2025 ESCMID共识文件：免疫功能低下患者COVID-19的管理

ARTICLE INFO

Article history: Received 31 March 2025 Received in revised form 25 May 2025 Accepted 27 May 2025 Available online 23 June 2025

Editor: L. Leibovici

Keywords: COVID-19 ESCMID Immunocompromised patients SARS-CoV-2

ABSTRACT

Introduction: Data on treatment of COVID-19 in immunocompromised patients emerged recently; however, published guidelines for the management of COVID-19 in immunocompromised patients are lacking.

Aim and Methods: To develop consensus statements derived from evidence and expert opinion on management of COVID-19 in immunocompromised patients, an expert panel was convened by European Society for Clinical Microbiology and Infectious Diseases. The expert panel developed a list of questions which are of general interest for clinicians and readers with backgrounds in clinical microbiology and infectious diseases. Six questions were selected. For each question, systematic literature searches were undertaken. We considered most study types, including clinical trials, observational studies with or without a control group, systematic reviews, case series, and case reports. Detailed inclusion criteria were defined for each research question using the Population Intervention Comparison Outcome format. Immunocompromised patients included patients with (a) primary immune deficiencies; (b) active malignancy or malignancy diagnosed or received cancer therapies within 1 year of COVID-19 diagnosis, (c) HIV with a CD4+ T-lymphocyte count <200 cells/mm$^{3}$ or percentage <14%; (d) receipt of solid organ transplant within 1 year of COVID-19 diagnosis; (e) receipt of haematopoietic cell transplant or chimeric antigen receptor T-cell therapy within 1 year of COVID-19 diagnosis; (f) receipt of systemic corticosteroid therapy with a dose of ≥20 mg prednisone or equivalent daily for ≥14 days or a cumulative dose of >600 mg of prednisone; (g) receipt of biological immune modulators; or (h) receipt of disease-modifying antirheumatic drugs or other immunosuppressive drugs. The panel's consensus statements were based on evidence, supplemented by experience and expert opinion, especially in cases when evidence was limited or scarce. This document is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard. Michele Bartoletti, Clin Microbiol Infect

2025:31:1655

© 2025 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Scope

Despite major advances in the management of COVID-19, current recommendations for the treatment of COVID-19 in immunocompromised patients are limited. At the beginning of the pandemic, immunocompromised patients were excluded or were minimally represented in most randomized controlled trials of COVID-19 therapy. More recently, data on the treatment of COVID-19 in immunocompromised patients emerged; however, published guidelines for the management of COVID-19 in immunocompromised patients are lacking. This document provides consensus statements derived from evidence and expert opinion on the management of COVID-19 in immunocompromised patients.

Introduction

Despite the WHO's May 2023 declaration of the end of the COVID-19 pandemic and a shift to an endemic phase, COVID-19-related morbidity and mortality among vulnerable patients remain a concern. The burden of COVID-19 among immunocompromised patients remains considerable [1,2]. In a large population-based cohort study from the United Kingdom estimating rates of hospitalization and death due to COVID-19 in 2022, immunocompromised patients accounted for only 3.9% of the study population but 22% of hospitalizations, 28% of intensive care unit admissions, and 24% of all deaths [1]. Additionally, immunocompromised patients with haematological malignancies, particularly patients with underlying B-cell depletion, may develop atypical features of COVID-19 such as persistent infection and relapsing infection [3].

At the beginning of the pandemic, immunocompromised patients were excluded or were minimally represented in most randomized controlled trials of COVID-19 therapy [4]. More recently, data on the treatment of COVID-19 in immunocompromised patients emerged; however, published guidelines for the management of COVID-19 in immunocompromised patients are

lacking. We aimed to develop consensus statements derived from evidence and expert opinion on the management of COVID-19 in immunocompromised patients. This document is not intended to serve as a clinical practice guideline but rather to provide insights into this important topic.

Methods

Panel composition and overarching methodology

In 2022, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) published a first set of COVID-19 guidelines, covering prevention, diagnosis, and treatment [5,6]. At the end of 2022, a new expert panel was formed to develop a consensus document addressing the management of COVID-19 in immunocompromised patients. The expert panel comprised members of the ESCMID COVID-19 treatment guidelines panel, ESCMID Study Group for Infections in Compromised Hosts, and ESCMID Study Group for Respiratory Viruses, and was approved by the ESCMID Executive Committee. As is the case for all ESCMID initiatives, the expert panel was balanced in terms of gender, clinical specialty, and country of origin. In addition, the document was developed according to the ESCMID methodology for consensus documents [7].

Development and selection of research questions

The expert panel developed an initial list of questions. After initial screening, questions were selected through voting. Criteria for selection included that the question be of general interest for clinicians and readers with backgrounds in clinical microbiology and infectious diseases. Six questions were selected.

Literature searches and evidence synthesis

For each question, systematic literature searches were undertaken in PubMed without time restrictions or language filters.

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

1657

Searches for questions 1–4 were conducted in February–March 2023 and updated again in October 2023. Searches for questions 5 and 6 were conducted only once, in September–October 2023. In addition, manual searches for relevant studies were performed periodically. Detailed search strategies and the numbers of search results are presented in the supplement (Tables S1–S18).

The retrieved references were screened in two stages: first the title and abstract were reviewed, and then, if the title and abstract indicated that the article might be relevant, the full text was reviewed. References were screened by one reviewer, except for references related to treatment questions (questions 1–3), which were screened by two reviewers in tandem. A total of eight reviewers participated in screening. The screening was done using Rayyan (www.rayyan.ai). We did not employ artificial intelligence tools for the literature review. Disagreements between reviewers were resolved through discussion or by involving a third reviewer.

We considered most study types, including clinical trials, observational studies with or without a control group, systematic reviews, case series, and case reports. We included only reports written in English. Detailed inclusion criteria were defined for each research question using the Population Intervention Comparison Outcome format, and the inclusion criteria are presented in the supplement. This document is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard [8]. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams for each question, including exclusion reasons, are presented in the supplement.

Data extraction was done by one reviewer and checked by another. A narrative synthesis of evidence was used to summarize the included studies.

Expert panel meetings and development of consensus statements

The expert panel met virtually every 2–3 months from August 2022 through November 2024 and met face to face during ESCMID Global 2023 and ESCMID Global 2024. All virtual communications were accomplished via e-mail or regular teleconferences. After evaluating the evidence, the panel discussed the findings, the conclusions based on those findings, and the suggested consensus statements, which were voted on. At least 80% of panel members had to agree for a conclusion to be included in a consensus statement. The panel's consensus statements were based on evidence, supplemented by experience and expert opinion, especially in cases when evidence was limited or scarce.

Definitions

WHO severity criteria for COVID-19 were applied [9]. Immunocompromised patients included patients with (a) primary immune deficiencies; (b) active malignancy or malignancy diagnosed or received cancer therapies within 1 year of COVID-19 diagnosis, excluding patients with localized skin cancers or early-stage cancers (e.g. stage 1 lung cancer); (c) HIV with a CD4+T-lymphocyte count <200 cells/mm$^{3}$ or percentage <14%; (d) receipt of solid organ transplant (SOT) within 1 year of COVID-19 diagnosis; (e) receipt of haematopoietic cell transplant (HCT) or chimeric antigen receptor T-cell therapy within 1 year of COVID-19 diagnosis; (f) receipt of systemic corticosteroid therapy with a dose of ≥20 mg prednisone or equivalent daily for ≥14 days or a cumulative dose of >600 mg of prednisone; (g) receipt of biological immune modulators; or (h) receipt of disease-modifying antirheumatic drugs or other immunosuppressive drugs [10].

Immunocompromised patients were considered at high risk for worse outcomes from COVID-19 if they had B-cell-depleting diseases or were receiving B-cell-depleting therapy, including (a)

primary immunodeficiency causing hypogammaglobulinaemia (i.e. X-linked agammaglobulinaemia, common variable immunodeficiency, or other primary hypogammaglobulinemia) or (b) secondary immunodeficiency, including (i) anti-CD20 treatment in the past year; (ii) chronic lymphocytic leukaemia, non-Hodgkin lymphoma, multiple myeloma accompanied by hypogammaglobulinaemia, or receipt of immunotherapy directed against B cells (bispecific antibodies or antibody-drug conjugates against CD19, CD20, or B-cell maturation antigen); or (iii) chimeric antigen receptor T-cell therapy or allogeneic or autologous HCT within 1 year of COVID-19 diagnosis [11].

Finally, because of a lack of available literature on which to base definitions, we arbitrarily defined:

1. Rebound as worsening of some or all the signs and symptoms of COVID-19 after at least 2 weeks but less than 4 weeks of significant improvement.

2. Relapse as recurrent signs and symptoms of COVID-19 at least 4 weeks but not more than 3 months after resolution of signs and symptoms plus a positive SARS-CoV-2 test result.

3. Persistence as prolonged signs and symptoms of COVID-19 with or without minimal improvement for at least 4 weeks from onset regardless of SARS-CoV-2 test result.

4. Reinfection as new signs and symptoms of COVID-19 occurring after resolution and at least 3 months (90 days) after the initial diagnosis of COVID-19 plus a positive SARS-CoV-2 test result.

5. Progression as worsening of signs and/or symptoms of COVID-19 compared with initial presentation.

Results

Summary of the questions and statements is depicted in Table 1.

Question 1. How should immunocompromised patients with mild/ moderate or severe COVID-19 be treated at the first occurrence of infection?

Evidence summary

We identified 101 studies relevant for answering question 1: 4 randomized controlled trials [12–15], 10 prospective studies [16–25], 84 retrospective studies or case series [2,16,18,20,22–24, 26–36,37–57,58–78,79–90,91–101], and 3 systematic reviews [102–104] (Table S4).

The number of patients included in the studies ranged from 3 to 45 542. In total, 107 970 immunocompromised patients were included, including 6701 SOT recipients, 53.5% of whom had kidney transplant; 4141 patients with haematological malignancies, including 47 HCT recipients and 308 patients receiving anti-CD20 antibody therapy; 323 patients with primary immunodeficiency, most commonly common variable immunodeficiency; 25 people living with HIV; and 401 patients with autoimmune diseases.

