Coronavirus disease (COVID-19)

Unavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections.

The German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues.

This study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints.

between October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic.

Vaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.

The start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.

We explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.

We developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.

Among 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51–29.67) and a positive perception of employer’s encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36–12.22). The strongest association of a knowledge item was identifying the statement ‘Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.’ as false (OR: 2.36; 95% CI: 1.73–3.22).

The results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.

The COVID-19 pandemic presented new challenges for the existing respiratory surveillance systems, and adaptations were implemented. Systematic assessment of the syndromic and sentinel surveillance platforms during the pandemic is essential for understanding the value of each platform in the context of an emerging pathogen with rapid global spread.

We aimed to evaluate systematically the performance of various respiratory syndromic surveillance platforms and the sentinel surveillance system in Israel from 1 January to 31 December 2020.

We compared the 2020 syndromic surveillance trends to those of the previous 3 years, using Poisson regression adjusted for overdispersion. To assess the performance of the sentinel clinic system as compared with the national SARS-CoV-2 repository, a cubic spline with 7 knots and 95% confidence intervals were applied to the sentinel network's weekly percentage of positive SARS-CoV-2 cases.

Syndromic surveillance trends changed substantially during 2020, with a statistically significant reduction in the rates of visits to physicians and emergency departments to below previous years' levels. Morbidity patterns of the syndromic surveillance platforms were inconsistent with the progress of the pandemic, while the sentinel surveillance platform was found to reflect the national circulation of SARS-CoV-2 in the population.

Our findings reveal the robustness of the sentinel clinics platform for the surveillance of the main respiratory viruses during the pandemic and possibly beyond. The robustness of the sentinel clinics platform during 2020 supports its use in locations with insufficient resources for widespread testing of respiratory viruses.

Households appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.

We aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.

A prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.

We included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31–43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.

Rates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.

SARS-CoV-2 infections in preschool and school settings potentially bear occupational risks to educational staff.

We aimed to assess the prevalence of SARS-CoV-2 infection in teachers and preschool educators and at identifying factors associated with infection.

We analysed cross-sectional data derived from 17,448 voluntary, PCR-based screening tests of asymptomatic educational staff in Berlin, Germany, between June and December 2020 using descriptive statistics and a logistic regression model.

Participants were largely female (73.0%), and median age was 41 years (range: 18-78). Overall, SARS-CoV-2 infection proportion was 1.2% (95% CI: 1.0–1.4). Proportion of positive tests in educational staff largely followed community incidence until the start of the second pandemic wave, when an unsteady plateau was reached. Then, the proportion of positive tests in a (concurrent) population survey was 0.9% (95% CI: 0.6–1.4), 1.2% (95% CI: 0.8–1.8) in teachers and 2.6% (95% CI: 1.6–4.0) in preschool educators. Compared with teachers, increased odds of infection were conferred by being a preschool educator (adjusted odds ratio (aOR): 1.6; 95% CI: 1.3–2.0) and by contact with a SARS-CoV-2 infected individual outside of work (aOR: 3.0; 95% CI: 1.5–5.5). In a step-wise backward selection, the best set of associated factors with SARS-CoV-2 infection involved age, occupation, and calendar week.

These results indicate that preschool educators bear increased odds of SARS-CoV-2 infection compared with teachers. At the same time, the private environment appeared to be a relevant source of SARS-CoV-2 infection for educational staff in 2020.

Human mobility was considerably reduced during the COVID-19 pandemic. To support disease surveillance, it is important to understand the effect of mobility on transmission.

We compared the role of mobility during the first and second COVID-19 wave in Switzerland by studying the link between daily travel distances and the effective reproduction number (Rt) of SARS-CoV-2.

We used aggregated mobile phone data from a representative panel survey of the Swiss population to measure human mobility. We estimated the effects of reductions in daily travel distance on Rt via a regression model. We compared mobility effects between the first (2 March–7 April 2020) and second wave (1 October–10 December 2020).

