Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity.

BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

Vaccination has proven very effective in protecting against severe disease and hospitalization of people with COVID-19, the disease caused by SARS-CoV-2. It is still unclear, however, how the different components of the immune system respond to SARS-CoV-2 vaccination and protect from infection and severe disease. Two of the most predominant components of the immune system are specialized proteins and cells. The proteins circulate in the blood and help clear the virus by binding to it, while the cells either kill the virus or help other cells to produce more antibodies. Here, we examined the response of these two components to the SARS-CoV-2 vaccine in 655 Danish citizens. The response of both components was lower in people over 75 years old and with other diseases. These findings help in understanding the immune responses following SARS-CoV-2 vaccination in people at increased risk of severe symptoms of COVID-19.

Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone.

BACKGROUND: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. METHODS: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. RESULTS: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. CONCLUSIONS: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

Risk factors for fatigue and impaired function eight months after hospital admission with COVID-19.

INTRODUCTION: We aimed to evaluate post-COVID-19 fatigue, change in functional capacity and health-related quality of life (HRQoL) eight months after discharge from hospital due to COVID-19. METHODS: A total of 83 patients (35 women) admitted to the Copenhagen University Hospital - North Zealand Hospital, Denmark, for COVID-19 during the period from March to June 2020 were evaluated eight months after discharge using validated questionnaires quantifying fatigue, HRQoL and post-COVID-19 functional status. Follow-up data were correlated with measures of pre-COVID-19 status (anthropometrics, comorbidities) and measures of severity of the acute infection. RESULTS: A total of 22 (65%) women and 12 (26%) men reported excessive fatigue. In all, 20 women (67%) and 17 men (37%) reported decreased physical function. Female sex was associated with fatigue. Loss of physical function was associated with pre-COVID-19 presence of heart disease and absence of lung disease. Severity of the acute COVID-19 infection was not associated with fatigue or change in functional status. Fatigue and functional status were correlated with both generic HRQoL and lung disease-specific HRQoL. CONCLUSIONS: Female sex was associated with a higher risk of fatigue eight months after hospitalisation with COVID-19 infection. Regarding loss of functional capacity after COVID-19, we found an apparently protective effect of pre-COVID-19 lung disease. Our findings underscore the urgent need for further research and the importance of evaluating those recovering from COVID-19 for symptoms of excessive fatigue and change in functional capacity irrespective of the severity of the initial infection. FUNDING: none. TRIAL REGISTRATION: not relevant.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

BACKGROUND: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38-.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29-.46). CONCLUSIONS: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.

First wave of COVID-19 hospital admissions in Denmark: a Nationwide population-based cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, comorbidity and laboratory determinants of death and of ICU admission were explored in all Danish hospitalised patients. METHODS: National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis. RESULTS: Among 2431 hospitalised patients with COVID-19 between February 27 and July 8 (median age 69 years [IQR 53-80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia, neutrophilia and thrombocytopenia within ±24-h of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP, LDH, creatinine, urea and neutrophil count were independently associated with death within 30 days. Males presented with more pronounced laboratory abnormalities on admission. CONCLUSIONS: Advanced age, male sex, comorbidity, higher levels of systemic inflammation and cell-turnover were independent factors for mortality. Age was the strongest predictor for death, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher in males after surviving the first week.

[Pulmonary thromboembolism as contributing cause of severe respiratory insufficiency in a patient with COVID-19 infection].

We report a case of multiple peripheral pulmonary thromboembolisms in a 69-year-old male hospitalised due to SARS-CoV-2 infection. There were no evident risk factors for pulmonary thromboembolism, the patient had a Wells' score of zero, and the diagnosis only became evident after repeated CT pulmonary angiographies.

Intraventricular neurocysticercosis: Presentation, diagnosis and management.

Neurocysticercosis is thought to be the most common helminthic infection of the central nervous system and its epidemiology is changing due to increasing travel and migration. Evidence to guide management of the intraventricular form is limited. We aimed to review the clinical presentation, diagnosis and treatment of intraventricular neurocysticercosis with reference to two recent cases seen at our institution. The intraventricular variant of neurocysticercosis is less common than parenchymal disease and usually presents with acutely raised intracranial pressure and untreated it progresses rapidly with high mortality. The diagnosis is based on imaging and serological tests but more invasive testing including histopathological examination of surgically acquired tissue specimens is sometimes required. Treatment is mainly surgical, using a neuroendoscopic approach if possible. Patients should also receive antihelmintic treatment with concomitant corticosteroids to reduce the incidence of shunt failure if a ventricular shunt is inserted and to treat viable lesions elsewhere.

Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward.

We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. © 2016 Wiley Periodicals, Inc.

A signal-to-cutoff ratio in the Abbott architect HIV Ag/Ab Combo assay that predicts subsequent confirmation of HIV-1 infection in a low-prevalence setting.

A rapid diagnosis is considered important in HIV care. In 138,911 testing episodes with the Abbott Architect HIV Ag/Ab Combo assay (3,705 reactive samples), a signal-to-cutoff ratio of >151.17 had a positive predictive value of 100% and a sensitivity of 67.4% for the detection of subsequently confirmed HIV infection. We suggest that results higher than this signal-to-cutoff ratio threshold may be reported to clinicians before the completion of confirmatory testing.