Coronavirus disease (COVID-19)

Population-level mathematical models of outbreaks typically assume that disease transmission is not impacted by population density (‘frequency-dependent’) or that it increases linearly with density (‘density-dependent’).

We sought evidence for the role of population density in SARS-CoV-2 transmission.

Using COVID-19-associated mortality data from England, we fitted multiple functional forms linking density with transmission. We projected forwards beyond lockdown to ascertain the consequences of different functional forms on infection resurgence.

COVID-19-associated mortality data from England show evidence of increasing with population density until a saturating level, after adjusting for local age distribution, deprivation, proportion of ethnic minority population and proportion of key workers among the working population. Projections from a mathematical model that accounts for this observation deviate markedly from the current status quo for SARS-CoV-2 models which either assume linearity between density and transmission (30% of models) or no relationship at all (70%). Respectively, these classical model structures over- and underestimate the delay in infection resurgence following the release of lockdown.

Identifying saturation points for given populations and including transmission terms that account for this feature will improve model accuracy and utility for the current and future pandemics.

The COVID-19 pandemic has put healthcare workers (HCW) at significant risk. Presence of antibodies can confirm prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

This study investigates the prevalence of IgA and IgG antibodies against SARS-CoV-2 in HCW.

Performance of IgA and IgG antibody ELISA assays were initially evaluated in positive and negative SARS-CoV-2 serum samples. IgA and IgG antibodies against SARS-CoV-2 were measured in 428 asymptomatic HCW. We assessed the risk of two groups: HCW with high exposure risk outside work (HROW) residing in areas where COVID-19 was endemic (n = 162) and HCW with high exposure risk at work (HRAW) in a COVID-19 intensive care unit (ICU) (n = 97).

Sensitivities of 80% and 81.2% and specificities of 97.2% and 98% were observed for IgA and IgG antibodies, respectively. Of the 428 HCW, three were positive for IgG and 27 for IgA. Only 3/27 (11%) IgA-positive HCW had IgG antibodies compared with 50/62 (81%) in a group of previous SARS-CoV-2-PCR-positive individuals. Consecutive samples from IgA-positive HCW demonstrated IgA persistence 18–83 days in 12/20 samples and IgG seroconversion in 1/20 samples. IgA antibodies were present in 8.6% of HROW and 2% of HRAW.

SARS-CoV-2 exposure may lead to asymptomatic transient IgA response without IgG seroconversion. The significance of these findings needs further study. Out of work exposure is a possible risk of SARS-CoV-2 infection in HCW and infection in HCW can be controlled if adequate protective equipment is implemented.

Many countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity.

We aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours.

We conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020.

Among the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%.

The lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

Robust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.

To conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.

Using a cross-sectional study design, we selected population samples from individuals aged 12–69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age–sex distribution, and by simple random sampling within age–sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.

Participation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05–4.53) and 0.58% (95% CI: 0.18–1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13–2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772–85,176) people aged 12–69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0–4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.

The majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June–July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.

Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic.

We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy.

We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA).

Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area.

Continuous monitoring of clinical performance within more clearly defined target populations is needed.

Numerous CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) are offered in Europe, several of them with unconfirmed quality claims.

We performed an independent head-to-head evaluation of the sensitivity of SARS-CoV-2 Ag RDT offered in Germany.

We addressed the sensitivity of 122 Ag RDT in direct comparison using a common evaluation panel comprised of 50 specimens. Minimum sensitivity of 75% for panel specimens with a PCR quantification cycle (Cq) ≤ 25 was used to identify Ag RDT eligible for reimbursement in the German healthcare system.

The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with Cq ≤ 25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which failed completely. Some RDT exhibited high sensitivity, e.g. 97.5 % for Cq < 30.

This comparative evaluation succeeded in distinguishing less sensitive from better performing Ag RDT. Most of the evaluated Ag RDT appeared to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

Many countries have attempted to mitigate and control COVID-19 through non-pharmaceutical interventions, particularly with the aim of reducing population movement and contact. However, it remains unclear how the different control strategies impacted the local phylodynamics of the causative SARS-CoV-2 virus.

We aimed to assess the duration of chains of virus transmission within individual countries and the extent to which countries exported viruses to their geographical neighbours.

We analysed complete SARS-CoV-2 genomes to infer the relative frequencies of virus importation and exportation, as well as virus transmission dynamics, in countries of northern Europe. We examined virus evolution and phylodynamics in Denmark, Finland, Iceland, Norway and Sweden during the first year of the COVID-19 pandemic.

The Nordic countries differed markedly in the invasiveness of control strategies, which we found reflected in transmission chain dynamics. For example, Sweden, which compared with the other Nordic countries relied more on recommendation-based rather than legislation-based mitigation interventions, had transmission chains that were more numerous and tended to have more cases. This trend increased over the first 8 months of 2020. Together with Denmark, Sweden was a net exporter of SARS-CoV-2. Norway and Finland implemented legislation-based interventions; their transmission chain dynamics were in stark contrast to their neighbouring country Sweden.

Sweden constituted an epidemiological and evolutionary refugium that enabled the virus to maintain active transmission and spread to other geographical locations. Our analysis reveals the utility of genomic surveillance where monitoring of active transmission chains is a key metric.

Detailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic.

We aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany.

Between March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset.

Median age was 35 years (range 18–74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7–14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively.

Our study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.

Up-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions.

We estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign.

We conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).

Among 3,355 individuals (54.1% women; 20.8% aged < 18 years and 13.4% aged ≥ 65 years), 2,161 (64.4%) had anti-S antibodies and 906 (27.0%) had anti-N antibodies. The total seroprevalence was 66.1% (95% credible interval (CrI): 64.1–68.0). We estimated that 29.9% (95% Crl: 28.0–31.9) of the population developed antibodies after infection; the rest having developed antibodies via vaccination. Seroprevalence estimates differed markedly across age groups, being lowest among children aged 0–5 years (20.8%; 95% Crl: 15.5–26.7) and highest among older adults aged ≥ 75 years (93.1%; 95% Crl: 89.6–96.0). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with higher educational level.

Most of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.

The occupational risk of COVID-19 may be different in the first versus second epidemic wave.

To study whether employees in occupations that typically entail close contact with others were at higher risk of SARS-CoV-2 infection and COVID-19-related hospitalisation during the first and second epidemic wave before and after 18 July 2020, in Norway.

We included individuals in occupations working with patients, children, students, or customers using Standard Classification of Occupations (ISCO-08) codes. We compared residents (3,559,694 on 1 January 2020) in such occupations aged 20–70 years (mean: 44.1; standard deviation: 14.3 years; 51% men) to age-matched individuals in other professions using logistic regression adjusted for age, sex, birth country and marital status.

Nurses, physicians, dentists and physiotherapists had 2–3.5 times the odds of COVID-19 during the first wave when compared with others of working age. In the second wave, bartenders, waiters, food counter attendants, transport conductors, travel stewards, childcare workers, preschool and primary school teachers had ca 1.25–2 times the odds of infection. Bus, tram and taxi drivers had an increased odds of infection in both waves (odds ratio: 1.2–2.1). Occupation was of limited relevance for the odds of severe infection, here studied as hospitalisation with the disease.

Our findings from the entire Norwegian population may be of relevance to national and regional authorities in handling the epidemic. Also, we provide a knowledge foundation for more targeted future studies of lockdowns and disease control measures.