Daily travel distances decreased by 73% in the first and by 44% in the second wave (relative to February 2020). For a 1% reduction in average daily travel distance, Rt was estimated to decline by 0.73% (95% credible interval (CrI): 0.34–1.03) in the first wave and by 1.04% (95% CrI: 0.66–1.42) in the second wave. The estimated mobility effects were similar in both waves for all modes of transport, travel purposes and sociodemographic subgroups but differed for movement radius.

Mobility was associated with SARS-CoV-2 Rt during the first two epidemic waves in Switzerland. The relative effect of mobility was similar in both waves, but smaller mobility reductions in the second wave corresponded to smaller overall reductions in Rt. Mobility data from mobile phones have a continued potential to support real-time surveillance of COVID-19.

To control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken.

To assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000–4,000 residual samples during seven periods between 30 March and 17 October 2020.

We analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.

The weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0–2.6) to 5.3% (95% CrI: 4.2–6.4), implying a seroincidence of 3.4% (95% CrI: 2.4–4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1–5.2).

During lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.

COVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.

We examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.

The relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.

In the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.

During the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.

Universal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.

To investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.

We characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March–12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman’s rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.

From March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).

From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3–5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8–6.3).

This study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.

The COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.

We explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.

We used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.

Although we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.

Our results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.

The COVID-19 pandemic is one of the most serious global public health threats of recent times. Understanding SARS-CoV-2 transmission is key for outbreak response and to take action against the spread of disease. Transmission within the household is a concern, especially because infection control is difficult to apply within this setting.

The objective of this observational study was to investigate SARS-CoV-2 transmission in Danish households during the early stages of the COVID-19 pandemic.

We used comprehensive administrative register data from Denmark, comprising the full population and all COVID-19 tests from 27 February 2020 to 1 August 2020, to estimate household transmission risk and attack rate.

We found that the day after receiving a positive test result within the household, 35% (788/2,226) of potential secondary cases were tested and 13% (98/779) of these were positive. In 6,782 households, we found that 82% (1,827/2,226) of potential secondary cases were tested within 14 days and 17% (371/2,226) tested positive as secondary cases, implying an attack rate of 17%. We found an approximate linear increasing relationship between age and attack rate. We investigated the transmission risk from primary cases by age, and found an increasing risk with age of primary cases for adults (aged ≥ 15 years), while the risk seems to decrease with age for children (aged < 15 years).

Although there is an increasing attack rate and transmission risk of SARS-CoV-2 with age, children are also able to transmit SARS-CoV-2 within the household.

Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.

We aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.

We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.

The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55–1.57 times the level of historical lineages (95% CrI: 1.45–1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03–1.23) with complete immune evasion to 1.39 (95% CrI: 1.26–1.56) for complete cross-protection.

We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Immunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.

We aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.

A multicentre prospective cross-sectional study was undertaken (April–July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.

We included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2–89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).

SARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.

Since the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data.

This study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.

This retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders.

In 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54–78) than the patients with influenza (median 74 years; IQR: 61–84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22–4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00–3.00, p < 0.001) for ICU admission.

Community-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.

Serosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected.

This observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave.

Using an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March–June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases.

Adjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1–1.5) from 27 March–30 April, 1.5% (95% CI: 0.7–2.2) from 26–31 May, and 1.1% (95% CI: 0.8–1.3) from 5–30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March–April (1.3%; 95% CI: 0.2–4.6), in those aged 20–59 years in May (2.1%; 95% CI: 0.8–3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1–2.1). Regional seroprevalence varied, and was highest for Toronto in March–April (0.9%; 95% CI: 0.1–3.1), for Toronto in May (3.2%; 95% CI: 1.0–5.3) and for Toronto (1.5%; 95% CI: 0.9–2.1) and Central East in June (1.5%; 95% CI: 1.0–2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9.

Our results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.