Effect of COVID-19 treatment on hospitalization rate. The use of remesivir favourably reduced hospitalization rates in one study in patients with haematological malignancies [24] and in two studies in immunocompromised patients with a variety of conditions [12,21], including one study in which more than 70% of patients received COVID-19 vaccine before remdesivir [21].

Five studies assessed the impact of other antivirals (the combination of nirmatrelvir and ritonavir [nirmatrelvir/ritonavir] or molnupiravir) on hospitalization rates in immunocompromised patients with a variety of conditions. Two large cohort studies and one large retrospective study demonstrated a reduction in hospitalization with nirmatrelvir/ritonavir [47,58,86]. Another

1658

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

Table 1

Summary of questions and statements

|Question|Setting/condition|Statement| |---|---|---| |(1) How should immunocompromised patients with mild/moderate or severe COVID-19 be treated at the first occurrence of infection?|Mild disease|Initial standard treatment with either nirmatrelvir/ritonavir, remdesivir, or monoclonal antibodies (when available and active against circulating variants) Consider prolonged and/or combination therapy in selected highly immunosuppressed patients Consider combination and prolonged therapy Consider a second course of monotherapy with an oral antiviral agent such as nirmatrelvir/ritonavir, or intravenous remdesivir in case of major concerns for drug-drug interactions Consider prolonged monotherapy (7-14 d) or escalation to a combination regimen in case of clinical progression to severe infection Consider combination therapy and potentially prolonging therapy in case of non-resolving symptoms Consider nirmatrelvir/ritonavir + remdesivir Consider adding to the standard regimen either monoclonal antibodies (when available and active against circulating variants)circulating variants) and/or intravenous immunoglobulins A symptom-based approach for screening for SARS-CoV-2 infection is generally appropriate Consider local infection control policies as asymptomatic screening for SARS-CoV-2 could be appropriate Consider a course of antiviral therapy and keeping the patient on the waiting list| |(2) Should a second course (or multiple courses) of treatment be administered in case of persistent or relapsed COVID-19?|Mild and persistent or relapsed COVID-19 in high-risk patients Mild and persistent or relapsed COVID-19 in high-risk patients|A case-by-case decision should be made based on local practices Consider proceeding with transplantation while administering antiviral therapy Consider postponing HCT for at least 48 h after resolution of COVID-19 symptomatology Consider proceeding with scheduled chemotherapy Consider proceeding with scheduled chemotherapy| |(3) In case of combination therapy, which regimens should be favoured?|Initial treatment Salvage treatment|Consider proceeding with scheduled chemotherapy Consider nirmatrelvir/ritonavir + remdesivir Consider adding to the standard regimen either monoclonal antibodies (when available and active against circulating variants) and/or intravenous immunoglobulins A symptom-based approach for screening for SARS-CoV-2 infection is generally appropriate Consider local infection control policies as asymptomatic screening for SARS-CoV-2 could be appropriate Consider a course of antiviral therapy and keeping the patient on the waiting list| |(4) Should asymptomatic patients be universally tested for SARS-CoV-2 before chemotherapy or transplantation?|In an endemic situation In an ongoing outbreak situation|A symptom-based approach for screening for SARS-CoV-2 could be appropriate Consider a course of antiviral therapy and keeping the patient on the waiting list| |(5) Should asymptomatic patients and a positive SARS-CoV-2 test undergo solid organ or haematopoietic cell transplantation (SOT, HCT) and if so, when?|In patients who tested positive for SARS-CoV-2 and are asymptomatic or have mild COVID-19 and an urgent need for SOT In patients with moderate/severe COVID-19 and an urgent need for SOT For asymptomatic patients with positive SARS-CoV-2 tests and planned HCT For patients with moderate/severe COVID-19 and planned HCT Asymptomatic or mild COVID-19 in a patient with aggressive cancer Aggressive cancer Asymptomatic or mild COVID-19 in a patient receiving treatment with low risk for infectious complications All other situations|A case-by-case decision should be made based on local practices Consider proceeding with transplantation while administering antiviral therapy Consider postponing HCT for at least 48 h after resolution of COVID-19 symptomatology Consider proceeding with scheduled chemotherapy Consider proceeding with scheduled chemotherapy Consider nirmatrelvir/ritonavir + remdesivir Consider resolution of symptoms| |(6) When can chemotherapy be resumed after an episode of COVID-19 in patients with cancer?|Asymptomatic or mild COVID-19 in a patient with aggressive cancer Asymptomatic or mild COVID-19 in a patient receiving treatment with low risk for infectious complications All other situations|Consider proceeding with scheduled chemotherapy Consider postponing chemotherapy for up to 7 d after complete resolution of symptoms|

HCT, haematopoietic cell transplant; SOT, solid organ transplant.

retrospective study showed that treatment with nirmatrelvir/ritonavir (62% of patients) or molnupiravir (38% of patients) was associated with a reduction in the composite outcome of "hospitalization or death" in veterans with immunocompromising conditions (most of the veterans identified on the basis of an order for an immunosuppressive medication), 75% of whom had received a primary SARS-CoV-2 vaccine [105]. Conversely, one smaller retrospective study on the use of molnupiravir in a very heterogeneous group of immunocompromised patients, most of whom were receiving treatment for cancer, found no difference in the hospitalization rate between treated and untreated patients [13].

The impact of monoclonal antibody (mAb) treatment in SOT recipients was evaluated in two studies with inconclusive results. In a Swiss cohort of kidney transplant recipients, early administration of mAbs (within 5–7 days after COVID-19 diagnosis) was associated with a reduced risk of the composite outcome “hospitalization or death” [77]. However, a subgroup analysis showed no benefit during the predominant circulation of the Omicron variant and/or in patients with adequate vaccination status [77]. In a study that compared 77 mAb-treated and 72 mAb-treated but eligible SOT recipients, all unvaccinated, no significant difference was observed between the groups in hospitalization rate [84].

Effect of COVID-19 treatment on progression to severe disease. The efficacy of COVID-19 treatment in reducing progression to severe disease was highly variable across studies, reflecting

differences between patient populations in terms of immunoprospression, disease severity at treatment initiation, circulating variants, and vaccination status.

Two studies suggested a potential benefit of remdesivir in SOT recipients [40,81], whereas two other studies showed no impact of remdesivir on the need for mechanical ventilation in SOT recipients [48,85]. In addition, mAb treatment showed a positive impact on disease progression in SOT recipients in studies performed in the early years of the pandemic [23,29,48,52,81,106].

In patients with haematological malignancies, limited evidence suggested benefit of antiviral treatment in the prevention of disease progression. The severity of underlying conditions and the degree of immunosuppression appeared to play a significant role. Remdesivir did not reduce the need for non-invasive ventilation in hospitalized patients, most of whom were treated at the time of severe disease [16]. In a small exploratory cohort, no differences in the rate of progression to severe disease were observed between 5-day and 3-day remesivir regimens [72]. Neither the use of mAbs nor the type of mAb altered the rate of progression to severe disease [70,92], although one study showed a reduced need for non-invasive ventilation but no overall reduction in mechanical ventilation requirements in mAb-treated patients [38].

In patients with autoimmune rheumatic diseases, most of whom had mild-to-moderate COVID-19, remdesivir was not associated with reduced requirements for mechanical ventilation, non-invasive ventilation, or high-flow nasal cannula. Furthermore,

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

1659

convalescent plasma therapy did not significantly alter the pro- gression to severe COVID-19 or the need for mechanical ventilation across multiple studies [14,15,34,102,103].

Effect of COVID-19 treatment on mortality. Twelve studies examined the impact of remdesivir on mortality, with conflicting findings influenced by clinical severity, study periods, and population characteristics [16,32,39,40,48,51,68,71,78,80,100,101]. Three studies including patients with haematological malignancies yielded inconclusive and reduced [16,51,68]. The first study was a prospective cohort study of 200 hospitalized patients in the United States, in whom remdesivir reduced 14-day but not 30-day adjusted mortality [16]. In contrast, the second study, a registry-based study that included both patients with haematological malignancies and patients with solid tumours, linked remdesivir to increased adjusted mortality, as most patients received remdesivir after hospitalization and 58% presented with moderate-to-severe COVID-19 [51]. The study was not designed to assess treatment options, and it is not clear from the report which patients received remdesivir and which received other options. The third study, a retrospective study from Israel, showed reduced mortality among 55 remdesivir-treated patients, including 78% who had severe disease [68].

Remdesivir showed a reduced all-cause mortality in a study of 196 immunocompromised patients with a variety of conditions, most of whom had received SARS-CoV-2 vaccine [21], and in patients with cancer requiring oxygen but not mechanical ventilation [78].

Nirmatrelvir/ritonavir and molnupiravir showed reduced mortality in patients with haematological malignancies [73]. Two studies comparing nirmatrelvir/ritonavir and molnupiravir showed no significant mortality differences [20,82].

In one study, the use of mAbs in patients with haematological malignancies and mild-to-moderate COVID-19 reduced COVID-19-related mortality even among patients who underwent chemotherapy within 30 days of infection [38]. However, in another study, MAbs in patients with haematological malignancies were associated with worse outcome than remdesivir, nirmatrelvir/ritonavir, or molnupiravir [73].

In kidney transplant recipients, mAbs significantly reduced mortality [52]. Specifically, in this population, early sotrovimab use (within 5 days of symptom onset) lowered mortality compared with delayed sotrovimab [107].

In SOT recipients, three studies showed no association between remdesivir and mortality [32,40,48], even with early remdesivir administration (within 48 hours of symptom onset) [339]. COVID-19 severity in the included patients varied widely across these studies, and no subgroup analyses by severity were provided. Three retrospective studies in SOT recipients showed no deaths among patients treated with remdesivir during the mild or moderate phase of COVID-19 [71,100,101].

Convalescent plasma therapy showed no significant mortality benefit in immunocompromised patients across two studies [100,102,105] or in a randomized controlled trial in which 20% of enrolled patients had HIV [15].

