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Antibodies predating infection Immunological memory after infection with seasonal human coronaviruses (hCoVs) may potentially contribute to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ng et al. report that in a cohort of 350 SARS-CoV-2–uninfected individuals, a small proportion had circulating immunoglobulin G (IgG) antibodies that could cross-react with the S2 subunit of the SARS-CoV-2 spike protein (see the Perspective by Guthmiller and Wilson). By contrast, COVID-19 patients generated IgA, IgG, and IgM antibodies that recognized both the S1 and S2 subunits. The anti-S2 antibodies from SARS-CoV-2–uninfected patients showed specific neutralizing activity against both SARS-CoV-2 and SARS-CoV-2 S pseudotypes. A much higher percentage of SARS-CoV-2–uninfected children and adolescents were positive for these antibodies compared with adults. This pattern may be due to the fact that children and adolescents generally have higher hCoV infection rates and a more diverse antibody repertoire, which may explain the age distribution of COVID-19 susceptibility. Science, this issue p. 1339; see also p. 1272, SARS-CoV-2 neutralizing antibodies can be found in some uninfected individuals—predominantly children and adolescents., Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)–reactive antibodies were detectable using a flow cytometry–based method in SARS-CoV-2–uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S–reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2–uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.

The transition from shutdown of elective orthopaedic services to the resumption of pre-COVID-19 activity presents many challenges. These include concerns about patient safety, staff safety, and the viability of health economies. Careful planning is necessary to allow patients to benefit from orthopaedic care in a safe and sustainable manner. Cite this article: Bone Joint J 2020;102-B(7):807–810.

BackgroundCOVID-19 has restricted singing in communal worship. We sought to understand variations in droplet transmission and the impact of wearing face masks.MethodsUsing rapid laser planar imaging, we measured droplets while participants exhaled, said ‘hello’ or ‘snake’, sang a note or ‘Happy Birthday’, with and without surgical face masks. We measured mean velocity magnitude (MVM), time averaged droplet number (TADN) and maximum droplet number (MDN). Multilevel regression models were used.ResultsIn 20 participants, sound intensity was 71 Decibels (dB) for speaking and 85 dB for singing (p85% reduction wearing face masks. Droplet transmission varied widely, particularly for singing. Masks decreased TADN by 99% (pConclusionsWide variation exists for droplet production. This significantly reduced when wearing face masks. Singing during religious worship wearing a face mask appears as safe as exhaling or talking. This has implications for UK public health guidance during the COVID-19 pandemic.

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Background: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. Little is known about the impact their increased infectivity has on transmission within hospitals. Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. Findings: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. Interpretation: Notwithstanding evidence from community studies that the Alpha variant is more transmissible, we find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern. Funding Information: COG-UK HOCI funded by COG-UK consortium. The COG-UK consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. Declaration of Interests: None to declare. Ethics Approval Statement: Ethical approval for the HOCI study was provided by REC 20/EE/0118.

Background: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raise concerns pertinent to the current mass vaccination campaigns and use of monoclonal antibodies. We describe emergence of the variant of concern (VOC) B.1.1.7 in two North Central London (NCL) hospitals including virological characteristics and clinical severity in contemporaneous patients with and without the new variant. The strength of our study is the depth and granularity of clinical data. Methods: SARS-CoV-2 PCR positive samples collected from 9th November 2020 for patients acutely admitted to one of 2 NCL hospitals on or before 20th December 2020 were sequenced and analysed for the presence of VOC-defining mutations. We compared illness severity in those with variant of concern (VOC) and non-VOC infections and conducted supplementary genomic analyses in a cohort of chronically shedding immunocompromised/treated patients. Viral loads were compared by Ct value and sequencing read-depth. Findings: Of 341 successfully sequenced patients, 198 (58%) had VOC infections. There was no evidence of an association with severe disease by lineage (VOC vs non-VOC) in unadjusted analyses (PR 0.97, 95% CI 0.72-1.31), or analyses adjusted for sex, age, comorbidities and ethnicity (aPR 1.07, 95% CI 0.79-1.43). We detected no VOC-defining mutations in immunocompromised/treated patients; viral loads were higher in VOC samples. Interpretation: Despite emerging evidence of increased transmissibility of the VOC, we did not identify an association with severe disease, suggesting the surge in hospitalisations was more likely related to a significant increase in cases overall rather than virus characteristics. Funding Statement: UCLH APDU receives funding from the University College London Hospitals NHS Trust. DF was funded by the i-sense EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (EP/R00529X/1). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The clinical information and SARS-CoV-2 PCR samples were collected as part of routine clinical care. Data were extracted and analysed using permission granted by the NHS REC (IRAS:284088, REC reference:20/HRA/2505).

