Variant-specific symptoms of COVID-19 among 1,542,510 people in England

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.

The Omicron SARS-CoV-2 epidemic in England during February 2022

BackgroundThe third wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron variant. However, rates of hospitalisations and deaths were substantially lower than in the first and second waves MethodsIn the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022). FindingsWe estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round reproduction number (R) overall of 0.94 (0{middle dot}91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,195 positive samples with sublineages determined, only one (0.1% [0.0-0.5]) corresponded to AY.39 Delta sublineage and the remainder were Omicron: N=390, 32.7% (30.0-35.4) were BA.1; N=473, 39.6% (36.8-42.5) were BA.1.1; and N=331, 27.7% (25.2-30.4) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36-0.43). The highest proportion of BA.2 among positives was found in London. InterpretationIn February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required. FundingDepartment of Health and Social Care, England. O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSA search of PubMed using title or abstract terms ("Omicron" or "BA.1" or "BA.2") and "prevalence" without language or other restrictions, identified 51 results (with no duplicates). All 51 results were evaluated, with 18 deemed relevant. One study focused on Omicron case rates in South Africa during the early stage after the discovery of the new variant (November 2021), one described genomic surveillance of SARS-CoV-2 in the USA (June - December 2021), one analysed clinical outcomes based on health records (January - December 2021), one described the results of whole-genome sequencing of SARS-CoV-2 samples collected in North Africa (March - December 2021), and one was from a previous REACT survey round (November - December 2021). The others focused on the mutation distribution of Omicron, disease severity, immune response, vaccine effectiveness, and prevalence in animal hosts. Added value of this studyWe analysed data from throat and nose swabs collected at home by a randomly selected sample of residents of England, aged 5 years and older, obtained during round 18 (8 February to 1 March 2022) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. We estimated a weighted prevalence of SARS-CoV-2 of 2.88% (95% CrI 2.76-3.00) in England in February 2022, which was substantially lower than that estimated in January 2022 (4.41% [4.25-4.56]). The within-round dynamics differed by age group with weighted prevalence falling among children (aged 5 to 17 years) with an R of 0.79 (0.74-0.84) and adults aged 18 to 54 years with an R of 0.92 (0.89-0.96), in contrast to the level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Exponential models estimated a daily growth rate advantage of 0.12 (0.11-0.13) in the odds of BA.2 (vs BA.1 or BA.1.1) corresponding to an R additive advantage of 0.40 (0.36-0.43). Implications of all the available evidenceRandom community surveys of SARS-CoV-2 provide robust insights into transmission dynamics and identify groups at heightened risk of infection based on estimates of population prevalence that are unbiased by test-seeking behaviour or availability of tests. In England, replacement by BA.2 of other Omicron sublineages, the level or increasing rates of infection in older people and the uptick in hospitalisations in England toward the end of February 2022 require ongoing surveillance, both to monitor the levels of current (and future) SARS-CoV-2 variants and the risks of severe disease. C_TEXTBOX

Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022

BackgroundRapid transmission of the SARS-CoV-2 Omicron variant has led to the highest ever recorded case incidence levels in many countries around the world. MethodsThe REal-time Assessment of Community Transmission-1 (REACT-1) study has been characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results from self-administered throat and nose swabs from randomly-selected participants in England at ages 5 years and over, approximately monthly since May 2020. Round 17 data were collected between 5 and 20 January 2022 and provide data on the temporal, socio-demographic and geographical spread of the virus, viral loads and viral genome sequence data for positive swabs. ResultsFrom 102,174 valid tests in round 17, weighted prevalence of swab positivity was 4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than in December 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages were determined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages) cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022, and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1 and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03, 0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92). Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years and older had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a high level of infection among a highly vulnerable group. Among the 3,613 swab-positive individuals reporting whether or not they had had previous infection, 2,334 (64.6%) reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to 30 days before their swab date. Risks of infection were increased among essential/key workers (other than healthcare or care home workers) with mutually adjusted Odds Ratio (OR) of 1.15 (95% CI, 1.05, 1.26), people living in large compared to single-person households (6+ household size OR 1.73; 95% CI, 1.44, 2.08), those living in urban vs rural areas (OR 1.24, 95% CI, 1.13, 1.35) and those living in the most vs least deprived areas (OR 1.34, 95% CI, 1.20, 1.49). ConclusionsWe observed unprecedented levels of infection with SARS-CoV-2 in England in January 2022, an almost complete replacement of Delta by Omicron, and evidence for a growth advantage for BA.2 compared to BA.1. The increase in the prevalence of infection with Omicron among children (aged 5 to 17 years) during January 2022 could pose a risk to adults, despite the current trend for prevalence in adults to decline. (Funded by the Department of Health and Social Care in England.)