Combination treatment as frontline treatment. Sixteen studies evaluated combination regimens, including 11 that evaluated remdesivir-based combinations. Remdesivir combined with mAbs was evaluated in six studies [22,25,54,60,88,108], whereas remdesivir combined with convalescent plasma was evaluated in five [66,69,74,88,98]. Four of the 11 studies of remdesivir-containing combinations showed a reduction in mortality over monotherapy, although in some studies, the difference was not statistically significant [22,54,60,66]. The remaining studies

did not specifically assess the mortality benefit of remdesivir use. A multicentre European study of patients with haematological malignancies treated for COVID-19 in the outpatient setting showed that "no treatment" was linked to higher mortality than combination therapy. In this study, combination therapy included oral antiviral agents and/or mAbs with or without convalescent plasma, frequently combined with corticosteroids [42].

Panel statement

Initial treatment for mild disease. For initial treatment of mild COVID-19, nirmatrelvir/ritonavir, remdesivir, and mAbs with demonstrated activity against circulating variants are effective options in most cases. For patients requiring immunosuppressive therapy, evidence also supports consideration of prolonged therapy or combination regimens. Additionally, it is important to assess drug–drug interactions, particularly when nirmatrelvir/ritonavir is used, consistent with practices in the general population.

Initial treatment for moderate or severe disease. For treating moderate or severe COVID-19, a combination regimen (see question 3 below for suggested regimens) has potential benefit. In specific situations, such as non-resolving symptoms or signs after 5–10 days of therapy, prolonging the duration of therapy may be appropriate. Although early initiation of antiviral therapy is associated with better outcomes in the general population, in immunocompromised patients, late initiation of therapy may still offer clinical benefit compared with no therapy and should be considered.

Question 2. Should a second course (or multiple courses) of treatment be administered in case of persistent or relapsed COVID-19?

Evidence summary

We identified 63 studies relevant to answering question 2 [109–171]: 49 case reports, 13 case series, and 1 retrospective observational study [table S8]). The number of patients included in the publications ranged from 1 to 22. In total, 148 patients were described. A total of 122 patients had haematological malignancies, of whom 103 had received anti-CD20 antibodies. Other underlying diseases included primary immunodeficiency (n = 5), SOT (n = 6), HIV (n = 5), and other diseases, such as multiple sclerosis and granulomatosis with polyangiitis (n = 10).

Positive clinical outcomes were achieved in 122 of the 148 patients after a second or subsequent course of treatment. Successful second course regimens included (a) a single antiviral agent only, (b) a mAb or convalescent plasma or intravenous immunoglobulins only, (c) combinations of a single antiviral agent plus a mAb or convalescent plasma or intravenous immunoglobulins, (d) combinations of antiviral agents, and (e) combinations of antiviral agents plus a mAb. A study in 15 patients with haematological malignancies evaluated the combination of remdesivir and nirmatrelvir/ritonavir either alone (9 patients) or with tixagevimab and cilgavimab (6 patients) as a 5-day second course of treatment [147]. Tixagevimab and cilgavimab were administered at a median of 55 days after initiation of combination antiviral therapy. None of the six patients who received mAbs experienced recurrent symptoms, compared with six of the nine who received combination antiviral therapy alone. Similarly, in another study, 22 immunocompromised patients with persistent or relapsed COVID-19, 19 of whom had underlying haematological malignancies and 15 of whom were pretreated with anti-CD20 antibodies, received combinations of

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

antiviral agents (mainly remdesivir and nirmatrelvir/ritonavir) either alone (4 patients) or with mAbs (18 patients). At day 14 and 30 after initiation of combination antiviral therapy, response rates were significantly higher in the patients who received mAbs [149].

Intravenous immunoglobulin was used alone [164] or in combination with other drugs [118–120,137,148] in five case reports in which patients had favourable results, but the impact of intravenous immunoglobulins in these cases was unclear.

Several limitations need to be considered when interpreting these findings. First, we found no relevant randomized controlled trials; therefore, only case reports, case series, and a retrospective observational study were included in our evidence summary. Second, publication bias may have led to reporting of only positive outcomes. Third, most publications omitted data on the delay between symptom onset and initiation of the first course of treatment for COVID-19, and any delay in initiating the first treatment course might have affected outcomes. Finally, the quality of evidence is very low.

Panel statement

Second or subsequent course of treatment for mild disease. In patients with persistent or relapsed COVID-19 and mild symptoms, prolonging the first course of monotherapy or prescribing a second course of monotherapy might be appropriate. Oral antiviral agents, such as nirmatrelvir/ritonavir, appear suitable in the outpatient setting for patients without progression to moderate or severe disease or with no contraindications in terms of drug-drug interactions. In high-risk patients with persistent or relapsed COVID-19, prolonged therapy (i.e. 7–14 days or until clinical improvement) can be considered. In addition, escalation to combination therapy might be considered in the case of progression to moderate, severe, or critical disease. Similar to what is true for the general population, it is important to assess drug-drug interactions when nirmatrelvir/ritonavir is used.

Second or subsequent course of treatment for moderate, severe, or critical disease. For patients with persistent or relapsed COVID-19 and moderate or severe disease, a second course of treatment with a combination regimen may be appropriate. In specific situations, such as non-resolving symptoms or signs after 5–10 days of therapy, either a second course of subsequent course, prolonging the duration of therapy might be beneficial.

Question 3. In case of combination therapy, which regimens should be favoured?

Evidence summary

The sel statement for question 3 is based on the evidence summarized under questions 1 and 2.

Panel statement

There is no single preferred regimen for combination therapy. However, there is general agreement that combination regimens should include at least two antiviral agents. For initial combination therapy, there is a preference for a regimen including n-matrelvir/ritonavir and remdesivir, if available. For subsequent combination therapy, there is a preference for a regimen including n-matrelvir/ritonavir, remdesivir, and an anti-spike mAb if available and effective against the prevalent circulating variants or lineages. In patients with severe disease, and particularly in high-risk patients, the addition of intravenous immunoglobulins may be considered.

Question 4: Should asymptomatic patients be universally tested for SARS-CoV-2 before chemotherapy or transplant?

Evidence summary

We searched the literature for articles published between 1 January 2020 and 1 January 2024 (date of last query for this question). Five different search queries were run that specifically targeted people living with primary immunodeficiency, people with HIV infection, patients with cancer, SOT and HCT recipients, and patients receiving chronic systemic corticosteroids or immunodomulatory or other immunosuppressive therapy. The intervention of interest, oropharyngeal or nasopharyngeal swab for SARS-CoV-2 detection by antigen and/or RT-PCT, was generated a priori based on expert consensus achieved via online panel discussions. Detailed synthesis of retrieved papers is reported in Table S12.

We included in our summary one guideline, one systematic review, and seven observational studies. In a systematic review done in early 2020 [172], the authors found that most data favoured routine testing for SARS-CoV-2 among asymptomatic adult patients with cancer before systemic chemotherapy, but the evidence to support this recommendation was not strong. The analysis was based on 2 cohort studies and 16 expert consensus statements and guidelines; a meta-analysis was deemed not possible.

In a study conducted mainly during the pre-Omicron era, 931 and 230 patients with cancer were screened for SARS-CoV-2 in the outpatient and inpatient settings, respectively, before receiving anticancer therapy. Overall, 71 patients tested positive on routine screening, and these patients had lower odds of death and oxygen supplementation compared with the patients who were not screened [173]. In a study of 1636 patients with cancer who were screened before surgery between May and October 2020, the positivity rate for SARS-CoV-2 was 6.2%. An adjusted logistic regression analysis of the whole cohort showed that longer length of stay (OR 1.08; 95% CI: 1.04–1.11) and readmission rate (OR: 9.02; 95% CI: 2.30–35.48) were independent predictors of postoperative COVID-19. The authors recommended screening of patients with cancer before elective surgery to reduce in-hospital SARS-CoV-2 transmission [174].

A study published before the COVID-19 pandemic of screening for other respiratory viruses showed that patients with and without respiratory symptoms with respiratory viruses detected before HCT had fewer days alive and out of the hospital and lower survival at day 100 compared with patients with negative samples (adjusted hazard ratio 2.4; 95% CI: 1.3–4.5; p 0.007). However, in an analysis limited to asymptomatic patients, the detection of a respiratory virus was not associated with mortality [175].

Panel statement

Universal screening of asymptomatic patients for SARS-CoV-2 before chemotherapy, transplant, or admission to units housing immunocompromised patients is not supported by evidence except when required to manage local outbreaks or clusters of cases. A symptom-based approach to screening for SARS-CoV-2 infection is generally appropriate unless otherwise dictated by local infection control policies.

Question 5. Should asymptomatic patients with a positive SARS-CoV-2 test under SGO or HCT and if so, when?

Evidence summary

Answering question 5 was hampered by the lack of good-quality published data on asymptomatic SOT or HCT recipients with a positive SARS-CoV-2 testing. The largest case series

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

1661

included only 12 SOT recipients (7 with renal transplants, 4 with liver transplants, and 1 with a heart transplant), of whom 10 were given remidesvir after transplant and the other two had mild COVID-19 before transplant and were treated with 3 days of remdesivir before being reinstated on the transplant waiting list. Rates of graft survival and patient survival at follow-up (median of 143 days) were 100% [176].

Panel statement

In the case of an urgent need for SOT, patients with asymptomatic or mild COVID-19 should be kept on the waiting list and treated with standard antiviral therapy for SARS-CoV-2. In the case of planned HCT in a patient with asymptomatic SARS-CoV-2, proceeding with the transplant while the patient receives anti-SARS-CoV-2 therapy is acceptable. In this scenario, prolonged anti-SARS-CoV-2 therapy, or combination therapy could be considered, with attention paid to potential interactions between nirmatrelvir/ritonavir and any immunosuppressive agents administered for prevention of graft-vs.-host disease (e.g. tacrolimus or cyclosporine) or azoles administered for prevention or treatment of fungal infections. In the case of planned HCT in a patient with moderate or more severe COVID-19, it is reasonable to postpone the transplant until at least 48 hours after resolution of symptoms. As in the previous scenario, prolonged or combination therapy could be considered. We suggest balancing the risks and benefits in each situation by considering factors such as the urgency of transplant, the underlying malignancy, the severity of COVID-19, the availability of antiviral agents and/or other drugs (e. g. effective anti-spike mAbs), the patient's COVID-19 vaccination status, the type of transplant, and the donor and recipient matching status.

