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Background COVID-19 vaccines are protective against disease. Pregnant women benefit from vaccination as they are at higher risk of poor maternal and neonatal outcomes following infection. Methods Following regulatory approval of two COVID-19 vaccines in the United Kingdom, a rapid national study of vaccination in pregnancy was instituted using three existing safety surveillance platforms: UKOSS, UKTIS and VIP. This preliminary report describes the data collected up to the 15th June 2021. Results There were 971 reports of COVID-19 vaccination in the UKOSS/UKTIS ( n = 493) and VIP ( n = 478) monitoring systems describing 908 individual pregnancies. Pfizer-BioNTech mRNA vaccination was most common ( n = 501, 55.2%), most women were vaccinated in their second or third trimester ( n = 566, 62.3%), and were mainly vaccinated due to occupational infection risk ( n = 577, 63.5%). Conclusion Obstetric outcome data will be obtained by December 2021. However, women should not delay vaccination whilst awaiting further safety data to emerge.

Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England.In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets.Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection.The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes.UK Health Security Agency.

Background: Several studies have reported post-COVID-19 fatigue in the general population, but none explored post-COVID-19 fatigue among pregnant women. The objectives of this study were to determine the prevalence over time, duration and risk factors of post-viral fatigue among pregnant women infected with SARS-CoV-2. Methods: Longitudinal comparative study involving 588 pregnant women with SARS-CoV-2 investigation during pregnancy or at delivery in Sao Paulo, Brazil. Three groups were investigated: G1 (N=259) women with COVID-19 (symptomatic SARS-CoV-2 infection) identified during pregnancy; G2 (N=131) women with positive SARS-CoV-2 serology determined at delivery; G3 (N=198) women with negative SARS-CoV-2 serology at delivery. Questionnaires investigating fatigue were applied at 6 weeks, 3 and 6 months after SARS-CoV-2 identification for G1; and at delivery, 6 weeks, 3 and 6 months after delivery for all groups. The prevalence of fatigue, fatigue most of the time, and significant fatigue were determined at all timepoints. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the risk of remaining with fatigue over time in G1 women.Results: Prevalence of overall fatigue in G1 women at 6 weeks, 3 and 6 months were 40.6%, 33.6% and 27.8%, respectively. The cumulative risk of remaining with fatigue increased over time according to the severity of disease, with HR of 1.69 (95%CI: 0.89-3.20) and 2.43 (95%CI: 1.49-3.95) for women with moderate and severe symptoms, respectively. In multivariate analysis, the independent risk factors of fatigue in G1 women were cough and myalgia. At and after delivery the prevalence of fatigue was significantly higher in G1 women compared to G2 and G3 women at all time points. Conclusions: The prevalence of post-viral fatigue is higher in pregnant women acquiring SARS-CoV-2 during pregnancy, and the risk and duration of fatigue increase with severity of infection.

The duration of immunity after first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. This is a retrospective population-based matched observational study where we identified the first polymerase chain reaction (PCR) positive of primary SARS-CoV-2 infection case tests between 1 March 2020 and 30 September 2020. Each case was matched by age, sex, upper tier local authority of residence and testing route to one individual testing negative in the same week (controls) by PCR. After a 90-day pre-follow-up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. We used a conditional logistic regression to analyse the results. There were 517 870 individuals in the matched cohort with 2815 reinfection cases and 12 098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (odds ratio (OR) 0.22, 0.21–0.23). Protection rose to 82% (OR 0.18, 0.17–0.19) after a sensitivity analysis excluded 933 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20–0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42–0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.

Objective We aimed to look at the burden of disease caused by SARS-COV-2 reinfections and identified potential risk factors for disease severity. Methods We used national surveillance data to collect information on all SARS-CoV-2 primary infection and suspected reinfection cases between January 2020 until early May 2021. Reinfection cases were positive COVID-19 PCR or antigen test, 90 days after their first COVID-19 positive test. We collected information on case demographics, hospital and ICU admission, immunisation status and if individuals were at risk of complication for COVID-19. Results Deaths reported within 28 days of testing positive were 61% (95% confidence interval: 56% to 65%) lower in suspected COVID-19 reinfection than primary infection cases. In the unvaccinated cohort, reinfections were associated with 49% (37% to 58%) lower odds of hospital admission in cases aged 50 to 65 years in the population not identified at risk of complication for COVID-19, and 34% (17% to 48%) in those at risk. ICU admission at reinfection compared to primary infection decreased 76% (55% to 87%). Individuals at risk and those aged below 50 years, who received at least 1 dose of vaccine against COVID-19, were 62% (39% to 74%) and 58% (24% to 77%) less likely to get admitted to hospital at reinfection, respectively. Conclusion Prior SARS-CoV-2 infection was associated with lower odds of dying, and both prior infection and immunisation showed a protective effect against severe disease in selected populations. Older age, sex and underlying comorbidities appeared as principal risk factors for illness severity at reinfection. Funding PHE/UKHSA