Rapid increase in Omicron infections in England during December 2021: REACT-1 study

BackgroundThe highest-ever recorded numbers of daily severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in England has been observed during December 2021 and have coincided with a rapid rise in the highly transmissible Omicron variant despite high levels of vaccination in the population. Although additional COVID-19 measures have been introduced in England and internationally to contain the epidemic, there remains uncertainty about the spread and severity of Omicron infections among the general population. MethodsThe REal-time Assessment of Community Transmission-1 (REACT-1) study has been monitoring the prevalence of SARS-CoV-2 infection in England since May 2020. REACT-1 obtains self-administered throat and nose swabs from a random sample of the population of England at ages 5 years and over. Swabs are tested for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) and samples testing positive are sent for viral genome sequencing. To date 16 rounds have been completed, each including [~]100,000 or more participants with data collected over a period of 2 to 3 weeks per month. Socio-demographic, lifestyle and clinical information (including previous history of COVID-19 and symptoms prior to swabbing) is collected by online or telephone questionnaire. Here we report results from round 14 (9-27 September 2021), round 15 (19 October - 05 November 2021) and round 16 (23 November - 14 December 2021) for a total of 297,728 participants with a valid RT-PCR test result, of whom 259,225 (87.1%) consented for linkage to their NHS records including detailed information on vaccination (vaccination status, date). We used these data to estimate community prevalence and trends by age and region, to evaluate vaccine effectiveness against infection in children ages 12 to 17 years, and effect of a third (booster) dose in adults, and to monitor the emergence of the Omicron variant in England. ResultsWe observed a high overall prevalence of 1.41% (1.33%, 1.51%) in the community during round 16. We found strong evidence of an increase in prevalence during round 16 with an estimated reproduction number R of 1.13 (1.06, 1.09) for the whole of round 16 and 1.27 (1.14, 1.40) when restricting to observations from 1 December onwards. The reproduction number in those aged 18-54 years was estimated at 1.23 (1.14, 1.33) for the whole of round 16 and 1.41 (1.23, 1.61) from 1 December. Our data also provide strong evidence of a steep increase in prevalence in London with an estimated R of 1.62 (1.34, 1.93) from 1 December onwards and a daily prevalence reaching 6.07% (4.06%, 9.00%) on 14 December 2021. As of 1 to 11 December 2021, of the 275 lineages determined, 11 (4.0%) corresponded to the Omicron variant. The first Omicron infection was detected in London on 3 December, and subsequent infections mostly appeared in the South of England. The 11 Omicron cases were all aged 18 to 54 years, double-vaccinated (reflecting the large numbers of people who have received two doses of vaccine in this age group) but not boosted, 9 were men, 5 lived in London and 7 were symptomatic (5 with classic COVID-19 symptoms: loss or change of sense of smell or taste, fever, persistent cough), 2 were asymptomatic, and symptoms were unknown for 2 cases. The proportion of Omicron (vs Delta or Delta sub-lineages) was found to increase rapidly with a daily increase of 66.0% (32.7%, 127.3%) in the odds of Omicron (vs. Delta) infection, conditional on swab positivity. Highest prevalence of swab positivity by age was observed in (unvaccinated) children aged 5 to 11 years (4.74% [4.15%, 5.40%]) similar to the prevalence observed at these ages in round 15. In contrast, prevalence in children aged 12 to 17 years more than halved from 5.35% (4.78%, 5.99%) in round 15 to 2.31% (1.91%, 2.80%) in round 16. As of 14 December 2021, 76.6% children at ages 12 to 17 years had received at least one vaccine dose; we estimated that vaccine effectiveness against infection was 57.9% (44.1%, 68.3%) in this age group. In addition, the prevalence of swab positivity in adults aged 65 years and over fell by over 40% from 0.84% (0.72%, 0.99%) in round 15 to 0.48% (0.39%,0.59%) in round 16 and for those aged 75 years and over it fell by two-thirds from 0.63% (0.48%,0.82%) to 0.21% (0.13%,0.32%). At these ages a high proportion of participants (>90%) had received a third vaccine dose; we estimated that adults having received a third vaccine dose had a three- to four-fold lower risk of testing positive compared to those who had received two doses. ConclusionA large fall in swab positivity from round 15 to round 16 among 12 to 17 year olds, most of whom have been vaccinated, contrasts with the continuing high prevalence among 5 to 11 year olds who have largely not been vaccinated. Likewise there were large falls in swab positivity among people aged 65 years and over, the vast majority of whom have had a third (booster) vaccine dose; these results reinforce the importance of the vaccine and booster campaign. However, the rapidly increasing prevalence of SARS-CoV-2 infections in England during December 2021, coincident with the rapid rise of Omicron infections, may lead to renewed pressure on health services. Additional measures beyond vaccination may be needed to control the current wave of infections and prevent health services (in England and other countries) from being overwhelmed. SummaryThe unprecedented rise in SARS-CoV-2 infections is concurrent with rapid spread of the Omicron variant in England and globally. We analysed prevalence of SARS-CoV-2 and its dynamics in England from end of November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high during December 2021 with rapid growth nationally and in London, and of the proportion of infections due to Omicron. We observed a large fall in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third vs. two doses of vaccine. Our results reiterate the importance of vaccination and booster campaigns; however, additional measures may be needed to control the rapid growth of the Omicron variant.

Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people

BackgroundLong COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorly defined syndrome. There is uncertainty about its predisposing factors and the extent of the resultant public health burden, with estimates of prevalence and duration varying widely. MethodsWithin rounds 3-5 of the REACT-2 study, 508,707 people in the community in England were asked about a prior history of COVID-19 and the presence and duration of 29 different symptoms. We used uni-and multivariable models to identify predictors of persistence of symptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12 weeks, and used unsupervised learning to cluster individuals by symptoms experienced. FindingsAmong the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2% (95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and 2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people (8,771/28,713 [30.5%]) with at least one symptom lasting 12 weeks or more reported having had severe COVID-19 symptoms ("significant effect on my daily life") at the time of their illness, giving a weighted prevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptoms was higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life. Obesity, smoking or vaping, hospitalisation, and deprivation were also associated with a higher probability of persistent symptoms, while Asian ethnicity was associated with a lower probability. Two stable clusters were identified based on symptoms that persisted for 12 weeks or more: in the largest cluster, tiredness predominated, while in the second there was a high prevalence of respiratory and related symptoms. InterpretationA substantial proportion of people with symptomatic COVID-19 go on to have persistent symptoms for 12 weeks or more, which is age-dependent. Clinicians need to be aware of the differing manifestations of Long COVID which may require tailored therapeutic approaches. Managing the long-term sequelae of SARS-CoV-2 infection in the population will remain a major challenge for health services in the next stage of the pandemic. FundingThe study was funded by the Department of Health and Social Care in England. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSRecent systematic reviews have documented the wide range of symptoms and reported prevalence of persistent symptoms following COVID-19. A dynamic review of Long COVID studies (NIHR Evidence) in March 2021 summarised the literature on the prevalence of persistent symptoms after acute COVID19, and reported that most studies (14) were of hospitalised patients, with higher prevalence of persistent symptoms compared with two community-based studies. There was limited evidence from community studies beyond 12 weeks. Another systematic review reported a median of over 70% of people with symptoms lasting at least 60 days. A review of risk factors for Long COVID found consistent evidence for an increased risk amongst women and those with high body mass index (BMI) but inconsistent findings on the role of age and little evidence concerning risks among different socioeconomic or ethnic groups which are often not well captured in routine healthcare records. Long COVID is increasingly recognised as heterogenous, likely underpinned by differing biological mechanisms, but there is not yet consensus on defining subtypes of the condition. Added value of this studyThis community-based study of over half a million people was designed to be representative of the adult population of England. A random sample of adults ages 18 years and above registered with a GP were invited irrespective of previous access to services for COVID-19, providing an estimate of population prevalence that was representative of the whole population. The findings show substantial declines in symptom prevalence over the first 12 weeks following Covid-19, reported by nearly one fifth of respondents, of whom over a third remained symptomatic at 12 weeks and beyond, with little evidence for decline thereafter. Risk factors identified for persistent symptoms (12 weeks or more) suggestive of Long COVID confirm some previous findings - an increased risk in women, obese and overweight individuals and those hospitalised for COVID-19, with strong evidence for an increasing risk with age. Additional evidence was found for an increased risk in those with lower income, smoking or vaping and healthcare or care home workers. A lower risk was found in those of Asian ethnicity. Clustering identified two distinct groups of individuals with different symptom profiles at 12 weeks, highlighting the heterogeneity of clinical presentation. The smaller cluster had higher prevalence of respiratory and related symptoms, while for those in the larger cluster tiredness was the dominant symptom, with lower prevalence of organ-specific symptoms. Implications of available evidenceThere is a high prevalence of persistent symptoms beyond 12 weeks after acute COVID-19, with little evidence of decline thereafter. This highlights the needs for greater support for patients, both through specialised services and, for those from low-income settings, financial support. The understanding that there are distinct clusters of persistent symptoms, the most common of which is dominated by fatigue, is important for the recognition and clinical management of the condition outside of specialised services.

Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults

BackgroundThe prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity. MethodsPrevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed. ResultsThere were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, -23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: -14.9% [-21.6, -8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: -39.0% [-50.8, -27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (-64.0% [-75.6, -52.3]), compared to -22.3% ([-27.0, -17.7]) in those with SARS-CoV-2 infection confirmed on PCR. DiscussionThese findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.

Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults

BackgroundEngland, UK has experienced a large outbreak of SARS-CoV-2 infection. As in USA and elsewhere, disadvantaged communities have been disproportionately affected. MethodsNational REal-time Assessment of Community Transmission-2 (REACT-2) prevalence study using a self-administered lateral flow immunoassay (LFIA) test for IgG among a random population sample of 100,000 adults over 18 years in England, 20 June to 13 July 2020. ResultsData were available for 109,076 participants, yielding 5,544 IgG positive results; adjusted (for test performance) and re-weighted (for sampling) prevalence was 6.0% (95% Cl: 5.8, 6.1). Highest prevalence was in London (13.0% [12.3, 13.6]), among people of Black or Asian (mainly South Asian) ethnicity (17.3% [15.8, 19.1] and 11.9% [11.0, 12.8] respectively) and those aged 18-24 years (7.9% [7.3, 8.5]). Adjusted odds ratio for care home workers with client-facing roles was 3.1 (2.5, 3.8) compared with non-essential workers. One third (32.2%, [31.0-33.4]) of antibody positive individuals reported no symptoms. Among symptomatic cases, most (78.8%) reported symptoms during the peak of the epidemic in England in March (31.3%) and April (47.5%) 2020. We estimate that 3.36 million (3.21, 3.51) people have been infected with SARS-CoV-2 in England to end June 2020, with an overall infection fatality ratio (IFR) of 0.90% (0.86, 0.94); age-specific IFR was similar among people of different ethnicities. ConclusionThe SARS-CoV-2 pandemic in England disproportionately affected ethnic minority groups and health and care home workers. The higher risk of infection in minority ethnic groups may explain their increased risk of hospitalisation and mortality from COVID-19.

Celiac Disease.

Gluten-related disorders, including celiac disease, wheat allergy, and nonceliac gluten sensitivity (NCGS), are increasingly reported worldwide. Celiac disease is caused by an immune-mediated reaction to ingested gluten in genetically susceptible persons. NCGS is largely a diagnosis of exclusion when other causes of symptoms have been ruled out. All patients with celiac disease should be referred to a registered dietitian nutritionist with expertise in celiac disease and a gastroenterologist who specializes in celiac disease and malabsorptive disorders, and they should remain on a strict gluten-free diet indefinitely. This article provides an overview of gluten- and wheat-related disorders.