The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody.
Humans
Retrospective Studies
Male
Female
Middle Aged
Virus Shedding
/ drug effects
SARS-CoV-2
/ immunology
COVID-19
/ virology
Antiviral Agents
/ therapeutic use
Aged
Lymphoma, B-Cell
/ drug therapy
Risk Factors
Viral Load
/ drug effects
COVID-19 Drug Treatment
Immunocompromised Host
Adult
Antibodies, Monoclonal
/ therapeutic use
Antibodies, Viral
/ blood
Rituximab
/ therapeutic use
Antibodies, Neutralizing
/ immunology
Aged, 80 and over
Anti-CD20
B-cell lymphoma
Bendamustine
COVID-19
Persistent infection
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
22 Jul 2024
22 Jul 2024
Historique:
received:
18
02
2024
accepted:
18
07
2024
medline:
23
7
2024
pubmed:
23
7
2024
entrez:
22
7
2024
Statut:
epublish
Résumé
The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.
Sections du résumé
BACKGROUND
BACKGROUND
The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection.
METHODS
METHODS
This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression.
RESULTS
RESULTS
Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding.
CONCLUSIONS
CONCLUSIONS
Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.
Identifiants
pubmed: 39039440
doi: 10.1186/s12879-024-09631-3
pii: 10.1186/s12879-024-09631-3
doi:
Substances chimiques
Antiviral Agents
0
Antibodies, Monoclonal
0
Antibodies, Viral
0
Rituximab
4F4X42SYQ6
Antibodies, Neutralizing
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
715Informations de copyright
© 2024. The Author(s).
Références
Duléry R, Lamure S, Delord M, et al. Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy. Am J Hematol. 2021;96(8):934–44.
doi: 10.1002/ajh.26209
pubmed: 33909916
pmcid: 8212109
Avouac J, Drumez E, Hachulla E, et al. COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study. Lancet Rheumatol. 2021;3(6):e419–26.
doi: 10.1016/S2665-9913(21)00059-X
pubmed: 33786454
pmcid: 7993930
Elliott EK, Hensen R, Haupt LM, Griffiths LR. Global reported impacts of COVID-19 on lymphoma patients and the emerging clinical management approaches in response to the ongoing pandemic. Eur J Haematol. 2023;110(5):457–69.
doi: 10.1111/ejh.13926
pubmed: 36656099
Wada D, Nakamori Y, Maruyama S, et al. Novel treatment combining antiviral and neutralizing antibody-based therapies with monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. Exp Hematol Oncol. 2022;11(1):53.
doi: 10.1186/s40164-022-00307-9
pubmed: 36085172
pmcid: 9462070
Shimazu H, Wada D, Maruyama S, et al. Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study. BMC Infect Dis. 2023;23(1):780.
doi: 10.1186/s12879-023-08797-6
pubmed: 37946111
pmcid: 10636837
VanBlargan LA, Errico JM, Halfmann PJ, et al. An infectious SARS-CoV-2 B. 1.1. 529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med. 2022;28(3):490–5.
doi: 10.1038/s41591-021-01678-y
pubmed: 35046573
pmcid: 8767531
Takashita E, Kinoshita N, Yamayoshi S, et al. Efficacy of antibodies and antiviral drugs against Covid-19 omicron variant. N Engl J Med. 2022;386(10):995–8.
doi: 10.1056/NEJMc2119407
pubmed: 35081300
Takashita E, Kinoshita N, Yamayoshi S, et al. Efficacy of antiviral agents against the SARS-CoV-2 omicron subvariant BA. 2. N Engl J Med. 2022;386(15):1475–7.
doi: 10.1056/NEJMc2201933
pubmed: 35263535
Takashita E, Yamayoshi S, Simon V, et al. Efficacy of antibodies and antiviral drugs against Omicron BA. 2.12. 1, BA. 4, and BA. 5 subvariants. N Engl J Med. 2022;387(5):468–70.
doi: 10.1056/NEJMc2207519
pubmed: 35857646
Brown LK, Moran E, Goodman A, et al. Treatment of chronic or relapsing COVID-19 in immunodeficiency. J Allergy Clin Immunol. 2022;149(2):557–61.
doi: 10.1016/j.jaci.2021.10.031
pubmed: 34780850
Weinbergerová B, Demel I, Víšek B, et al. Successful early use of anti-SARS-CoV-2 monoclonal neutralizing antibodies in SARS-CoV-2 infected hematological patients - a Czech multicenter experience. Hematol Oncol. 2022;40(2):280–6.
doi: 10.1002/hon.2974
pubmed: 35120267
pmcid: 9015292
Assanto GM, Di Rocco A, Malfona F, et al. Impact of anti-SARS-CoV-2 monoclonal antibodies in the management of patients with lymphoma and COVID19: A retrospective study. Hematol Oncol. 2023;41(3):343–53.
doi: 10.1002/hon.3113
pubmed: 36521843
Combes P, Bisseux M, Bal A, et al. Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing. Clin Microbiol Infect. 2022;28(11):1503.e5-e8.