Background There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. Methods Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. Results Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of Conclusions In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children Trial registration Reported in individual primary studies.

Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition affecting multiple body systems, with unknown cause, unclear pathogenesis mechanisms, and fluctuating symptoms which may lead to severe debilitation. It is frequently reported to have been triggered by an infection, particularly with herpes virus family members; however, there are no clear differences in exposure to, or seroprevalence of, any herpes virus in people with ME/CFS and healthy individuals. Herpes viruses exist in lytic and latent forms, and it is possible that ME/CFS is associated with viral reactivation, which has not been detectable previously due to insensitive testing methods.Saliva samples were collected from 30 people living with ME/CFS at monthly intervals for six months and at times when they experienced symptom exacerbation, as well as from 14 healthy control individuals. The viral DNA load of the nine human herpes viruses was determined by digital droplet PCR. Symptoms were assessed by questionnaire at each time point.Human herpes virus (HHV) 6B, HHV-7, herpes simplex virus 1 and Epstein Barr virus were detectable within the saliva samples, with higher HHV-6B and HHV-7 viral loads detected in people with ME/CFS than in healthy controls. Participants with ME/CFS could be broadly separated into two groups: one group displayed fluctuating patterns of herpes viruses detectable across the six months while the second group displayed more stable viral presentation. In the first group, there was positive correlation between HHV-6B and HHV-7 viral load and severity of symptom scores, including pain, neurocognition and autonomic dysfunction.The results indicate that fluctuating viral load, related to herpesvirus reactivation state, may play a role in ME/CFS pathogenesis, or might be a consequence of dysregulated immune function. The sampling strategy and molecular tools developed permit large-scale epidemiological investigations.Contribution to the FieldThe cause of ME/CFS and the mechanisms underlying disease pathogenesis are not known, although symptoms are often triggered by infection. Human herpes virus (HHV) family members have been implicated, although there is no difference in the seroprevalence of any HHV in people with ME/CFS and healthy controls, showing there is similar prior infection rate. HHVs exist in either latent or active, lytic, phases in the human host, and it is possible that ME/CFS symptoms and their severity is related to HHV reactivation from a latent state. We have used droplet digital PCR, a sensitive and specific method, to measure the prevalence and DNA concentration of HHVs in the saliva of people with ME/CFS and controls, and analysed the correlation with disease over a six-month timecourse. We found that two HHVs, HHV-7 and HHV-6B, were elevated in saliva from people with ME/CFS, and that in people who were severely affected by ME/CFS, the concentration HHV DNA correlated with symptom severity over time in a subgroup of patients with fluctuating salivary HHV repertoire. Our study demonstrates the feasibility of measuring HHV concentration in readily acquired samples, enabling future large-scale studies aimed at testing the causal role of HHV reactivation in ME/CFS disease.

BackgroundReinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity or outcomes of reinfection in children.MethodsWe used national SARS-CoV-2 testing data in England to estimate the risk of reinfection ≥90 days after primary infection from 01 January 2020 to 31 July 2021, which encompassed both the Alpha and Delta waves in England. Disease severity was assessed by linking reinfection cases to national hospitalisation, intensive care admission and death registrations datasets.FindingsReinfection rates closely followed community infection rates, with a small peak during the Alpha wave and a larger peak during the Delta wave. In children aged ≤16 years, there were 688,418 primary infections and 2,343 reinfections. The overall reinfection rate was 66·88/100,000 population, being higher in adults (72.53/100,000) than in children (21·53/100,000). Reinfection rates after primary infection were 0·68% overall, 0·73% in adults and 0·34% in children. Of the 109 reinfections in children admitted to hospital, 78 (72%) had underlying comorbidities. Hospitalisation rates were similar for the first (64/2343, 2·73%) and second episode (57/2343, 2·43%). Intensive care admission was rare after primary infection (n=7) or reinfection (n=4), mainly in children with comorbidities. 44 deaths occurred after primary infection within 28 days of diagnosis (44/688,418, 0·01%), none after possible reinfections.InterpretationThe risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the Delta variant wave. Children had a lower risk of reinfection than adults, but reinfections were not associated with more severe disease or fatal outcomes.FundingPHE/UKHSAResearch in ContextEvidence Before this studyWe searched PubMed with the terms “COVID-19” or “SARS-CoV-2” with “reinfection” to identify publications relating to SARS-CoV-2 reinfections from 01 January until 15 November 2021. There were few publications relating to SARS-CoV-2 reinfections, and these primarily related to adults. Published studies reported very low rates of reinfection during the first few months after primary infection in adults. COVID-19 vaccines provide effective immune protection against SARS-CoV-2 infection, but recent studies have reported increasing risk of breakthrough infection with time since primary vaccination due to waning immunity. Several SARS-CoV-2 variants, including the beta, gamma and delta variants have been shown to partially evade immunity after natural infection and vaccination, potentially increasing the risk of reinfections and breakthrough infections, respectively. Data on reinfections in children are lacking and restricted mainly to case reports in immunocompromised children.Added Value of This StudyWe used national SARS-CoV-2 testing data during the first 19 months of the pandemic to estimate the risk of reinfection in children compared to adults during a period that encompassed both the Alpha and the Delta variant waves in England. We found that the risk of reinfection correlated with the risk of SARS-CoV-2 exposure and therefore, closely reflected community infection rates, with most reinfections occurring during the Delta variant wave. Whilst acknowledging the limitation of using national testing data, we found that children had a lower risk of reinfection compared to adults and that the risk of reinfection in children increased with age. Reinfections were not associated with severe disease in terms of hospitalization or intensive care admission and there were no fatalities within 28 days of the reinfection episode in children.Implications of all the Available EvidenceSARS-CoV-2 reinfections are rare in children, especially younger children, and occurred mainly during the Delta wave in England. Reinfections were not associated with more severe disease or fatal outcomes in children. COVID-19 vaccination will provide further protection against primary infections and reinfections in children.

Additional file 1: Table S1. Number (%) of mRDT-positive patients i) not prescribed ACT and ii) prescribed other medications. Table S2. Risk factors associated with non-prescription of ACT in mRDT-positive patients not prescribed ACT. Table S3. Risk factors associated with prescription of medications in mRDT-positive patients not prescribed ACT.

We propose a framework for the understanding of the pathophysiology and management of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to an insult, or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune and autonomic manifestations, underlined by a hyper-metabolic state, that characterise early disease, may be followed by various processes leading to multi-systemic related symptoms. This abnormal metabolic state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiralling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. Disease management and research efforts should seek to identify and apply strategies targeted at the different pathophysiological dysfunctions that characterise different disease stages. As disease presentation varies over time, no single case description, set of diagnostic criteria, or molecular feature is currently diagnostic for all patients at all times. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may improve research design and health care interventions for people with ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease characterized by unexplained incapacitating fatigue, accompanied by variable multi-systemic symptoms. ME/CFS causes a significant personal and public health burden, and urgently requires the coordination of research efforts to investigate its etiology and pathophysiology and to develop and validate sensitive and specific biomarkers to confirm diagnosis. This narrative paper describes how people with ME/CFS, together with a multidisciplinary team of researchers, have established the UK ME/CFS Biobank (UKMEB), a unique research infrastructure specifically designed to expedite biomedical research into ME/CFS. We describe the journey that led to its conceptualization and operation, and how the resource has served as a model disease-specific biobank, aggregating human biospecimens alongside comprehensive health information on participants. The UKMEB currently has data and samples from 600 donors including people with ME/CFS and a comparison group with multiple sclerosis and healthy controls. A longitudinal sub-cohort has been established of participants having follow-up assessments at multiple time-points. As an open resource for quality and ethical research into ME/CFS, biological samples and data have not only been analyzed within our research team but have also been shared with researchers across Europe, America and the Middle East. We continue to encourage researchers from academic and commercial sectors to access the UKMEB. Major steps have been taken and challenges remain; these include sustainability and expansion, and harmonization of processes to facilitate integration with other bioresources and databanks internationally.