Table 1 Study characteristics of selected records
From: Viral reactivations and co-infections in COVID-19 patients: a systematic review
Author (year) | Study site | Study design | Study setting | Total sample size | Agea | Outcome measure/Diagnosis of interest | COVID-19 Diagnostic method | Diagnostic method for outcome measure and relevant clinical outcomesb |
|---|---|---|---|---|---|---|---|---|
Aldhaleei et al. (2020) [36] | United Arab Emirates | Case report | Inpatient (ICU) | 1 | 36 years | COVID-19 induced HBV reactivation | RT-PCR | Blood tests (biochemistry, CBC, serology for HB core Ab, HBe Ag and Ab) |
Aldehaim et al. (2022) [41] | Saudi Arabia | Case report | Inpatient (ICU) | 1 | 47 years | CMV Pneumonitis in a COVID-19 patient with systemic lupus erythematosus and interstitial pneumonia | RT-PCR | Chest examination, CMV PCR, microscopy and staining, blood tests (CBC, biochemistry) |
Ananthegowda et al. (2021) [42] | Qatar | Case report | Inpatient (ICU) | 1 | 55 years | CMV meningoencephalitis in severe COVID-19 patients | RT-PCR | CMV CSF PCR, CSF analysis, Brain MRI, blood tests (CBC, biochemistry) |
Carll et al. (2021) [43] | United states | Case report | Inpatient | 1 | Not reported | CMV hemorrhagic enterocolitis in severe COVID-19 patient | RT-PCR | Blood tests (biochemistry, CBC, CMV PCR), IHC |
Das et al. (2022) [19] | India | Case report | Ambulatory care | 1 | 73 years | Recurrent herpes simplex keratitis in a patient with a previous history of COVID-19 diagnosis | Tool not specified, based on the patient history | Ophthalmological exam, HSV-1 RT-PCR |
Drago et al. (2021) [16] | Italy | Editorial letter (case report) | Ambulatory care | 1 | 16 years | Pityriasis rosea (PR) diagnosis from the EBV, HHV-6, HHV-7 reactivations | RT-PCR | Blood tests (CBC, serology for all three viruses, including EBV IgM, EBV VCA, anti-VCA IgG, anti-early antigen IgG, anti EBV nuclear antigen IgG, HHV-6 and 7 IgM and IgG, RT-PCR for all three viruses, physical examination |
Duong et al. (2021) [44] | Not reported | Case report | Inpatient | 1 | 59 years | CMV induced acute hepatitis in COVID-19 patient | Tool not specified, based on medical records | CMV PCR, CBC |
Ferreira et al. (2020) [45] | Brazil | Case report | Ambulatory care | 1 | 39 years | VZV and COVID-19 co-infection | RT-PCR | Physical examination, brain MRI, blood tests (cytokine biochemistry, CBC, VZV IgM serology) |
Figueredo et al. (2021) [46] | USA | Case report | Inpatient (ICU) | 1 | 55 years | HBV reactivation in COVID-19 patient post tocilizumab therapy | Tool not specified, based on medical records | HBV PCR and serology for for HBV core Ab, HBe Ab, HBe Ag, HBV surface Ab, HBV surface Ag |
Gardini et al. (2021) [47] | Italy | Case report | Inpatient (ICU) | 1 | 61 years | Kaposi sarcoma in immunocompetent patient with SARS-CoV-2 infection | RT-PCR | Blood tests (CBC, biochemistry), neck ultrasound, CT scan, histologic examination, HHV-8 PCR |
Ghobrial et al. (2021) [48] | USA | Case report | Inpatient (ICU) | 1 | 72 years | CMV induced rectal ulcer in immunocompromised COVID-19 patient | Tool not specified, based on medical records | Biopsy and plasma CMV PCR |
Gonzalez et al. (2021) [49] | Puerto Rico | Case report | Inpatient | 1 | 32 years | HSV-2 induced ARN reactivation | RT-PCR | Ophthalmological exam, vitreous PCR for HSV-2, serology test for HSV-2 IgG |
Librero et al. (2021) [50] | Spain | Case report | Inpatient | 1 | 37 years | HBV reactivation in COVID-19 patient with a history of chronic HBV infection | Tool not specified, but indicated as laboratory confirmed | HBV PCR, blood test (biochemistry) |
