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Comparison and correlation of commercial SARS-CoV-2 real-time-PCR assays, Ireland, June 2020
More LessWe report the performance of a variety of commercially available SARS-CoV-2 PCR kits, used in several different sites across Ireland to determine if Ct values across platforms are comparable. We also investigate whether a Ct value, a surrogate for calculated viral loads in the absence of viral culture of > 34 can be used to exclude SARS-CoV-2 infection and its complications. We found a variation in Ct values from different assays for the same calculated viral load; this should be taken into consideration for result interpretation.
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Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021
More LessThe BNT162b2 mRNA COVID-19 vaccine showed high efficacy in clinical trials but observational data from populations not included in trials are needed. We describe immunogenicity 21 days post-dose 1 among 514 Israeli healthcare workers by age, ethnicity, sex and prior COVID-19 infection. Immunogenicity was similar by ethnicity and sex but decreased with age. Those with prior infection had antibody titres one magnitude order higher than naïve individuals regardless of the presence of detectable IgG antibodies pre-vaccination.
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Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020
More LessAnna Jeffery-Smith , Nalini Iyanger , Sarah V Williams , J Yimmy Chow , Felicity Aiano , Katja Hoschler , Angie Lackenby , Joanna Ellis , Steven Platt , Shahjahan Miah , Kevin Brown , Gayatri Amirthalingam , Monika Patel , Mary E Ramsay , Robin Gopal , Andre Charlett , Shamez N Ladhani and Maria ZambonTwo London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7–99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8–99.3%) using a penalised logistic regression model.
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Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020
More LessHelle Daugaard Larsen , Jannik Fonager , Frederikke Kristensen Lomholt , Tine Dalby , Guido Benedetti , Brian Kristensen , Tinna Ravnholt Urth , Morten Rasmussen , Ria Lassaunière , Thomas Bruun Rasmussen , Bertel Strandbygaard , Louise Lohse , Manon Chaine , Karina Lauenborg Møller , Ann-Sofie Nicole Berthelsen , Sarah Kristine Nørgaard , Ute Wolff Sönksen , Anette Ella Boklund , Anne Sofie Hammer , Graham J. Belsham , Tyra Grove Krause , Sten Mortensen , Anette Bøtner , Anders Fomsgaard and Kåre MølbakIn June–November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25–30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.
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Attitudes of healthcare workers towards COVID-19 vaccination: a survey in France and French-speaking parts of Belgium and Canada, 2020
More LessIn October and November 2020, we conducted a survey of 2,678 healthcare workers (HCWs) involved in general population immunisation in France, French-speaking Belgium and Quebec, Canada to assess acceptance of future COVID-19 vaccines (i.e. willingness to receive or recommend these) and its determinants. Of the HCWs, 48.6% (n = 1,302) showed high acceptance, 23.0% (n = 616) moderate acceptance and 28.4% (n = 760) hesitancy/reluctance. Hesitancy was mostly driven by vaccine safety concerns. These must be addressed before/during upcoming vaccination campaigns.
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Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020
More LessAntonin Bal , Gregory Destras , Alexandre Gaymard , Karl Stefic , Julien Marlet , Sébastien Eymieux , Hadrien Regue , Quentin Semanas , Constance d’Aubarede , Geneviève Billaud , Frédéric Laurent , Claudia Gonzalez , Yahia Mekki , Martine Valette , Maude Bouscambert , Catherine Gaudy-Graffin , Bruno Lina , Florence Morfin , Laurence Josset and the COVID-Diagnosis HCL Study GroupWe report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69–V70 (ΔH69/ΔV70), identified in certain SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.
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Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020
More LessSarah K. Nørgaard , Lasse S. Vestergaard , Jens Nielsen , Lukas Richter , Daniela Schmid , Natalia Bustos , Toon Braye , Maria Athanasiadou , Theodore Lytras , Gleb Denissov , Tatjana Veideman , Oskari Luomala , Teemu Möttönen , Anne Fouillet , Céline Caserio-Schönemann , Matthias an der Heiden , Helmut Uphoff , Kassiani Gkolfinopoulou , Janos Bobvos , Anna Paldy , Naama Rotem , Irene Kornilenko , Lisa Domegan , Joan O’Donnell , Francesca De Donato , Matteo Scortichini , Patrick Hoffmann , Telma Velez , Kathleen England , Neville Calleja , Liselotte van Asten , Lenny Stoeldraijer , Richard A White , Trine H Paulsen , Susana P da Silva , Ana P Rodrigues , Petra Klepac , Metka Zaletel , Mario Fafangel , Amparo Larrauri , Inmaculada León , Ahmed Farah , Ilias Galanis , Christoph Junker , Damir Perisa , Mary Sinnathamby , Nick Andrews , Mark G O'Doherty , David Irwin , Sharon Kennedy , Jim McMenamin , Cornelia Adlhoch , Nick Bundle , Pasi Penttinen , Jukka Pukkila , Richard Pebody , Tyra G Krause and Kåre MølbakThe European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.