ObjectivesCOVID-19 is spreading in long-term care facilities with devastating outcomes worldwide, especially for people with chronic health conditions. There is a pressing need to adopt effective measures prevention and containment of in such settings.DesignRetrospective cohort study assessing the effect of enhanced surveillance and early preventative strategies and comparing outcomes for people with severe epilepsy and other comorbiditiesSettingThree long-term care facilities: Chalfont Centre for Epilepsy (CCE), St. Elisabeth (STE), and The Meath (TM) with different models of primary and specialist care involvement, in the United KingdomParticipants286 long-term residents (age range 19–91 years), 740 carers who had been in contact with the residents during the observation period between 16 March and 05 June 2020.InterventionsEarly preventative and infection control measures with identification and isolation of symptomatic cases, with additional enhanced surveillance and isolation of asymptomatic residents and carers at one site (CCE)Main outcome measuresInfection rate for SARS-CoV-2 among residents and carers, asymptomatic rate and case fatality rate, if available.ResultsDuring a 12-week observation period, we identified 29 people (13 residents) who were SARS-CoV-2 positive with confirmed outbreaks amongst residents in two long-term care facilities (CCE, STE). At CCE, two out of 98 residents were symptomatic and tested positive, one of whom died. A further seven individuals testing positive on weekly enhanced surveillance had a completely asymptomatic course. One asymptomatic carer tested positive after contact with confirmed COVID-19 patients in another institution. Since 30 April 2020, during on-site weekly enhanced surveillance all 275 caregivers tested repeatedly negative. At STE, three out of 146 residents were symptomatic and tested positive, a fourth tested positive during hospital admission for symptoms not related to COVID-19. Since April 6, 2020, 105/215 carers presenting with typical symptoms for COVID-19 were tested, of whom 15 tested positive. At TM, testing of symptomatic carers only started from early/mid-April, whilst on-site testing, even of symptomatic residents, was not available until recently.During the observation period, eight of 80 residents were symptomatic but none was tested. Twenty-six of 250 carers were symptomatic and were tested, of whom two tested positive.ConclusionsInfection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic cases are identified through enhanced surveillance at individual and care staff level. We observed a low rate of morbidity and mortality which confirmed that preventative measures with isolation of suspected and confirmed cases of COVID-19 can reduce resident-to-resident and reverse resident-to-carer transmission.

Coronavirus disease 2019 (COVID-19) can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66 of 435 (15%) COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures.

Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.

The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), a respiratory tract infection. The standard molecular diagnostic test is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). Laboratories across the globe face constraints on equipment and reagents during the COVID-19 pandemic. We have developed a simplified qRT-PCR assay that removes the need for an RNA extraction process and can be run on a real-time thermal cycler. The assay uses custom primers and probes, and maintains diagnostic sensitivity within 98.0% compared to the assay run on a high-throughput, random-access automated platform, the Panther Fusion (Hologic). This assay can be used to increase capacity for COVID-19 testing for national programmes worldwide.

While the UK immunisation schedule is a national immunisation policy for the general population, several groups of patients and persons require a different approach to be taken. For example, some groups of patients cannot safely receive certain vaccine because they may be allergic (anaphylaxis) to some vaccine components and some patients cannot receive, e.g. live attenuated vaccines because they are severely immunocompromised. Other patients require additional vaccines to protect them from vaccine preventable diseases because they are immunocompromised in some way, e.g. asplenia. The following groups require special consideration: ● Pregnant women; ● Severely immunocompromised patients; ● Asplenic patients or those with dysfunctional spleens; ● Severe allergy to vaccine components; ● healthcare workers (HCWs); ● Patients with certain chronic medical conditions; ● Morbid obesity; and ● Persons travelling abroad, especially to developing countries. In general, giving vaccines to pregnant women is not recommended due to the potential risk of medicines and vaccines harming the foetus. Specifically, live attenuated vaccines should not be given to pregnant women. It is relatively safer to give inactivated/killed vaccines to pregnant women, but most vaccines can and should be postponed until after delivery. However, in the UK it is recommended that pregnant women receive two particular vaccines during pregnancy in order to protect the mother and foetus from avoidable harm. These are the inactivated influenza vaccine and a vaccine against Bordetella pertussis infection. For these two vaccines, the benefits of vaccination for the pregnant women and the foetus or newborn baby outweigh any theoretical risks of harm. Severely immunocompromised patients should not receive live attenuated vaccines due to a risk of uncontrolled viral replication resulting in clinical disease. Patients who are considered to be severely immunocompromised include: ● Severe primary immunodeficiency, e.g. severe combined immunodeficiency; ● Patients receiving cancer chemotherapy and those within six months of completing chemotherapy; ● Patients who have received a solid organ transplant and are on immunosuppressive therapy; ● Patients who have received a bone marrow transplant until twelve months after all immunosuppressive therapy has stopped; and ● Patients receiving high-dose systemic corticosteroids until at least three months after treatment ends.

