Surveillance outcomes of respiratory pathogen infections during the 2021-2022 season among U.S. Military Health System beneficiaries, October 3, 2021-October 1, 2022.

The Department of Defense Global Respiratory Pathogen Surveillance Program conducts continuous surveillance for influenza, severe acute respiratory syndrome 2 (SARS-CoV-2), and other respiratory pathogens at 104 sentinel sites across the globe. These sites submitted 65,475 respiratory specimens for clinical diagnostic testing during the 2021-2022 surveillance season. The predominant influenza strain was influenza A(H3N2) (n=777), of which 99.9% of strains were in clade 3C.2a1b.2a2. A total of 21,466 SARSCoV-2-positive specimens were identified, and 12,225 of the associated viruses were successfully sequenced. The Delta variant predominated at the start of the season, until December 2021, when Omicron became dominant. Most circulating SARS-CoV-2 viruses were subsequently held by Omicron sublineages BA.1, BA.2, and BA.5 during the season. Clinical manifestation, obtained through a self-reported questionnaire, found that cough, sinus congestion, and runny nose complaints were the most common symptoms presenting among all pathogens. Sentinel surveillance can provide useful epidemiological data to supplement other disease monitoring activities, and has become increasingly useful with increasing numbers of individuals utilizing COVID-19 rapid self-test kits and reductions in outpatient visits for routine respiratory testing.

Surveillance trends for SARS-CoV-2 and other respiratory pathogens among U.S. military health system beneficiaries, 27 September 2020­2 October 2021

Laboratory-based respiratory pathogen surveillance for SARS-CoV-2 and other respiratory pathogens was conducted in the 2020-2021 surveillance season among U.S. Military Health System (MHS) beneficiaries through the Department of Defense Global Respiratory Pathogen Surveillance Program (DoDGRPSP). Sentinel and participating sites submitted 96,660 specimens for clinical diagnostic testing. A total of 12,282 SARS-CoV-2 positive cases were identified, and 7,286 of the associated viruses were successfully sequenced. Two overlapping waves of SARS-CoV-2 activity were observed during the season. The B.1.1.7 (Alpha) lineage was dominant during February 2021 through May 2021. By July 2021, and continuing through the rest of the season, B.1.617.2/AY.x (Delta) lineage predominated and by September 2021 comprised 100% of identified SARS-CoV-2 lineages. The emergence of SARS-CoV-2 coincided with substantial reductions in the circulation of seasonal influenza viruses and most other non-SARS-CoV-2 respiratory pathogens. A total of 4,426 non-SARS-CoV-2 respiratory pathogens were identified, including 71 influenza. Of the 71 influenza positives, 64 were successfully sequenced. The majority of influenza strains sequenced belonged to influenza A(H3N2) clades 3C.2a1b.2a2. The most common non-SARSCoV-2 respiratory pathogen detected was rhinovirus/enterovirus (n=3,058).

Regression from pathological hypertrophy in mice is sexually dimorphic and stimulus specific.

Pathological cardiac hypertrophy is associated with increased morbidity and mortality. Understanding the mechanisms whereby pathological cardiac growth can be reversed could be of therapeutic value. Here, we show that pathways leading to regression of pathological cardiac hypertrophy are strongly dependent on the hypertrophic trigger and are significantly modified by sex. Two pathological stimuli causing hypertrophy via distinct pathways were administered to male and female mice: angiotensin II (ANG II) or isoproterenol (Iso). Stimuli were removed after 7 days of treatment, and left ventricles (LVs) were studied at 1, 4, and 7 days. ANG II-treated females did not show regression after stimulus removal. Iso-treated males showed rapid LV hypertrophy regression. Somewhat surprisingly, RNAseq analysis at day 1 after removal of triggers revealed only 45 differentially regulated genes in common among all the groups, demonstrating distinct responses. Ingenuity pathway analysis predicted strong downregulation of the TGFß1 pathway in all groups except for ANG II-treated females. Consistently, we found significant downregulation of Smad signaling after stimulus removal including in ANG II-treated females. In addition, the ERK1/2 pathway was significantly reduced in the groups showing regression. Finally, protein degradation pathways were significantly activated only in Iso-treated males 1 day after stimulus removal. Our data indicate that TGFß1 downregulation may play a role in the regression of pathological cardiac hypertrophy via downregulation of the ERK1/2 pathway and activation of autophagy and proteasome activity in Iso-treated males. This work highlights that the reversal of pathological hypertrophy does not use universal signaling pathways and that sex potently modifies this process.NEW & NOTEWORTHY Pathological cardiac hypertrophy is a major risk factor for mortality and is thought to be largely irreversible in many individuals. Although cardiac hypertrophy itself has been studied extensively, very little is understood about its regression. It is important that we have a better understanding of mechanisms leading to regression, why this process is not reversible in some individuals and that sex differences need to be considered when contemplating therapies.