Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: a case-control study

Introduction Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. Methods Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n=199) and controls (random population sample, n=447), seronegative for IgG and IgA. The replication analysis included seropositive (n=134) and seronegative (n=152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. Results The 932 participants (54.1% women) were aged 48.6±20.2 years (±SD), BMI 25.0±4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831;0.465], P<0.001;replication analyses: 0.294 [0.0893;0.968], P<0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. Conclusion Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection.

Lessons from a pandemic

Several interventions have been used around the world trying to contain the SARS-CoV-2 pandemic, such as quarantine, prohibition of mass demonstrations, isolation of sick people, tracing of virus carriers, semi-containment, promotion of barrier gestures, development of rapid self-tests and vaccines among others. We propose a simple model to evaluate the potential impact of such interventions. A model for the reproduction number of an infectious disease including three main contexts of infection (indoor mass events, public indoor activities and household) and seven parameters is considered. We illustrate how these parameters could be obtained from the literature or from expert assumptions, and we apply the model to describe 20 scenarios that can typically occur during the different phases of a pandemic. This model provides a useful framework for better understanding and communicating the effects of different (combinations of) possible interventions, while encouraging constant updating of expert assumptions to better match reality. This simple approach will bring more transparency and public support to help governments to think, decide, evaluate and adjust what to do during a pandemic.

On the impacts of the COVID-19 pandemic on mortality: Lost years or lost days?

Objective: To quantify the (direct and indirect) impacts of the COVID-19 pandemic on mortality for actual populations of persons living in 12 European countries in 2020. Method: Based on demographic and mortality data, as well as remaining life expectancies found in the Human Mortality Database, we calculated a "population life loss" in 2020 for men and women living in Belgium, Croatia, Denmark, Finland, Hungary, Lithuania, Luxembourg, Norway, Portugal, Spain, Sweden, and Switzerland. This quantity was obtained by dividing the total number of years lost in 2020 (estimated from all-cause mortality data and attributed directly or indirectly to COVID-19) by the size of the population. Results: A significant population life loss was found in 8 countries in 2020, with men losing an average of 8.7, 5.0, 4.4, 4.0, 3.7, 3.4, 3.1, and 2.7 days in Lithuania, Spain, Belgium, Hungary, Croatia, Portugal, Switzerland, and Sweden, respectively. For women, this loss was 5.5, 4.3, 3.7, 3.7, 3.1, 2.4, 1.6, and 1.4 days, respectively. No significant losses were found in Finland, Luxembourg, Denmark and Norway. Life loss was highly dependent on age, reaching 40 days at the age of 90 in some countries, while only a few significant losses occurred under the age of 60. Even in countries with a significant population life loss in 2020, it was on average about 30 times lower than in 1918, at the time of the Spanish flu. Conclusions: Our results based on the concept of population life loss were consistent with those based on the classical concept of life expectancy, confirming the significant impact of COVID-19 on mortality in 8 European countries in 2020. However, while life expectancy losses were typically counted in months or years, population life losses could be counted in days, a potentially useful piece of information from a public health perspective.

Mortality in Switzerland in 2021.

OBJECTIVE: To analyze mortality trends in Switzerland in 2021, the second year of the COVID-19 pandemic. METHODS: Using data from the Swiss Federal Statistical Office, we compared mortality in Switzerland in 2021 with that of previous years in terms of standardized weekly deaths, standardized (annual) mortality rates (overall and stratified by age and sex) and life expectancy. The latter is a well-known demographic concept defining the average lifespan of a hypothetical cohort living and dying according to the mortality rates of a given year. RESULTS: After a favorable first half of the year and a fairly standard second half in terms of mortality in Switzerland, the year 2021 ended with a wave of deaths of moderate intensity related to the 5th wave of COVID-19. Overall, and after a notable increase in mortality in 2020 (+9.2%, 95%CI: +8.0%; +10.3%, compared to 2019, and +5.1%, 95%CI: +4.3%; +6.0%, compared to 2015-19), the pre-pandemic mortality level was approximately recovered in 2021 (+0.8%, 95%CI: -0.3%; +0.8%, compared to 2019, and -2.9%, 95%CI: -3.7%; -2.2%, compared to 2015-19). Life expectancy, after declining by 10 months for men and 6 months for women in 2020 (i.e. men would have lost 10 months and women 6 months had they lived their entire lives with COVID-19 as it was in 2020), returned in 2021 to 2019 levels for women (85.6 years) and regained 2018 levels for men (81.6 years, still -0.3 years from 2019). The age group responsible for the small remaining loss for men was the 50-70 age group, which had similar mortality in 2020 and 2021. CONCLUSIONS: The second year of the COVID-19 pandemic in Switzerland was characterized by an approximate return to pre-pandemic mortality levels, with a faster recovery for women than for men with respect to 2020.