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Control of a COVID-19 outbreak in a nursing home by general screening and cohort isolation in Germany, March to May 2020
More LessElderly care facilities have become a major focus of coronavirus disease (COVID-19) control. Here, we describe an outbreak of COVID-19 in a nursing home in Germany from 8 March to 4 May 2020 (58 days), and the effect of an intervention of general screening and cohort isolation. COVID-19 cases among residents and staff were recorded on a daily basis from the first positive SARS-CoV-2 test from a resident on 8 March 2020, until 4 May 2020 when the last staff member was classified COVID-19 negative. Eighty of 160 residents (50%) and 37 of 135 staff members (27%) tested positive for SARS-CoV-2. Twenty-seven of the 80 residents were asymptomatic but tested positive during the first general screening. Cohort isolation of SARS-CoV-2 positive residents by reorganising the facility proved to be a major effort. After the intervention, four further asymptomatic residents tested positive in follow-up screenings within a period of 6 days, and were possibly infected prior to the intervention. Thereafter, no further infections were recorded among residents. The described outbreak was controlled by implementing general screening and rigorous cohort isolation, providing a blueprint for similar facilities.
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Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020
More LessTwo new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70, circulating mainly between early September and mid-November, was 10% (6–13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion Δ69/Δ70, circulating since late September, was 75% (70–80%) more transmissible than the 501N lineage.
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Impact of mass testing during an epidemic rebound of SARS-CoV-2: a modelling study using the example of France
More LessWe used a mathematical model to evaluate the impact of mass testing in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Under optimistic assumptions, one round of mass testing may reduce daily infections by up to 20–30%. Consequently, very frequent testing would be required to control a quickly growing epidemic if other control measures were to be relaxed. Mass testing is most relevant when epidemic growth remains limited through a combination of interventions.
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Minimal transmission of SARS-CoV-2 from paediatric COVID-19 cases in primary schools, Norway, August to November 2020
More LessAn intense debate on school closures to control the COVID-19 pandemic is ongoing in Europe. We prospectively examined transmission of SARS-CoV-2 from confirmed paediatric cases in Norwegian primary schools between August and November 2020. All in-school contacts were systematically tested twice during their quarantine period. With preventive measures implemented in schools, we found minimal child-to-child (0.9%, 2/234) and child-to-adult (1.7%, 1/58) transmission, supporting that under 14 year olds are not the drivers of SARS-CoV-2 transmission.
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Early assessment of the impact of mitigation measures to control COVID-19 in 22 French metropolitan areas, October to November 2020
More LessGuillaume Spaccaferri , Sophie Larrieu , Jérôme Pouey , Clémentine Calba , Thomas Benet , Cécile Sommen , Daniel Lévy-Bruhl , Sabira Smaili , Didier Che , Laurent Filleul , Céline Caserio-Schönemann , Fatima Ait-El-Belghiti , Sylvie Haeghebaert , Jean-Claude Desenclos , Laëtitia Huiart , Anne Laporte and Patrick RollandIn France, measures including curfew and lockdown were implemented to control the COVID-19 pandemic second wave in 2020. This study descriptively assesses their possible effects, also relative to their timing. A considerable decrease in incidence of COVID-19 cases and hospital admissions was observed 7 to 10 days after mitigation measures were put in place, occurring earlier in metropolitan areas which had implemented these first. This temporal coincidence suggests the measures’ positive impact, consistent with international experiences.
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Estimating the false-negative test probability of SARS-CoV-2 by RT-PCR
More LessBackgroundReverse-transcription PCR (RT-PCR) assays are used to test for infection with the SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives are possible depending on swab type and time since symptom onset.
AimTo determine how the probability of obtaining a false-negative test in infected patients is affected by time since symptom onset and swab type.
MethodsWe used generalised additive mixed models to analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once.
