3
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Can COVID-19 Increase the Risk of Herpes Zoster? A Narrative Review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Herpes zoster (HZ) is associated with substantial morbidity. It is caused by reactivation of the latent varicella zoster virus (VZV) following decline in cell-mediated immunity, which is commonly age-related, but also occurs in individuals with immunosuppressive diseases and/or treatment. Since coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with T cell immune dysfunction and there have been reports of HZ in COVID-19 patients, we have performed a review of available literature on whether COVID-19 could trigger HZ. We identified 27 cases of HZ following COVID-19, which most frequently occurred within 1–2 weeks of COVID-19, and the majority of cases had typical presentation. Atypical presentations of HZ were noted especially in patients with lymphopenia. It has been hypothesized that VZV reactivation occurs as a consequence of T cell dysfunction (including lymphopenia and lymphocyte exhaustion) in COVID-19 patients. Based on current evidence, which is limited to case reports and case series, it is not possible to determine whether COVID-19 increases the risk of HZ. Practitioners should be aware of the possible increased risk of HZ during the pandemic period and consider timely therapeutic and preventive measures against it.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s13555-021-00549-1.

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: found

          Hematological findings and complications of COVID ‐19

          Abstract COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia

            Abstract Background In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. Methods The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. Results Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. Conclusions Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients

              The novel contagious primary atypical pneumonia epidemic, which broke out in Wuhan, China, in December 2019, is now formally called Coronavirus Disease 2019 (COVID-19), with the causative virus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 1,2 Recent studies have shown that in addition to dyspnea, hypoxemia, and acute respiratory distress, lymphopenia, and cytokine release syndrome are also important clinical features in patients with severe SARS-CoV-2 infection. 3 This suggests that homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. To provide direct evidence on leukocyte homeostasis, we studied the immunological characteristics of peripheral blood leukocytes from 16 patients admitted to the Yunnan Provincial Hospital of Infectious Diseases, Kunming, China. Among them, 10 were mild cases, 6 were severe cases; 7 were ≥50 years old, 11 were younger; and 6 had baseline diabetes, hypertension, or coronary atherosclerosis (Supplementary Table S1). Similar to the healthy group (n = 6), the absolute numbers of cells of major leukocyte subsets in peripheral blood remained at a normal level in both mild and severe patients. Different from that reported by Chen et al., 4 we did not observe increased neutrophils or decreased lymphocytes. Instead, we found that the severe group had a significant reduction in granulocytes compared to the mild group (Fig. 1a). It has been reported that elevated inflammatory mediators play a crucial role in fatal pneumonia caused by pathogenic human coronaviruses such as SARS and MERS (Middle East respiratory syndrome). 5 We therefore examined whether inflammatory mediators can impact progression in COVID-19 patients. However, no statistical differences in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) plasma concentrations were found among the three groups. Although patients had higher sCD14 levels than healthy people, there were no significant differences between the severe and mild groups (Fig. 1b). Fig. 1 COVID-19 patients, especially those with severe infection, showed increased levels of regulatory molecules and decreased levels of multiple cytokines in peripheral blood T cells. a Heat maps comparing peripheral blood leukocyte subset concentrations in healthy (n = 6), mild (n = 10), and severe (n = 6) patients. Rainbow-colored squares represent mean values of each group. Red-black-green squares represent log 10 P values, and white asterisk indicates P ≤ 0.05 by post hoc ANOVA test. H, healthy; M, mild; S, severe. b Comparisons of IL-6, TNF-α, and sCD14 plasma concentrations in healthy, mild, and severe groups. n.s., P > 0.05, *, P ≤ 0.05, by Kruskal–Wallis test. c Comparisons of expression levels of activation-, regulation-, and function-related molecules in CD4+ and CD8+ T cells among groups. Rainbow-colored squares represent mean positive cell rate for each group. d Comparisons of cell expression modules of exhaustion-related (CTLA-4, PD-1, and TIGIT) and function-related (IFN-γ, TNFα, and IL-2) molecules in CD4+ or CD8+ T cells among groups. “Single” indicates that cell only expresses one of the three molecules, “Multi” indicates that cell expresses at least two of the three molecules, “Non” indicates that cell expresses none of the three molecules. Red-yellow-blue squares indicate average cell expression rates of different modules of three groups, respectively. e Correlation network analysis of markers with significant differences among groups. Nodes are colored based on cell type for three groups. Node size indicates relative strength value according to centrality analysis. Thicker lines indicate more correlated genes. Green lines represent significantly positive Spearman’s correlation coefficients ≥0.40; red lines represent significantly negative Spearman’s correlation coefficients ≤−0.40. f Hierarchical clustering of participants based on all immunological risk indicators Virus-induced inflammatory factor storms can cause a systemic T cell response, reflected as changes in the differentiation and activity of T cells. 6 Here, as significant differences in virus-induced inflammatory cytokines were not detected, we next examined whether homeostasis was perturbed in T cells at the cellular level (Supplementary Table S2, Supplementary Fig. S1). As shown in Fig. 1c, the proportions of multiple molecules related to T cell activation and regulation increased significantly in patients compared to healthy controls, but several functional molecules showed a marked decrease. Among the differentially expressed functional molecules, the levels of interferon-γ (IFN-γ) and TNF-α in CD4+ T cells were lower in the severe group than in the mild group, whereas the levels of granzyme B and perforin in CD8+ T cells were higher in the severe group than in the mild group. The activation molecules showed no differences in CD4+ T cells, whereas the levels of HLA-DR and TIGIT in CD8+ T cells were higher in the severe group than in the mild group (Fig. 1c). These data indicate that COVID-19, similar to some chronic infections, damages the function of CD4+ T cells and promotes excessive activation and possibly subsequent exhaustion of CD8+ T cells. Together, these perturbations of T cell subsets may eventually diminish host antiviral immunity. 7 Usually a single molecule does not adequately predict disease progression. We therefore further performed cluster analysis on marker expression using data obtained from flow cytometry. Our results showed significant differences among the three subject groups in the level of exhaustion modules, including PD-1, CTLA-4, and TIGIT, and functional modules, including IFN-γ, TNF-α, and IL-2 (Supplementary Figs. S2, 3). Compared with the healthy control and mild group, the frequency of multi-functional CD4+ T cells (positive for at least two cytokines) decreased significantly in the severe group, whereas the proportion of non-functional (IFN-γ−TNF-α−IL-2−) subsets increased significantly. Studies have shown that multi-functional T cells can better control human immunodeficiency virus in natural infection and are correlated with better outcomes during vaccination; thus, the functional damage of CD4+ T cells may have predisposed COVID-19 patients to severe disease. 8 Li et al. 9 showed that these multi-functional CD4+ T cells occur more frequently in patients with severe SARS infections than in moderate infections. This indicates that SARS-CoV-2 may possess a unique immune pathology compared to other coronaviruses. In CD8+ T cells, the frequency of the non-exhausted (PD-1−CTLA-4−TIGIT−) subset in the severe group was significantly lower than that in the other two groups (Fig. 1d). Because functional blockade of PD-1, CTLA-4, and TIGIT is beneficial for CD8+ T cells to maintain lasting antigen-specific immunity and antiviral effects, 10,11 the excessive exhaustion of CD8+ T cells in severe patients may reduce their cellular immune response to SARS-CoV-2. To gain a comprehensive view of the above measured parameters, we also performed a correlation network analysis, and identified variables significantly related to COVID-19 disease progression, including age, chronic ailment, loss of functional diversity in CD4+ T cells, and increased expression of regulatory molecules, especially TIGIT, in CD8+ T cells (Fig. 1e). Subsequent hierarchical cluster analysis showed that these immunological factors could better distinguish healthy, mild, and severe patients, independent of age and chronic ailment (Fig. 1f). In conclusion, our study identified potential immunological risk factors for COVID-19 pneumonia and provided clues for its clinical treatment. Supplementary information Supplementary material
                Bookmark

