Challenges in COVID-19 and Related Complications

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Personalized Therapy and Drug Delivery".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 19127

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Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy
Interests: clinical pharmacology; personalized medicine; pharmacogenomics; therapeutic appropriateness; oxidative stress; exercise training; aging and age-associated diseases
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Guest Editor
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy
Interests: clinical pharmacology; pharmacogenetics; pharmacoeconomy; appropriateness of drug prescribing; personalized medicine; oxidative stress; aging; cardiovascular diseases; exercise training
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The coronavirus disease 2019 (COVID-19) pandemic has held the world in its thrall since early March 2020 and, unfortunately, it still represents a very difficult challenge.

COVID-19 manifests a spectrum of signs and symptoms from mild to critical illness with rapid clinical deterioration and death. Especially at the beginning of the pandemic, physicians were faced with the challenge of caring for infected patients in the complete absence of scientific evidence and guidelines. Therefore, they used drugs already approved for other diseases, often without assuring optimal therapeutic appropriateness.

Emerging evidence highlights societal and physical impacts of the ongoing pandemic that might worsen clinical conditions, mainly in elderly and frail subjects. Apart from the direct effects of SARS-CoV-2, it is evident that several mechanisms can influence COVID-19 prognosis and patient outcome. This syndrome is associated with several extra-pulmonary manifestations leading to dysfunction and damage to many parts of the body even after the recovery. As a matter of fact, terms such as “long COVID” and “chronic COVID syndrome” have been coined to define the persistence of clinical manifestations or laboratory abnormalities beyond the acute phase of the disease. Therefore, understanding the short- and long-term consequences of COVID-19 represents an urgent issue.

The purpose of this Special Issue is to provide an overview of several concerns related to COVID-19 syndrome and address questions regarding clinical management, including the proper utilization of healthcare resources.

Particular attention will be focused on therapeutic appropriateness and the use of pharmacological and complementary approaches useful to care for both infected patients and patients showing post-COVID sequelae.

This Special issue is open to both reviews and original research papers targeting any of these topics.

Prof. Dr. Amelia Filippelli
Dr. Valeria Conti
Guest Editors

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Keywords

  • COVID-19 syndrome 
  • SARS-CoV-2 
  • long COVID
  • post-COVID sequelae 
  • COVID-19 management 
  • immune system 
  • therapeutic appropriateness 
  • healthcare

Published Papers (9 papers)

