key: cord-0993388-ry09v3qe authors: Cai, Li; Zhou, Xi; Wang, Miao; Mei, Heng; Ai, Lisha; Mu, Shidai; Zhao, Xiaoyan; Chen, Wei; Hu, Yu; Wang, Huafang title: Reply to “Mortality-related immune features and COVID-19” date: 2021-02-04 journal: J Allergy Clin Immunol Pract DOI: 10.1016/j.jaip.2020.12.006 sha: af763bdddf91bdeec415cef150b7e65420757bdc doc_id: 993388 cord_uid: ry09v3qe nan To the Editor: We would like to share ideas on the report ''Predictive nomogram for severe COVID-19 and identification of mortality-related immune features.'' 1 Cai et al 1 noted that ''the abundance of CD45RO 1 CD3 1 T cells and neutrophil-to-lymphocyte and neutrophil-to-natural killer cell ratios may serve as useful prognostic predictors in severe patients.'' The finding from this small study is interesting. Indeed, the change in white blood cells in coronavirus disease 2019 (COVID-19) is possible and might contribute to the clinical manifestations. 2 Several factors can additionally contribute to the severity of infection. The underlying disease of the patient might also be reactivated because of COVID-19. Nevertheless, as noted by Lupia et al, 3 there is a role of cytokine response during COVID-19 illness that is an important determinant for severity, and the clinical problem due to change in white cells might be overt during the recovery stage of COVID-19 when there is a decreased level of cytokine response. Reply to ''Mortality-related immune features and COVID-19'' To the Editor: We have read with interest the comments by Mungmunpuntipantip and Wiwanitkit, 1 and we agree that cytokines are associated with disease severity and have an effect on the underlying disease. We would like to share our understanding of the role of cytokines in coronavirus disease 2019 (COVID-19). It is well known that an uncontrolled immune response to viral infection may lead to extensive cytokine release, called ''cytokine storm,'' consisting of a collection of proinflammatory cytokines (such as IL-6, IL-5, IL-8, and IL-1b) and chemokines. 2 The cytokine storm plays a major role in the development of acute respiratory distress syndrome and multiple organ failure in patients with COVID-19. Intensive care with sufficient hospital resources may reduce the mortality rate of severely ill patients. 3 However, invasive intervention in those patients with irregular immunity may lead to other complications, and death is inevitable in some patients. 4 Monitoring these cytokines provides clinicians with early signs of an overactive immune response and enables timely intervention. Nowadays, the use of anti-inflammatory agents (corticosteroid, tocilizumab, and so on) to suppress the cytokine storm is undergoing multiple trials and some results are encouraging. 5 Nevertheless, the impact of these agents on antiviral immunity and the appropriate timing of their use remain to be studied. In our study, 6 cytokine analysis was performed in 21 patients with COVID-19 (8 nonsevere and 13 severe) and showed that IL-6 and IL-10 levels were significantly higher in the death group than those in the recovery group. No significant difference, except for IFN-a, was observed between the nonsevere and severe groups, which may due to a decreased level of cytokine during the recovery stage of COVID-19 or the small sample size. 7 Many thanks for allowing us to reply to the comment on our article. Managing T2-high severe asthma in HIV-infected patients To the Editor: We read with interest and pleasure the case report by Curto et al 1 of the use of mepolizumab in HIV-infected patients suffering from severe corticosteroid-dependent eosinophilic asthma. Only few data concerning the treatment of asthma in HIV-positive patients with biologicals can be found in the literature. In this context, we would like to share our own experience with a seemingly similar case, but with a different choice of targeted therapy for type 2-high inflammation. 2 Two possible pathways lead to type 2 inflammation associated with a variable level of eosinophilia. The first pathway is distinguished by ''nonspecific'' innate immunity orchestrated by innate lymphoid cells 2 and IL-5. The second pathway is characterized by the specific adaptive immunity reactions mediated by T helper lymphocytes with the crucial role of IL-4 inducing the production of IgE. 3 Both pathways can overlap to a certain degree, supported by IL-13 in addition to IL-5. 4, 5 Eosinophilia can be the result of either allergic or nonallergic mechanisms, that is, almost each case of asthma to certain degree is eosinophilic, but not every case of eosinophilic asthma is allergic. Clinicians have to decide which asthmatic endotype is dominant and critical in the patient according to the clinical biomarkers and history and nominate which direction the ''weapon,'' that is, the biologics, should be targeted. In the case of HIV-positive patients, selecting a particular biologic is even more important because the role of eosinophils in antiviral defense, especially in case of HIV, remains unclear. 6 Curto et al correctly selected anti-IL-5 targeted therapy for their patient. The patient suffered from eosinophilic, though nonallergic, adult-onset asthma. In this case report, however, we are missing the data on the eventual nonsteroidal antiinflammatory drug hypersensitivity or chronic rhinosinusitis with nasal polyposis typical for this endo/phenotype. 7 For our patient, in October 2019, we selected anti-IL-4/-13 targeted therapy with dupilumab. 7 Our patient suffered from eosinophilic allergic asthma with early onset in childhood in the context of so-called atopic march. Anti-IgE therapy, that is, omalizumab, could not be introduced because of an extremely high concentration of total IgE. Selecting anti-IL-5 therapy would have targeted only nonspecific but not ''allergen-specific'' eosinophilia. 3, 5 The logical consequence was administering dupilumab, which is the first targeted monoclonal antibody also designed for the treatment of severe forms of atopic dermatitis. [3] [4] [5] From a theoretical point of view, this treatment supports a lower possible negative effect on the course of HIV infection. 6 The differences in the characteristics of both patients are reported in Table I. Both cases confirm the efficacy of the correctly selected biologic therapy in severe forms of bronchial asthma with HIV- The forced renaissance of telemedicine during COVID-19: a fellow-in-training's perspective Work Group Report: COVID-19: unmasking telemedicine Home self-monitoring in patients with asthma using a mobile spirometry system Predictive nomogram for severe COVID-19 and identification of mortality-related immune features Differential white blood cell count in the COVID-19: a cross-sectional study of 148 patients Giardiasis reactivation during severe SARS-CoV-2 infection Mortality-related immune features and COVID-19 The pathogenesis and treatment of the 'cytokine storm' in COVID-19 Hospital resources may be an important aspect of mortality rate among critically ill patients with COVID-19: the paradigm of Greece Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study Emerging pharmacotherapies for COVID-19 Predictive nomogram for severe COVID-19 and identification of mortality-related immune features Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients