The UCSF COMET Consortium, Michael Matthay, David J. E rl e , P re scot t G. Woodruff, Charles Langelier, Kirsten K an ge la ri s, C ar ol yn M.

Sexually transmitted diseases (STDs) disproportionately affect gay, bisexual, and other men who have sex with men (MSM) in the United States ( 1 ). Because chlamydia and gonorrhea at extragenital (rectal and pharyngeal) anatomic sites are often asymptomatic, these anatomic sites serve as a reservoir of infection, which might contribute to gonococcal antimicrobial resistance ( 2 ) and increased risk for human immunodeficiency virus (HIV) transmission and acquisition ( 3 ). To ascertain prevalence of extragenital STDs, MSM attending community venues were recruited in five U.S. cities to provide self-collected swabs for chlamydia and gonorrhea screening as part of National HIV Behavioral Surveillance (NHBS). Overall, 2,075 MSM provided specimens with valid results, and 13.3% of participants were infected with at least one of the two pathogens in at least one of these two extragenital anatomic sites. Approximately one third of participating MSM had not been screened for STDs in the previous 12 months. MSM attending community venues had a high prevalence of asymptomatic extragenital STDs. The findings underscore the importance of sexually active MSM following current recommendations for STD screening at all exposed anatomic sites at least annually ( 4 ).

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

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