☆ 4.5 Review

Viral reactivations and co-infections in COVID-19 patients: a systematic review

BMC INFECTIOUS DISEASES (2023)

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Summary: In this study, reactivation of EBV and CMV in critically ill patients with severe COVID-19 was common, especially in those receiving corticosteroid treatment. The impact of these reactivations on patient outcomes and the potential benefits of targeted treatments remain uncertain, warranting further investigation. However, early initiation of treatment showed a decrease in viral load, suggesting a potential benefit for patients with EBV and CMV reactivations.

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Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers

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Summary: Reactivation of HSV-1 is frequently detected in intubated patients with COVID-19, requiring possible antiviral treatment. However, no independent predictors of HSV-1 reactivation were identified in this study, and no association was found between HSV-1 reactivation and patient mortality.

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Cytomegalovirus reactivation in critically-ill Coronavirus Disease 2019 patients: A case series of 11 patients

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Ilenia Gatto et al.

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The effect of Epstein-Barr virus viremia on the progression to severe COVID-19

Jae Hyoung Im et al.

Summary: Epstein-Barr virus (EBV) is frequently reactivated by COVID-19, and a high incidence of EBV viremia has been reported in severe COVID-19 patients. The impact of EBV viremia on progression to severe COVID-19 is still unclear. This study aimed to evaluate the effect of EBV on COVID-19 progression. EBV viremia was investigated at the time of admission for COVID-19 patients hospitalized between February 1, 2020, and April 11, 2021. A cross-sectional study showed that the EBV viremia group had more severe pneumonia compared to the EBV-negative group. However, a retrospective cohort study limited to mild cases did not find any association between EBV viremia and COVID-19 progression.

MEDICINE (2022)

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Kristina E. Fuest et al.

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Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis

Shanshan Yang et al.

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COVID-19 associated EBV reactivation and effects of ganciclovir treatment

Mei Meng et al.

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Suhail S. Siddiqui et al.

Summary: The COVID-19 pandemic has led to new challenges in managing viral infections, particularly cytomegalovirus (CMV), belonging to the Herpesviridae family. Limited experience exists regarding CMV reactivation or coinfection during the COVID-19 pandemic, and further research is needed.

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Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis

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PRECISION CLINICAL MEDICINE (2022)

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Cytomegalovirus Reactivation in Critically-ill COVID-19 Patients

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Stefania Paolucci et al.

Summary: This study monitored the immunologic profile and opportunistic viral DNA increase in Italian patients with COVID-19 to identify markers of disease severity. It found a correlation between reduced CD8(+) T cells and NK counts, elevated EBV DNA levels, and COVID-19 severity, highlighting the importance of further evaluating the relationship between EBV load and disease severity in longitudinal studies.

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Ye Liu et al.

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Yun Xie et al.

Summary: This retrospective single-center study found that COVID-19 patients with EBV reactivation had higher rates of tachypnoea, greater decreases in lymphocyte and albumin levels, higher levels of D-dimer and serum calcium, higher rates of CRP and occurrence of respiratory failure, ARDS, and hypoproteinaemia, as well as significantly higher 28-day and 14-day mortality rates compared to patients without EBV reactivation. These patients also received more immuno-supportive treatment.

BMC INFECTIOUS DISEASES (2021)

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Viral coinfections in COVID-19

Parisa S. Aghbash et al.

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JOURNAL OF MEDICAL VIROLOGY (2021)

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Acute Retinal Necrosis as a presenting ophthalmic manifestation in COVID 19 recovered patients

Aniruddh Soni et al.

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OCULAR IMMUNOLOGY AND INFLAMMATION (2021)

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High rate of HSV-1 reactivation in invasively ventilated COVID-19 patients: Immunological findings

Jessica Seeßle et al.

PLoS One (2021)

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Positive Epstein-Barr virus detection in coronavirus disease 2019 (COVID-19) patients

Ting Chen et al.

Summary: This study revealed a high incidence of EBV coinfection in COVID-19 patients. Coinfection with EBV and SARS-CoV-2 was associated with fever and increased inflammation, indicating a potentially more severe condition.