Question 6. When can chemotherapy be resumed after an episode of SARS-CoV-2 infection in patients with cancer?

Evidence summary

For question 6, we excluded case reports and small case series. We identified only three articles that included comparator groups.

A multicentre study [177] examined changes in anticancer treatment for patients with solid tumours who developed COVID-19 between March 2020 and February 2021. Most frequent treatment changes were delay/interruption (20.1% and 16.0% for non-curative and curative setting, respectively), and full cancellation (10.6% and 6.1% for noncurative and curative setting, respectively) of systemic treatment. Thirty-day COVID-19 related mortality was not significantly different between patients with and without treatment modifications (21.4% vs. 20.5%).

Another large study [178] reported outcome data across patients with solid tumours and haematologic malignancies across Europe. Patients who continued or resumed systemic anticancer therapy with dose or regimen adjustments had similar outcomes compared with those who continued or resumed systemic anticancer therapy without changes to dosage or regimen. Similarly, in another literature review of small case series not included in our selection [179], there was no association between the continuation of anticancer treatment and adverse COVID-19 outcomes. Finally, in a cohort of patients with breast cancer, resuming chemotherapy 7 to -14 days after diagnosis of SARS-CoV-2 infection was not associated with higher rates of emergency department visits, hospitalizations, or deaths than the rates observed in matched patients treated before the COVID-19 pandemic [180].

Panel statement

For patients with asymptomatic or mild COVID-19, proceeding with scheduled chemotherapy may be appropriate, particularly in

cases of aggressive cancer or when anticancer treatments are not associated with an increased risk of infection or its complications (see definitions for high-risk patients above). In all other situations (i.e. moderate or severe COVID-19), postponing chemotherapy for up to 2–7 days after complete resolution of symptoms might be considered.

Limitations

One of the limitations of this document is that the risk of bias or the certainty of evidence was not formally assessed, as this is a consensus document. This limitation should be considered when interpreting our findings and our statements. Another limitation is that the literature search was last updated in October 2023, and studies published thereafter were not systematically included or assessed. However, no new publications have emerged that would alter the significance or strength of our statements, particularly given the lack of new randomized controlled trials or high-quality studies on the management of COVID-19 in immunocompromised patients. Finally, for three research questions, references were screened by a single reviewer. Nevertheless, for the treatment-related questions, two reviewers independently screened the references in parallel.

Topics not covered in this document and future directions

Several aspects of COVID-19 management were not fully addressed in this document including prevention such as vaccines and monoclonal antibodies, diagnostics, long-term follow-up, the use of corticosteroids, other immunosuppressive regimens, or anticoagulants. These topics can be addressed in separate documents. On the other hand, after review of the published literature, lack of data was identified for specific questions such as the optimal approaches for managing both mild and severe COVID-19 in immunocompromised patients including the exact choice of drugs for combination therapy, duration of therapy, and the benefit of prolonged (and in some cases intravenous) therapy. These knowledge gaps should be addressed in future studies and clinical trials that are often lacking in immunocompromised patients.

Author contributions

M.B. and R.F.C. co-chaired the panel, supervised the work, selected and voted for Population, Intervention, Comparison, Outcome (PICO) questions and made other relevant decisions, performed literature searches, and drafted and approved the voted for PICO questions and for other relevant decisions, performed literature searches, and drafted and approved the manuscript. B.N. was an ESCMID-appointed methodologist who supported the panel with literature searches in PubMed and reviewed the manuscript.

Transparency declaration

Potential conflict of interest

M.B. received honoraria/consulting fees from Pfizer, Gilead, Advanz, Tillots, Infectopharm, BioMerieux, MSD, Menarini, and Angelini. P.A.G. received honoraria/consulting fees from Merck, Sharp & Dohme, Takeda, Astra-Zeneca, Gilead Sciences, Menarini. L.C.P. received honoraria/consulting fees from Astra-Zeneca, Pfizer. M.A.S. received grants paid to her institution from Gilead, F2G and Merck and honoraria/consulting fees from Roche, Pfizer, Gilead,

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

Takeda, Merck, F2G, Elion, Basilea, Cidara, I.Z.-S. received support for attending meetings and participation on a Data Safety Monitoring Board or Advisory Board from Pfizer, Gilead. R.F.C. received research grants paid to his institution from the NIH/NCI (RO1), AiCuris, Ansun Biopharma, Genentech, Karius, Symbio, Merck, Oxford Immunotec, Pulmetec, Freestyle, Takeda, and Viracero-Eurofins; honoraria/Consulting fees from Ansun Biopharma, Merck, Merck, Oxford Immunotec, Tether, Takeda, Shionogi, Assembly Bio, IntegerBio, Symbio, InflaRX, Gilead, Pfizer, Moderna, Invyvid, Viracor-Eurofins, and Karius All. The other authors declare that they have no conflicts of interest.

Financial report

European Society for Clinical Microbiology and Infectious Diseases (ESCMID) provided support in organizing online meetings and two onsite meetings during ESCMID Global held in Copenhagen in 2023 and ESMID Global held in Barcelona in 2024.

Acknowledgements

We thank Stephanie Deming, an Associate Scientific Editor, at The University of Texas MD Anderson Cancer Center, for editing this article.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.cmi.2025.05.032.

References

1) Evans RA, Dube S, Lu Y, Wales M, Arnetorp S, Barnes E, et al. Corrigendum to impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study [the Lancet Regional health—Europe 35 (2023) 100747]. Lancet Reg Health Eur 2024-44:101008. https://doi.org/10.1016/j.Cmi.2023.1979c. e-200322 Dec 2023 Dec 2023. Dec 2023. Dec 2023. Dec 2023; An: B. E. (2013) 2023;330: 1611. https://doi.org/10.1001/j.Cmi.2023.1979c. 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023. Dec 2023.

[12] Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med 2022;386:305–15. https://doi.org/10.1056/NEJMoa2116846. [13] Johnson MG, Strizki JM, Brown ML, Wan H, Shamsuddin HH, Ramgopal M, et al. Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial. Infection 2023;51. https://doi.org/10.1007/s15010-022-01959-9. [14] Menichetti F, Popoli P, Puopolo M, Spila Alegiani S, Tiseo G, Bartoloni A, et al. Effect of high-titer convalescent plasma progression to severe respiratory failure or death in hospitalized patients with COVID-19 pneumonia: a randomized clinical trial. JAMA Netw Open 2021;4. https://doi.org/10.1001/jamanetworkopen.2021.36246. [15] van den Berg K, Glatt TN, Vermeulen M, Little F, Swanevelder R, Barrett C, et al. Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial). Sci Rep 2022;12. https://doi.org/10.1038/s41598-022-06221-8. [16] Aksak-Was BJ, Chober D, Serwin K, Scheibe K, Níscigorska-Olsen J, Niedźwiedź A, et al. Remdesivir reduces mortality in hemato-oncology patients with COVID-19. J Inflamm Res 2022;15:4907–20. https://doi.org/10.2147/JIR.S378347. [17] Donato ML, Park S, Baker M, Korngold R, Morawski A, Geng X, et al. Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma. JCI Insight 2021;6. https://doi.org/10.1172/jci.insight.143196. [18] Charbarban A, GeurtsvanKessel CH, Jordans CCE, Blauw M, van der Klift M, Hassing R-J, et al. Effects of treatment of Coronavirus disease 2019 with convalescent plasma in 25 B-cell-depleted patients. Clin Infect Dis 2022;74:1271–4. https://doi.org/10.1093/cid/ciab647. [19] Martin-Blondel G, Marcelin A-G, Soulié C, Kaisaridi S, Lusivika-Nzinga C, Zafilaza K, et al. Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BaM1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir. Clin Microbiol Infect 2023;29:543. https://doi.org/10.1016/j.cmi.2022.12.016. e5-e9. [20] Minoia C, Diella L, Perrone T, Loseto G, Pelligrino C, Attolico I, et al. Oral anti-viral therapy for early COVID-19 infection in patients with haematological malignancies: a multirentre prospective cohort. Br J Haematol 2023;202. https://doi.org/10.1111/bjh.18895. [21] Rajme-López S, Martinez-Guerra BA, Zalapa-Soto J, Román-Montes CM, Tamez-Torres KM, González-Lara MF, et al. Early outpatient treatment with remdesivir in patients at high risk for severe COVID-19: a prospective cohort study. Open Forum Infect Dis 2022;9. https://doi.org/10.1093/o6d/ofac502. [22] Scotto R, Buomo or AR, luliano A, Foggia M, Sardanelli A, Villari R, et al. Remdesivir alone or combination with monoclonal antibodies as an early treatment to prevent severe COVID-19 in patients with mild/moderate disease at high risk of progression: a single centre, real-life study. Vaccines (Basel) 2023;11:200. https://doi.org/10.3390/vaccines11020200. [23] Solera JT, Árbol BG, Aisharani A, Bahinskaya I, Marks N, Humar A, et al. Impact of vaccination and early monoclonal antibody therapy on coronavirus disease 2019 outcomes in organ transplant recipients during the Omicron wave. E, Clin Infect Dis 2022;75:2193–200. https://doi.org/10.1093/cid/ciac324. [24] Vicente-Valor J, Rodríguez-González C, Ferris-Villanueva M, Chamorro-de-Gyan Ve, Romero-Jimenez R, Gómez-Costas D, et al. Remdesivir and SARS-CoV-2 monoclonal antibodies to prevent COVID-19 progression in hematological patients: an observational study. Pharmacol Rep 2023;75. https://doi.org/10.1007/s43440-2023-00519-8. [25] Pulvirenti F, Milito C, Cinetto F, Fernandez Salinas A, Terreri S, Piano Mortari E, et al. Severe acute respiratory syndrome coronavirus 2 monoclonal antibody combination therapy in patients with coronavirus disease 2019 and primary antibody deficiency. J Infect Dis 2022;225. https://doi.org/10.1093/nifds/jab554. [26] Aearnia MJ, Thawin M, Mehta R, Emamaullee J, Kim J, Blodget E, et al. A programmatic response, including bamlanivimab or casirivimab-imdevimab administration, reduces hospitalization and death in COVID-19 positive abdominal plant recipients. Transplantation 2022;106. https://doi.org/10.1097/TP.000000000003953. [27] Ahluwalia M, Giavertz MM, Mehra MR A proposed strategy for management of immunosuppression in heart transplant patients with COVID-19. Clin Transplant 2020;34. https://doi.org/10.1111/ctr.14032. [28] Ahlukairi AN, Ahaldabbah Y, Adoub SA, Mourier T, Abumelha KY, Albishi GE, et al. Outcome of transplant recipients infected with Omicron BA.1 and BA.2: a single-center retrospective study in Saudi Arabia. J Epiemidol Glob Health 2023;13. https://doi.org/10.1007/s44197-023-00084-6. [29] Arimura K, Tagaya E, Kikuchi K, Mitsuda T, Ebihara F, Maruyama T, et al. The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19. Transpl Immunol 2023;77:101777. https://doi.org/10.1016/j.trim.2022.101777. [20] Assato GM, Di Rocco A, Malfona F, Capriata M, Del Giudice I, Petrucci L, 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. https://doi.org/10.1002/hon.3113. [31] Bachmann F, Budde K, Suttorp N, Lingscheid T, Stegemann MS, Osmanodja B, et al. Initial experience with SARS-CoV-2-neutralizing

