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

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.

The burden of viral infections in pediatric intensive care unit between endemic and pandemic coronavirus infections: A tertiary care center experience

Objectives: To measure the prevalence of viral infections, length of stay (LOS), and outcome in children admitted to the pediatric intensive care unit (PICU) during the period preceding the COVID-19 pandemic in a MERS-CoV endemic country. Methods: A retrospective chart review of children 0–14 years old admitted to PICU with a viral infection. Results: Of 1736 patients, 164 patients (9.45%) had a positive viral infection. The annual prevalence trended downward over a three-year period, from 11.7% to 7.3%. The median PICU LOS was 11.6 days. Viral infections were responsible for 1904.4 (21.94%) PICU patient-days. Mechanical ventilation was used in 91.5% of patients, including noninvasive and invasive modes. Comorbidities were significantly associated with intubation (P-value = 0.025). Patients infected with multiple viruses had median pediatric index of mortality 2 (PIM 2) scores of 4, as compared to 1 for patients with single virus infections (p < 0.001), and a median PICU LOS of 12 days, compared to 4 in the single-virus group (p < 0.001). Overall, mortality associated with viral infections in PICU was 7 (4.3%). Patients with viral infections having multiple organ failure were significantly more likely to die in the PICU (p = 0.001). Conclusion: Viral infections are responsible for one-fifth of PICU patient-days, with a high demand for mechanical ventilation. Patients with multiple viral infections had longer LOS, and higher PIM 2 scores. The downward trend in the yearly rate of PICU admissions for viral infections between the end of the MERS-CoV outbreak and the start of the COVID-19 pandemic may suggest viral interference that warrants further investigations. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Persistence Infection of TGEV Promotes Enterococcus faecalis Infection on IPEC-J2 Cells.

Transmissible gastroenteritis virus (TGEV) is a coronavirus causing diarrhea with high incidence in swine herds. Its persistent infection might lead to epithelial-mesenchymal transition (EMT) of swine intestinal epithelial cells, followed by subsequent infections of other pathogens. Enterococcus faecalis (E. faecalis) is a member of the enteric microorganisms and an opportunistic pathogen. There is no report of secondary E. faecalis infection to TGEV, even though they both target to the intestinal tracts. To investigate the interactions between TGEV and E. faecalis, we set up an in vitro infection model by the swine IPEC-J2 cells. Dynamic changes of cell traits, including EMT and cell motility, were evaluated through qPCR, Western blot, electronic microscopy, scratch test, Transwell migration test and invasion test, respectively. The adhesion and invasion tests of E. faecalis were taken to verify the impact of the preceding TGEV infection. The cell morphology and molecular marker evaluation results showed that the TGEV persistent infection induced EMT on IPEC-J2 cells; increased cellular motility and invasion potential were also observed. Spontaneously, the expression levels of fibronectin (FN) and the membrane protein integrin-α5, which are dominant bacterial receptors on IPEC-J2 cells, were upgraded. It indicated that the bacteria E. faecalis adhered to IPEC-J2 cells through the FN receptor, and then invaded the cells by binding with the integrin-α5, suggesting that both molecules were critical for the adhesion and invasion of E. faecalis to IPEC-J2 cells. Additionally, it appeared that E. faecalis alone might trigger certain EMT phenomena, implying a vicious circle might occur. Generally, bacterial and viral co-infections are frustrating yet common in both human and veterinary medicines, and our observations on enteric TGEV and E. faecalis interactions, especially the diversity of bacterial invasion strategies, might provide new insights into the mechanisms of E. faecalis pathogenicity.

Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants.