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Research

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28 pages, 5399 KiB  
Article
Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension
by Nadia Baalbaki, Jelle M. Blankestijn, Mahmoud I. Abdel-Aziz, Jan de Backer, Somayeh Bazdar, Inés Beekers, Rosanne J. H. C. G. Beijers, Joop P. van den Bergh, Lizan D. Bloemsma, Harm Jan Bogaard, Job J. M. H. van Bragt, Vera van den Brink, Jean Paul Charbonnier, Merel E. B. Cornelissen, Yennece Dagelet, Elin Haf Davies, Anne M. van der Does, George S. Downward, Cornelis M. van Drunen, Debbie Gach, J. J. Miranda Geelhoed, Jorrit Glastra, Kornel Golebski, Irene H. Heijink, Judith C. S. Holtjer, Sebastiaan Holverda, Laura Houweling, John J. L. Jacobs, Renée Jonker, Renate Kos, Ramon C. J. Langen, Ivo van der Lee, Asabi Leliveld, Firdaus A. A. Mohamed Hoesein, Anne H. Neerincx, Lieke Noij, Johan Olsson, Marianne van de Pol, Simon D. Pouwels, Emiel Rolink, Michael Rutgers, Havva Șahin, Daphne Schaminee, Annemie M. W. J. Schols, Lisanne Schuurman, Gitte Slingers, Olie Smeenk, Brigitte Sondermeijer, Paul J. Skipp, Marisca Tamarit, Inge Verkouter, Roel Vermeulen, Rianne de Vries, Els J. M. Weersink, Marco van de Werken, Yolanda de Wit-van Wijck, Stewart Young, Esther J. Nossent and Anke H. Maitland-van der Zeeadd Show full author list remove Hide full author list
J. Pers. Med. 2023, 13(7), 1060; https://doi.org/10.3390/jpm13071060 - 28 Jun 2023
Cited by 4 | Viewed by 2537
Abstract
Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by [...] Read more.
Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40–65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3–6 and 12–18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient’s home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3–6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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10 pages, 1146 KiB  
Article
Feasibility of Ultrasound-Guided, Peripherally Inserted Central Catheter Placement at the Bedside in a Communicable-Disease Isolation Unit
by Kyoung Won Yoon, Wongook Wi, Moon Suk Choi, Eunmi Gil, Chi-Min Park and Keesang Yoo
J. Pers. Med. 2023, 13(5), 863; https://doi.org/10.3390/jpm13050863 - 20 May 2023
Cited by 2 | Viewed by 1796
Abstract
Background: Previous studies have investigated the safety of peripherally inserted central catheters (PICCs) in the intensive care unit (ICU). However, it remains uncertain whether PICC placement can be successfully carried out in settings with limited resources and a challenging environment for procedures, such [...] Read more.
Background: Previous studies have investigated the safety of peripherally inserted central catheters (PICCs) in the intensive care unit (ICU). However, it remains uncertain whether PICC placement can be successfully carried out in settings with limited resources and a challenging environment for procedures, such as communicable-disease isolation units (CDIUs). Methods: This study investigated the safety of PICCs in patients admitted to CDIUs. These researchers used a handheld portable ultrasound device (PUD) to guide venous access and confirmed catheter-tip location with electrocardiography (ECG) or portable chest radiography. Results: Among 74 patients, the basilic vein and the right arm were the most common access site and location, respectively. The incidence of malposition was significantly higher with chest radiography compared to ECG (52.4% vs. 2.0%, p < 0.001). Conclusions: Using a handheld PUD to place PICCs at the bedside and confirming the tip location with ECG is a feasible option for CDIU patients. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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14 pages, 799 KiB  
Article
Laboratory Findings and Clinical Outcomes of ICU-admitted COVID-19 Patients: A Retrospective Assessment of Particularities Identified among Romanian Minorities
by Alexandra Mocanu, Voichita Elena Lazureanu, Ruxandra Laza, Adelina Raluca Marinescu, Talida Georgiana Cut, Suzana-Vasilica Sincaru, Adina Maria Marza, Irina-Maria Popescu, Lucian-Flavius Herlo, Andreea Nelson-Twakor, Mircea Rivis, Felix Bratosinand, Tamara Mirela Porosnicu and Alexandru Ovidiu Mederle
J. Pers. Med. 2023, 13(2), 195; https://doi.org/10.3390/jpm13020195 - 21 Jan 2023
Cited by 8 | Viewed by 1840
Abstract
The Roma population accounts for over 3% (approximately 10 to 15 million) of Romania’s permanent population, and it represents one of Europe’s most impoverished populations. Due to poverty and unemployment, Romania’s Roma minority may have diminished access to healthcare and preventive medicine. The [...] Read more.
The Roma population accounts for over 3% (approximately 10 to 15 million) of Romania’s permanent population, and it represents one of Europe’s most impoverished populations. Due to poverty and unemployment, Romania’s Roma minority may have diminished access to healthcare and preventive medicine. The limited existing evidence suggests that the European Roma group has been at a higher risk of becoming ill and dying during the pandemic owing to their lifestyle choices, socioeconomic circumstances, and genetic pathophysiological traits. As a result, the purpose of the present research was to investigate the link between the inflammatory markers implicated and the clinical progression of COVID-19 in Roma patients who were brought to the intensive care unit. We considered 71 Roma patients admitted to the ICU with SARS-CoV-2 infection and 213 controls from the general population with the same inclusion criteria. The body mass index of patients was statistically significantly higher among Roma patients, with more than 57% being overweight, compared with 40.7% in the control group. Frequent smoking was more prevalent in patients of Roma ethnicity admitted to the ICU and the number of comorbidities. We observed a significantly higher proportion of severe imaging features at admission in the group of cases, although this difference may have been associated with the higher prevalence of smoking in this group. The mean duration of hospitalization was longer by 1.8 days than the control group. Elevated ESR levels were observed in 54.0% of Roma patients at admission, compared with 38.9% in the control group. Similarly, 47.6% of them had elevated CRP levels. IL-6 increased significantly at the time of ICU admission, similarly to the significant rise in the CRP levels, compared with the general population. However, the proportion of intubated patients and mortality did not differ significantly. On multivariate analysis, the Roma ethnicity significantly influenced the CRP (β = 1.93, p-value = 0.020) and IL-6 (β = 1.85, p-value = 0.044). It is necessary to plan different healthcare strategies aimed at special populations, such as the Roma ethnicity, to prevent the reduced disparities presented in in this study. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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16 pages, 1276 KiB  
