key: cord-0903143-awda9bxp
authors: Weinbergerova, Barbora; Mayer, Jiri; Kabut, Tomas; Hrabovsky, Stepan; Prochazkova, Jirina; Kral, Zdenek; Herout, Vladimir; Pacasova, Rita; Zdrazilova‐Dubska, Lenka; Husa, Petr; Bednar, Petr; Ruzek, Daniel; Lengerova, Martina
title: Successful early treatment combining remdesivir with high‐titer convalescent plasma among COVID‐19‐infected hematological patients
date: 2021-08-16
journal: Hematol Oncol
DOI: 10.1002/hon.2908
sha: dd109d1fe2b9ab2668eafb787fa1e0ba827a1c94
doc_id: 903143
cord_uid: awda9bxp

nan

Immunocompromised patients with hematological malignancies are at high risk for a severe course of COVID-19 (Coronavirus Disease 2019) with a deadly outcome. 1, 2 With remdesivir use, several randomized trials have recorded abbreviated recovery periods, lower mortality, and positive consequences of early treatment initiation. 3, 4 Based on randomized trial results, the FDA has approved remdesivir for the treatment of COVID-19. Regarding convalescent plasma (CP), evidence from recently published large trials implies that early administration of high-titer CP is most efficacious. 5 However, no published studies assessing the effect of remdesivir or CP in COVID-19 have included a substantial proportion of hematooncology patients, and available data are limited to case reports. 6, 7 In view of this dearth of data, we decided to analyze the efficacy of early combination therapy of remdesivir and high-titer CP among hematological patients. This treatment strategy was implemented after observing several grim COVID-19 outcomes among these patients.

Our retrospective study from 30 December 2020 through 29 March 2021 included unselected consecutive hematological patients diagnosed with COVID-19 (presence of SARS-CoV-2 verified by Reverse Transcription Polymerase Chain Reaction, RT-PCR, or antigen from nasopharyngeal swab) and subsequently treated with a remdesivir and high-titer CP combination at our hospital. Disease severity was assessed according to adapted definitions. 8 Data were obtained from source medical documentation covering comorbidities, pulmonary imaging, COVID-19 diagnostics, therapy, and outcome. High-titer CP was manufactured from plasma of convalescent male donors with SARS-CoV-2 anti-S antibody levels at least 200 U/ml (Elecsys® Anti-SARS-CoV-2 S) at the time of plasma collection.

All patients received intravenous remdesivir 200 mg on day 1, followed by 100 mg daily for a total of 5 days. Two units of high-titer CP (SARS-CoV-2 neutralizing antibodies at a titer 1:160 and higher) were administered per one treatment cycle. Several underwent retreatment due to either prolonged SARS-CoV-2 positivity or repositivity, eventually supported by culture virus viability, or as a secondary prophylaxis during ongoing oncological treatment. A descriptive analysis was conducted separately for two divided cohorts: "Pneumonia Cohort" versus "No Pneumonia Cohort" at the onset of combination therapy. Pneumonia was diagnosed based on chest x-ray pulmonary infiltrates or high-resolution computer tomography. Our research was undertaken in accordance with relevant guidelines and regulations. All patients involved signed an informed consent form.

Basic statistical methods describing absolute and relative frequency for categorical variables, mean, median, minimum and maximum for continuous variables, respectively, were employed.

Categorical parameter relations were evaluated using Fisher's exact tests; continuous variables were compared using the Mann-Whitney U test with α = 0.05 as a level of statistical significance.

A total of 32 hematological patients (75% not in remission), with acute leukemias, lymphomas, and myeloma as the most frequent underlying diagnoses (81%), were evaluated with a median followup of 36 days (min-15, max-92). Baseline characteristics are described in Table 1 . In both cohorts, median time from SARS-CoV-2 positivity to treatment onset was 1 day. When initiating remdesivir, 56% of patients already had evidence of pneumonia. The SARS-CoV-2 diagnosis was primarily determined by RT-PCR test (72%). While not substantial, our "Pneumonia Cohort" exhibited more comorbidities and worse white blood cell parameters than the "No Pneumonia Cohort." When COVID-19 was diagnosed, our "Pneumonia Cohort" had a remarkably higher stage of disease severity (moderate-severe-critical) compared to the "No Pneumonia Cohort" (83% vs. 14%; p < 0.001) ( Table 1 ). Corticosteroids and low-molecular-weight heparins were employed among 47% and 91% of study patients, respectively, without a considerable difference between cohorts. During the first treatment cycle, Our study's major strength is its focus on a uniform single-center cohort comprised exclusively of hematological patients and limited only in terms of sample size and control group participation. diagnosis. We believe that this treatment strategy is especially effective in patients who have not yet developed pneumonia.

Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients

Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

Remdesivir for the treatment of Covid-19 -final report

A shorter symptom onset to remdesivir treatment (SORT) interval is associated with a lower mortality in moderate-to-severe COVID-19: a real-world analysis

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

Prolonged severe acute respiratory syndrome coronavirus 2 replication in an immunocompromised patient

Persistent replication of SARS-CoV-2 in a severely immunocompromised patient treated with several courses of remdesivir

Mild or moderate Covid-19

COVID-19 in patients (pts) with chronic myeloid leukemia (CML): results from the International CML Foundation (iCMLf) CML and COVID-19 (CANDID) study

COVID-19 infection in chronic myeloid leukemia after 1 year of the pandemic in Italy. A CAMPUS CML analysis

This study was carried out as part of our routine work and supported by Ministry of Health, Czech Republic-conceptual development of research organization (FNBr, 65269705).

The authors declare no competing or conflicting interests.

Ministry of Health, Czech Republic; FNBr, 65269705. Lenka Zdrazilova-Dubska 7 Petr Husa 8, 9 Petr Bednar 10, 11 Daniel Ruzek 10, 12 Martina Lengerova 1,2 1