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

1663

monoclonal antibodies in kidney or combined kidney-pancreas transplant recipients. Transpl Int 2022;35:10109. https://doi.org/10.3389/ti.2022.10109. [32] Bansal S8, Rabras M, Rana A, Gadde A, Jha P, Jain M, et al. Treatment and outcomes of coronavirus disease 29 in idney transplant recipients: a single-center experience. Saudi J Kidney Dis Transpl 2022:33:5159–68. https://del.org/10.4103139-2442.384188. [33] Belden KA, Yeager S, Schulte J, Cantarin MMP, Moss S, Royer T, et al. Saving lives with nirmatrelvir/ritonavir one transplant patient at a time. Transpl Infect Dis 2023;25. https://doi.org/10.1111/nid1-4037. [34] Biernat MM, Kolasínska A, Kwiatkowski J, Urbaniak-Kujda D, Biernat P, Janocha-Litwin J, et al. Early administration of convalescent plasma improves survival in patients with hematological malignancies and COVID-19. Viruses 2021;13. https://doi.org/10.3390/v13030436. [35] Birk NK, Jain S, Massoud L, Ramesh D, Monday L, Muma B, et al. Real-world experience of sobrotuvab in high-risk, immunocompromised COVID-19 patients. Open Forum Infect Dis 2022;29; 52:22;99:29:10. https://doi.org/10.3390/fid/ofac282. [36] Biscarini S, Villa S, Genovese C, Tomasello M, Tonizzo A, Fava M, et al. Safety profile and outcomes of early COVID-19 treatments in immunocompromised patients: a single-centre cohort study. Biomedicines 2022;10. https://doi.org/10.3390/biomedicines10082002. [37] Bronstein Y, Avivi I, Cohen YC, Feigin E, Perry C, Herishanu Y. REGEN-COV antibody combination in patients with lymphoproliferative and SARS-CoV-2 infection. EJHaem 2022;3. https://doi.org/10.1002/ha2.403. [38] Bussini L, Testi D, Tazza B, Oltolini C, Mastaglio S, Sepulci C, et al. Neutralizing monoclonal antibodies for early treatment of hospital-acquired SARS-CoV-2 infection in hematologic patients. EJHaem 2022;3. https://doi.org/10.1002/ha2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.1002/ja2.554. https://doi.org/10.10

[52] Guerguen J, Colosio C, Del Bello A, Scemla A, N'Guyen Y, Rouzaud C, et al. Early administration of anti-SARS-CoV-2 monoclonal antibodies prevents severe COVID-19 in kidney transplant patients. Kidney Int Rep 2022;7. https://doi.org/10.1016/j.ekir.2022.03.020. [53] Guzmán Cordero C, Saez-Torres de Vicente M. Management of nirmatrelvir/ ritonavir and tacrolimus interaction in kidney transplant recipients infected by COVID-19: a three-case series. Eur J Hosp Pharm 2024;31. https://doi.org/10.1136/ejhphmar-2022-003544. [54] Hirai J, Mori N, Sakashi D, Ohashi W, Shibata Y, Asai N, et al. Real-world experience of the comparative effectiveness and safety of combination therapy with remeditur and monoclonal antibodies versus remdesivir alone for patients with mild-to-moderate COVID-19 and immunosuppression: a retrospective single-center study in Aichi, Japan. Viruses 2023;15:1952. https://doi.org/10.3390/v15091952. [55] Hueso T, Pouderoux C, Péré H, Beaumont A-L, Raillon L-A, Ader F, et al. Convalescent plasma therapy for B-cell-depleted patients with protracted A-VOB-19. 2020;136:2290–5. https://doi.org/10.1018/wibod.2020.0008423. [56] Infante M S, Neirovsky D, Devlin S, DeWolf S, Tamari R, Dahi PB, et al. Outcomes and management of the SARS-CoV2 Omicron variant in recipients after transplantation and chimeric antigen receptor T cell therapy. Transplant Cell Ther 2024;30:116. https://doi.org/10.1016/j.ctj.2023.09.027; e1–e12. [57] Jasuja S, Sagar G, Bahl A, Jasuja N, Chawla R, Bansal A, et al. A comprehensive comparison of clinical presentation and outcomes of kidney transplant recipients with COVID-19 during wave 1 versus wave 2 at a tertiary care center, India. Int J Nephrol 2022;2022. https://doi.org/10.1155/2022/908393. [58] Kabore J-L, Lafton B, Duurna Q, Muntar, Murgeon AF, Dumaresq J, et al. Real-world effectiveness of nirmatrelvir/ritonavir on coronavirus disease 2019-associated hospitalization prevention: a population-based cohort study in the province of Québec, Canada. Clin Infect Dis 2023;77. https://doi.org/10.1093/cid/cid/2827.10.1093/cid/cid/2827.10.1093/cid/microorganisms 2022;10. https://doi.org/10.3390/microorganisms 10122490. [60] Kneidinger N, Hecker M, Bessa V, Hettich I, Wald A, Wege S, et al. Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study. Infection 2023;51:749–57. https://doi.org/10.1007/150102-022-01914-8. [61] Kutter HL, Kuzaro HA, Serrano OK, Feingold A, Morgan G, Cheema F. Initial experience of bamlav inimab monotherapy use in solid organ transplant recipients. Transpil Infect Dis 2021;23. https://doi.org/10.1111/tid.13662. [62] Lafont E, Pere H, Lebeaux D, Cheminet G, Thervet E, Guillemain R, et al. Targeted SARS-CoV treatment is associated with decreased mortality in immunocompromised patients with COID-19. J Antimicrob Chemother org(10.1093/jac/dkac253). [63] Lahouati M, Cazanave C, Labadie A, Gohier P, Guirlé L, Desclaux A, et al. Outcomes of targeted treatment in immunocompromised patients with asymptomatic or mild COVID-19: a retrospective study. Sci Rep 2023;13: 15357. https://doi.org/10.1038/s41598-023-42727-5. [64] Lanza F, Monaco F, Ciceri F, Cairoli R, Sacchi MV, Guidetti A, et al. Lack of efficacy of convalescent plasma in COVID-19 patients with concomitant hematological malignancies: an Italian retrospective study. Hematol Oncol 2022;40. https://doi.org/10.1002/hon.3060. [65] Laothamatas K, Hum J, Benvenuto L, Shah L, Gewral HS, Pereira M, et al. One year into the pandemic: evolving COVID-19 outcomes in lung transplant recipients, a single-center experience. Transplant Direct 2022;8:e1296. https://doi.org/10.1097/TXD.000000000000001296. [66] Lawrence A, Mahan L, Mohanka MR, Bollinen S, Kaza V, La Hoz RM, et al. Predictors and outcomes of respiratory failure among lung transplant patients with COVID-19. Clin Transplant 2022;36. https://doi.org/10.1111/cr.14540. [67] Lee J, Kim AR, Kang SW, Chang E, Bae S, Jung J, et al. Protracted course of SARS-CoV-2 pneumonia in moderately to severely immunocompromised patients. Clin Examp Med 2023;23. https://doi.org/10.1007/s10238-022-009084-0 [68] Levy I, Lavi A, Zimran E, Grisariu S, Aumann S, Itchaki G, et al. COVID-19 among patients with hematological malignancies: a national Israeli retrospective analysis with special emphasis on treatment and outcome. Leuk lymphoma 2021;62, https://doi.org/10.1080/10428194.2021.1966782. [69] Magyari F, Pinczés Lá, Payer E, Farkas K, Ujfalusi S, Diószegi Á, et al. Early administration of rendesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell-depleted patients with hemological malignancies: 0227-022-04924-6. https://doi.org/10.1007/cr.10111/bjh.18385. [70] Marasco V, Piciocchi A, Candoni A, Pagano L, Guidetti A, Musto P, et al. Neutralizing monoclonal antibodies in haematological patients paucilymomatic for COVID-19: the GIMEMA EMATO-0321 study. Br J Haematol 2022;199. https://doi.org/10.1111/bjh.18385. [71] Marbun MBH, Saragih RJ, Andina T. Management of COVID-19 in kidney transplant recipients: a single-center case series. Int J Nephrol 2022;2022. https://doi.org/10.1155/2022/9636624.

