A SARS-CoV-2 Omicron outbreak among crew members on a cruise ship in Germany in early 2022.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks on cruise ships have rarely been investigated. In early 2022, we were informed about a SARS-CoV-2 outbreak on a cruise ship calling Port of Hamburg after 10 infections among crew members were detected. We conducted an outbreak investigation in collaboration between ship owners, the ship physician and Hamburg's Institute for Hygiene and Environment, to identify risk factors and to achieve containment. The aim was to identify risk factors for SARS-CoV-2 infection and SARS-CoV-2 variants in a cohort of 165 crew members. MATERIALS AND METHODS: For this purpose, we collected data on age, sex, nationality, boarding-time, cabin use (single/shared), work place, and vaccination status of the study participants. Cases were defined as individuals who tested SARS-CoV-2 positive at least once in daily screenings during the outbreak period (10 days) by polymerase chain reaction or antigen test. We investigated risk factors for infection by descriptive, univariable and multivariable analysis. We performed whole genome sequencing to identify SARS-CoV-2 variants. RESULTS: We verified 103 SARS-CoV-2 positive cases (attack rate [AR] 62.4%); 39/41 sequenced samples were BA.2.3 Omicron subtype, one BA.1 and one BA.1.1. Among boostered crew members, AR was 38% vs. 65% among those vaccinated once or twice. Among those who stayed < 30 days on board, AR was 31% vs. 72% among those staying on board longer. Among Europeans, the AR was 53% vs. 71% in non- -Europeans. Adjusting for age and sex, cases were more likely to have received no booster vaccine (odds ratio [OR]: 2.66, 95% confidence interval [CI]: 0.99-7.13), to have spent more time on board (≥ 30 days, OR: 6.36, 95% CI: 2.81-14.40 vs. < 30 days) and to have a non-European nationality (OR: 2.14, 95% CI: 1.08-4.27). The outbreak stopped shortly after offboard isolation of cases. CONCLUSIONS: This investigation confirms the importance of a booster vaccine against COVID-19. Longer stays onboard could facilitate social mixing. Further studies could investigate the impact of social, cultural/ behavioural patterns and public health access on the infection risk. Physical distancing together with screening and isolation can contain SARS-CoV-2 outbreaks on cruise ships.

Gene Expression and Protein Abundance of Nuclear Receptors in Human Intestine and Liver: A New Application for Mass Spectrometry-Based Targeted Proteomics.

BACKGROUND: Unwanted drug-drug interactions (DDIs), as caused by the upregulation of clinically relevant drug metabolizing enzymes and transporter proteins in intestine and liver, have the potential to threaten the therapeutic efficacy and safety of drugs. The molecular mechanism of this undesired but frequently occurring scenario of polypharmacy is based on the activation of nuclear receptors such as the pregnane X receptor (PXR) or the constitutive androstane receptor (CAR) by perpetrator agents such as rifampin, phenytoin or St. John's wort. However, the expression pattern of nuclear receptors in human intestine and liver remains uncertain, which makes it difficult to predict the extent of potential DDIs. Thus, it was the aim of this study to characterize the gene expression and protein abundance of clinically relevant nuclear receptors, i.e., the aryl hydrocarbon receptor (AhR), CAR, farnesoid X receptor (FXR), glucocorticoid receptor (GR), hepatocyte nuclear factor 4 alpha (HNF4α), PXR and small heterodimer partner (SHP), in the aforementioned organs. METHODS: Gene expression analysis was performed by quantitative real-time PCR of jejunal, ileal, colonic and liver samples from eight human subjects. In parallel, a targeted proteomic method was developed and validated in order to determine the respective protein amounts of nuclear receptors in human intestinal and liver samples. The LC-MS/MS method was validated according to the current bioanalytical guidelines and met the criteria regarding linearity (0.1-50 nmol/L), within-day and between-day accuracy and precision, as well as the stability criteria. RESULTS: The developed method was successfully validated and applied to determine the abundance of nuclear receptors in human intestinal and liver samples. Gene expression and protein abundance data demonstrated marked differences in human intestine and liver. On the protein level, only AhR and HNF4α could be detected in gut and liver, which corresponds to their highest gene expression. In transfected cell lines, PXR and CAR could be quantified. CONCLUSIONS: The substantially different expression pattern of nuclear receptors in human intestinal and liver tissue may explain the different extent of unwanted DDIs in the dependence on the administration route of drugs.