Article
Clinical Features and Paraclinical Findings in Patients with SARS CoV-2 Pneumonia and the Impact of Pulmonary Rehabilitation on the Instrumental Activities of Daily Living in POST-COVID-19 Patients
by Paraschiva A. Postolache, Alexandru Nechifor, Ioana Buculei, Ioana Soare, Horia Mocanu and Florin Dumitru Petrariu
J. Pers. Med. 2023, 13(2), 182; https://doi.org/10.3390/jpm13020182 - 20 Jan 2023
Cited by 1 | Viewed by 1696
Abstract
The functional sequelae grouped under the name “long COVID” most often bring the patient in front of a team of specialists in pulmonary rehabilitation. The aim of this study was to evaluate clinical features and paraclinical findings in patients with SARS CoV-2 (Severe [...] Read more.
The functional sequelae grouped under the name “long COVID” most often bring the patient in front of a team of specialists in pulmonary rehabilitation. The aim of this study was to evaluate clinical features and paraclinical findings in patients with SARS CoV-2 (Severe Acute Respiratory Syndrome-Corona Virus-2) pneumonia and to also evaluate the impact of rehabilitation in this category of patients. This study included 106 patients diagnosed with SARS CoV-2. The division of the patients into two groups was performed based on the presence of SAR-CoV-2 pneumonia. Clinical symptoms, biochemical parameters, and pulmonary functional and radiological examinations were recorded and analyzed. The Lawton Instrumental Activities of Daily Living (IADL) scale was applied to all patients. Patients in group I were included in the pulmonary rehabilitation program. Among demographic characteristics, age over 50 years (50.9%; p = 0.027) and the female sex (66%; p = 0.042) were risk factors for pneumonia in patients with SARS CoV-2. Over 90% of the 26 patients included in the rehabilitation program were less able to feed, bathe, dress, and walk. After 2 weeks, approximately 50% of patients were able to eat, wash, and dress. It is important to provide longer rehabilitation programs in cases of moderate, severe, and very severe COVID-19 patients, in order to significantly improve patients’ participation in daily activities and their quality of life. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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17 pages, 3652 KiB  
Article
Assessing the Mental Condition of Paramedics and Nurses during the SARS-CoV-2 Pandemic
by Maksymilian Kilian, Piotr Gałecki and Agata Orzechowska
J. Pers. Med. 2023, 13(1), 70; https://doi.org/10.3390/jpm13010070 - 28 Dec 2022
Viewed by 1478
Abstract
Background: The COVID-19 pandemic has significantly affected many aspects of life. The aim of this study was to assess the mental state of medical personnel most involved with patients affected by SARS-CoV-2. Methods: The survey research was conducted between October 2021 and March [...] Read more.
Background: The COVID-19 pandemic has significantly affected many aspects of life. The aim of this study was to assess the mental state of medical personnel most involved with patients affected by SARS-CoV-2. Methods: The survey research was conducted between October 2021 and March 2022. The study group included 46 paramedics, 48 nurses, and 6 individuals from both professions, ranging in age from 21 to 67 years. Data were collected using paper questionnaires that contained 44 questions. Results: During the pandemic, respondents maintained good contact with their colleagues and were competent enough to help their patients. The main factors that influenced their stress or dissatisfaction were the number of patients and the number of tasks. The nurses and paramedics most frequently reported symptoms related to tension, insomnia, and problems with intellectual performance. The pandemic situation led to the abandonment of hobbies and deterioration of relationships with friends and family. Conclusion: As a result of high stress levels, paramedics and nurses frequently suffered from tension and insomnia. The factors described were associated with poorer well-being of the subjects in various functional areas, even before the pandemic period. This was mainly related to the large number of patients and the tasks. However, this work, as well as studies by other authors, come to alarming conclusions that should draw attention to the mental state of medical staff, as this is the group that is highly responsible for the medical care of patients, especially in such a difficult time as a pandemic. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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11 pages, 463 KiB  
Article
Physical Activity and Sedentary Time in Korean Adults before and during the COVID-19 Pandemic Using Data from the Korea National Health and Nutritional Examination Survey
by So Young Kim, Dae Myoung Yoo, Mi Jung Kwon, Ji Hee Kim, Joo-Hee Kim, Woo Jin Bang and Hyo Geun Choi
J. Pers. Med. 2022, 12(8), 1217; https://doi.org/10.3390/jpm12081217 - 26 Jul 2022
Cited by 2 | Viewed by 1609
Abstract
Several recent studies suggested reduced physical activity (PA) related to the COVID-19 pandemic without consensus. This study investigated the changes in PA and sedentary time during the COVID-19 pandemic compared to before the COVID-19 era. The Korea National Health and Nutrition Examination Survey [...] Read more.
Several recent studies suggested reduced physical activity (PA) related to the COVID-19 pandemic without consensus. This study investigated the changes in PA and sedentary time during the COVID-19 pandemic compared to before the COVID-19 era. The Korea National Health and Nutrition Examination Survey 2019 and 2020 were used. The ≥19-year-old population was examined in 2019 and 2020 for time spent engaging in high- and moderate-intensity PA and sedentary time. Based on the recommended level of PA by the World Health Organization, ≥75 min/wk of high PA and ≥150 min/of moderate PA were classified. A sedentary time of ≥120 min/d was selected. Multiple logistic regression analysis with complex sampling was conducted for ≥75 min/wk of high PA, ≥150 min/wk of moderate PA, and ≥120 min/d of sedentary time in the 2020 group compared to the 2019 group. The ≥75 min/wk high PA was not lower in the 2020 group than in the 2019 group (adjusted odds ratio (aOR) = 0.96, 95% confidence intervals (95% CIs) = 0.79–1.18, P = 0.696). The ≥150 min/wk of moderate PA was also not lower in the 2020 group (aOR = 1.12, 95% CI = 0.94–1.32, p = 0.201). However, the ≥150 min/wk of moderate PA in the female group was higher in the 2020 group than in the 2019 group (aOR = 1.29, 95% CI = 1.01–1.65, p = 0.042). Sedentary time ≥ 120 min/d was lower in the 2020 group (aOR = 0.35, 95% CI = 0.17–0.72, p = 0.005). This association was consistent in the 19–39-year-old and female group. In conclusion, during the COVID-19 pandemic, high and moderate PA were not decreased in Korean adults, while sedentary time was reduced. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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Review

