin, PhD, Neal Navani, PhD, Prof Charles Swanton, FRS, Prof Georgios Lyratzopoulos, PhD, Ethna McFerran, PhD, Prof Mark Lawler, PhD, Prof Richard Houlston, DSc, Prof Clare Turnbull, PhD

Published: July 20, 2020 | DOI: https://doi.org/10.1016/S1470-2045(20)30392-2

 

Summary

Background

During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.

Methods

In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008–17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013–16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I–III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1–6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.

Findings

Across England in 2013–16, an average of 6281 patients with stage I–III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1–3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3–8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.

Interpretation

Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.

Funding

None.

Keywords: SARS-CoV-2; COVID-19; Cancer; UK.

——

#Clinical characteristics and #outcome of #SARS-CoV-2 infection in #Italian #pediatric #oncology patients: a study from the Infectious Diseases Working Group of the AIEOP (J Pediatr Infect Dis Soc., abstract)

[Source: Journal of the Pediatric Infectious Diseases Society, full page: (LINK). Abstract, edited.]

Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP

Gianni Bisogno, Massimo Provenzi, Daniele Zama, Annalisa Tondo, Cristina Meazza, Antonella Colombini, Federica Galaverna, Francesca Compagno, Francesca Carraro, Raffaela De Santis, Linda Meneghello, Valentina Baretta, Simone Cesaro

Journal of the Pediatric Infectious Diseases Society,  piaa088, https://doi.org/10.1093/jpids/piaa088

Published: 11 July 2020

 

ABSTRACT

Background

Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer.

Methods

We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1).

Results

The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir.

Conclusions

SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.

Issue Section: Original Article

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© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Cancer; Pediatrics; Italy; Antivirals; Chloroquine; Lopinavir / Ritonavir.

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Successful #Treatment With #Baloxavir Marboxil of a Patient With #Peramivir #Resistant #Influenza A / #H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell #Transplantation: A Case Report (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2020 Jul 6;20(1):478. doi: 10.1186/s12879-020-05205-1.

Successful Treatment With Baloxavir Marboxil of a Patient With Peramivir-Resistant Influenza A/H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell Transplantation: A Case Report

Naonori Harada 1, Wataru Shibata 2 3, Hideo Koh 4, Emi Takashita 5, Seiichiro Fujisaki 5, Hiroshi Okamura 1, Satoru Nanno 1, Koichi Yamada 2 3, Hirohisa Nakamae 1, Masayuki Hino 1, Hiroshi Kakeya 2 3

Affiliations: 1 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. 2 Department of Infection Control Science, Graduate School of Medicine, Osaka City University, Osaka, Japan. 3 Research Center for Infectious Disease Sciences (RCIDS), Graduate School of Medicine, Osaka City University, Osaka, Japan. 4 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. hide_koh@med.osaka-cu.ac.jp. 5 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

PMID: 32631240 DOI: 10.1186/s12879-020-05205-1

 

Abstract

Background:

Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir.

Case presentation:

A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/μL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2.

Conclusions:

In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.

Keywords: Allogeneic hematopoietic cell transplantation; Baloxavir marboxil; Dual E119D/R292K substitution; Immunocompromised host; Influenza A/H3N2; Neuraminidase mutation; Peramivir resistance.

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Hematology; H3N2; Cancer; Immunosuppression; Peramivir; Baloxavir.

—–

Characterization of #Neuraminidase #Inhibitor #Resistant #Influenza Virus Isolates From Immunocompromised Patients in the Republic of #Korea (Virol J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virol J. 2020 Jul 6;17(1):94. doi: 10.1186/s12985-020-01375-1.

Characterization of Neuraminidase Inhibitor-Resistant Influenza Virus Isolates From Immunocompromised Patients in the Republic of Korea

Heui Man Kim 1, Namjoo Lee 1, Mi-Seon Kim 1, Chun Kang 1, Yoon-Seok Chung 2

Affiliations: 1 Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea. 2 Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea. rollstone93@korea.kr.

PMID: 32631440 DOI: 10.1186/s12985-020-01375-1

 

Abstract

Background:

The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission.

Methods:

Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates.

Results:

Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus.

Conclusions:

Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.

Keywords: Drug resistance; H275Y; Immunocompromised patients; Influenza virus.

Keywords: Seasonal Influenza; H1N1pdm09; Cancer; Immunosuppression; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; S. Korea.

——