Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Patients with Philadelphia-Negative Myeloproliferative Neoplasm: A Single Center Experience

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent responsible for the coronavirus disease of 2019. The disease is primarily a respiratory illness; however, multisystem involvement is not uncommon. The infection is reported to be more severe in patients with multiple comorbidities and immunocompromised patients. Patients with hematological malignancies are immunocompromised and prone to develop severe SARS-CoV-2 infection. The SARS-CoV-2 had developed several mutations that resulted in different strains with different virulence and different degree of protection by vaccination or prior infection. The Omicron variant is reported to cause mild illness; however, the effect on patients with hematological malignancies like myeloproliferative neoplasms (MPNs) is not clear. We present patients with MPNs who had infection with the Omicron variant of the SARS-CoV-2 and their outcomes. Methods: Retrospective data from the National Center for Cancer Care and Research records from December 20, 2021, to January 30, 2022. Participants were adults over the age of 18 years with Omicron infection who had been diagnosed with Philadelphia-negative MPNs, essential thrombocythemia, polycythemia vera (PV), and primary myelofibrosis according to the 2008/2016 WHO classification for MPN. Results: Twenty-two patients with Philadelphia-negative MPN had Omicron infection. All patients had a mild disease according to the WHO classification of COVID-19 severity. Most of the patients had medical comorbidities, with hypertension being the most common comorbidity. However, only one patient with PV required hospitalization. Discussion/Conclusions: In patients with Philadelphia-negative MPN, the Omicron variant of SARS-CoV-2 usually results in mild infection.

© 2022 The Author(s). Published by S. Karger AG, Basel

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread swiftly worldwide, causing global outbreaks. Patients with several comorbidities are more prone to develop severe illness [1, 2]. The SARS-CoV-2 infection manifests primarily with respiratory symptoms, although other major organs such as the liver, kidney, pancreas, and skin can also be affected [3-5]. Since the first outbreak, SARS-CoV-2 has developed changes in the spike proteins; these mutations resulted in variation in the shape of the binding site on the viral surface and the affinity to bind angiotensin-converting enzyme 2 (ACE-2). Variation in the affinity to bind the cell receptors provides a good explanation for the difference in virulence, disease severity, and cytokine activation. Myeloproliferative neoplasms (MPNs) are a group of hematological disorders with the overproduction of mature blood cells of the myeloid cell line. They are classified as Philadelphia-positive and Philadelphia-negative MPN [6]. Philadelphia negative-MPN includes polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) [7]. The effect of SARS-CoV-2 on patients with MPN with the wild virus had shown results of increased adverse outcomes and reduced efficacy of vaccination, particularly in patients on ruxolitinib [8]. However, scarce data are there about the effect of the Omicron strain of the SARS-CoV-2 on patients with Philadelphia-negative MPN. We are reporting case series of patients with MPN who developed infection with the Omicron variant of the SARS-CoV-2. The series demonstrates the effect of the Omicron variant on this group of patients and their outcomes.

Methods

Retrospective data from records of the National Center for Cancer Care & Research (NCCCR) in Doha, Qatar, in the period between 20 December 2021 and 30 January 2022. The study included 22 patients with MPN who had Omicron infection. All patients are residing in the state of Qatar, with regular follow-up in NCCCR. Inclusion criteria: adult patients aged ≥18 years old, diagnosed with Philadelphia-negative MPNs (ET, PV, and PMF) according to 2008 and/or 2016 WHO criteria who had Omicron infection during the Omicron pandemic when the strain was 100% Omicron based on PCR result. Patients not fulfilling inclusion criteria (chronic myeloid leukemia) were excluded.

Ethical Approval

It was approved by the Medical Research Center with MRC MRC-04-22-170 for PV and MRC-04-22-183 for ET and PMF.

Result

A total of 22 patients with Philadelphia-negative MPN had Omicron infection (Table 1). Twelve patients with PV, 9 patients with ET, and 1 patient with PMF. All patients had a mild disease as per WHO guidelines [9]. The data show that the patients had low inflammatory markers (Table 1). All patients were managed in home isolation with supportive treatment like paracetamol and vitamin C and received no specific treatment for SARS-CoV-2, except 1 patient who was hospitalized and received favipiravir. Also, all patient had their MPN treatment continued as scheduled except the same patient who was started on favipiravir. There is no clear interaction between MPN treatment and the treatment for SARS-CoV-2 as patients did not receive specific SARS-CoV-2 treatment except for 1 patient who had stopped the MPN treatment during the SARS-CoV-2 infection. Among patients with PV, 7 patients were females and five were males. As seen in Table 1, all patients had good outcomes and no major complications. Only 1 patient with PV required hospitalization. The most prevalent comorbidity among PV patients was hypertension (8/12). PV patients have been diagnosed for more than 2 years and were on active treatment. Treatment received for PV included hydroxyurea, aspirin ruxolitinib, and interferon. Seven patients were vaccinated with Pfizer, two with Moderna, and 2 patients did not receive vaccination; one of them had a previous SARS-CoV-2 infection with no sequela. Among patients with ET, five were females and four were males. All patients had good outcomes with no major complications or hospitalization. Hypertension was the most common comorbidity among patients with ET (4/9). ET patients had the disease diagnosed for a minimum of 4 years, except for 1 patient who had the disease for a 4-month duration. Medications used to treat ET included hydroxyurea and aspirin. Five patients were vaccinated with Pfizer, three with Moderna, and 1 patient did not receive any vaccine.

