Evaluation of Prevalence and Risk Factors of Persistent COVID-19 in Immunocompromised Patients

Spontaneous international multicenter retrospective and prospective observational study which objective is to evaluate the prevalence and risk factors of persistent SARS-CoV-2 infection within a population of hematology patients with humoral immunity deficiency.

The retrospective recruitment period will span from January, 1st, 2022 to the date of authorisation by hospital directorates following the Ethics Committees' approvals. This period has been established considering the prevalent diffusion of the omicron variant and its subvariants, which has led to significant changes in the clinical manifestations of COVID-19. The prospective recruitment will be carried out over the 12 months immediately following the retrospective period. During the study period, screening for persisting SARS-CoV-2 infection and therapeutic management of all patients will be carried out by the attending physicians according to routine practice.

This study is enclosed in the EU Horizon 2020 project "Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic: ORCHESTRA" (Grant Agreement No. 101016167) and is located within Task 4.6 "Prevalence, risk factors and therapeutic management of persistent COVID-19 in frail patients." It is expected to enroll approximately 1,000 patients (500 at the coordinating center).

• Persisting SARS-CoV-2 infection (Other): Prevalence of persisting SARS-CoV-2 infection among immunocompromised patients defined as the persistence or the recurrence of symptoms and signs (fever, dyspnea, hypoxemia, changes on chest-X ray or CT scan) and positive SARS-CoV-2 PCR ≥ 21 days after the time 0 (day of the first test positive for SARS-CoV-2 infection)

Primary outcomes

• Prevalence of persisting SARS-CoV-2 infection among immunocompromised patients [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: The first primary endpoint variable will be the rate of patients with persisting SARS-CoV-2 infection among study patients with new diagnosis of SARS Cov2 during the study period Persisting COVID19 will be defined as the persistence or the recurrence of symptoms and signs (fever, dyspnea, hypoxemia, changes on chest-X ray or CT scan) and positive SARS-CoV-2 PCR ≥ 21 days after the time 0 (day of the first test positive for SARS-CoV-2 infection)

Secondary outcomes

• Risk factors for persisting COVID19 [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: Univariate and multivariate analysis will be carried out to investigate factors associated with persisting COVID-19 among the study population
• Duration of viral shedding [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: Duration of viral shedding, defined as the number of days between the first positive test and first negative PCR test
• Duration of symptoms [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: Duration of symptoms, defined as the number of days between symptoms onset and the clinical cure
• Prevalence of imaging alterations [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: Prevalence of imaging alterations, defined as the presence of new ground-glass and/or crazy paving and/or interstitial infiltrates at chest CT scan during the persisting infection (starting from 21 days after the first positive test until viral clearance)
• Re-infection within 120 days [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: Re-infection within 120 days, define as new positive test with or without symptoms after viral clearance has been achieved
• All-cause 120-day mortality [Retrospective recruitment period will span from January 1st, 2022 to to the date of authorisation by hospital directorates following the Ethics Committees' approvals]: All-cause 120-day mortality

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosis of B cell malignancies or previous treatment with B cell targeting therapies.
* Diagnosis of proven SARS-CoV-2 infection confirmed by a PCR test (only the first infection during the study period will be considered, re-infection will be counted as a secondary endpoint).
* Provision of signed and dated informed consent.

Exclusion Criteria:

* None

• Study Protocol and Statistical Analysis Plan (PDF, 2023-10-06)

• Maddalena Giannella, MD PhD, Principal investigator, University of Bologna