                Author and article information

                Contributors
                javier.diez@fisabio.es
                raunak.p.parikh@gsk.com
                amit.b.bhavsar@gsk.com
                elisa.x.cisneros@gsk.com
                natalia.x.mccormick@gsk.com
                nicolas.lecrenier@gsk.com
                Journal
                Dermatol Ther (Heidelb)
                Dermatol Ther (Heidelb)
                Dermatology and Therapy
                Springer Healthcare (Cheshire )
                2193-8210
                2190-9172
                17 May 2021
                17 May 2021
                : 1-8
                Affiliations
                [1 ]GRID grid.428862.2, FISABIO-Public Health, ; Valencia, Spain
                [2 ]GRID grid.425090.a, GSK, ; Wavre, Belgium
                [3 ]GRID grid.419327.a, ISNI 0000 0004 1768 1287, GSK, ; Madrid, Spain
                [4 ]GRID grid.425090.a, GSK, ; Rixensart, Belgium
                Author information
                http://orcid.org/0000-0003-1008-3922
                http://orcid.org/0000-0002-8412-307X
                http://orcid.org/0000-0002-5956-2003
                http://orcid.org/0000-0003-0243-1405
                http://orcid.org/0000-0002-2108-3250
                http://orcid.org/0000-0002-0321-6283
                Article
                549
                10.1007/s13555-021-00549-1
                8126597
                33999370
                a491edcf-1adb-45a4-bf6b-40b74d11971e
                © GlaxoSmithKline Biologicals SA 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 22 March 2021
                Funding
                Funded by: GlaxoSmithKline Biolgicals SA
                Categories
                Review

                Dermatology
                covid-19,herpes zoster,lymphopenia,sars-cov-2,shingles,cell-mediated immunity
                Dermatology
                covid-19, herpes zoster, lymphopenia, sars-cov-2, shingles, cell-mediated immunity

                Comments

                Comment on this article