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14 pages, 1054 KiB  
Review
T Lymphocyte Subset Counts and Interferon-Gamma Production in Adults and Children with COVID-19: A Narrative Review
by Domenico Umberto De Rose, Pier Giorgio Pace, Francesca Ceccherini-Silberstein, Andrea Dotta, Massimo Andreoni, Loredana Sarmati and Marco Iannetta
J. Pers. Med. 2023, 13(5), 755; https://doi.org/10.3390/jpm13050755 - 28 Apr 2023
Cited by 3 | Viewed by 1778
Abstract
Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously [...] Read more.
Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously healthy subjects. Understanding these differences is still an ongoing challenge, that can lead to new therapeutic strategies and avoid unfavorable outcomes. In this review, we discuss the different roles of T lymphocyte subsets and interferon-γ (IFN-γ) in the immune responses of adults and children. Lymphopenia can influence these responses and represent a good predictor for the outcome, as reported by most authors. The increased IFN-γ response exhibited by children could be the starting point for the activation of a broad response that leads to MIS-C, with a significantly higher risk than in adults, although a single IFN signature has not been identified. Multicenter studies with large cohorts in both age groups are still needed to study SARS-CoV-2 pathogenesis with new tools and to understand how is possible to better modulate immune responses. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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27 pages, 466 KiB  
Review
Long COVID: Clinical Framing, Biomarkers, and Therapeutic Approaches
by Valeria Conti, Graziamaria Corbi, Francesco Sabbatino, Domenico De Pascale, Carmine Sellitto, Berenice Stefanelli, Nicola Bertini, Matteo De Simone, Luigi Liguori, Ilenia Di Paola, Maddalena De Bernardo, Angela Tesse, Nicola Rosa, Pasquale Pagliano and Amelia Filippelli
J. Pers. Med. 2023, 13(2), 334; https://doi.org/10.3390/jpm13020334 - 15 Feb 2023
Cited by 15 | Viewed by 4395
Abstract
More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and/or complications from COVID-19. [...] Read more.
More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and/or complications from COVID-19. The risk factors and clinical manifestations are many and various. Advanced age, sex/gender, and pre-existing conditions certainly influence the pathogenesis and course of this syndrome. However, the absence of precise diagnostic and prognostic biomarkers may further complicate the clinical management of patients. This review aimed to summarize recent evidence on the factors influencing PCS, possible biomarkers, and therapeutic approaches. Older patients recovered approximately one month earlier than younger patients, with higher rates of symptoms. Fatigue during the acute phase of COVID-19 appears to be an important risk factor for symptom persistence. Female sex, older age, and active smoking are associated with a higher risk of developing PCS. The incidence of cognitive decline and the risk of death are higher in PCS patients than in controls. Complementary and alternative medicine appears to be associated with improvement in symptoms, particularly fatigue. The heterogeneous nature of post-COVID symptoms and the complexity of patients with PCS, who are often polytreated due to concomitant clinical conditions, suggest a holistic and integrated approach to provide useful guidance for the treatment and overall management of long COVID. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)