Table 1.

Characteristics of patients with Philadelphia-negative MPN who had SARS-CoV-2 Omicron variant infection

/WebMaterial/ShowPic/1447020Discussion

MPN is a group of hematological conditions with uncontrolled production of mature cells of the granulocytic cell line. They can present accidentally during routine testing or with complications. Patients with MPN are at risk of having thrombotic as well as hemorrhagic complications [10, 11]. Additionally, SARS-CoV-2 infection causes an increased risk of thrombotic events [12]. MPN patients with SARS-CoV-2 are at significant risk of thrombosis, particularly patients with ET [13]. Such thrombotic risk can affect their quality of life which is already affected in a negative way [14].

Tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, nilotinib, and ponatinib are approved drugs used for CML patients. Despite the presence of new therapies for CML, TKIs are still the conventional therapy for CML [15]. It was thought that these TKIs (imatinib, dasatinib, and nilotinib) [16] might have a protective effect on CML patients against developing worse outcomes [16, 17]. However, large-scale studies in CML patients showed overall increased mortality with SARS-CoV-2 [18]. For patients with Philadelphia-negative MPN, some studies showed high mortality in patients who had sudden withdrawal of the TKI ruxolitinib [19]. This might indicate that TKI has a major role in the outcome of patients with MPN; although, there is no clear reason or explanation why TKI has these effects on patients with SARS-CoV-2. On the other hand, MPN patients on ruxolitinib had lower vaccine efficacy. This may indicate that TKI had an immune-modulatory effect that may reduce the efficacy of vaccination but makes patients vulnerable to severe COVID-19 infection when the drug is stopped abruptly. Data regarding the impact of SARS-CoV-2 infections in patients with MPN are few. In patients with MPN, infection with SARS-CoV-2 was not associated with worse outcomes or increased mortality even in the 9-month follow-up [20].

All these data were in patients with previous strains of the SARS-CoV-2. The data regarding COVID-19 infection in patients with PV are scarce, and they are mainly on the wild (alpha) variant. The rapid replication rate [21], capacity to resist the immune response, and high reinfection rate distinguish Omicron from other SARS-COV-2 strains [22]. With the Omicron variant, our reported cases showed that MPN patients presented with mild illness. This looks similar to patients with Philadelphia-positive MPN, chronic myeloid leukemia, and acute leukemia, where the Omicron infection results in mild disease [23, 24]. Infection with Omicron strain complicates our understanding of SARS-CoV-2; it makes the effect of the infection on MPN patients more complex, as currently, most of the population, including patients with MPN, have received vaccinations. The data showed that 20/22 patients had the vaccination, and 1 patient had a previous infection, so 21/22 patients had at least partial immunity to SARS-CoV-2. Furthermore, because MPN patients are immunocompromised, the vaccine’s efficacy in this group is likely lower than in other populations [25]. Therefore, a third dosage is advised to improve immunity against Omicron, which probably is a partial immunity after two vaccination doses. Moreover, the SARS-CoV-2 infection was mild, and no serious complications were reported despite the that most of the patients had at least one comorbidity, including hypertension, diabetes mellitus, heart failure, coronary artery disease, chronic kidney disease, and chronic liver disease. This could be because Omicron produces milder disease in this group of patients than in the general population, or it could be because of the protective effect of vaccination, which resulted in milder disease and low hospitalization rates.

Conclusions

These data suggest that, in patients with Philadelphia-negative MPN, the Omicron version of SARS-COV-2 usually causes mild disease. This appears to be similar to the general population who are not immunocompromised, where Omicron is usually milder and does not necessitate hospitalization. To better understand the Omicron impact in patients with Philadelphia-negative MPN, a large-scale study is needed.

Acknowledgments

I would like to thank the Internal Medicine Residency Program, Dr. Dabia Hamad Almohanadi, and Qatar National Library for scientific support.

Statement of Ethics

The study was reviewed and approved by the Medical Research Center (Doha), with MRC MRC-04-22-170 for PV and MRC-04-22-183 for ET and PMF. Written informed consent was taken from participants.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

Open access payment by the Qatar National Library. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author Contributions

Dr. Elrazi Ali, Dr. Ibrahim Khamees, Dr. Awni Alshurafa, Dr. Hanaa Qasem, Dr. Mohammad. Abdullah Abu-Tineh, Dr. Khaled Ahmed, and Dr. Eltaib Saad: writing, editing, and final approval. Dr. Mohamed Yassin: concept, writing, editing, and final approval.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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