There is very little to argue against in the editorial by Stott and colleagues.1 Apart from the climate denier fringe, it is received wisdom that climate change is a real phenomenon, it is caused by human activity, and it is an existential threat to almost all life on Earth. I agree with the response …

Thacker’s comprehensive review of the Wuhan laboratory leak hypothesis makes for uncomfortable reading.1 That a small group of scientists, with (apparently) hitherto undeclared links to the Wuhan Institute of Virology, were able to prevent open minded, critical analysis of the origins of SARS-CoV-2 for much of 2020 is regrettable. Their actions to shut down debate about a possible laboratory incident as a source of SARS-CoV-2 escaping …

I agree with Khunti and colleagues’ well reasoned editorial on why the collective terms black, Asian, and minority ethnic (BAME) and black and minority ethnic (BME) should be abandoned.1 These homogenising terms attempt to group together people who vary greatly …

McCartney makes the controversial claim that “even if the nuclear weapons are never used, they do harm.”1 The whole point of a strategic nuclear deterrent is to deter any enemy from considering a nuclear first strike, a strategy predicated on the concept of mutually assured destruction. The fact that no nuclear weapons have been used in anger since the end of …

I commend The BMJ on its extensive efforts to reduce the environmental impact of its postal distribution.1 It is obvious a lot of thought has gone into the sustainability of the journal throughout each issue’s …

Summary Objectives To determine the prevalence of cryptococcal antigenemia in a UK HIV cohort and compare baseline characteristics of patients with and without cryptococcal antigenemia. Methods Stored sera were retrospectively tested for cryptococcal antigen (CRAG) among newly diagnosed HIV-infected persons with CD4

We are concerned by the General Medical Council’s laissez faire approach to reports of undeclared financial conflicts of interest in the form of financial inducements that may have influenced the referral patterns of UK doctors.1 We are glad that the editorial prompted a response to these serious allegations from the GMC.2 We agree that doctors should make conflicts of interest declarations if these conflicts could affect prescribing and clinical …

We welcome Sadiq Khan’s leadership on air pollution in London. We support all the initiatives that he has launched as mayor of London and his future plans to tackle this major threat to public health.1 But, as he knows, …

The House of Commons Public Accounts Committee recently reported that public sector whistleblowers have received “shocking” treatment from public sector organisations, including NHS ones.1 2 The Francis Inquiry concluded that NHS staff have a “duty of candour” to raise patient safety and other concerns,3 …

We agree with Ramanathan and Haines about the harmful effects of short lived climate pollutants and carbon dioxide on climate change.1 We also agree that if unchecked, climate change poses a grave threat to global public health. Although we concur that healthcare professionals should be active …

Wellesley stated that only 59% of relatives of organ donors give consent for organ donation to go ahead1—a disconcertingly low proportion. It may be standard practice to ask relatives to …

To assess the feasibility and acceptability of delivering a human papillomavirus (HPV) vaccine to adolescent girls.Prospective cohort study.36 secondary schools in two primary care trusts in Greater Manchester, United Kingdom.2817 schoolgirls in year 8 (12 and 13 year olds).Delivery of the bivalent vaccine at 0, 1, and 6 months over one school year.Vaccine uptake for doses 1 and 2 of a three dose schedule.Vaccine uptake was 70.6% (1989/2817) for the first dose and 68.5% (1930/2817) for the second dose. Uptake was significantly lower in schools with a higher proportion of ethnic minority girls (P0.001 for trend) or higher proportion of girls entitled to free school meals (P=0.029 for trend). The main reason for parents' refusal of vaccination was insufficient information about the vaccine and its long term safety. Maintaining the vaccine schedule was challenging as 16.3% (dose 1) and 23.6% (dose 2) of girls missed their vaccination day and had to be offered alternative appointments. No serious adverse events were reported.Delivery of the first two doses of HPV vaccine to adolescent schoolgirls is encouraging, but the success of the vaccination programme depends on high coverage for the third dose.

Mozaffarian and colleagues propose an interesting concept of “soft healing,” as opposed to “hard healing,” which is what goes on in primary care (GP practices) and secondary care (NHS hospitals).1 Although they refer to the limits of “hard power” they do not mention the shortcomings of “soft power.” We think it …

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