SCIENTIFIC REPORTS (2021)

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Hypopharyngeal Ulcers in COVID-19: Histopathological and Virological Analyses - A Case Report

Andrea Porzionato et al.

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FRONTIERS IN IMMUNOLOGY (2021)

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Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU

Lorena Vigon et al.

Summary: A study on 61 COVID-19 patients revealed an enhanced but ineffective immune response in critical cases, leading to potential latent herpesvirus reactivation. This should be considered in the clinical management of patients with severe COVID-19 due to its contribution to disease severity.

FRONTIERS IN IMMUNOLOGY (2021)

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SARS-CoV-2 and Cytomegalovirus Co-Infections-A Case Series of Critically Ill Patients

Patricia Moniz et al.

Summary: The COVID-19 pandemic has led to increased cases of CMV reactivation in critically ill patients, although the exact relationship between the two remains unclear. The significant immune suppression in severe COVID-19 patients may impact CMV reactivation, potentially affecting the clinical course. Multiple confounding factors in these patients will pose challenges for future research.

JOURNAL OF CLINICAL MEDICINE (2021)

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COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report

Yi-Feng Wu et al.

Summary: COVID-19 or treatment-associated immunosuppression may trigger HBV reactivation in patients with chronic hepatitis B.

WORLD JOURNAL OF CLINICAL CASES (2021)

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Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study

Erica Franceschini et al.

Summary: This study analyzed the re-activation of HSV-1 in hospitalized COVID-19 patients and found a relatively high incidence of viremia and clinical manifestations, especially in patients treated with steroids.

MICROORGANISMS (2021)

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Article Microbiology

Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Jeffrey E. Gold et al.

Summary: The study found a prevalence of 30.3% for long COVID symptoms among COVID-19 patients, with some initially asymptomatic patients developing long-term symptoms. Additionally, a significantly higher rate of EBV reactivation was observed in long COVID subjects compared to control subjects, suggesting a potential association between COVID-19 inflammation and EBV reactivation.

PATHOGENS (2021)

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Review Medicine, Research & Experimental

Disseminated Kaposi sarcoma following COVID-19 in a 61-year-old Albanian immunocompetent man: a case report and review of the literature

Giulia Gardini et al.

Summary: The reactivation of latent infections, including HHV-8 and Kaposi sarcoma, may occur in patients with COVID-19 and its treatment, possibly influenced by factors such as Interleukin-6 activity and steroid-induced immunodeficiency. Despite the high incidence of COVID-19 in areas with medium-high prevalence of HHV-8 infection, no published case of disseminated KS following COVID-19 in otherwise healthy individuals was found through systematic literature review, suggesting a potential role of individual genetic susceptibility factors.

EUROPEAN JOURNAL OF MEDICAL RESEARCH (2021)

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Cytomegalovirus meningoencephalitis in a case of severe COVID-19 Pneumonia. A case report

Dore C. Ananthegowda et al.

Summary: The use of steroids and other immune modulatory therapies in severe COVID-19 pneumonia treatment can lead to the reemergence of opportunistic infections like CMV, requiring high suspicion. Altered sensorium in COVID-19 cases may have multifactorial causes, and vigilance for complications such as CMV meningoencephalitis is crucial.

IDCASES (2021)

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Article Infectious Diseases

Herpesvirus reactivation during severe COVID-19 and high rate of immune defect

A. Saade et al.

Summary: The study found that the incidence of herpesvirus reactivation in patients treated in the ICU for severe COVID-19 was high, but in most cases did not require antiviral treatment. Pre-existing hematological malignancy and solid organ transplantation were independently associated with viral reactivation, but viral reactivation was not associated with mortality.

INFECTIOUS DISEASES NOW (2021)

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Article Critical Care Medicine

HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients

Antoine Meyer et al.

Summary: The study found that HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and hospital-acquired pneumonia/ventilator-associated pneumonia.

CRITICAL CARE (2021)

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Review Multidisciplinary Sciences

Corticosteroids for treatment of COVID-19: effect, evidence, expectation and extent

Vijay K. Patel et al.