Objective: COVID-19 can rarely lead to severe illness in pediatric patients. The aim of this study was to determine if severe outcomes in pediatric COVID-19 have changed over the course of the pandemic. Methods: This was a multicenter, observational cohort analysis from a large regional healthcare system in metro Detroit using electronic health record data to evaluate emergency visits, hospitalization, and severe COVID-19 disease in pediatric patients. Consecutive pediatric patients presenting to the emergency department with a primary diagnosis of COVID-19 were included. Outcomes data was gathered from three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance (Time interval 1 (T1) 1/1/2021-6/30/2021: Alpha, T2 7/1/2021-12/31/2021: Delta, T3 1/1/2022-6/16/2022): Omicron. The primary outcome was severe disease inclusive of composite intensive care unit admission, mechanical ventilation, multisystem inflammatory syndrome in children (MIS-C), myocarditis, or death. Secondary outcomes included severe outcomes considering viral coinfection and vaccination status. Results: Between 1/1/2021 and 6/16/2022, there were 4517 emergency COVID-19 visits, of which 12.5% (566) of children were hospitalized. 24.4% (138), 31.6% (179), and 44.0% (249) of admissions occurred during T1, T2 and T3 respectively. Most patients were male (55.1%) and 59.9% identified as Caucasian. The median age was 5.0 (interquartile range 1.0, 13.0) with infants comprising 22.8% (129), toddlers 25.1% (142), children 23.0% (130), and teenagers 29.2% (165). Over the course of the pandemic, the proportion of infants in hospitalization increased from 16.7% in T1 to 19.6% in T2 to 28.5% in T3 (p < 0.01) while the proportion of teenagers in hospitalization decreased from 39.1% in T1 to 31.3% in T2 to 22.1% in T3 (p < 0.001). Oxygen therapy was required in a minority (29.9%) of cases with supplemental oxygen utilized the least in T3 (16.5%) and most in T2 (30.2%). Composite severe disease decreased throughout the pandemic occurring in 36.2% in T1, 27.4% in T2, and 18.9% in T3. A multivariable logistic regression analysis revealed the odds of composite severe disease was significantly lower in T3 compared to T1 (adjusted odds ratio [aOR] 0.35, 95% Confidence Interval 0.21-0.60, p < 0.001). Fully vaccinated or fully vaccinated and boosted admission rates remained low throughout all periods with 4.4% in T1, 4.5% in T2 and 8.4% in T3. Viral coinfection was most common during T2 (16.8%) followed by T3 (12.5%) and least common in T1 (5.1%) (p = 0.006). Coinfection occurred more commonly in younger children with a median age of 1.2 (0.0, 4.5) compared to those with mono-infection with a median age of 6 (1.0, 14.0) (p < 0.001). Severe outcomes occurred in 45.6% of coinfection cases compared to 22.1% without coinfection (p < 0.001). Conclusions: While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children. Funding: None.

Viral epidemiology and SARS-CoV-2 co-infections with other respiratory viruses during the first COVID-19 wave in Paris, France.

OBJECTIVES: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2. METHODS: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by multiplex PCR if they presented ILI symptoms. RESULTS: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2-positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (P = .013) and headaches (P = .048), than single SARS-CoV-2 infections. CONCLUSIONS: SARS-CoV-2-infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2.

Lessons of the month: Co-infection with SARS-CoV-2 and influenza B virus in a patient with community-acquired pneumonia.

Why we only infrequently detect or report two or more respiratory viruses co-infecting an adult host is poorly understood. We report a rare case where influenza B and SARS-CoV-2 caused viral pneumonia in a 74-year-old man diagnosed during the UK winter epidemic/pandemic for these organisms and discuss concepts of co-infection.

Dynamics and predisposition of respiratory viral co-infections in children and adults.

OBJECTIVES: The epidemiology of respiratory co-infection pairings is poorly understood. Here we assess the dynamics of respiratory viral co-infections in children and adults and determine predisposition for or against specific viral pairings. METHODS: Over five respiratory seasons from 30 November 2013 through 6 June 2018, the mono-infection and co-infection prevalence of 13 viral pathogens was tabulated at The Cleveland Clinic. Employing a model to proportionally distribute viral pairs using individual virus co-infection rate with prevalence patterns of concurrent co-circulating viruses, we compared predicted occurrence with observed occurrence of 132 viral pairing permutations using binomial analysis. RESULTS: Of 30 535 respiratory samples, 9843 (32.2%) were positive for at least one virus and 1018 (10.8%) of these were co-infected. Co-infected samples predominantly originated from children. Co-infection rate in paediatric population was 35.0% (2068/5906), compared with only 5.8% (270/4591) in adults. Adenovirus C (ADVC) had the highest co-infection rate (426/623, 68.3%) while influenza virus B had the lowest (55/546, 10.0%). ADVC-rhinovirus (HRV), respiratory syncytial virus A (RSVA)-HRV and RSVB-HRV pairings occurred at significantly higher frequencies than predicted by the proportional distribution model (p < 0.05). Additionally, several viral pairings had fewer co-infections than predicted by our model: notably metapneumovirus (hMPV)-parainfluenza virus 3, hMPV-RSVA and RSVA-RSVB. CONCLUSIONS: This is one of the largest studies on respiratory viral co-infections in children and adults. Co-infections are substantially more common in children, especially under 5 years of age, and the most frequent pairings occurred at a higher frequency than would be expected by random. Specific pairings occur at altered rates compared with those predicted by proportional distribution, suggesting either direct or indirect interactions result between specific viral pathogens.