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

[72] Tom-Inonār et, Barrentos-Flores C, Vilar-Compte D, Pérez-Jimenez C, Alatorre-Fernandez P. Use of remdesivir for COVID-19 in patients with hematologic cancer. Clin Exp Med 2023;23. https://doi.org/10.1007/s10238-022-0094-4, 022-0094-4, M. "Kilmsuka M, Testi D, Russo C, Balletto E, Sepulcri C, Bussini I, et al. Outcome of early treatment of SARS-CoV-2 infection in patients with haematological disorders. Br J Haematol 2023;201. https://doi.org/10.1111/bjh.18690, 7491 (Milta O, Sotbokova M, Smetanova J, Bloomfield M, Vydlakova J, Chovancova Z, et al. Risk factors for severe COVID-19 and hospital admission in patients with inborn errors of immunity—results from a multicenter nationwide study. Front Immunol 2022;13. https://doi.org/10.3389/fimmu.2022.835770. [74] Moazfari E, Chandak A, Zang, S. Thun M, G.,bb RL, et al. Remidesvir treatment in hospitalized patients with Coronavirus disease 2019 (COVID-19): a comparative analysis of in-hospital and cause mortality in a large multicenter observational cohort. Clin Infect Dis 2022.75. https://doi.org/10.1093/cid/ciab7975. [76] Naeem S, Gohh R, Bayliss G, Cosgrove C, Farmakiotis D, Merhi B, et al. Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy. Transpl Infect Dis 2021;23. https://doi.org/10.1093/cid/ciab7975. [77] Papadimitriou-Olivgeris M, Cipriano A, Guggisberg N, Kroemer M, Tschopp J, Manuel O, et al. Outcome of COVID-19 in kidney transplant recipients through the SARS-CoV-2.1352. https://doi.org/10.5111/bjh.18690, 2 monoclonal antibodies. Transpl Int 2022;35. https://doi.org/10.3389/ti.2022.10721. [78] Pilgram I, Appel, Ruethrich MM, Koll CEM, Vehreschild MJGT, de Miranda SMN, et al. Use and effectiveness of remdesivir for the treatment of patients with Covid-19 using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS): a multicenter cohort study. Infection 2023;51. https://doi.org/10.1007/s15010-023-01994-0. [79] Radcliffe C, Palacios CF, Azar MM, Cohen E, Malinis M. Real-world experience with available, outpatient COVID-19 the therapies in solid organ transport recipients during the omicron surge. Am J Transplant 2022;22:2458-63. https://doi.org/10.1111/bj.17098. [80] Rorat M, Zarqbska-Michaluk D, Kowalska J, Kujawa K, Rogalska M, Kozelewicz D, et al. The course of COVID-19 in patients with systemic autoimmune rheumatic diseases. J Clin Med 2022;11. https://doi.org/10.3390/jcm11247342. [81] Sait AS, Chiang TP-Y, Marr KA, Massie AB, Cochran W, Shah P, et al. Outcomes of SOT recipients with COVID-19 in different eras of COVID-19 (therapeutics. Transplant Direct 2022;8. https://doi.org/10.1097/DX.00000000000001268). [82] Salmanton-Carca M., Coherl, F. Koehler P, Weinbergerová, B. Colovic N, Falces-Romero I, et al. Moluniravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICVIDEHA registry. Int J Antimicrok Agents 2023;62. https://doi.org/10.1016/j.ijantimicag.2023.106952. [83] Santos A, Sousa L'Ida Ca, Lima A, Nascimento C, Jorge C, et al. SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes—a single center experience. J Bras Netrol 2022;44. https://doi.org/10.1590/2175-8239-JBN-2021-0164. [84] Rasrell BA, Bloch K, El Chediak A, Kumm K, Tracy K, Forbes RC, et al. Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients. Transpl Infect Dis 2022;24. https://doi.org/10.1111/dit.13759. [85] Shafiekhan M, Shabinezhad F, Niknam T, Tara SA, Haem E, Mardani P, et al. Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand? Virol J 2021;18. https://doi.org/10.1186/s12985-021-01700-2. [86] Shah MM, Joyce B, Pfumb ID, Sahakian S, Feldstein LR, Barkley E, et al. Paxlovid associated with decreased hospitalization rate among adults with COVID-19—United States, April-September 2022. Am J Transplant 2023;23:150-5. https://doi.org/10.1016/j.ajt.2022.12.004. [87] Shields AM, Anantharachagan A, Rumalugazaki G, Baker K, Bahal S, Baxendale H, et al. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK. Clin Exp Immunol 2022;209. https://doi.org/10.1039/ci/uxac008. [88] Thompson MA, Henderson JP, Shah PK, Rubinstein SM, Joyner MJ, Chouei TK, et al. Association of convalescent plasma therapy with survival in patients with hematologic cancers and COVID-19. JAMA Oncol 2021;7. https://doi.org/10.1001/jamaoncol.2021.1799. [89] Wang AX, Busque S, Kuus R, Overtégton K, Pinsky BA, et al. SARS-CoV-2 neutralizing monoclonal antibodies for the treatment of COVID-19 in kidney transplant recipients. Kidney360 2022;3:133-43. https://doi.org/10.340675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX603007.2010.94675/DX60300

treated with antispike monoclonal antibodies. Open Forum Infect Dis 2022;9. https://doi.org/10.1093/ofid/ofac204. [93] Zimmermann J, Glueck OM, Fertmann JM, Sienel WG, Yavuz G, Damirov F, et al. COVID-19 in recent lung transplant recipients: clinical outcomes and management strategies. Transplant Proc 2022;54. https://doi.org/10.1016/j.transproceed.2021.12.014. [94] Christensen J, Kumar D, Moinuddin I, Bryson A, Kashi Z, Kimball P, et al. Coronavirus disease 2019 viremia, serologies, and clinical course in a case series of transplant recipients. Transplant Proc 2020;52. https://doi.org/10.1016/j.transproceed.2020.08.042. [95] Fung M, Nambiar A, Pandey S, Aldrich JM, Teraoka J, Freise C, et al. Treatment of immunocompromised COVID-19 patients with convalescent plasma. Transpl Infect Dis 2021;23. https://doi.org/10.1111/tid.13477. [96] Gachoud G, Dillon Tell, Stilimidos G, Battolla D, Dumas D, Opota O, et al. Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents. Br J Haematol 2022;199. https://doi.org/10.1111/bjh.18450. [97] Kenig A, Ishay Y, Kharouv F, Rubin L Treatment of B-cell depleted COVID-19 successful patients pre-exposed plasma and plasma-based products. Clin Immunol 2021;227. https://doi.org/10.1016/j.clim.2021.108723. [98] Lesichkova S, Manaova E, Yankova P, Krasteva Y, Marinova R. Mild to moderate clinical course of COVID-19 infection in patients with common variable immune deficiency. Cent Eur J Immunol 2022;47:357–61. https://doi.org/10.5114/cceji.2022.124079. [99] Takeda K, Kasai H, Sakao S, Saito M, Shikano K, Naito A, et al. Clinical outcomes of sotrovimab treatment in 10 high-risk patients with mild COVID-19: a case series. J Case Rep 2022;23. https://doi.org/10.12659/) A.KC.936832. [100] Mesbram HS, Kute VB, Banerjee S, Navadiya V, Desai S, et al. Fea-sibility and safety of remesdivir in SARS-CoV2 infected renal transplant recipients: a retrospective cohort from a developing nation. Transpl Infect Dis 2021;23. https://doi.org/10.1011/tid.13629.3. [101] Kute VB, Meshram HS, Petal HV, Engineer D, Banerjee S, Navadiya VV, et al. Clinical profiles and outcomes of COVID-19 in kidney transplant recipients: experience from a high-volume public sector transplant center in India. Exp. Clin Transplant 2021;19:899–909. https://doi.org/10.6002/ect.2021.0188. [12] Chai KL, Valk SJ, Piechto V, Kimber C, Monsef I, Doree C, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a perive systematic review. Cochrane Database Syst Rev 2020;10. https://doi.org/10.1002/14651858.CD013600.pub2. [13] lannizzi C, Chai KL Piechto V, Valk SJ, Kimber C, Monsef I, et al. Con-sulcent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev 2023;5. https://doi.org/10.1002/14651858.CD013600.pub5. [140] Raja MA, Mendoza MA, Villavicencio A, Anjan S, Reynolds JM, Kittipibul V, et al. CDV-19 in high-risk patients with metaal analysis of organ transplant recipients: a systematic review and meta-analysis of current literature. Transplant Rev (Orlando) 2021;35: 1005888. https://doi.org/10.1016/j.trte.2020.100588. [150] Gentry CA, Nguyen V, Thind SK, Kurdgelashvili G, Williams RJ 2nd. Char-acteristics and outcomes of US veterans with immunocompromised conditions at high risk of SARS-CoV-2 infection with or without receipt of oral 2007. https://doi.org/10.1016/j.ctr.2020.100588. [16] Spagnuolo V, Voarino M, Tonelli M, Galli L, Poli A, Bruzesi E, et al. Impact of remesdivir on SARS-CoV-2 clearance in a real-life setting: a matched-cohort study. Drug Des Level Ther 2022;16:3645–54. https://doi.org/10.2147/DDDT.S369473. [17] Villanego F, Mazuecos A, Cubillo B, Merino MJ, Poveda I, Saura IM, et al. Treatment with sotrovinsab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients. Clin Kidney J 2022;15:1847–55. https://doi.org/10.1093/cjtsfacf177. [18] Utzon AN, Johansen IS, Bang LL, Pedersen RM, Andersen TE, Madsen LW. Viral dynamics of SARS-CoV-2 in immunocompromised patients. Clin Microbiol Infect 2023;29:1087. https://doi.org/10.1016/j.cmi.2023.05.013 e1–e3. [19] Adachi E, Saito M, Koga M, Tsutsumi T, Yotsuyanagi H. Favorable outcome following sotrovimab monoclonal antibody in a patient with prolonged with sotrovimab infection with HIV/AIDS. Intern Med 2022;61:43592;61:46. https://doi.org/10.2169/internalmedicine.0485–22. [19] Ambati S, Ali B, Seddon O, Godkin A, Surr M, Moore C, et al. Resolution of persistent SARS-CoV-2 infection with prolonged intravenous remesdivir and vaccination in a patient post CAR-T. Int J Hematol 2023;117. https://doi.org/10.1007/s12185-023-0518-2. [19] Avanzete VA, Matso M, Jeifert SN, Pryce R, Williamson BN, Anzick SL, et al. Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell 2020;183: 1901–1912.e9. https://doi.org/10.1016/j.cell.2020.10.049. [18] LaanB, JH Smith, Mirabelli C, Valesano AL, Manthei DM, Bachman MA, et al. Prolonged severe acute respiratory syndrome coronavirus 2 replication in an immunocompromised patient. J Infect Dis 2021;223. https://doi.org/10.1009/37idis/jaa666. [11] Bailly B, Péré H, Veyer D, Berceanu A, Daguindau E, Roux P, et al. Persistent coronavirus disease 2019 (COVID-19) in an immunocompromised host treated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies. Clin Infect Dis 2022;74. https://doi.org/10.1093/cjtsab868.

