Background There are few primary care studies of the COVID-19 pandemic. We aimed to identify demographic and clinical risk factors for testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre primary care network. MethodsWe analysed routinely collected, pseudonymised data for patients in the RCGP Research and Surveillance Centre primary care sentinel network who were tested for SARS-CoV-2 between Jan 28 and April 4, 2020. We used multivariable logistic regression models with multiple imputation to identify risk factors for positive SARS-CoV-2 tests within this surveillance network. Findings We identified 3802 SARS-CoV-2 test results, of which 587 were positive. In multivariable analysis, male sex was independently associated with testing positive for SARS-CoV-2 (296 [18•4%] of 1612 men vs 291 [13•3%] of 2190 women; adjusted odds ratio [OR] 1•55, 95% CI 1•27-1•89). Adults were at increased risk of testing positive for SARS-CoV-2 compared with children, and people aged 40-64 years were at greatest risk in the multivariable model (243 [18•5%] of 1316 adults aged 40-64 years vs 23 [4•6%] of 499 children; adjusted OR 5•36, 95% CI 3•28-8•76). Compared with white people, the adjusted odds of a positive test were greater in black people (388 [15•5%] of 2497 white people vs 36 [62•1%] of 58 black people; adjusted OR 4•75, 95% CI 2•65-8•51). People living in urban areas versus rural areas (476 [26•2%] of 1816 in urban areas vs 111 [5•6%] of 1986 in rural areas; adjusted OR 4•59, 95% CI 3•57-5•90) and in more deprived areas (197 [29•5%] of 668 in most deprived vs 143 [7•7%] of 1855 in least deprived; adjusted OR 2•03, 95% CI 1•51-2•71) were more likely to test positive. People with chronic kidney disease were more likely to test positive in the adjusted analysis (68 [32•9%] of 207 with chronic kidney disease vs 519 [14•4%] of 3595 without; adjusted OR 1•91, 95% CI 1•31-2•78), but there was no significant association with other chronic conditions in that analysis. We found increased odds of a positive test among people who are obese (142 [20•9%] of 680 people with obesity vs 171 [13•2%] of 1296 normal-weight people; adjusted OR 1•41, 95% CI 1•04-1•91). Notably, active smoking was linked with decreased odds of a positive test result (47 [11•4%] of 413 active smokers vs 201 [17•9%] of 1125 non-smokers; adjusted OR 0•49, 95% CI 0•34-0•71). Interpretation A positive SARS-CoV-2 test result in this primary care cohort was associated with similar risk factors as observed for severe outcomes of COVID-19 in hospital settings, except for smoking. We provide evidence of potential sociodemographic factors associated with a positive test, including deprivation, population density, ethnicity, and chronic kidney disease. Funding Wellcome Trust.

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

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Thanks to: the patients who consent to provide respiratory viral swabs and other samples, and for allowing (not opting out of) data sharing; the practices who agree to contribute data; the collaboration of GP computerised medical record systems (EMIS, INPS, and TPP); data extraction providers (Apollo) for their expertise; and public health reference laboratories.

The “Spanish influenza pandemic swept the globe in the autumn and winter of 1918–19, and resulted in the deaths of approximately 40 million people. Clinically, epidemiologically, and pathologically, the disease was remarkably uniform, which suggests that similar viruses were causing disease around the world. To assess the homogeneity of the 1918 pandemic influenza virus, partial hemagglutinin gene sequences have been determined for five cases, including two newly identified samples from London, United Kingdom. The strains show 98.9% to 99.8% nucleotide sequence identity. One of the few differences between the strains maps to the receptor-binding site of hemagglutinin, suggesting that two receptor-binding configurations were co-circulating during the pandemic. The results suggest that in the early stages of an influenza A pandemic, mutations that occur during replication do not become fixed so that a uniform “consensus” strain circulates for some time.

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

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The influenza virus continues to pose a significant threat to public health throughout the world. Current avian influenza outbreaks in humans have heightened the need for improved surveillance and planning. Despite recent advances in the development of vaccines and antiviral drugs, seasonal epidemics of influenza continue to contribute significantly to general practitioner workloads, emergency hospital admissions, and deaths. In this paper we review data produced by the Royal College of General Practitioners Weekly Returns Service, a sentinel general practice surveillance network that has been in operation for over 40 years in England and Wales. We show a gradually decreasing trend in the incidence of respiratory illness associated with influenza virus infection (influenza-like illness; ILI) over the 40 years and speculate that there are limits to how far an existing virus can drift and yet produce substantial new epidemics. The burden of disease caused by influenza presented to general practitioners varies considerably by age in each winter. In the pandemic winter of 1969/70 persons of working age were most severely affected; in the serious influenza epidemic of 1989/90 children were particularly affected; in the millennium winter (in which the NHS was severely stretched) ILI was almost confined to adults, especially the elderly. Serious confounders from infections due to respiratory syncytial virus are discussed, especially in relation to assessing influenza vaccine effectiveness. Increasing pressure on hospitals during epidemic periods are shown and are attributed to changing patterns of health-care delivery.