Other

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7 pages, 2444 KiB  
Case Report
Multisystem Inflammatory Syndrome in Adults (MIS-A) Reported in Patient with Hematological Malignancy: A Case Report
by Elżbieta Kalicińska, Paula Jabłonowska and Tomasz Wróbel
J. Pers. Med. 2023, 13(2), 178; https://doi.org/10.3390/jpm13020178 - 19 Jan 2023
Cited by 1 | Viewed by 1211
Abstract
Background: The coronavirus disease 2019 (COVID-19) has persisted for over 2 years worldwide and has long-term effects on the health and quality of life of convalescents. Multisystem inflammatory syndrome, primary observed in children is currently increasingly recognized in adults. Immunopathology might play a [...] Read more.
Background: The coronavirus disease 2019 (COVID-19) has persisted for over 2 years worldwide and has long-term effects on the health and quality of life of convalescents. Multisystem inflammatory syndrome, primary observed in children is currently increasingly recognized in adults. Immunopathology might play a crucial role in the pathogenesis of multisystem inflammatory syndrome in adults (MIS-A); therefore, the occurrence of MIS-A in non-immunocompetent patients is a significant challenge in diagnosis and treatment. Case presentation: We described a 65-year-old patient with Waldenström’s macroglobulinemia (WM) who suffered from MIS-A after COVID-19 and was successfully treated with high doses of immunoglobulins and steroids. Conclusion: Our study presents for the first time a case of MIS-A in a hematological patient with a broad spectrum of symptoms reflecting multiorgan damage and suggests the long-term consequences of MIS-A as persistent immune dysregulation involving T-cell response. Full article
(This article belongs to the Special Issue Challenges in COVID-19 and Related Complications)
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