Observed protection against SARS-CoV-2 reinfection following a primary infection: A Danish cohort study among unvaccinated using two years of nationwide PCR-test data.

Background: The level of protection after a SARS-CoV-2 infection against reinfection and COVID-19 disease remains important with much of the world still unvaccinated. Methods: Analysing nationwide, individually referable, Danish register data including RT-PCR-test results, we conducted a cohort study using Cox regression to compare SARS-CoV-2 infection rates before and after a primary infection among still unvaccinated individuals, adjusting for sex, age, comorbidity and residency region. Estimates of protection against infection were calculated as 1 minus the hazard ratio. Estimates of protection against symptomatic infections and infections leading to hospitalisation were also calculated. The prevalence of infections classified as symptomatic or asymptomatic was compared for primary infections and reinfections. The study also assessed protection against each of the main viral variants after a primary infection with an earlier variant by restricting follow-up time to distinct, mutually exclusive periods during which each variant dominated. Findings: Until 1 July 2021 the estimated protection against reinfection was 83.4% (95%CI: 82.2-84.6%); but lower for the 65+ year-olds (72.2%; 95%CI: 53.2-81.0%). Moderately higher estimates were found for protection against symptomatic disease, 88.3% overall (95%CI: 85.9-90.3%). First-time cases who reported no symptoms were more likely to experience a reinfection (odds ratio: 1.48; 95%CI: 1.35-1.62). By autumn 2021, when infections were almost exclusively caused by the Delta variant, the estimated protection following a recent first infection was 91.3% (95%CI: 89.7-92.7%) compared to 71.4% (95%CI: 66.9-75.3%) after a first infection over a year earlier. With Omicron, a first infection with an earlier variant in the past 3-6 months gave an estimated 51.0% (95%CI: 50.1-52.0%) protection, whereas a first infection longer than 12 months earlier provided only 19.0% (95%CI: 17.2-20.5%) protection. Protection by an earlier variant-infection against hospitalisation due to a new infection was estimated at: 86.6% (95%CI: 46.3-96.7%) for Alpha, 97.2% (95%CI: 89.0-99.3%) for Delta, and 69.8% (95%CI: 51.5-81.2%) for the Omicron variant. Interpretation: SARS-CoV-2 infection offered a high level of sustained protection against reinfection, comparable with that offered by vaccines, but decreased with the introduction of new main virus variants; dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections. The level of estimated protection against serious disease was somewhat higher than that against infection and possibly longer lasting. Decreases in protection against reinfection, seemed primarily to be driven by viral evolution. Funding: None

Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study.

BACKGROUND: The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period. METHODS AND FINDINGS: A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals. CONCLUSIONS: Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds

Cryptococcal rib osteomyelitis as primary and only symptom of idiopathic CD4 penia

A 59-year old man with idiopathic CD4 lymphopenia presented with extensive disseminated Cryptococcus neoformans infection including a large rib cryptoccocoma, vertebral spondylitis and pleural empyema. Complete resection of the affected part of the rib was necessary after failure of initial antifungal treatment. The vertebral spondylitis has been successfully managed at 3 years of follow-up by continuous itraconazole treatment and regular MRI combined with leucocyte scintigraphy assessment

Five-year risk of HIV diagnosis subsequent to 147 hospital-based indicator diseases:a Danish nationwide population-based cohort study

