Frequency and risk of SARS-CoV-2 reinfections in Norway: a nation-wide study, February 2020 to January 2022.

BACKGROUND: SARS-CoV-2 reinfection rates have been shown to vary depending on the circulating variant, vaccination status and background immunity, as well as the time interval used to identify reinfections. This study describes the frequency of SARS-CoV-2 reinfections in Norway using different time intervals and assesses potential factors that could impact the risk of reinfections during the different variant waves. METHODS: We used linked individual-level data from national registries to conduct a retrospective cohort study including all cases with a positive test for SARS-CoV-2 from February 2020 to January 2022. Time intervals of 30, 60, 90 or 180 days between positive tests were used to define potential reinfections. A multivariable Cox regression model was used to assess the risk of reinfection in terms of variants adjusting for vaccination status, demographic factors, and underlying comorbidities. RESULTS: The reinfection rate varied between 0.2%, 0.6% and 5.9% during the Alpha, Delta and early Omicron waves, respectively. In the multivariable model, younger age groups were associated with a higher risk of reinfection compared to older age groups, whereas vaccination was associated with protection against reinfection. Moreover, the risk of reinfection followed a pattern similar to risk of first infection. Individuals infected early in the pandemic had higher risk of reinfection than individuals infected in more recent waves. CONCLUSIONS: Reinfections increased markedly during the Omicron wave. Younger individuals, and primary infections during earlier waves were associated with an increased reinfection risk compared to primary infections during more recent waves, whereas vaccination was a protective factor. Our results highlight the importance of age and post infection waning immunity and are relevant when evaluating vaccination polices.

Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 Omicron BA.1 variant compared with the Delta variant, Norway, December 2021 to January 2022.

We included 39,524 COVID-19 Omicron and 51,481 Delta cases reported in Norway from December 2021 to January 2022. We estimated a 73% reduced risk of hospitalisation (adjusted hazard ratio: 0.27; 95% confidence interval: 0.20-0.36) for Omicron compared with Delta. Compared with unvaccinated groups, Omicron cases who had completed primary two-dose vaccination 7-179 days before diagnosis had a lower reduced risk than Delta (66% vs 93%). People vaccinated with three doses had a similar risk reduction (86% vs 88%).

No difference in risk of hospitalization between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway.

OBJECTIVES: To estimate the risk of hospitalization among reported cases of the Delta variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with the Alpha variant in Norway, and the risk of hospitalization by vaccination status. METHODS: A cohort study was conducted on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were calculated using multi-variable log-binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. RESULTS: In total, 7977 cases of the Delta variant and 12,078 cases of the Alpha variant were included in this study. Overall, 347 (1.7%) cases were hospitalized. The aRR of hospitalization for the Delta variant compared with the Alpha variant was 0.97 (95% CI 0.76-1.23). Partially vaccinated cases had a 72% reduced risk of hospitalization (95% CI 59-82%), and fully vaccinated cases had a 76% reduced risk of hospitalization (95% CI 61-85%) compared with unvaccinated cases. CONCLUSIONS: No difference was found between the risk of hospitalization for Delta cases and Alpha cases in Norway. The results of this study support the notion that partially and fully vaccinated cases are highly protected against hospitalization with coronavirus disease 2019.

Prevalence of HIV, Hepatitis C and its related risk behaviours among women who inject drugs in the Kathmandu Valley, Nepal: a cross-sectional study.

