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.

Caffeine confers radiosensitization of PTEN-deficient malignant glioma cells by enhancing ionizing radiation-induced G1 arrest and negatively regulating Akt phosphorylation.

PTEN mutations are frequently found in malignant glioma and can result in activated phosphatidylinositol-3-kinase/Akt survival signaling associated with resistance to radiotherapy. Strategies to interfere with aberrant PI3K/Akt activity are therefore being developed to improve the therapeutic efficacy of radiotherapy in patients with malignant glioma. The methylxanthine caffeine has been described as a PI3K inhibitor and is also known to sensitize cells to ionizing radiation. However, a direct association between these two caffeine-mediated effects has not been reported yet. Therefore, we asked whether caffeine or its derivative pentoxifylline differentially affect the radiosensitivity of malignant gliomas with different PTEN status. As models, we used the radiosensitive EA14 malignant glioma cell line containing wild-type PTEN and the radioresistant U87MG malignant glioma cell line harboring mutant PTEN. Our study revealed that caffeine and pentoxifylline radiosensitized PTEN-deficient but not PTEN-proficient glioma cells. Radiosensitization of PTEN-deficient U87MG cells by caffeine was significantly correlated with the activation of the G(1) DNA damage checkpoint that occurred independently of de novo synthesis of p53 and p21. The p53 independency was also confirmed by a significant caffeine-mediated radiosensitization of the glioma cell lines T98G and U373MG that are deficient for both PTEN and p53. Furthermore, caffeine-mediated radiosensitization was associated with the inhibition of Akt hyperphosphorylation in PTEN-deficient cells to a level comparable with PTEN-proficient cells. Our data suggest that the methylxanthine caffeine or its derivative pentoxifylline are promising candidate drugs for the radiosensitization of glioma cells particularly with PTEN mutations.