ResultsThe probability of a positive test decreased with time since symptom onset, with oropharyngeal (OP) samples less likely to yield a positive result than nasopharyngeal (NP) samples. The probability of incorrectly identifying an uninfected individual due to a false-negative test was considerably reduced if negative tests were repeated 24 hours later. For a small false-positive test probability (<0.5%), the true number of infected individuals was larger than the number of positive tests. For a higher false-positive test probability, the true number of infected individuals was smaller than the number of positive tests.
ConclusionNP samples are more sensitive than OP samples. The later an infected individual is tested after symptom onset, the less likely they are to test positive. This has implications for identifying infected patients, contact tracing and discharging convalescing patients who are potentially still infectious.
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Evaluation of lockdown effect on SARS-CoV-2 dynamics through viral genome quantification in waste water, Greater Paris, France, 5 March to 23 April 2020
More LessS Wurtzer , V Marechal , JM Mouchel , Y Maday , R Teyssou , E Richard , JL Almayrac and L MoulinIntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease (COVID-19). People infected with SARS-CoV-2 may exhibit no or mild non-specific symptoms; thus, they may contribute to silent circulation of the virus among humans. Since SARS-CoV-2 RNA can be detected in stool samples, monitoring SARS-CoV-2 RNA in waste water (WW) has been proposed as a complementary tool to investigate virus circulation in human populations.
AimTo test if the quantification of SARS-CoV-2 genomes in WW correlates with the number of symptomatic or non-symptomatic carriers.
MethodWe performed a time-course quantitative analysis of SARS-CoV-2 by RT-qPCR in raw WW samples collected from several major WW treatment plants in Greater Paris. The study period was 5 March to 23 April 2020, including the lockdown period in France (from 17 March).
ResultsWe showed that the increase of genome units in raw WW accurately followed the increase of human COVID-19 cases observed at the regional level. Of note, the viral genome could be detected before the epidemic grew massively (around 8 March). Equally importantly, a marked decrease in the quantities of genome units was observed concomitantly with the reduction in the number of new COVID-19 cases, 29 days following the lockdown.
ConclusionThis work suggests that a quantitative monitoring of SARS-CoV-2 genomes in WW could generate important additional information for improved monitoring of SARS-CoV-2 circulation at local or regional levels and emphasises the role of WW-based epidemiology.
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Occupation- and age-associated risk of SARS-CoV-2 test positivity, the Netherlands, June to October 2020
More LessHigh coronavirus incidence has prompted the Netherlands to implement a second lockdown. To elucidate the epidemic’s development preceding this second wave, we analysed weekly test positivity in public test locations by population subgroup between 1 June and 17 October 2020. Hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation. Workers in childcare, education and healthcare showed lower test positivity.
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The first wave of the COVID-19 pandemic in Spain: characterisation of cases and risk factors for severe outcomes, as at 27 April 2020
More LessBackgroundThe first wave of the coronavirus disease (COVID-19) pandemic spread rapidly in Spain, one of Europe’s most affected countries. A national lockdown was implemented on 15 March 2020.
AimTo describe reported cases and the impact of national lockdown, and to identify disease severity risk factors.
MethodsNational surveillance data were used to describe PCR-confirmed cases as at 27 April 2020. We compared case characteristics by severity categories (hospitalisation, admission to intensive care unit (ICU), death) and identified severity risk factors using multivariable regression.
ResultsThe epidemic peaked on 20 March. Of 218,652 COVID-19 cases, 45.4% were hospitalised, 4.6% were admitted to ICU and 11.9% died. Among those who died, 94.8% had at least one underlying disease. Healthcare workers (HCWs) represented 22.9% of cases. Males were more likely to have severe outcomes than females. Cardiovascular disease was a consistent risk factor. Patients with pneumonia had higher odds of hospitalisation (odds ratio (OR): 26.63; 95% confidence interval (CI): 25.03–28.33). The strongest predictor of death was age ≥ 80 years (OR: 28.4; 95% CI: 19.85–40.78). Among underlying diseases, chronic renal disease had highest odds of death (OR: 1.47; 95% CI: 1.29–1.68).
ConclusionsCOVID-19 case numbers began declining 6 days after the national lockdown. The first wave of the COVID-19 pandemic in Spain had a severe impact on elderly people. Patients with cardiovascular or renal conditions were at higher risk for severe outcomes. A high proportion of cases were HCWs. Enhanced surveillance and control measures in these subgroups are crucial during future COVID-19 waves.