BACKGROUND: People who inject drugs (PWID) are at great risk of HIV and Hepatitis C Virus (HCV). In order to properly design interventions and develop programmes for women who inject drugs, this study assessed the prevalence of HIV, Hepatitis B, Hepatitis C, and syphilis and its risk behaviours among women who inject drugs in the Kathmandu Valley, Nepal. METHODS: Through modified network sampling in three districts in the Kathmandu Valley, Nepal, this cross-sectional study enrolled a total of 160 women who inject drugs. Participants' serum samples were tested for HIV, HCV, Hepatitis B virus (HBV) and syphilis and risk behaviours were assessed through a structured questionnaire. Primary outcome variables were HIV, HCV, HBV and syphilis prevalence, and secondary outcome variables were sharing needles in the past month and using condom in last sexual intercourse. Stepwise logistic regression was used to determine micro- and macroenvironmental factors associated with secondary outcomes. RESULTS: The prevalence of HIV, HCV, and HBV was 8.8%, 21.3%, and 1.9%, respectively. HIV-HCV co-infection rate was 5.6%. Fifteen percent of women who inject drugs reported transactional sex for drugs or money. One in four women who inject drugs (27.5%) reported that they were imprisoned or detained for drug related reasons. In multivariable analysis, women living with HIV who inject drugs were almost four times more likely to use a previously used needle/syringe than women who inject drugs who were HIV negative (aOR: 4.2 CI: 1.1-15.9, p = 0.03), but were almost four times more likely to use a condom during sexual intercourse (aOR: 3.5 CI: 1.1-28.9, p = 0.03). Enrolment in family planning was the main determinant for using condoms in last sexual intercourse (aOR 4.9 CI: 1.6-16.7, p = 0.006). Participants with access to HIV test and counselling (HTC) services were less likely to share needles (aOR: 0.3, 95% CI: 0.1-0.8, p = 0.01). CONCLUSION: Prevalence of HIV and HCV is high among women who inject drugs in Kathmandu valley of Nepal. Women who inject drugs enrolled in national programmes such as family planning and HTC were positively associated with condom use, and less likely to share needles.

Increased risk of hospitalisation and intensive care admission associated with reported cases of SARS-CoV-2 variants B.1.1.7 and B.1.351 in Norway, December 2020 -May 2021.

INTRODUCTION: Since their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC. MATERIALS AND METHODS: Using linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC. RESULTS: We included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall, 1,017 cases were hospitalised (3.6%) and 206 admitted to ICU (0.7%). B.1.1.7 was associated with a 1.9-fold increased risk of hospitalisation (aRR 95%CI 1.6-2.3) and a 1.8-fold increased risk of ICU admission (aRR 95%CI 1.2-2.8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2.4-fold increased risk of hospitalisation (aRR 95%CI 1.7-3.3) and a 2.7-fold increased risk of ICU admission (aRR 95%CI 1.2-6.5) compared to non-VOC. DISCUSSION: Our findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. This highlights the importance of prevention and control measures to reduce transmission of these VOC in society, particularly ongoing vaccination programmes, and preparedness plans for hospital surge capacity.

Diagnostic performance of a SARS-CoV-2 rapid antigen test in a large, Norwegian cohort.

BACKGROUND: Rapid antigen tests (RATs) may be included in national strategies for handling the SARS-CoV-2 pandemic, as they provide test results rapidly, are easily performed outside laboratories, and enable immediate contract tracing. However, before implementation further clinical evaluation of test sensitivity is warranted. OBJECTIVES: To examine the performance of Abbott's Panbio™ COVID-19 Ag Rapid Test Device for SARS-CoV-2 testing in a low to medium prevalence setting in Norway. STUDY DESIGN: A prospective study comparing the results of the Panbio RAT with PCR in 4857 parallel samples collected at a SARS-CoV-2 test station in Oslo, and from COVID-19 outbreaks in six Norwegian municipalities. RESULTS: A total of 4857 cases were included in the study; 3991 and 866 cases from the test station and the outbreak municipalities, respectively. The prevalence at the test station in Oslo was 6.3 %, and the overall sensitivity of the RAT was 74 %. Increased sensitivity was observed in patients who experienced symptoms (79 %) and when considering samples with viral loads above estimated level of infectivity (84 %), while it was lower in asymptomatic persons (55 %). In the outbreak municipalities, the overall prevalence was 6.9 %, and the total sensitivity of the RAT was 70 %. CONCLUSIONS: Our results indicate that the test correctly identified most infectious individuals. Nevertheless, the sensitivity is considerably lower than for PCR, and it is important that the limitations of the test are kept in mind in the follow-up of tested individuals.

Prevalence of HIV, syphilis, and assessment of the social and structural determinants of sexual risk behaviour and health service utilisation among MSM and transgender women in Terai highway districts of Nepal: findings based on an integrated biological and behavioural surveillance survey using respondent driven sampling.

