Mild COVID-19 induces early, quantifiable, persistent troponin I elevations in elder men.

Importance: Elderly patients, especially men, are at risk of increased morbidity from coronavirus disease 2019 (COVID-19). Long-term data on troponin I levels in longitudinal observational studies of outpatients with mild to moderate COVID-19 are scarce. Objective: This controlled cohort study aimed to evaluate the course of troponin I concentrations over a long period in convalescent COVID-19 outpatients with mild to moderate symptoms. Setting and participants: In this cohort study, individuals with PCR-confirmed, mild to moderate SARS-CoV-2 infection as well as control individuals with confirmed negative PCR and negative SARS-CoV-2 serology were included. Study visits were performed from April 2020 through July 2021 (initialized during the first wave of the corona pandemic in Switzerland). A study visit in patients comprised blood draws every week in the first month and additionally after 8 weeks. This course was repeated in patients observed long-term. Results: This study enrolled 278 individuals from the Canton of St. Gallen, Switzerland, aged 12-92 years (59.5% women), who had mild to moderate COVID-19 symptoms (outpatients only) and a diagnosis confirmed by positive RT-PCR. Fifty-four of the participants with confirmed SARS-CoV-2 infection were followed for 14 months with repeat cycles of the testing protocol. In addition, 115 symptomatic patients that were PCR and serology negative were enrolled in the same time period as a control group. In COVID-19 patients, low-level troponin I concentrations (cTnI) were significantly increased from baseline until week 9 after positive RT-PCR diagnosis in men older than 54 years [ΔcTnI = 5.0 ng/L (median); 95% CI 4.1-6.0; p = 0.02]. The troponin I concentration remained elevated throughout 14 months in men older than 54 years within the cohort with a prolonged observation period. This statistically significant change in troponin I concentration was not dependent on co-morbidities in this group. ALT, Creatinine, BNP, and D-Dimer values after convalescence did not differ in comparison to the control cohort. Conclusion: In this analysis of individuals with confirmed SARS-CoV-2 infection, hs troponin I levels of men aged 54 or older significantly increased after infection. They remained elevated for at least 14 months after diagnosis. This suggests the possibility of an ongoing, long-term, low-grade myocardial injury. Further studies with focus on elderly patients and a prolonged observational period are necessary to elucidate whether the phenomenon observed is associated with detectable structural changes to the heart muscle or is without further clinical consequences.

Age-related model for estimating the symptomatic and asymptomatic transmissibility of COVID-19 patients.

Estimation of age-dependent transmissibility of COVID-19 patients is critical for effective policymaking. Although the transmissibility of symptomatic cases has been extensively studied, asymptomatic infection is understudied due to limited data. Using a dataset with reliably distinguished symptomatic and asymptomatic statuses of COVID-19 cases, we propose an ordinary differential equation model that considers age-dependent transmissibility in transmission dynamics. Under a Bayesian framework, multi-source information is synthesized in our model for identifying transmissibility. A shrinkage prior among age groups is also adopted to improve the estimation behavior of transmissibility from age-structured data. The added values of accounting for age-dependent transmissibility are further evaluated through simulation studies. In real-data analysis, we compare our approach with two basic models using the deviance information criterion (DIC) and its extension. We find that the proposed model is more flexible for our epidemic data. Our results also suggest that the transmissibility of asymptomatic infections is significantly lower (on average, 76.45% with a credible interval (27.38%, 88.65%)) than that of symptomatic cases. In both symptomatic and asymptomatic patients, the transmissibility mainly increases with age. Patients older than 30 years are more likely to develop symptoms with higher transmissibility. We also find that the transmission burden of asymptomatic cases is lower than that of symptomatic patients.

Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modelling study.

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.

The optimality of age-based lockdown policies.

This paper studies an age-based lockdown that keeps over-60 workers at home as policy response to COVID-19 pandemic in a sample of thirty countries of the European single market. Three main policy issues are addressed, and the results can be summarized as follows. First, age-based lockdown policies are associated with limited output losses and, therefore, are an efficient strategy to limit the spread of the virus in a pandemic, especially in presence of strong age-dependent fatality rates. Second, lockdown policies generate substantial spillover effects; hence, international policy coordination avoiding that too many countries are in lockdown contemporaneously or that such coordination takes place across the countries with the highest integration of over-60 workers along GVCs may be helpful in reducing disruptions. Third, non-targeted lockdowns are much more costly than age-based ones; therefore, other things equal, age-based policies should always be preferred to non-targeted ones. Our analysis also suggests that, in our sample, the over-60 workers are relatively more numerous in sectors where the value added and the integration in GVCs is lower; this feature should be kept in mind in the design of other policies as it might play an important role.

Immune Responses Against SARS-CoV-2 WT and Delta Variant in Elderly BNT162b2 Vaccinees.

Background: Residents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in >70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years. Methods: Peripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2). Results: Our results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups. Conclusions: Our data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2.

Age Dependent Epidemic Modeling of COVID-19 Outbreak in Kuwait, France, and Cameroon.

