Evidence map›Paper›PMID 40668805›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2026

Protracted SARS-CoV-2 Infection in B-cell Depleted Patients: Immunologic and Viral Characteristics and Response to Dual and Extended Antiviral Therapy.

Jessica S Little, Gregory E Edelstein, Zoe Swank, Manish C Choudhary, Ella Borberg, Cameron T Nutt, Hayden S Andrews, Muneerah Aleissa, Urwah Kanwal, Katherine D Friedman and 15 more

Abstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Acute SARS-CoV-2 infection.Nature reviews. Disease primers · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Jessica S LittleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-8093-5647
Gregory E EdelsteinDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0008-3415-3167
Zoe SwankDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Manish C ChoudharyDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ella BorbergDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-7154-6225
Cameron T NuttDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hayden S AndrewsDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0009-3777-9744
Muneerah AleissaDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Urwah KanwalDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Katherine D FriedmanDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Anna PiermatteiDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hannah LevineDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Rinki DeoDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aidan EustaceDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0001-7019-343X
Xiaofang LiDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Scott Dryden-PetersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-8487-9731
Lisa CosimiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Pritha SenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Meghan A BakerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Ann E WoolleyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan Z LiDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-9914-9662
David R WaltDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-5524-7348
Nicolas C IssaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-6596-0518
Lindsey R BadenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Amy C ShermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
High-dimensional single-cell mapping to define immune signatures of cytomegalovirus-associated rejection in cardiac transplantationK08HL157725 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SEN, PRITHA · 2021 to 2025
$929k
Chleck FoundationNational Institute of Allergy and Infectious DiseasesNCATS NIH HHS UL1 TR002541NCATS NIH HHS UL1TR002541NHLBI NIH HHS K08 HL157725NIAID NIH HHS P30 AI060354
6 · The paper itself

Abstract

backgroundImmunocompromised patients remain at risk for protracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections with persistent viral shedding that could pose a wider public health risk. The optimal therapeutic strategy remains unknown.

methodsWe describe a sequential case series of immunocompromised adults with protracted SARS-CoV-2 infection who received dual/extended antiviral therapy (median 23d nirmatrelvir/r; 8d remdesivir). Protracted infection was defined as persistent viral shedding and prolonged symptoms unresponsive to antiviral monotherapy in B-cell-depleted patients. Plasma anti-spike immunoglobulin G (IgG) and spike antigen were analyzed using the single molecule array assay (Simoa), viral RNA levels defined by cycle thresholds (Ct) from clinical assays and quantitative RNA polymerase chain reaction (PCR) testing, and whole virus and targeted nsp5/nsp12 sequencing were performed.

resultsSixteen patients with protracted SARS-CoV-2 infection were treated with dual/extended antivirals. Viral sequencing supported the presence of protracted infections in all tested, but only 1 participant demonstrated mutations conferring antiviral resistance. Humoral immune responses were blunted both at initiation and completion of therapy. All participants responded to dual/extended antiviral therapy with negative PCR at a median of 13 days post-treatment, no evidence of virologic recurrence, and no clinical relapse at 1 year. One patient with recurrent positive SARS-CoV-2 testing was demonstrated to have a new infection by sequencing.

conclusionsDual/extended antiviral therapy with nirmatrelvir/r and remdesivir can be effective for protracted SARS-CoV-2 infection in B-cell-depleted patients who fail antiviral monotherapy, despite persistently blunted humoral immune responses. Additionally, immunocompromised hosts are at risk of both protracted infection and early re-infection, which can be differentiated by viral sequencing.

Indexed as

Antiviral AgentsB-LymphocytesCOVID-19 Drug TreatmentSARS-CoV-2Adenosine MonophosphateAdultAgedAlanineAntibodies, ViralCOVID-19Drug Therapy, CombinationFemaleHumansImmunocompromised HostImmunoglobulin GMaleAdenosine MonophosphateAlanineAntibodies, ViralAntiviral AgentsImmunoglobulin GremdesivirRNA, ViralB-cell depleteddual antiviral therapyimmunocompromisedprotracted infectionSARS-CoV-2

Identifiers

PMID40668805
PMCPMC13375567

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.