Summary: Corticosteroids such as dexamethasone, methylprednisolone, hydrocortisone, and prednisone are used for the treatment of moderate to critically ill COVID-19 patients who require hospitalization and supplemental oxygen. However, they should not be used for non-severe patients as they may suppress the immune response and increase the risk of death. Further research is needed to fully understand the mechanisms and importance of corticosteroid therapy in preventing and treating COVID-19.

BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES (2021)

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Article Medicine, General & Internal

Epstein-Barr Virus Coinfection in COVID-19

Asim Nadeem et al.

Summary: EBV, a member of the herpes virus family, is a causative agent for infectious mononucleosis. Most cases are asymptomatic, but hepatitis has been found to be related to acute EBV and cytomegalovirus reactivation versus acute infection.

JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS (2021)

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Article Infectious Diseases

Cytomegalovirus proctitis as a complication of COVID-19 with immunosuppressive treatments

Francois Maillet et al.

Summary: This case report describes a patient with reactivated cytomegalovirus proctitis complicating severe COVID-19 pneumonia treated with dexamethasone, anakinra, and lopinavir/ritonavir. The herpes virus proctitis was attributed to iatrogenic immunosuppression and immune dysregulation related to COVID-19, highlighting the immunosuppressive risks associated with using immunomodulators in the treatment of severe COVID-19 pneumonia.

IDCASES (2021)

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Review Public, Environmental & Occupational Health

COVID-19 pandemic as a risk factor for the reactivation of herpes viruses

M. D. Maldonado et al.

Summary: Some patients exhibit herpes virus infections during the COVID-19 pandemic, possibly influenced by the underlying SARS-CoV-2 infection. The study suggests that the COVID-19 pandemic can cause immunodeficiencies that increase the risk of other viral infections.

EPIDEMIOLOGY AND INFECTION (2021)

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Article Infectious Diseases

High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19

A. Simonnet et al.

Summary: Critically ill patients with COVID-19 in the ICU are prone to herpesvirus reactivation, particularly with EBV, which occurs early and is associated with longer ICU stays.

INFECTIOUS DISEASES NOW (2021)

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Article Medicine, General & Internal

Tocilizumab-induced cytomegalovirus colitis in a patient with COVID-19

Mohamad Y. Khatib et al.

Summary: Clinicians should monitor for early signs of CMV reactivation in COVID-19 patients presenting with gastrointestinal complications after receiving immunosuppressive therapy, to prevent life-threatening complications and mortality.

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Article Gastroenterology & Hepatology

Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19

Warren C. Carll et al.

Summary: This case report describes a patient with SARS-CoV-2 who developed haemorrhagic enterocolitis after recovering from respiratory failure with venovenous extracorporeal membrane oxygenation. The study suggests a possible link between systemic coinfection/reactivation of cytomegalovirus and the prolonged resolution of gastrointestinal inflammation in COVID-19 patients. Additionally, the proposed synergistic pathophysiologic mechanisms for enterocolitis complicating severe COVID-19 infection include T lymphocyte depletion, immune response dysregulation, use of immunomodulators, and high concentration of ACE-2 receptors in the gastrointestinal tract for COVID-19 virus.

BMJ OPEN GASTROENTEROLOGY (2021)

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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou et al.

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Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19

Yabo Ouyang et al.

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Simin Ma et al.

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Fei Zhou et al.

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Bo Diao et al.

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Fabio Ciceri et al.

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Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis

Stefano Figliozzi et al.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION (2020)

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Co-reactivation of the human herpesvirus alpha subfamily (herpes simplex virus-1 and varicella zoster virus) in a critically ill patient with COVID-19

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Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection

Jiaye Liu et al.

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The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak

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Herpesviruses: latency and reactivation – viral strategies and host response

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Review Virology

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FUTURE VIROLOGY (2011)

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Review Microbiology

Viral Latency and Its Regulation: Lessons from the γ-Herpesviruses

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Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

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Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

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Is HSV serology useful for the management of first episode genital herpes?

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