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

1665

[114] Ballotta L, Simonetti O: D'Agaro P, Segat L, Koncan R, Martinez-Orellana P. et al. Case report: long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: the emerging therapeutic role of casirivaimb/imdevimab. Front Oncol 2022;12. https://doi.org/10.3389/fonc.2022.945060. [115] Breeden M, Aitken SL, Baang JH, Gravelin M, Kaul DR, Lauring AS, et al. Successful treatment of prolonged severe acute respiratory syndrome coronavirus 2 infection in patients with immunodeficiency with extended nirmatrelvir/ritonavir: case series. Open Forum Infect Dis 2023;10. https://doi.org/10.1093/jofd/ofd189d. [116] Buckland MS, Galloway JB, Fhogairtaah CN, Meredith L, Provinq NM, Boor, et al. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nat Commun 2020;11:6385. https://doi.org/10.1038/s41467-020-19761-2. [117] Camprubi D, Gaya A, Marcos MA, Martí-Soler H, Soriano A, Mosquera MDM, et al. Persistent replication of SARS-CoV-2 in a severely immunocompro- mediet tested with several countries of remdesivir. Int J Infect Dis 2021;104:379-81. https://doi.org/10.1016/j.ijid.2020.12.050. [118] Carujo A, Ferreira L, Bergantim R, Santos Silva A, Vasconcelos AL. Relapsing COVID-19 in a patient with non-Hodgkin lymphoma on chemotherapy. Cure2023;11:389474. https://doi.org/10.7759/curecus.49974. [119] Casarola G, D'Abbondanza M, Curcio R, Alcidi R, Campanella T., Rossi R, et al. Efficacy of convalescent plasma therapy in immunocompromised patients on 100/25-01: a case report. Clin Infect Pract 2021;12. https://doi.org/10.1016/j.jclinpr.2021.100096. [120] Colombo D, Gatti A, Alabardi B, Pompane D, Bonardi G, Mumoli N, et al. Covid-19-associated von praetin in un immunodeficiency with non-methylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphylphy

immunocompromised patient infected with SARS-CoV-2. Med 2023;4: 813–824.e4. https://doi.org/10.1016/j.medj.2023.08.001. 1343 Huygens S, Gharbaran A, Serroukh Y, Snoek B, Franken B, Oude Munnink BB, et al. High-titer convalescent plasma plus nirmatrelvir/ritor-navir treatment for non-resolving COVID-19 in six immunocompromised patients. J Antimicrob Chemother 2023;78. https://doi.org/10.1093/jac/dikad44. 1355 Jung S, Yagi Y, Fukushima K, Nishikawa Y, Tanaka M, Kobayashi T, et al. Successful dual antiviral therapy with remdesivir and ensitrelvir in a case of prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma. IDCases 2023;34. https://doi.org/10.1016/j.idcr.2023. e01890. 1363 Keitel V, Bode JG, Feldt T, Walker A, Müller L, Kunstein A, et al. Case report: convalescent plasma achieves SARS-CoV-2 viral clearance in a patient with persistently high viral replication over 8 weeks due to severe combined immunodeficiency (SCID) and graft failure. Front Immunol 2021;12. https://doi.org/10.33899/hu.2021.645989. 1373 Kinrilis N. Viral shedding and persistence of anosmia and ageusia in an asymptomatic SARS-CoV-2 in infection. Cureus 2023;45:196754. https://doi.org/10.7759/cureus.36574. 1385 Lewis C, Gupta NK. An atypical case of prolonged COVID-19 infection. Cureus 2022;14:e26921. https://doi.org/10.7759/cureus.26921. 1393 Lindahl AL, Ahava MJ, Haukipä M, Kreivi HR, Lipponen A, Kortela E. Suc-ravient treatment of persisting SARS-CoV-2 infection in an immunocompromised patient with repeated nirmatrelvir/ritonavir courses: a case report. Infect Dis (Lond) 2023;55:585-9. https://doi.org/10.1080/23744235.2023.22235 1400 Longo BM, Venuti F, Gaviraghi A, Lupia T, Ranzani FA, Pepe A, et al. Sequential or combination treatments as rescue therapies in immunocompromised patients with persistent SARS-CoV-2 infection in the omicron era: a case series. Antibiotics (Basel) 2023;12:1460. https://doi.org/10.3390/antibiotics 12091460. 141 (Luitel P, Vais D, Gidron A. Successful treatment of persistent coronavirus disease 2019 infection in a patient with hypogammaglobulinemia with REGN-COV2: a case report. Open Forum Infect Dis 2021;8:ofab335. https://doi.org/10.0393/ofab335. 142 (Malsy J, Veletzky I, Hdeide J, Hennigs A, Gil-Ibanez I, Stein A, et al. Sustained response after remdesivir diocventeras plasma therapy in a B-cell-depleted patient with protracted coronavirus disease 2019 (COVID-19). Clin Infect Dis 2021;73: https://doi.org/10.1093/cid/ciaa1637. 143 (Marangini D., Antonello RM, Coppi M, Palazzo M, Nassi L, Streva N, et al. Combination regimes in nirmatrelvir/ritonavir, and molupiravir for the treatment of persistent SARS-CoV-2 infection: a case report and a scoping review of the literature. Int J Infect Dis 2023;133:53-6. https://doi.org/10.1016/j.2023.04.412. 144 (MartineA, MA, Chen W, Choi H, Hwang M, Navarathna D, Hao L, et al. Extended remdesivir infusion for persistent coronavirus disease 2019 infection. Open Forum Infect Dis 2022;9. https://doi.org/10.1093/ofid/ofac382. 145 (Martinez-Barranco P, García-Roa M, Trelles-Martínez R, Arribalzaga K, Velasco M, Guijarro C, et al. Management of persistent SARS-CoV-2 infections with follicular lymphoma. Acta Haematol 2022;145. https://doi.org/10.1159/000521121. 146 (Martinez-Chinchilla C, Vazquez-Montero L, Palazón-Carrión N, Fernández-Ramín IM, López-Mar, B de la Cruz-Merino L, et al. Persistence of SARS-CoV-2 infection in severely immunocompromised patients with complete remission B-cell lymphoma and anti-CD20 monoclonal antibody therapy: a case report of two cases. Front Immunol 2022;13. https://doi.org/10.3389/fimmu.2022.860891. 147 (Meijer SE, Halutz O, Adler A, Levytsky K, Tau L, Dekel M, et al. Dual anti-viral treatment for persistent COVID-19 in immunocompromised hematoto-conological patients is associated with a favorable prognosis and minor side effects. J Infect Chemother 2024;30. https://doi.org/10.1016/j.jiac.2023.10.022. 148 (Mendel A, Colmegna I, Bourque G, Rajda E, Lee TC, Gálvez JH, et al. More than a "Hundred Days war": persistent SARS-CoV-2 infection in a patient with ANCA-associated vasculitis. J Assoc Med Microbiol Infect Dis Can 2022;7:131-4. https://doi.org/10.3138/jammi-2021-0033. 149 (Mikulka S, Sepulcri C, Dentone C, Magne F, Balletto E, Baldi F, et al. Triple combination therapy with 2 antivirals and monoclonal antibodies for persistent or elapsed severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad181. 150 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19 infection. Clin Case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 151 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 152 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hundred Days war: persistent SARS-CoV-2 infection in a patient with ANCA-associated vasculitis. J Assoc Med Microbiol Infect Dis Can 2022;7:131-4. https://doi.org/10.3138/jammi-2021-0033. 146 (Mikulka S, Sepulcri C, Dentone C, Magne F, Balletto E, Baldi F, et al. Triple combination therapy with 2 antivirals and monoclonal antibodies for persistent or elapsed severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad181. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19 infection. Clin Case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 153 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 154 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hundred Days war: persistent SARS-CoV-2 infection in a patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or elapsed severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad181. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hundred Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or separated severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad/181. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hundred Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or separated severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad/181. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hundred Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or separated severe acute respiratory syndrome coronavirus 2 infection in immunocompromised patients. Clin Infect Dis 2023;77:280-6. https://doi.org/10.1093/cid/ciad/181. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Monrad I, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hrodmed Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or transfirals and monoclonal antibodies for persistent or transfirals (Lind. Journal of 10.1093/cid/ciad/181). https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Miyamoto Y, Matsumura Y, Sumiyoshi S, Morikami Y, Nagao M. Hospital-at-home care for undeficient patients with COVID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Miyazato Y, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. Persistent severe acute respiratory syndrome coronavirus 2 infection in a Hrodmed Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for persistent or transfirals and conoclonal antibodies for persistent or transfirals (Lind. Journal of 10.1093/cid/ciad/181). https://doi.org/10.1016/j.jiac.2023.02.002. 155 (Miyamoto Y, Matsumura Y, Matsumura Y, Samiyoshi S, Morikami Y, Nagao M. M. Hospital-at-home care for undeficient patients with COID-19: approach to persistent COVID-19. In case Rep 2023;11. https://doi.org/10.1002.00c37.2943. 155 (Miyazato Y, Yamoto K, Nakaya Y, Morioka S, Takeuchi JS, Takamatsu Y, et al. Successful useful in degucimab / imdevimab - anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19. J Infect Chemother 2022;28:991-4. https://doi.org/10.1016/j.jiac.2023.02.002.002. 155 (Miyazato Y, Sahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. President severe acute respiratory syndrome coronavirus 2 infection in a Hrodmed Days war: persistent SARS-CoV-2 infection in an patient combination therapy with 2 antivirals and monoclonal antibodies for present or transfirals and conoclonal antibodies for抗estor or transfirals (Lind. Journal of 10.1093/cid/ciad/181. https://doi.org/10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al.�. President severe acute respiratory syndrome coronavirus 2 infection in a Hrodmed Days war: persistent SARS-CoV-2 in an patient combination therapy with 2 antivirals and monoclonal antibodies for抗estor or transfirals and conoclonal antibodies for抗estor or transfirals (Lind. Journal of 10.1093/cid/ciad/181. https://doi.org/10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al. Persistent were acute respiratory syndrome coronavirus 2 infection in a Hrodmed Days war: persistent SARS-CoV-2 in an patient combination therapy with 2 antivirals and conoclonal antibodies for抗estor or transfirals and conoclonal antibodies for抗estor or transfirals (Lind. Journal of 10.1093/cid/ciad/181. https://doi.org/10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nielsen SSF, Pedersen LØ, Petersen MS, Kobel CM, et al. et al.耐meder足-10.1016/j.jiac.2023.02.0022. 155 (Miyazato Y, Mahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Nahlertz SR, Na

