#Immunity Interrupted: Links Between #SARS-CoV-2 and the #Tripledemic of 2022

 

Highlights

    • SARS-CoV-2 infection was associated with fewer subsequent respiratory viral infections in children.

    • Children with prior SARS-CoV-2 infection had a longer interval before reinfection than those with other respiratory viral illnesses.

    • Rates of respiratory viral coinfection were lower following SARS-CoV-2 infection compared with other viral infections.

    • Prior SARS-CoV-2 infection was not associated with increased susceptibility to recurrent respiratory viral infections.

    • Findings support a potential role for viral interference and post-infection immune modulation in respiratory virus dynamics.

Abstract

Background

The post-pandemic resurgence of respiratory viral infections, commonly referred to as the "tripledemic," raised concerns that prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may increase susceptibility to subsequent respiratory illnesses. However, the relationship between SARS-CoV-2 infection and future respiratory viral infections in children remains poorly understood.

Objectives

To determine whether pediatric patients with SARS-CoV-2 infection were at increased risk of subsequent respiratory viral infections within 120 days compared with children diagnosed with other respiratory viral infections and to evaluate coinfection frequency and clinical outcomes.

Study Design

We conducted a retrospective cohort study of pediatric patients aged 6 months to <18 years presenting to emergency departments within a large healthcare system between January 1, 2021, and December 31, 2023. Patients were categorized as SARS-CoV-2 only (n=4,004), SARS-CoV-2 with respiratory viral coinfection (n=1,678), or other respiratory viral infection only (n=31,434). Patients were followed for 120 days after the index encounter. Primary outcomes included subsequent respiratory viral infections and laboratory-confirmed reinfections. Secondary outcomes included coinfection rates, oxygen supplementation, mechanical ventilation, and hospital length of stay.

Results

A total of 37,116 pediatric patients met inclusion criteria. Subsequent respiratory viral infections occurred less frequently among patients with SARS-CoV-2-only infection (4.4%) compared with patients with SARS-CoV-2 coinfection (6.0%; OR 1.39, 95% CI 1.08–1.79) and those with other respiratory viral infections (6.1%; OR 1.43, 95% CI 1.22–1.68). The mean time to subsequent infection was longest in the SARS-CoV-2-only group (68.4 days) compared with the SARS-CoV-2 coinfection (60.8 days) and other viral infection groups (58.8 days). Laboratory-confirmed reinfections occurred in 2.0% of patients with SARS-CoV-2-only infection and 2.8% of patients in both comparison groups. Coinfections were less common among patients with SARS-CoV-2 infection than among those with other respiratory viral infections. Severe clinical outcomes were uncommon across all groups. Although patients with SARS-CoV-2-only infection had slightly longer hospital stays and higher rates of mechanical ventilation, absolute event rates remained low.

Conclusions

Prior SARS-CoV-2 infection was not associated with an increased risk of subsequent respiratory viral infections in children. Instead, SARS-CoV-2 infection was associated with fewer subsequent infections, lower coinfection rates, and a longer interval before reinfection compared with other respiratory viral illnesses. These findings support the possibility of viral interference or transient immune-mediated protection following SARS-CoV-2 infection and suggest that factors other than prior SARS-CoV-2 infection were more likely responsible for the increased burden of respiratory viral illnesses observed during the post-pandemic period.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S1386653226000855?dgcid=rss_sd_all

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Prior #influenza virus #infection alleviates an #arbovirus #encephalitis by reducing viral titer, #inflammation, and cellular infiltrates in the central nervous system

ABSTRACT

Respiratory and encephalitic virus infections represent a significant risk to public health globally. Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis. We used a model system in which mice were given influenza A virus (IAV) infection 8 days prior to Semliki Forest virus (SFV) infection (IAV→SFV). IAV infection clearly attenuated the subsequent SFV infection with reduced titers of infectious SFV and lower levels of cytokines and chemokines in the central nervous system (CNS). In contrast, the SFV viremia in both IAV→SFV and SFV-only mice was comparable. Increased type I interferon (IFN) levels in the CNS after IAV infection might have contributed to some level of protection towards SFV infection in the CNS, suggesting that early control of SFV replication in the CNS during IAV→SFV infection led to reduced adaptive response, given the lower number of CD8+ T cells recruited to the brain in IAV→SFV infection. In lungs, however, prior IAV infection elicited effector CD8+ T cells with highly activated CD38 and/or CD25 phenotypes, while SFV-only infection elicited distinct effector CD8+ T cells with increased frequencies of KLRG1 expression, a hallmark of short-lived effector T cells. Taken together, our findings demonstrate that prior IAV infection can confer protective immunity toward secondary SFV infection, confirmed by reduced disease severity and inflammatory immune responses in the brain. Our work provides important insights into therapies and vaccine regimens directed against unrelated pathogens.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.02108-24?af=R

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Respiratory Virus-Specific and #Time-Dependent #Interference of #Adenovirus Type 2, #SARS-CoV-2 and #Influenza Virus #H1N1pdm09 During Viral Dual Co-Infection and Superinfection In Vitro

Abstract

Background. 

Understanding the interference patterns of respiratory viruses could be important for shedding light on potential strategies to combat these human infectious agents. 

Objective. 

To investigate the possible interactions between adenovirus type 2 (AdV2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/H1N1 pandemic (H1N1pdm09) using the A549 cell line. 

Methods. 

Single infections, co-infections, and superinfections (at 3 and 24 h after the first virus infection) were performed by varying the multiplicity of infection (MOI). Virus replication kinetics and the mRNA expression of IFN-α, IL-1α and IL-6 were assessed by real-time qPCR. 

Results. 

Co-infection experiments showed different growth dynamics, depending on the presence of the specific virus and time. AdV2 replication remained stable or possibly enhanced in the presence of co-infection with each of the two H1N1pdm09 and SARS-CoV-2 viruses used. In contrast, SARS-CoV-2 replication was facilitated by H1N1pdm09 but hindered by AdV2, indicating possible different interactions. Finally, H1N1pdm09 replication exhibited variably effectiveness in the presence of AdV2 and SARS-CoV-2. Superinfection experiments showed that the replication of all viruses was affected by time and MOI. The mRNA expression of IFN-α, IL-1α and IL-6 showed divergent results depending on the virus used and the time of infection. 

Conclusions. 

Further investigation of co-infection or superinfection may be helpful in understanding the potential relationship involved in the outcome of viral respiratory infection in the human population.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1947

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