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      Cutaneous Leishmaniasis Hampers COVID-19: A Controlled Cross-Sectional Study in High-Burden Endemic Areas of Iran

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          Abstract

          Introduction

          Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case–control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history.

          Methods

          This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth’s bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups.

          Results

          The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06–0.20 and P < 0.001) and severity of COVID-19 in previous cases with CL scars were significantly diminished than that in the control group (credible interval − 2.57, − 1.62).

          Conclusions

          The results represented a durable negative relationship between cured CL and COVID-19 incidence and severity. Additional studies seem necessary and should be designed to further validate the true impact and underlying mechanistic action of CL on COVID-19.

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          Most cited references51

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          Leishmaniasis Worldwide and Global Estimates of Its Incidence

          As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see ‘Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101’). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.
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            Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

            The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.
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              Is a “Cytokine Storm” Relevant to COVID-19?

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                Author and article information

                Contributors
                mehdimorovat@ymail.com
                iraj.sharifi@yahoo.com
                Journal
                J Epidemiol Glob Health
                J Epidemiol Glob Health
                Journal of Epidemiology and Global Health
                Springer Netherlands (Dordrecht )
                2210-6006
                2210-6014
                8 January 2024
                8 January 2024
                March 2024
                : 14
                : 1
                : 142-153
                Affiliations
                [1 ]Leishmaniasis Research Center, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [2 ]Institute for Studies in Medicine History, Persian and Complementary Medicine, Iran University of Medical Sciences, ( https://ror.org/03w04rv71) Tehran, Iran
                [3 ]Deputy for Health, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [4 ]Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [5 ]Research Center for Modeling in Health, Institute for Futures Studies in Health, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [6 ]Department of Immunology, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [7 ]Research Center for Social Determinants of Health, Institute for Futures Studies in Health, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [8 ]Research Center for Tropical and Infectious Diseases, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                [9 ]Dadbin Health Clinic, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran
                Author information
                http://orcid.org/0000-0002-4900-4278
                http://orcid.org/0000-0002-6894-6834
                Article
                179
                10.1007/s44197-023-00179-0
                11043327
                38190050
                aaa8c6e3-8b7b-478f-b0da-048d1a87e5d1
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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/4.0/.

                History
                : 28 August 2023
                : 6 December 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004621, Kerman University of Medical Sciences;
                Award ID: 400000704
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © Springer Nature B.V 2024

                cutaneous leishmaniasis,covid-19,severity,trained innate immunity,cross-protection

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