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Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review
More LessBackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.
AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.
MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.
Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75–1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32–2.27; OR: 0.39; 95% CI: 0.18–0.84 and OR: 0.61; 95% CI: 0.45–0.85 for cohort, case–control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48–1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.
ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6–15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.
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Epidemiological characteristics of COVID-19 cases and estimates of the reproductive numbers 1 month into the epidemic, Italy, 28 January to 31 March 2020
More LessFlavia Riccardo , Marco Ajelli , Xanthi D Andrianou , Antonino Bella , Martina Del Manso , Massimo Fabiani , Stefania Bellino , Stefano Boros , Alberto Mateo Urdiales , Valentina Marziano , Maria Cristina Rota , Antonietta Filia , Fortunato D'Ancona , Andrea Siddu , Ornella Punzo , Filippo Trentini , Giorgio Guzzetta , Piero Poletti , Paola Stefanelli , Maria Rita Castrucci , Alessandra Ciervo , Corrado Di Benedetto , Marco Tallon , Andrea Piccioli , Silvio Brusaferro , Giovanni Rezza , Stefano Merler , Patrizio Pezzotti and the COVID-19 working groupBackgroundOn 20 February 2020, a locally acquired coronavirus disease (COVID-19) case was detected in Lombardy, Italy. This was the first signal of ongoing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the country. The number of cases in Italy increased rapidly and the country became the first in Europe to experience a SARS-CoV-2 outbreak.
AimOur aim was to describe the epidemiology and transmission dynamics of the first COVID-19 cases in Italy amid ongoing control measures.
MethodsWe analysed all RT-PCR-confirmed COVID-19 cases reported to the national integrated surveillance system until 31 March 2020. We provide a descriptive epidemiological summary and estimate the basic and net reproductive numbers by region.
ResultsOf the 98,716 cases of COVID-19 analysed, 9,512 were healthcare workers. Of the 10,943 reported COVID-19-associated deaths (crude case fatality ratio: 11.1%) 49.5% occurred in cases older than 80 years. Male sex and age were independent risk factors for COVID-19 death. Estimates of R0 varied between 2.50 (95% confidence interval (CI): 2.18–2.83) in Tuscany and 3.00 (95% CI: 2.68–3.33) in Lazio. The net reproduction number Rt in northern regions started decreasing immediately after the first detection.
ConclusionThe COVID-19 outbreak in Italy showed a clustering onset similar to the one in Wuhan, China. R0 at 2.96 in Lombardy combined with delayed detection explains the high case load and rapid geographical spread. Overall, Rt in Italian regions showed early signs of decrease, with large diversity in incidence, supporting the importance of combined non-pharmacological control measures.
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Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020
More LessCharlotte Kaeuffer , Coralie Le Hyaric , Thibaut Fabacher , Joy Mootien , Benjamin Dervieux , Yvon Ruch , Antonin Hugerot , Yves-Jean Zhu , Valentin Pointurier , Raphael Clere-Jehl , Valentin Greigert , Loic Kassegne , Nicolas Lefebvre , Floriane Gallais , Covid Alsace Study Group , Nicolas Meyer , Yves Hansmann , Olivier Hinschberger and François DanionBackgroundIn March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization.
AimOur objective was to identify risk factors predictive of severe disease and death in France.
MethodsIn this prospective cohort study, we included patients ≥ 18 years old with confirmed COVID-19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation.
ResultsAmong 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20–100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI ≥ 25 kg/m2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase; 95% CrI (credible interval): 1.0–1.2), male sex (OR: 2.1; 95% CrI: 1.5–2.8), BMI of 25–29.9 kg/m2 (OR: 1.8; 95% CrI: 1.2–2.7) or ≥ 30 (OR: 2.2; 95% CrI: 1.5–3.3), dyspnoea (OR: 2.5; 95% CrI: 1.8–3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase; 95% CrI: 2.1–3.4), male sex (OR: 1.7; 95% CrI: 1.1–2.7), immunosuppression (OR: 3.8; 95% CrI: 1.6–7.7), diabetes (OR: 1.7; 95% CrI: 1.0–2.7), chronic kidney disease (OR: 2.3; 95% CrI: 1.3–3.9), dyspnoea (OR: 2.1; 95% CrI: 1.2–3.4) and inflammatory parameters.
ConclusionsOverweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management.
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