M. Bartoletti et al. / Clinical Microbiology and Infection 31 (2025) 1655–1666

in immunocompromised host displaying treatment induced viral evolution. Open Forum Infect Dis 2021;8. https://doi.org/10.1093/ofid/abuf295. [153] Montejano R, Marcelo C, Falces-Romero I, Del Valle LG, De Soto T, Garcia-Rodríguez J, et al. Efficacy of sotrovimab for persistent coronavirus disease-2019 in a severely immunocompromised person living with HIV. AIDS 2022;36. https://doi.org/10.1097/QAD.000000000003179. [154] Nagai H, Saito M, Adachi E, Sakai-Tagawa Y, Yamayoshi S, Kiso M, et al. Casirivimab/imdevimab for active COVID-19 pneumonia which persisted for nine months in a patient with follicular lymphoma during anti-CD20 therapy. Jpn J Infect Dis 2022;75:608–11. https://doi.org/10.7883/yoken.JJID.2022.092. [155] Nagasaki Y, Kadowaki M, Nakamura A, Etoh Y, Shimo M, Ishihara S, et al. A case of a malignant lymphoma patient persistently infected with SARS-CoV-2 for more than 6 months. Medicina (Kaunas) 2023;59:108. https://doi.org/10.3390/medicina59010108. [156] Nakamura K, Sugiyama M, Ishizuka H, Sasajima T, Minakawa Y, Sato H, et al. Prolonged infective SARS-CoV-2 or comorant varhieding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remidesvir. J Infect Chemother 2023;29: https://doi.org/10.1016/j.ji.2023.05.003. [157] Nguyen H, Salkeld J, Agarwal S, Goodman A. Compassionate use of REGN-COV2 in the treatment of COVID-19 in a patient with impaired humoral immunity. Clin Infect Pract 2021;12: https://doi.org/10.1016/j.clinpr.2021.100089. [158] Palomba E, Carrabba M, Zuglian G, Alagna L, Saltini P, Fortina V, et al. Treatment of SARS-CoV-2 relapse with remdesivir and neutralizing antibodies cocktails in a patient with X-linked agmoglobulinaB. Int. In Metaz 2021;110. https://doi.org/10.1016/j.ijd.2021.07.064. [159] Pasquini Z, Toschi A, Casadei B, Pellegrini C, D'Abramo A, Viita S, 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. https://doi.org/10.1002/hon.32060. [160] Pérez Catalán I, García Muños Z, Roig Martí C, Gómez Alfaro I, Serrano Picoaz, L. Torres García M, et al. Nirmatrelvir/ritonavir as a potential treatment for prolonged SARS-CoV-2 infection in immunocompromised patients. Rev Esp Quimioter 2022;35. https://doi.org/10.37201/req/078.2022. [161] Pérez Catalán I, Gómez Alfaro I, García-Muños Z, Roig Martí C, Rodríguez Lozano N, Fabra-Kuana S, et al. Antiviral treatment or mAls for persistent and research: support in patients with hematologic malignancies: a case series. J Med Virol 2023;95:e28865. https://doi.org/10.1002/jmv.28865. [162] Rivalta B, Amodio D, Giancotta C, Santilli V, Pacillo L, Zangari P, et al. Case Report: successful treatment with monoclonal antibodies in one APDS patient with prolonged SARS-CoV-2 infection not responsive to previous lines of treatment. Front Immunol 2022;13. https://doi.org/10.3389/fimmu.2022.891274. [163] Rnjak D, Ravlicć S, Sola AM, Halassy B, Sšemniccki J, Superba M, et al. COVID-19 convalescent plasma as long-term therapy in immunodeficient patients? Transfus Clin Biol 2021;28. https://doi.org/10.1016/j.tracli.2021.04.004. [164] Seganfredo FB, Dias AR, Santos PR, Rebelo M, João C, Mendes D, et al. Successful treatment of persistent and severe SARS-CoV-2 infection in a high-risk chronic lymphocytic leukemia patient using Ronapreve™ antibodies. Clin Case Rep 2022;10:e6548. https://doi.org/10.1002/ccr3.6548. [165] Shimizu A, Shirai I, Ogawa K, Miura A, Haruhara K, Oshiro K, et al. Persistent SARS-CoV-2 infection in a patient with nephrotic syndrome under rituximab therapy: successful treatment with a combination of remdesivir and monoclonal antibodies. Intern Med 2022;61:3703–8. https://doi.org/10.20169/intalmedicine.0241–22. [166] Shimizu T, Shirasaki H, Okafuji K, Sawazaki A, Iwabuchi T, Matubayashi R. A case of prolonged COVID-19 treated with tixagevimab/cilgavimab. Respirol Case Rep 2023;11. https://doi.org/10.1002/rcr2.1099.

[167] Stoler S, van Hal SJ, Chadban S, Le T, Torzillo P, Scarlato RM, et al. Protracted COVID-19 pneumonitis early post-ABO incompatible kidney transplantation: management considerations and the role of whole genome sequencing. Nephrology (Carlton) 2023;28:639–43. https://doi.org/10.111/nep.14235. [168] Taha Y, Wardle H, Evans AB, Hunter ER, Marr H, Osborne W, et al. Persistent SARS-CoV-2 infection in patients with secondary antibody deficiency: successful clearance following combination casirivab and imdevimab (REGN-COV2) monoclonal antibody therapy. Ann Clin Microbiol Antimicrob 2021;20:85. https://doi.org/10.1186/s12941-021-00491-2. [169] Tayar E, Isber R, Isber N. Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2. Heliyon 2023;9:17419. https://doi.org/10.1016/j.heliyon.2023.e17149. [170] Thornton CS, Huntley K, Berenger BM, Bristow M, Evans DH, Fonseca K, 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;11:28. https://doi.org/10.1186/s13756-022-01067-1. [171] Trottie CL, Wong B, Kohli R, Boomsma C, Magro F, Kher S, et al. Dual clupr.2021;10:19. https://doi.org/10.1186/s13756-022-01067-1. [172] Haradaa G, Antonacio FF, Gongora AB, Behar MH, Carealli FC, Bastos DA, et al. SARS-CoV-2 testing for asymptomatic adult cancer patients before initiating systemic treatments: a systematic review. Ecancermedicalscience 2020;14: https://doi.org/10.1033/ecancer.2020.1100. [173] Di Lorenzo G, Iervolino M, Primino F, D'Ambroos M, Ingenito C, Buonerba L, et al. The impact of routine molecular screening for SARS-CoV-2 in patients receiving anticancer therapy: an interim analysis of the observational COICA study. Oncology 2022;10:505–11. https://doi.org/10.1159/000521086. [174] Lopes A, Pastore CBP, Deckers P, Halla IKMW, Dias ALR, da Mata MVM, et al. Oncological surgery during the COVID-19 pandemic: effectiveness of pre-operative screening and factors associated with postoperative SARS-CoV-2 infection. Ann Surg Oncol 2022;29. https://doi.org/10.1245/s10434-021-1195-4. [175] Campbell AP, Guthrie KA, Englund JA, Farney RM, Minerich EL, Kuypers J, et al. Clinical outcomes associated with respiratory virus detection before注意: neiche hematopoietic stem cell transplant. Clin Infect Dis 2015;61:192–202. DOI. https://doi.org/10.1033/cid/vi272. [176] Zavala S, DeLaurentis C, Aaron JG, Miko BA, Fox AN, Bergelson M, et al. When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients. Transpl Inf Infect Dis 2023;25. https://doi.org/10.1111/tid.14110. [177] Geukens T, Brandão M, Laenen A, Collignon J, Van Marcke C, Louviaux I, et al. Changes in anticancer treatment plans in patients with solid cancer hospitalized with COVID-19: analysis of the nationwide BSMO-COVID registry providing lessons for the future. ESMO Open 2022;7. https://doi.org/10.1016/j.esmoop.2022.100610. [178] Pinato DJ, Tabernero J, Bower M, Scotti L, Patel M, Colomba E, et al. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study. Lancet Oncol 2021;22. https://doi.org/10.1016/S1470-2045(21)00573-8. [179] Tripathi N, Sheikh D, Antimisiaris D. Anticancer therapy in COVID-19 patients: a descriptive literature review. Sr Care Pharm 2021;36:365–74. https://doi.org/10.4140/TCP.n.2021.365. [180] Halpern N, Boursi B, Shamch-Shmueli E, Gal-Yam EN, Margalit O, Golan T, et al. Early systemic anti-neoplastic treatment post SARS-CoV-2 infection in patients with breast cancer. Oncol Ther 2023;11. https://doi.org/10.1007/s40487-023-00247-2Abstract.