A Novel Anti-nucleocapsid Antibody Avidity Method for Identifying SARS-CoV-2 Reinfections.

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections.

DDIT4L regulates mitochondrial and innate immune activities in early life.

Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity. Using genetically engineered monocytic U937 cells, we confirmed that DDIT4L overexpression altered mitochondrial dynamics, suppressing their activity, and blunted LPS-induced cytokine responses. We also showed that monocyte mitochondrial function is more restrictive in earlier gestation, resembling the phenotype of DDIT4L-overexpressing U937 cells. Gene expression analyses in neonatal granulocytes and lung macrophages in preterm infants confirmed upregulation of the DDIT4L gene in the early postnatal period and also suggested a potential protective role against inflammation-associated chronic neonatal lung disease. Taken together, these data show that DDIT4L regulates mitochondrial activity and provide what we believe to be the first direct evidence for its potential role supressing innate immune activity in myeloid cells during development.

Loss of Respiratory Syncytial Virus Antibody Functions During the Peak of the COVID-19 Pandemic Mitigation Measures.

Studies have linked respiratory syncytial virus (RSV) antibody-mediated phagocytosis and complement deposition to severe RSV infection in humans. This study shows waning of these antibody functions in women of childbearing age in 2020-2021 during the implementation of COVID-19 mitigation measures, in absence of RSV circulation. These functions could be explored as correlates of protection against severe RSV disease.

Respiratory syncytial virus epidemiology and clinical severity before and during the COVID-19 pandemic in British Columbia, Canada: a retrospective observational study.

Background: The COVID-19 pandemic has perturbed the seasonality of respiratory syncytial virus (RSV) infections. However, we lack data on how this impacted the severity of paediatric RSV cases. The objective of this study was to describe the clinical severity of RSV cases before, during and after pandemic measures in British Columbia (BC), Canada. Methods: Retrospective study of RSV cases from September 1st, 2017 to May 15th, 2023, with a review of RSV outcomes in children below 18 years old at BC's paediatric hospital. Temporal changes in RSV cases and hospitalisations were quantified using interrupted time series. Findings: BC experienced only 11 RSV cases (from 95,266 tests) between September 2020 and August 2021. This was followed by a resurgence of 9,529 RSV cases (219,566 tests [4.3% positive tests]) in 2021-22 and 8,215 cases (124,449 tests [6.6% positive tests]) in 2022-23, increased compared to 1,750 cases (48,664 tests [3.6% positive tests]) per corresponding yearly period in 2017-20. From September 2017 to May 2023, the median age of children with RSV at BC Children's Hospital increased from 8.7 [IQR: 2.0-26.0] to 19.6 [3.9-43.7] months per yearly period. More children were hospitalised in 2022-23 (n = 360), compared to 2017-20 (n = 168 per period) and 2021-22 (n = 172). However, we detected no increase in hospitalisations or ICU admissions in children born prematurely or with chronic cardiorespiratory conditions. Interpretation: The increased detection of symptomatic RSV cases in older children in 2021-22 and increased RSV-related hospitalisations in 2022-23 suggest a gradual increase in the pool of immunologically vulnerable children due to a prolonged lack of viral exposure. Funding: Government of Canada via its COVID-19 Immunity Task Force.

Why has the epidemiology of RSV changed during the COVID-19 pandemic?

The coronavirus disease 2019 (COVID-19) pandemic has drastically perturbed the epidemiology of Respiratory Syncytial Virus (RSV) respiratory tract infections in children. The reasons for this are not clear. In this article, we review the current literature and critically discuss the different theories to explain why the epidemiology of RSV has changed during the COVID-19 pandemic. Proposed mechanisms include decreased viral immunity in vulnerable age groups caused by the prolonged lack of RSV circulation early in the pandemic, potential Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2)-induced immune dysregulation, viral interactions between SARS-CoV-2 and RSV, and modifications in health-seeking behaviors as well as heath systems factors. Research in viral genomics and phylogeny, and more robust immunology research is needed to guide RSV prevention and health care resource planning.