Lessons from a pandemic.

Several interventions have been used around the world trying to contain the SARS-CoV-2 pandemic, such as quarantine, prohibition of mass demonstrations, isolation of sick people, tracing of virus carriers, semi-containment, promotion of barrier gestures, development of rapid self-tests and vaccines among others. We propose a simple model to evaluate the potential impact of such interventions. A model for the reproduction number of an infectious disease including three main contexts of infection (indoor mass events, public indoor activities and household) and seven parameters is considered. We illustrate how these parameters could be obtained from the literature or from expert assumptions, and we apply the model to describe 20 scenarios that can typically occur during the different phases of a pandemic. This model provides a useful framework for better understanding and communicating the effects of different (combinations of) possible interventions, while encouraging constant updating of expert assumptions to better match reality. This simple approach will bring more transparency and public support to help governments to think, decide, evaluate and adjust what to do during a pandemic.

Prevalence of SARS-CoV-2 in Household Members and Other Close Contacts of COVID-19 Cases: A Serologic Study in Canton of Vaud, Switzerland.

BACKGROUND: Research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission within households and other close settings using serological testing is scarce. METHODS: We invited coronavirus disease 2019 (COVID-19) cases diagnosed between February 27 and April 1, 2020, in Canton of Vaud, Switzerland, to participate, along with household members and other close contacts. Anti-SARS-CoV-2 immunoglobulin G antibodies were measured using a Luminex immunoassay. We estimated factors associated with serological status using generalized estimating equations. RESULTS: Overall, 219 cases, 302 household members, and 69 other close contacts participated between May 4 and June 27, 2020. More than half of household members (57.2%; 95% CI, 49.7%-64.3%) had developed a serologic response to SARS-CoV-2, while 19.0% (95% CI, 10.0%-33.2%) of other close contacts were seropositive. After adjusting for individual and household characteristics, infection risk was higher in household members aged ≥65 years than in younger adults (adjusted odds ratio [aOR], 3.63; 95% CI, 1.05-12.60) and in those not strictly adhering to simple hygiene rules like hand washing (aOR, 1.80; 95% CI, 1.02-3.17). The risk was lower when more than 5 people outside home were met during semiconfinement, compared with none (aOR, 0.35; 95% CI, 0.16-0.74). Individual risk of household members to be seropositive was lower in large households (22% less per each additional person). CONCLUSIONS: During semiconfinement, household members of a COVID-19 case were at very high risk of getting infected, 3 times more than close contacts outside home. This highlights the need to provide clear messages on protective measures applicable at home. For elderly couples, who were especially at risk, providing external support for daily basic activities is essential.

A first analysis of excess mortality in Switzerland in 2020.

OBJECTIVE: To quantify excess all-cause mortality in Switzerland in 2020, a key indicator for assessing direct and indirect consequences of the COVID-19 pandemic. METHODS: Using official data on deaths in Switzerland, all-cause mortality in 2020 was compared with that of previous years using directly standardized mortality rates, age- and sex-specific mortality rates, and life expectancy. RESULTS: The standardized mortality rate was 8.8% higher in 2020 than in 2019, returning to the level observed 5-6 years before, around the year 2015. This increase was greater for men (10.6%) than for women (7.2%) and was statistically significant only for men over 70 years of age, and for women over 75 years of age. The decrease in life expectancy in 2020 compared to 2019 was 0.7%, with a loss of 9.7 months for men and 5.3 months for women. CONCLUSIONS: There was an excess mortality in Switzerland in 2020, linked to the COVID-19 pandemic. However, as this excess only concerned the elderly, the resulting loss of life expectancy was restricted to a few months, bringing the mortality level back to 2015.

Estimating the basic reproduction number for COVID-19 in Western Europe.

OBJECTIVE: To estimate the basic reproduction number (R0) for COVID-19 in Western Europe. METHODS: Data (official statistics) on the cumulative incidence of COVID-19 at the start of the outbreak (before any confinement rules were declared) were retrieved in the 15 largest countries in Western Europe, allowing us to estimate the exponential growth rate of the disease. The rate was then combined with estimates of the distribution of the generation interval as reconstructed from the literature. RESULTS: Despite the possible unreliability of some official statistics about COVID-19, the spread of the disease appears to be remarkably similar in most European countries, allowing us to estimate an average R0 in Western Europe of 2.2 (95% CI: 1.9-2.6). CONCLUSIONS: The value of R0 for COVID-19 in Western Europe appears to be significantly lower than that in China. The proportion of immune persons in the European population required to stop the outbreak could thus be closer to 50% than to 70%.