BACKGROUND: It has been suggested that targeted human immunodeficiency virus (HIV) testing programs are cost-effective in populations with an HIV prevalence >0.1%. Several indicator diseases are known to be associated with increased risk of HIV infection, but estimates of HIV frequency in persons with relevant indicator diseases are nonexistent. METHODS: In a nationwide population-based cohort study encompassing all Danish residents aged 20–60 years during 1994–2013, we estimated the 5-year risk of an HIV diagnosis (FYRHD) after a first-time diagnosis of 147 prespecified potential indicator diseases. To estimate the risk of HIV diagnosis in the general population without any indicator diseases, we calculated the FYRHD starting at age 25, 35, 45, and 55 years. RESULTS: The risk in the male general population was substantially higher than the female general population, and the risk was lower in the older age categories. Individuals of African origin had a higher FYRHD than individuals of Danish origin. A number of diseases were identified with a FYRHD >0.1%, with infectious diseases, such as syphilis, hepatitis, and endocarditis, associated with a particularly high FYRHD. Other potential indicator diseases, such as most urologic, nephrologic, rheumatologic, and endocrine disorders were generally associated with a low FYRHD. CONCLUSION: Our study identified a large number of indicator diseases associated with a FYRHD >0.1%. These data can be used as a tool for planning targeted HIV screening programs

Discontinuation and Dose Adjustment of Tenofovir in HIV Patients with Impaired Renal Function

Background: Impaired renal function is a major concern in HIV-infected patients treated with tenofovir. We undertook this study to clarify how reduced renal function in patients on tenofovir treatment is handled in routine clinical practice. Methods: From a population-based cohort of Danish HIV patients we identified all patients who started tenofovir for the first time and estimated relative risk (RR) of discontinuation of tenofovir in relation to baseline and last estimated glomerular filtration rate (eGFR, measured in ml/min per 1.73 m2). For patients who for the first time had eGFR<50, we calculated time to the combined endpoint of eGFR>50 or stop or dose modification.Results: 2,066 patients were included in the study. Patients with last eGFR<65 had increased risk of stopping tenofovir and the risk increased with decreasing eGFR (eGFR 60-65: adjusted RR 2.1; eGFR <50: adjusted RR 8.1). We identified 115 patients with eGFR<50. After 1 year only 12.3% were still on standard dose tenofovir and had eGFR<50.Conclusion: This study demonstrates that tenofovir treatment is stopped rapidly in patients who develop renal impairment. Patients with a normal baseline renal function have a low risk of treatment modification

Discontinuation and Dose Adjustment of Tenofovir in HIV Patients with Impaired Renal Function

Abstract: Background: Impaired renal function is a major concern in HIV-infected patients treated with tenofovir. We undertook this study to clarify how reduced renal function in patients on tenofovir treatment is handled in routine clinical practice. Methods: From a population-based cohort of Danish HIV patients we identified all patients who started tenofovir for the first time and estimated relative risk (RR) of discontinuation of tenofovir in relation to baseline and last estimated glomerular filtration rate (eGFR, measured in ml/min per 1.73 m 2). For patients who for the first time had eGFR<50, we calculated time to the combined endpoint of eGFR>50 or stop or dose modification. Results: 2,066 patients were included in the study. Patients with last eGFR<65 had increased risk of stopping tenofovir and the risk increased with decreasing eGFR (eGFR 60-65: adjusted RR 2.1; eGFR <50: adjusted RR 8.1). We identified 115 patients with eGFR<50. After 1 year only 12.3 % were still on standard dose tenofovir and had eGFR<50. Conclusion: This study demonstrates that tenofovir treatment is stopped rapidly in patients who develop renal impairment. Patients with a normal baseline renal function have a low risk of treatment modification

Smoking and renal function in people living with human immunodeficiency virus:a Danish nationwide cohort study

INTRODUCTION: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established. METHODS: We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft–Gault equation (CG-CrCl), and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart) and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs) for risk of CKD, aRRT, and mortality rate ratios (MRRs) following aRRT. RESULTS: From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7–1.7; adjusted IRR: 1.3, 95% CI: 0.9–1.8) or aRRT (adjusted IRR: 0.8, 95% CI: 0.4–1.7; adjusted IRR: 0.9, 95% CI: 0.5–1.7). Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3.8, 95% CI: 1.3–11.2). CONCLUSION: In Danish PLHIV, we observed no strong association between smoking status and renal function, risk of CKD, or risk of aRRT, but mortality was increased in smokers following aRRT