doi: 10.1016/j.cmi.2022.06.030
pubmed: 35792280
Ayadi W, Taktak A, Gargouri S, et al. Development of a simple genotyping method based on indel mutations to rapidly screen SARS-CoV-2 circulating variants: Delta, Omicron BA.1 and BA.2. J Virol Methods. 2022;307:114570.
doi: 10.1016/j.jviromet.2022.114570
pubmed: 35724698
pmcid: 9212420
Wilhelm A, Agrawal S, Schoth J, et al. Early detection of SARS-CoV-2 Omicron BA.4 and BA.5 in German wastewater. Viruses. 2022;14(9):1876.
doi: 10.3390/v14091876
pubmed: 36146683
pmcid: 9503272
Addetia A, Piccoli L, Case JB, et al. Neutralization, effector function and immune imprinting of Omicron variants. Nature. 2023;621(7979):592–601.
doi: 10.1038/s41586-023-06487-6
pubmed: 37648855
pmcid: 10511321
Bruel T, Vrignaud LL, Porrot F, et al. Antiviral activities of sotrovimab against BQ. 1.1 and XBB. 1.5 in sera of treated patients. medRxiv [Preprint]. 2023.
Stevens LJ, Pruijssers AJ, Lee HW, et al. Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms. Sci Transl Med. 2022;14(656):eabo0718.
doi: 10.1126/scitranslmed.abo0718
pubmed: 35482820
Alteri C, Fox V, Scutari R, et al. A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients. Commun Biol. 2022;5(1):1376.
doi: 10.1038/s42003-022-04322-8
pubmed: 36522489
pmcid: 9753865
Masyeni S, Iqhrammullah M, Frediansyah A, et al. Molnupiravir: a lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2-a narrative review. J Med Virol. 2022;94(7):3006–16.
doi: 10.1002/jmv.27730
pubmed: 35315098
pmcid: 9088670
Iketani S, Mohri H, Culbertson B, et al. Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. Nature. 2023;613(7944):558–64.
doi: 10.1038/s41586-022-05514-2
pubmed: 36351451
Hu Y, Lewandowski EM, Tan H, et al. Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. ACS Cent Sci. 2023;9(8):1658–69.
doi: 10.1021/acscentsci.3c00538
pubmed: 37637734
pmcid: 10451032
Ip JD, Wing-Ho Chu A, et al. Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance. EBioMedicine. 2023;91:104559.
doi: 10.1016/j.ebiom.2023.104559
pubmed: 37060743
pmcid: 10101811
Kiso M, Yamayoshi S, Iida S, et al. In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir. Nat Commun. 2023;14(1):4231.
doi: 10.1038/s41467-023-40018-1
pubmed: 37454219
pmcid: 10349878
Pasquini Z, Toschi A, Casadei B, et al. Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS-CoV-2 infection. Hematol Oncol. 2023;41(5):904–11.
doi: 10.1002/hon.3206
pubmed: 37452579
Mikulska M, Sepulcri C, Dentone C, et al. Triple combination therapy with 2 antivirals and monoclonal antibodies for persistent or relapsed severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis. 2023;77(2):280–6.
doi: 10.1093/cid/ciad181
pubmed: 36976301
Sun B, Feng Y, Mo X, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):940–8.
doi: 10.1080/22221751.2020.1762515
pubmed: 32357808
pmcid: 7273175
Yunoki M, Kubota KR, Imada T, et al. Changes in anti–SARS-CoV-2 antibody titers of pooled plasma derived from donors in Japan: a potential tool for mass-immunity evaluation. J Infect Dis. 2023;228(7):889–94.
doi: 10.1093/infdis/jiad178
pubmed: 37224513
Thornton CS, Huntley K, Berenger BM, et al. Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values. Antimicrob Resist Infect Control. 2022;11(1):1–6.
doi: 10.1186/s13756-022-01067-1
Franceschini E, Pellegrino M, Todisco V, et al. Persistent SARS-CoV-2 infection with multiple clinical relapses in two patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. Infection. 2023;51:1577–81.
doi: 10.1007/s15010-023-02039-2
pubmed: 37076752
Martínez-López J, De la Cruz J, Gil-Manso R, et al. COVID-19 severity and survival over time in patients with hematologic malignancies: a population-based registry study. Cancers (Basel). 2023;15(5):1497.
doi: 10.3390/cancers15051497
pubmed: 36900296
Ishio T, Tsukamoto S, Yokoyama E, et al. Anti-CD20 antibodies and bendamustine attenuate humoral immunity to COVID-19 vaccination in patients with B-cell non-Hodgkin lymphoma. Ann Hematol. 2023;102(6):1421–31.
doi: 10.1007/s00277-023-05204-7
pubmed: 37041299
pmcid: 10089694
Ichikawa T, Tamura T, Takahata M, et al. Prolonged shedding of viable SARS-CoV-2 in immunocompromised patients with haematological malignancies: a prospective study. Br J Haematol. 2024;204(3):815–20.
doi: 10.1111/bjh.19143
pubmed: 37795527
Visco C, Marcheselli L, Mina R, et al. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study. Blood Adv. 2022;6(1):327–38.
doi: 10.1182/bloodadvances.2021005691
pubmed: 34644385
pmcid: 8516438