Khatib et al. (2021) [51] | Qatar | Case report | Inpatient | 1 | 42 years | CMV colitis in SARS-CoV-2 patient on immunosuppressive treatment | RT-PCR | Blood test (cytokine, serology [not specified], biochemistry), CT scan, histologic examination |
Magri et al. (2021) [52] | Italy | Case report | Inpatient | 1 | 83 years | Kaposi Sarcoma in SARS-CoV-2 patient | NP swab, tool not specified | Physical examination, biopsy, histologic examination, serology test for HHV-8 antibodies (not specified) |
Maillet et al. (2021) [53] | France | Case report | Inpatient (ICU) | 1 | 75 years | CMV reactivation induced proctitis in an immunocompetent COVID-19 patient treated with immunomodulators | RT-PCR | Blood tests (biochemistry, CBC), CT scan, colonoscopy, stool culture, blood CMV PCR, rectal biopsy with immunohistochemistry staining |
Mikami et al. (2021) [54] | France | Case report | Ambulatory care | 1 | 28 years | CMV and parvovirus B19 infection in a SARS-CoV-2 IgG positive patient | RT-PCR, antibody test (tool not specified) | Physical examination, blood tests (serology for CMV-IgG, CMV-IgM, B19-IgM, biochemistry, CBC, coagulation) |
Nadeem et al. (2021) [55] | USA | Case report | Inpatient | 1 | 62 years | EBV coinfection with mild COVID-19 infection | Tool not specified, based on medical records | CT scan, blood tests (biochemistry, serology for EBV viral capsid (VCA) IgM, VCA IgG, EBV EA IgG, EBV NA IgG, coagulation) |
Porzionato et al. (2021) [56] | Italy | Case report | Autopsy | 1 | Not reported | HSV-1 DNA detection and hypopharyngeal ulcers in a deceased COVID-19 patient | RT-PCR | RT-PCR, immunohistochemistry, histologic examination |
Shi et al. (2021) [57] | China | Case report | Inpatient | 1 | 66 years | HHV-1 reactivation in a critically ill COVID-19 patient | RT-qPCR | Metagenomic next-generation sequencing, blood test (CBC, biochemistry), Chest X-rays |
Wu et al. (2021) [58] | China | Case report | Inpatient | 1 | 45 years | HBV reactivation in COVID-19 patient | RT-PCR | Blood tests (CBC, biochemistry, serology test for HBV surface antigen, HBV surface antibody, HBe Ag, HBe Ab, HBV core antibody), PCR |
Xu et al. (2020) [20] | China | Case report | Inpatient (ICU) | 1 | 73 years | Co-reactivations of HSV-1 and VZV in COVID-19 patient | RT-PCR | NGS tests on blood, sputum, and BALF samples, optic bronchoscopy |
Yun et al. (2022) [59] | South Korea | Case report | Inpatient | 1 | 18 years | VZV meningitis in COVID-19 patient | RT-PCR | CSF analysis for CBC, CSF PCR |
Busani et al. (2021) [60] | Italy | Case series | Inpatient (ICU) | 2 | Pt 1: 66 years, Pt 2: 49 years | HSV-1 induced acute liver failure in COVID-19 patients | NP swab, tool not specified | Blood tests (biochemistry, coagulation), RT-PCR, CT scan, CSF analysis, histologic examination, chemiluminescence-immunoassay |
Hashemi et al. (2020) [61] | Iran | Case series | Inpatient (ICU) | 2 | Pt 1: 78 years, Pt 2: 75 years | Detection of secondary respiratory pathogens (influenza viruses) in COVID-19 patients with suspected acute respiratory syndrome | NP swab, tool not specified | Blood tests (biochemistry, Influenza virus IgM serology, coagulation) |
Kim et al. (2022) [62] | USA | Case series | Retrospective database review | 11 | Mean age of 59.54 years | Clinical manifestations of patients with SARS-CoV-2 and CMV co-infection | Based on medical records (RT-PCR indicated) | Medical records (CMV PCR indicated) |
Moniz et al. (2021) [63] | NA | Case series | Inpatient (ICU) | 5 | Pt 1: 64 years, Pt 2: 61 years, Pt 3: 61 years, Pt 4: 77 years, Pt 5: 78 years | CMV infection in COVID-19 patients with pneumonia | RT-PCR | CMV PCR (plasma or BAL) |
Siddiqui et al. (2022) [64] | India | Case series | Inpatient (ICU) | 3 | Pt 1: 54 years, Pt 2: 57 years, Pt 3: 62 years | CMV and COVID-19 coinfection | RT-PCR | Blood tests (biochemistry, coagulation, blood smear, CBC), CMV PCR (BAL), bone marrow histologic examination, ophthalmologic examination |
Soni et al. (2021) [65] | India | Case series | Ambulatory care | 2 | Pt 1: 5 years, Pt 2: 61 years | HSV-1 induced ARN in patients with previous history of SARS-CoV-2 infection | RT-PCR | RT-PCR (vitreous sample), ophthalmologic examination |
Talan et al. (2022) [66] | Turkey | Case series | Inpatient (ICU) | 218 | 67.7 years (53–84) | CMV reactivation in severe COVID-19 patients | RT-PCR | PCR, CBC |
Chen et al. (2021) [67] | China | Cohort | Inpatient | 188 | 36 years (28–52) | Comparison of disease progression between EBV and SARS-CoV-2 co-infection and SARS-CoV-2 alone | RT-PCR | Blood tests (serology for anti-VCA IgM, anti-VCA IgG, anti-EBNA IgG, anti-EA IgM, anti-EA IgM, anti-VCA IgM, biochemistry) |
Franceschini et al. (2021) [68] | Italy | Cohort | Inpatient | 70 | 72 years (66–76) | Clinical manifestations from HSV-1 reactivations in COVID-19 patients | RT-PCR | HSV-1 BAL quantitative assay (PCR), blood tests (CBC, biochemistry, cytokine) |
Fuest et al. (2022) [69] | Germany | Cohort | Inpatient (ICU) | 134 | 72.5 years (60–78) | Prevalence of HSV-1 and CMV among critically ill COVID-19 patients and the impact of the viruses on patient outcomes, course of disease, and dexamethasone treatment | RT-PCR | CMV and HSV RT-PCR of endotracheal aspirates (ETA), bronchoalveolar lavage (BAL) fluid, and EDTA blood samples, blood tests (CBC, biochemistry) |
Gatto et al. (2022) [70] | Italy | Cohort | Inpatient (ICU) | 431 | 65 years (56–72) | Incidence and risk factors of CMV reactivation among critically ill COVID-19 patients | Tool not specified, but indicated as laboratory confirmed | CMV PCR, CT scan, chest X-ray, blood tests (CBC, biochemistry, PCT) |
Giacobbe et al. (2021) [71] | Italy | Cohort | Inpatient | 41 | 65 years (60–70) | Cumulative risk of HSV-1 reactivation, its risk factors, and impact on prognosis of critically ill SARS-CoV-2 patients | RT-PCR | HSV-1 BALF quantitative assay (PCR), blood tests (biochemistry, CBC, coagulation) |
Hu et al. (2020) [72] | China | Cohort | Inpatient | 70 | 62.8 ± 12.8 years | Comparison of COVID-19 severity and clinical outcomes between patients with and without Influenza A virus infection | RT-PCR | Blood tests (biochemistry, serology) |
le balc’h et al. (2020) [15] | France | Editorial letter (cohort) | Inpatient (ICU) | 39 | 64 years (55–72) | HSV and CMV reactivations in COVID-19 patients | RT-PCR | HSV and CMV qRT-PCR, blood tests (CBC) |
Lozano et al. (2021) [63] | Spain | Cohort | Inpatient (ICU) | 12 | 37 years (23–50) | Maternal and neonatal outcomes (including CMV reactivations) associated with tocilizumab treatment in pregnant women with severe COVID-19 | RT-PCR | Physical examinations, EMR review, blood tests (serology for CMV IgM, IgG, biochemistry, coagulation), CMV PCR |
Lino et al. (2022) [34] | Brazil | Cohort | Inpatient | 173 | 52.3 ± 22.9 years | Frequency and clinical impact of HHV-6 coinfection in moderate to critically ill COVID-19 patients | RT-PCR | RT-qPCR, Sanger sequencing, blood test (biochemistry, CBC) |
Liu et al. (2020) [35] | China | Cohort | Inpatient | 347 | Not reported | Comparing liver function changes and disease progression in COVID-19 patients with and without chronic hepatitis B virus infection | Tool not specified, but indicated as admission due to COVID-19 | Blood tests (biochemistry, serology for HBsAg), RT-PCR |
