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

Abstract

Background Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. Methods Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle–Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. Results In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. Conclusion Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Developing a Tool for Differentiation Between Bacterial and Viral Respiratory Infections Using Myxovirus Resistance Protein A and C-Reactive Protein

“…One limitation of the present study is the inclusion of patients infected by SARS-CoV-2. It is well known that COVID-19 infection increases the production of CRP either by the virus per se or by bacterial co-infection [ 13 , 14 ]. Further studies are required to further clarify if MxA and CRP may assist in the detection of bacterial co-infection in patients with COVID-19.…”

Pathophysiological, immunological, and inflammatory features of long COVID

“…Furthermore, this reactivation may enhance SARS-CoV-2’s entry into cells, potentially increasing viral load and symptom severity ( 285 ). While causal links have not been definitively established, it has been speculated that persistent EBV, HHV-6, and SARS-CoV-2 infections could fuel the chronic inflammation associated with long COVID ( 281 , 286 , 287 ). A study that compared patients with long COVID with 1 or more than 5 symptoms to those without long COVID found higher Epstein-Barr virus nuclear antigen (EBNA) IgG levels.…”

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

“…Течение и исходы COVID-19 связаны как с патогенным потенциалом вируса SARS-CoV-2, так и с характером вирус-индуцированного иммуновоспалительного процесса, зависящего от генетических, эпигенетических и иммунометаболических характеристик [24], патологии микробиома [25], гендерных и возрастных факторов (inflammaging) [26], выраженности активации тренированного иммунитета (training immunity) [27], коморбидной патологии (ожирение, сахарный диабет, аутоиммунные заболевания и др.) [28] и присоединения (или активации) латентной вирусной и бактериальной инфекций [29]. Кульминацией иммунопатологического процесса при COVID-19 является так называемый синдром «цитокинового шторма» -клинико-лабораторный симптомокомплекс, включающий несколько патологических состояний: гемофагоцитарный лимфогистиоцитоз (ГЛГ), синдром активации макрофагов (САМ) и синдром «высвобождения цитокинов», индуцированный CAR-T-клеточной (chimeric antigen receptor T cell) терапией [30].…”