A U‐shaped association between baseline neutrophil count and COVID‐19‐related mortality: A retrospective cohort study

Fu, Wei; Chen, Chi; Chen, Xin‐Lin; Wang, Kun; Zuo, Peiyuan; Liu, Yuwei; Zhang, Meng; Zhao, Xiaofang; Xie, Songpu; Zhang, Hao; Geng, Yan; Liu, Chengyun

doi:10.1002/jmv.26794

Cited by 9 publications

(7 citation statements)

References 23 publications

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“… 12–14 The relationship between baseline neutrophil count and mortality in COVID-19 is U-shaped with increased mortality risk for both neutropenia and neutrophilia. 37 While neutropenia is a common occurrence in patients with HM, whether depth and duration of neutropenia are associated with outcome in COVID-19 in the HM population is not well studied. Patients with acute leukemia usually have profound and long-lasting neutropenia due to both disease-related and treatment-related factors, so focus on the subpopulation of patients with cancer having leukemia might indirectly describe the role of neutropenia in COVID-19 prognosis.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

Goldman

Robinson

Uldrick

et al. 2021

J Immunother Cancer

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SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.

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Section: Introductionmentioning

confidence: 99%

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

Goldman

Robinson

Uldrick

et al. 2021

J Immunother Cancer

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“…Transitional B cells [114], as well as memory B cells [115], all exhibit these trends, with levels strongly correlated with decreased survival. Conversely, massive overactivation of B cells can herald worse outcomes [61], similar to the U-shaped correlation of disease severity and levels of neutrophils [92].…”

Section: Resultsmentioning

confidence: 99%

“…While neutropenia is associated with increased risk and severity of various infections, its effect on COVID-19 outcomes is not well understood. Both low and high neutrophil counts have been linked to higher mortality in COVID-19 [54, 92]. In a multicenter study from Spain including HM patients, neutropenia of less than 500 cells/µL was an independent risk factor for mortality [38].…”

Section: Resultsmentioning

confidence: 99%

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

et al. 2022

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Background: The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. Summary: Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. Key Messages: Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.

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“…The table below includes a list of studies which have also found ANC to be significantly associated with survival and severity. Another recent study by Wei et al evaluated neutrophil count as a predictor variable (23). They studied the correlation of baseline neutrophil count (bNC) and neutrophil change rate (NCR) with death.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 mortality prediction model, 3C-M, built for use in resource limited settings - understanding the relevance of neutrophilic leukocytosis in predicting disease severity and mortality

Agarwal

Dua

Sud

et al. 2021

Preprint

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In this study, a combination of clinical and hematological information, collected on day of presentation to the hospital with pneumonia, was evaluated for its ability to predict severity and mortality outcomes in COVID-19. Ours is a retrospective, observational study of 203 hospitalized COVID-19 patients. All of them were confirmed RT-PCR positive cases. We used simple hematological parameters (total leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil to lymphocyte ration and platelet to lymphocyte ratio); and a severity classification of pneumonia (mild, moderate and severe) based on a single clinical parameter, the percentage saturation of oxygen at room air, to predict the outcome in these cases. The results show that a high absolute neutrophil count on day of onset of pneumonia symptoms correlated strongly with both severity and survival in COVID-19. In addition, it was the primary driver of an initial high neutrophil-to-lymphocyte ratio (NLR) observed in patients with severe disease. The effect of low lymphocyte count was not found to be very significant in our cohort. Multivariate logistic regression was done using Python 3.7 to assess whether these parameters can adequately predict survival. We found that clinical severity and a high neutrophil count on day of presentation of pneumonia symptoms could predict the outcome with 86% precision. This model is undergoing further evaluation at our centre for validation using data collected during the second wave of COVID-19. We present the relevance of an elevated neutrophil count in COVID-19 pneumonia and review the advances in research which focus on neutrophils as an important effector cell of COVID-19 inflammation.

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A U‐shaped association between baseline neutrophil count and COVID‐19‐related mortality: A retrospective cohort study

Cited by 9 publications

References 23 publications

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

COVID-19 mortality prediction model, 3C-M, built for use in resource limited settings - understanding the relevance of neutrophilic leukocytosis in predicting disease severity and mortality

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