Meng et al. (2022) [73] | China | Cohort | Inpatient | 1314 | Not reported | Incidence of EBV reactivation and its impact on the effect of ganciclovir treatment in COVID-19 patients | RT-PCR | Blood tests (biochemistry, CBC, coagulation, ELISA for VCA-IgG, EBV nuclear antigen IgG (EBNA-IgG), VCA-IgM, EA-IgG, CMV-IgG, and CMV-IgM), APACHEII and SOFA scores |
Meyer et al. (2021) [74] | France | Cohort | Inpatient (ICU) | 153 | 61.9 years (50.9–70.8) | Impact of HSV reactivation on mortality and HAP/VAP among severe COVID-19 patients | RT-PCR | Blood tests (biochemistry, CBC, coagulation, culture), RT-PCR |
Paolucci et al. (2021) [75] | Italy | Cohort | Inpatient (ICU & SICU) | 104 | ICU: 61.5 years (55–71.25), SICU: 73.5 years (57.8–70) | Opportunistic viral reactivation (EBV reactivation) in COVID-19 patients of varying severity | RT-PCR | Blood test (flow cytometry, chemiluminescent assay) |
Peluso et al. (2022) [76] | NA | Cohort (preprint) | Inpatient | 280 | 45 years (35–56) | Comparing EBV prevalence in COVID patients with and without Long COVID symptoms | RT-PCR | qPCR, SIMOA |
Saade et al. (2021) [23] | France | Cohort | Inpatient (ICU) | 100 | 60 years (53–67) | Cumulative incidence and risk factors of HSV, EBV, CMV reactivations in severe COVID-19 patients | Not reported | RT-PCR (whole blood, BAL, skin swab) for all viruses, blood tests (CBC, biochemistry) |
Seeßle et al. (2021) [77] | Germany | Cohort | Inpatient (ICU) | 103 | 71 years (16) | Frequency and predisposing factors of HSV-1 reactivation in COVID-19 patients | RT-PCR | RT-PCR (BAL or tracheal aspirates) for viral nucleic acid detection and gene expression analysis, FACS for comprehensive immunophenotyping, blood tests (PCT, CBC, biochemistry, cytokine) |
Simonnet et al. (2021) [17] | France | Cohort | Inpatient (ICU) | 34 | 58 years (26–81) | Incidence of HHV-6, EBV, and CMV in critically ill COVID-19 patients | RT-PCR | qPCR for all three viruses, chemiluminescence immunoassays |
Yang et al. (2022) [78] | China | Cohort | Inpatient (ICU) | 2899 | 71.67 ± 10.07 years | Disease severity and risk factors comparison among SARS-CoV-2 positive patients with different stages of HBV infection | RT-PCR, Chest CT scan | Blood tests (serology test for HBsAg, HBeAg, anti-HBs, anti-HBe, anti-Hbc, biochemistry) |
Yue et al. (2020) [33] | China | Cohort | Not reported | 307 | Influenza A: 61 years (24–68), Influenza B: 56 years (43–66.5) | Clinical characteristics of influenza virus infections in SARS-CoV-2 positive patients | RT-PCR | Blood tests (serology for IAV and IBV IgM, biochemistry) |
Zubchenko et al. (2022) [79] | Ukraine | Cohort | Inpatient | 88 | 41.4 ± 6.7 years | Post-COVID manifestations and herpes virus reactivations including EBV, HHV-6, and CMV | Tool not specified, based on medical records | PCR on blood, saliva, and oropharynx samples, ELISA for EBNA-IgG and VCA-IgG, blood tests (CBC, biochemistry, coagulation) |
Xie et al. (2021) [22] | China | Cohort | Inpatient | 1516 | Mean age of 62 years | Clinical outcomes of critically ill COVID-19 patients with EBV reactivation | RT-PCR | EBV RT-PCR, Blood tests (serology for EBV EA IgG and IgM, capsid IgM) |
Im et al. (2022) [80] | South Korea | Cross-sectional (relevant to this study) | Inpatient | 269 | Mean age of 61.6 years | Impact of EBV viremia on COVID-19 severity and prognosis | RT-PCR | EBV RT-PCR, multicolor flow cytometry for lymphocyte subpopulation |
Vigón et al. (2021) [81] | Spain | Cross-sectional | Inpatient (ICU) | 61 | 66 years (42–90) | Immunological parameters and herpesvirus reactivations (CMV, EBV) in COVID-19 patients | RT-PCR | ELISA for anti-CMV/IgG, chemiluminescent immunoassay for EBV VCA IgG qPCR for both viruses, ADCC assay |