Revisiting the classical model by Ross and Kermack-McKendrick, the Susceptible-Infectious-Recovered (SIR) model used to formalize the COVID-19 epidemic, requires improvements which will be the subject of this article. The heterogeneity in the age of the populations concerned leads to considering models in age groups with specific susceptibilities, which makes the prediction problem more difficult. Basically, there are three age groups of interest which are, respectively, 0-19 years, 20-64 years, and >64 years, but in this article, we only consider two (20-64 years and >64 years) age groups because the group 0-19 years is widely seen as being less infected by the virus since this age group had a low infection rate throughout the pandemic era of this study, especially the countries under consideration. In this article, we proposed a new mathematical age-dependent (Susceptible-Infectious-Goneanewsusceptible-Recovered (SIGR)) model for the COVID-19 outbreak and performed some mathematical analyses by showing the positivity, boundedness, stability, existence, and uniqueness of the solution. We performed numerical simulations of the model with parameters from Kuwait, France, and Cameroon. We discuss the role of these different parameters used in the model; namely, vaccination on the epidemic dynamics. We open a new perspective of improving an age-dependent model and its application to observed data and parameters.

Age cohorts stratified according to age-distributions of COVID-19 morbidity statistics identify uniquely age-dependent CD3+CD8+ T-cell lymphocytopenia in COVID-19 patients without comorbidities on admission.

If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/µl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=‒0.435, p<0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.

Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia.

BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated by preeclampsia or preterm birth. This is important because the expression of decidual and placental angiotensin-converting enzyme 2 and transmembrane protease serine 2 across gestation may affect the susceptibility of pregnancies to vertical transmission of severe acute respiratory syndrome coronavirus 2. OBJECTIVE: This study aimed to investigate the expression pattern of specific severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across human pregnancy and in paired samples of decidua and placenta in pregnancies complicated by preterm birth or preeclampsia compared with those in term uncomplicated pregnancies. STUDY DESIGN: In this study, 2 separate cohorts of patients, totaling 87 pregnancies, were included. The first cohort was composed of placentae from first- (7-9 weeks), second- (16-18 weeks), and third-trimester preterm (26-31 weeks) and third-trimester term (38-41 weeks) pregnancies (n=5/group), whereas the second independent cohort included matched decidua and placentae from pregnancies from term uncomplicated pregnancies (37-41 weeks' gestation; n=14) and pregnancies complicated by preterm birth (26-37 weeks' gestation; n=11) or preeclampsia (25-37 weeks' gestation; n=42). Samples were subjected to quantitative polymerase chain reaction and next-generation sequencing or RNA sequencing for next-generation RNA sequencing for angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA expression quantification, respectively. RESULTS: In the first cohort, angiotensin-converting enzyme 2 and transmembrane protease serine 2, exhibited a gestational age-dependent expression profile, that is, angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA was higher (P<.05) in the first-trimester placenta than in second-trimester, preterm birth, and term placentae (P<.05) and exhibited a negative correlation with gestational age (P<.05). In the second cohort, RNA sequencing demonstrated very low or undetectable expression levels of angiotensin-converting enzyme 2 in preterm birth, preeclampsia, and term decidua and in placentae from late gestation. In contrast, transmembrane protease serine 2 was expressed in both decidual and placental samples but did not change in pregnancies complicated by either preterm birth or preeclampsia. CONCLUSION: The increased expression of these severe acute respiratory syndrome coronavirus 2 cell entry-associated genes in the placenta in the first trimester of pregnancy compared with those in later stages of pregnancy suggests the possibility of differential susceptibility to placental entry to severe acute respiratory syndrome coronavirus 2 across pregnancy. Even though there is some evidence of increased rates of preterm birth associated with severe acute respiratory syndrome coronavirus 2 infection, we found no increase in mRNA expression of angiotensin-converting enzyme 2 or transmembrane protease serine 2 at the maternal-fetal interface.

[A scenario to safely ease the covid-19 lockdown while allowing economic recovery]. / Un scénario de déconfinement compatible avec une reprise économique.

If they work as expected, the strict containment measures enforced to stop the French Covid-19 epidemic will leave a large proportion of the population "naive" about the SARS-CoV-2 virus. In these conditions, how can we prevent the epidemic from rebounding, at a time when this restrictive policy will soon become untenable economically and socially? Based on the figures, now well known, of the lethality of covid-19 according to age classes, I suggest that a gradual release of the containment be instituted, which will keep retirees in isolation (the 65+ age class), whose risk is maximal and the impact on economic production the lowest. This scenario might be applicable to most European countries that enforce mandatory retirement ages for most of workers.

Age-dependent Gender Differences in COVID-19 in Mainland China: Comparative Study.

BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging the global public health system. Sex differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compare gender differences in attack rate (AR), proportion of severe and critical cases (PSCC), and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in females than in males (63.9 vs 60.5 per 1 million persons; P ˂ .001). In contrast, PSCC and CFR were significantly lower among females (16.9% and 4.0%) than among males (19.5% and 7.2%), with odds ratios of 0.87 and 0.57, respectively (both P ˂ .001). The female-to-male differences were age dependent, and were significant among people aged 50-69 years for AR and in patients aged 30 years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC, and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC, and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province, and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC, and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.