Abstract

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery.

Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020 and Sept 1, 2020 and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months.

Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%) and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%) and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were readmitted for COVID-related reasons.

Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even one year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia and gastro-intestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8,5% requiring a COVID-19 related re-admission.

Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Data availability

Data Availability Statement: The study protocol, statistical analysis plan, lists of deidentified individual data, generated tables and figures will be made available upon request by qualified scientific and medical researchers for legitimate research purposes. Requests should be sent to achaftari@mdanderson.org and yijiang@mdanderson.org. Data will be available on request for 6 months from the date of publication. Investigators are invited to submit study proposal requests detailing research questions and hypotheses in order to receive access to these data.

Article and author information

Author details

  1. Hiba Dagher

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Anne-Marie Chaftari

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    For correspondence
    achaftari@mdanderson.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8097-8452
  3. Ishwaria M Subbiah

    Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandre E Malek

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ying Jiang

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter Lamie

    Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Bruno Granwehr

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Teny John

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Eduardo Yepez

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Jovan Borjan

    Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Cielito Reyes-Gibby

    Emergency Medicine-Research, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4500-6476
  12. Mary Flores

    Emergency Medicine-Research, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Fareed Khawaja

    Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Mala Pande

    Gastroenterology Research, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Noman Ali

    Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Raniv Rojo

    Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Daniel D Karp

    Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Patrick Chaftari

    Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Ray Hachem

    Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Issam I Raad

    Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (P30CA016672)

  • Hiba Dagher
  • Anne-Marie Chaftari
  • Ishwaria M Subbiah
  • Alexandre E Malek
  • Ying Jiang
  • Peter Lamie
  • Bruno Granwehr
  • Teny John
  • Eduardo Yepez
  • Jovan Borjan
  • Cielito Reyes-Gibby
  • Mary Flores
  • Fareed Khawaja
  • Mala Pande
  • Noman Ali
  • Raniv Rojo
  • Daniel D Karp
  • Ray Hachem
  • Issam I Raad

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved by the institutional review board at MD Anderson. A waiver of informed consent was obtained since this study posed no risk to the patients given that no clinical or laboratory interventions were done.

Copyright

© 2023, Dagher et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,411
    views
  • 338
    downloads
  • 21
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Hiba Dagher
  2. Anne-Marie Chaftari
  3. Ishwaria M Subbiah
  4. Alexandre E Malek
  5. Ying Jiang
  6. Peter Lamie
  7. Bruno Granwehr
  8. Teny John
  9. Eduardo Yepez
  10. Jovan Borjan
  11. Cielito Reyes-Gibby
  12. Mary Flores
  13. Fareed Khawaja
  14. Mala Pande
  15. Noman Ali
  16. Raniv Rojo
  17. Daniel D Karp
  18. Patrick Chaftari
  19. Ray Hachem
  20. Issam I Raad
(2023)
Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.
eLife 12:e81182.
https://doi.org/10.7554/eLife.81182

Share this article

https://doi.org/10.7554/eLife.81182

Further reading

    1. Epidemiology and Global Health
    2. Medicine
    3. Microbiology and Infectious Disease
    Edited by Diane M Harper et al.
    Collection

    eLife has published the following articles on SARS-CoV-2 and COVID-19.

    1. Cancer Biology
    2. Immunology and Inflammation
    Sofia V Krasik, Ekaterina A Bryushkova ... Ekaterina O Serebrovskaya
    Research Article

    The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.