A cross-sectional national investigation of COVID-19 outbreaks in nurseries during rapid spread of the Alpha (B.1.1.7) variant of SARS- CoV-2 in England (preprint)

Background: In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries and assess the risk of SARS-CoV-2 infection and incidence rates in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. Methods This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. Results 324 nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, incidence rates were lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest incidence rate when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and incidence rates were higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in

Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design (preprint)

Background: The potential impact of COVID-19 alongside influenza on morbidity, mortality and health service capacity is a major concern as the Northern Hemisphere winter approaches. This study investigates the interaction between influenza and COVID-19 during the latter part of the 2019-20 influenza season in England. Methods: Individuals tested for influenza and SARS-CoV-2 were extracted from national surveillance systems between 20/01/2020 and 25/04/2020. To estimate influenza infection on the risk of SARS-CoV-2 infection, univariable and multivariable analyses on the odds of SARS-CoV-2 in those who tested positive for influenza compared to those who tested negative for influenza. To assess whether a coinfection was associated with severe SARS-CoV-2 outcome, univariable and multivariable analyses on the odds of death adjusted for age, sex, ethnicity, comorbidity and coinfection status. Findings: The risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. Patients with a coinfection had a risk of death of 5.92 (95% CI, 3.21-10.91) times greater than among those with neither influenza nor SARS-CoV-2 suggesting possible synergistic effects in coinfected individuals. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Interpretation: Cocirculation of these viruses could have a significant impact on morbidity, mortality and health service demand. Testing for influenza alongside SARS-CoV-2 and maximising influenza vaccine uptake should be prioritised to mitigate these risks.

Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles (preprint)

The recently ermerging disease COVID-19 is caused by the new SARS-CoV-2 virus first detected in the city of Wuhan, China. From there it has been rapidly spreading inside and outside China. With initial death rates around 4%, COVID-19 patients at longer distances from Wuhan showed reduced mortality as was previously observed for the SARS coronavirus. However, the new coronavirus spreads more strongly, as it sheds long before onset of symptoms or may be transmitted by people without symptoms. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here we demonstrate that recombinantly expressed receptor binding domain (RBD) of the spike protein homologous to SARS binds to ACE2, the viral receptor. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro.

Estimating the case fatality ratio of the COVID-19 epidemic in China (preprint)

Background: Corona Virus Disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China since late December 2019. Crude case fatality ratio (CFR) with dividing the number of known deaths by the number of confirmed cases does not represent the true CFR and might be off by orders of magnitude. We aim to provide a precise estimate of the CFR of COVID-19 using statistical models at the early stage of the epidemic. Methods: We extracted data from the daily released epidemic report published by the National Health Commission P. R. China from 20 Jan 2020, to 1 March 2020. Competing risk model was used to obtain the cumulative hazards for death, cure, and cure-death hazard ratio. Then the CFR was estimated based on the slope of the last piece in joinpoint regression model, which reflected the most recent trend of the epidemic. Results: As of 1 March 2020, totally 80,369 cases were diagnosed as COVID-19 in China. The CFR of COVID-19 were estimated to be 70.9% (95% CI: 66.8%-75.6%) during Jan 20-Feb 2, 20.2% (18.6%-22.1%) during Feb 3-14, 6.9% (6.4%-7.4%) during Feb 15-23, 1.5% (1.4%-1.6%) during Feb 24-March 1 in Hubei province, and 20.3% (17.0%-25.3%) during Jan 20-28, 1.9% (1.8%-2.1%) during Jan 29-Feb 12, 0.9% (0.8%-1.1%) during Feb 13-18, 0.4% (0.4%-0.5%) during Feb 19-March 1 in other areas of China, respectively. Conclusions: Based on analyses of public data, we found that the CFR in Hubei was much higher than that of other regions in China, over 3 times in all estimation. The CFR would follow a downwards trend based on our estimation from recently released data. Nevertheless, at early stage of outbreak, CFR estimates should be viewed cautiously because of limited data source on true onset and recovery time.

Epidemic size of novel coronavirus-infected pneumonia in the Epicenter Wuhan: using data of five-countries' evacuation action (preprint)

Background: Since late December 2019, novel coronavirus-infected pneumonia (NCP) emerged in Wuhan, Hubei province, China. Meanwhile, NCP rapidly spread from China to other countries, and several countries' government rush to evacuate their citizens from Wuhan. We analyzed the infection rate of the evacuees and extrapolated the results in Wuhan's NCP incidence estimation. Methods: We collected the total number and confirmed cases of 2019-nCov infection in the evacuation of Korea, Japan, Germany, Singapore, and France and estimated the infection rate of the 2019 novel coronavirus (2019-nCov) among people who were evacuated from Wuhan with a meta-analysis. NCP incidence of Wuhan was indirectly estimated based on data of evacuation. Results: From Jan 29 to Feb 2, 2020, 1916 people have been evacuated from Wuhan, among them 17 have been confirmed 2019-nCov infected. The infection rate is estimated to be 1.1% (95% CI 0.4%-3.1%) using one group meta-analysis method with random effect model. We then estimated that almost 110,000 (95% CI: 40,000-310,000) people were infected with 2019-nCov in Wuhan around Feb 2, 2020, assuming the infection risk of evacuees is close to Chinese citizens in Wuhan. Conclusions: At the beginning of the outbreak, incidence of NCP may be vastly underestimated. Our result emphasizes that 2019-nCov has proposed a huge public health threats in Wuhan. We need to respond more rapidly, take large-scale public health interventions and draconian measures to limiting population mobility and control the epidemic.