BACKGROUND: Men who have sex with men (MSM) and transgender people are disproportionately affected by HIV and sexually transmitted infections. MSM and transgender people in Nepal experience considerable discrimination and marginalisation, they are subject to abuse from legal authorities and suffer from mental health issues. These social and structural factors can lead to increased sexual risk behaviour, barriers to accessing health care and result in adverse health outcomes. This study aims to assess the prevalence of HIV and syphilis, and how individual and socio-structural factors influence sexual risk behaviour and health care service uptake, among MSM and transgender women in the Terai highway districts of Nepal. METHODS: A cross-sectional survey was conducted in June 2016 in eight Terai highway districts of Nepal, recruiting 340 MSM and transgender women through respondent driven sampling. The primary outcome variables were HIV and syphilis prevalence. The secondary outcome variables were sexual risk behaviour and health care service uptake. Logistic regression models were used to assess the individual and socio-structural determinants of sexual risk behaviour and health care service uptake. RESULTS: The prevalence of HIV among MSM was 5%, whereas it was 13% in transgender women. The prevalence of active syphilis was 4% in MSM and 11% among transgender women. Among transgender women, 76% were involved in sex work, and 51% had experienced discrimination in one or more settings. In multivariable analysis, having visited an outreach centre was positively associated with condom use in the last sexual encounter among both MSM (AOR: 5.37, 95% CI: 2.42-11.94, p < 0.001) and transgender women (AOR: 2.37, 95% CI: 1.12-5.02, p = 0.025). Moreover, transgender women who reported being open towards family about sexual identity/behaviour were 2.4 more likely to have visited an outreach centre (AOR: 2.40, 95% CI: 1.04-5.57, p = 0.041). CONCLUSIONS: The high prevalence of HIV and syphilis, as well as indicators of marginalisation and discrimination among transgender women, highlights the increased burden transgender women in Nepal are facing and the need for tailored interventions. Moreover, since health care service uptake is an important factor in determining sexual risk behaviour among MSM and transgender women in Nepal, outreach services should be scaled up.

Prostate cancer and the unfolded protein response.

The endoplasmic reticulum (ER) is an essential organelle that contributes to several key cellular functions, including lipogenesis, gluconeogenesis, calcium storage, and organelle biogenesis. The ER also serves as the major site for protein folding and trafficking, especially in specialized secretory cells. Accumulation of misfolded proteins and failure of ER adaptive capacity activates the unfolded protein response (UPR) which has been implicated in several chronic diseases, including cancer. A number of recent studies have implicated UPR in prostate cancer (PCa) and greatly expanded our understanding of this key stress signaling pathway and its regulation in PCa. Here we summarize these developments and discuss their potential therapeutic implications.

Divergent androgen regulation of unfolded protein response pathways drives prostate cancer.

The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion and development of the normal prostate and drive prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that the canonical UPR pathways are directly and divergently regulated by androgens in PCa cells, through the androgen receptor (AR), which is critical for PCa survival. AR bound to gene regulatory sites and activated the IRE1α branch, but simultaneously inhibited PERK signaling. Inhibition of the IRE1α arm profoundly reduced PCa cell growth in vitro as well as tumor formation in preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were correlated in human PCa, and spliced XBP-1 expression was significantly upregulated in cancer compared with normal prostate. These data establish a genetic switch orchestrated by AR that divergently regulates the UPR pathways and suggest that targeting IRE1α signaling may have therapeutic utility in PCa.

TCTP is an androgen-regulated gene implicated in prostate cancer.

TCTP has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. In addition to these intracellular functions, TCTP has extracellular functions and plays an important role in immune cells. TCTP expression was previously shown to be deregulated in prostate cancer, but its function in prostate cancer cells is largely unknown. Here we show that TCTP expression is regulated by androgens in LNCaP prostate cancer cells in vitro as well as human prostate cancer xenografts in vivo. Knockdown of TCTP reduced colony formation and increased apoptosis in LNCaP cells, implicating it as an important factor for prostate cancer cell growth. Global gene expression profiling in TCTP knockdown LNCaP cells showed that several interferon regulated genes are regulated by TCTP, suggesting that it may have a role in regulating immune function in prostate cancer. In addition, recombinant TCTP treatment increased colony formation in LNCaP cells suggesting that secreted TCTP may function as a proliferative factor in prostate cancer. These results suggest that TCTP may have a role in prostate cancer development.