Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations.

BACKGROUND: Self-reported symptom studies rapidly increased understanding of SARS-CoV-2 during the COVID-19 pandemic and enabled monitoring of long-term effects of COVID-19 outside hospital settings. Post-COVID-19 condition presents as heterogeneous profiles, which need characterisation to enable personalised patient care. We aimed to describe post-COVID-19 condition profiles by viral variant and vaccination status. METHODS: In this prospective longitudinal cohort study, we analysed data from UK-based adults (aged 18-100 years) who regularly provided health reports via the Covid Symptom Study smartphone app between March 24, 2020, and Dec 8, 2021. We included participants who reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2 who subsequently developed long COVID (ie, symptoms lasting longer than 28 days from the date of the initial positive test). We separately defined post-COVID-19 condition as symptoms that persisted for at least 84 days after the initial positive test. We did unsupervised clustering analysis of time-series data to identify distinct symptom profiles for vaccinated and unvaccinated people with post-COVID-19 condition after infection with the wild-type, alpha (B.1.1.7), or delta (B.1.617.2 and AY.x) variants of SARS-CoV-2. Clusters were then characterised on the basis of symptom prevalence, duration, demography, and previous comorbidities. We also used an additional testing sample with additional data from the Covid Symptom Study Biobank (collected between October, 2020, and April, 2021) to investigate the effects of the identified symptom clusters of post-COVID-19 condition on the lives of affected people. FINDINGS: We included 9804 people from the COVID Symptom Study with long COVID, 1513 (15%) of whom developed post-COVID-19 condition. Sample sizes were sufficient only for analyses of the unvaccinated wild-type, unvaccinated alpha variant, and vaccinated delta variant groups. We identified distinct profiles of symptoms for post-COVID-19 condition within and across variants: four endotypes were identified for infections due to the wild-type variant (in unvaccinated people), seven for the alpha variant (in unvaccinated people), and five for the delta variant (in vaccinated people). Across all variants, we identified a cardiorespiratory cluster of symptoms, a central neurological cluster, and a multi-organ systemic inflammatory cluster. These three main clusers were confirmed in a testing sample. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. INTERPRETATION: Our unsupervised analysis identified different profiles of post-COVID-19 condition, characterised by differing symptom combinations, durations, and functional outcomes. Our classification could be useful for understanding the distinct mechanisms of post-COVID-19 condition, as well as for identification of subgroups of individuals who might be at risk of prolonged debilitation. FUNDING: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, UK Alzheimer's Society, and ZOE.

SYMPTOM BURDEN, SYMPTOM MANAGEMENT, AND SUPPORTIVE CARE NEEDS AMONG TISA-CEL AND LISO-CEL CAR T-CELL PATIENTS IN REMISSION: A QUALITATIVE STUDY

purpose was to explore the symptoms and supportive care needs experienced by patients in remission after tisa-cel or liso-cel chimeric antigen receptor (CAR) T-cell therapy. Though CAR T-cell therapy is expanding in application to various types of cancers, little information is available about the patient symptom experience, symptom management, and supportive care needs, especially three months or more after therapy. This was a qualitative study. Participants were recruited from a comprehensive medical center if they met the following criteria: > 18 years of age, English-speaking, history of B-cell lymphoma, received tisa-cel or liso-cel between 3 months to one year, and currently in remission. Data collection utilized semi-structured telephone interviews that were audio-recorded and transcribed. Two independent coders used NVivo Software to code transcripts. Content analysis was used to analyze the interview data. Data analysis is ongoing. Ten patients who received tisa-cel (n=7) or liso-cel (n=3) for B-cell lymphoma participated in the study. The average time since infusion was 187.5 days, ranging from 113 to 261 days. Participant mean age was 64.5 years. Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) toxicity grades were gathered from medical chart review: CRS grade 0 (n=3), CRS grade 1 (n=5), CRS grade 2 (n=i), CRS grade 3 (n=i), and ICANS grade 0 (n=io). The most commonly described symptoms included fatigue, weakness, joint pain, and memory-issues. Most participants reported they were self-sufficient in their activities of daily living. However, some participants expressed physical limitations and social isolation, due to compromised immune systems and concerns related to COVID -19. Participants described the perceived burden for their caregivers. Supportive care needs included cooking meals and grocery shopping. Though our study focused on patients in remission to avoid confounding with ongoing disease or treatment, patients still reported symptoms and side effects. Notably, some participants experience symptoms (e.g., neuropathy) from prior chemotherapy treatments. Participants expressed being unsure of whether ongoing symptoms were related to prior treatments or from the CAR T-cell therapy. Oncology nurses should continue to assess symptoms among adult CAR T-cell patients in remission and offer supportive care as needed. Future research may determine what patients are more at risk of developing long-term symptoms, to describe symptom trajectory, and develop targeted interventions to reduce symptom burden and meet supportive care needs.

Severity and Outcomes of SARS-CoV-2 Reinfection Compared with Primary Infection: A Systematic Review and Meta-Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection has brought new challenges to the global prevention and control of coronavirus disease 2019 (COVID-19) pandemic; however, current studies suggest that there is still great uncertainty about the risk of severe COVID-19 and poor outcomes after SARS-CoV-2 reinfection. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) of severity, outcomes and symptoms of reinfection. Random-effects were used to estimate the pooled odds ratios (OR) and its 95%CI of severity and outcomes between reinfections and primary infections. Nineteen studies involving a total of 34,375 cases of SARS-CoV-2 reinfection and 5,264,720 cases of SARS-CoV-2 primary infection were included in this meta-analysis. Among those SARS-CoV-2 reinfection cases, 41.77% (95%CI, 19.23-64.31%) were asymptomatic, and 51.83% (95%CI, 23.90-79.76%) were symptomatic, only 0.58% (95%CI, 0.031-1.14%) manifested as severe illness, and 0.04% (95%CI, 0.009-0.078%) manifested as critical illness. The PPs for SARS-CoV-2 reinfection-related hospitalization, admission to ICU, and death were, respectively, 15.48% (95%CI, 11.98-18.97%), 3.58% (95%CI, 0.39-6.77%), 2.96% (95%CI, 1.25-4.67%). Compared with SARS-CoV-2 primary infection cases, reinfection cases were more likely to present with mild illness (OR = 7.01, 95%CI, 5.83-8.44), and the risk of severe illness was reduced by 86% (OR = 0.14, 95%CI, 0.11-0.16). Primary infection provided some protection against reinfection and reduces the risk of symptomatic infection and severe illness. Reinfection did not contribute to extra risk of hospitalization, ICU, or death. It is suggested to scientifically understand the risk of reinfection of SARS-CoV-2, strengthen public health education, maintain healthy habits, and reduce the risk of reinfection.

Long-Term Consequences of Asymptomatic SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis.

Little is known about the long-term consequences of asymptomatic infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to review the data available to explore the long-term consequences of asymptomatic SARS-CoV-2 infection in the real world. We searched observational cohort studies that described the long-term health effects of asymptomatic SARS-CoV-2 infections. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) of long-term symptoms. Random effects were used to estimate the pooled odds ratios (OR) and its 95%CI of different long-term symptoms between symptomatic and asymptomatic infections. Five studies involving a total of 1643 cases, including 597 cases of asymptomatic and 1043 cases of symptomatic SARS-CoV-2 infection were included in this meta-analysis. The PPs of long-term consequences after asymptomatic SARS-CoV-2 infections were 17.13% (95%CI, 7.55−26.71%) for at least one symptom, 15.09% (95%CI, 5.46−24.73%) for loss of taste, 14.14% (95%CI, −1.32−29.61%) for loss of smell, and 9.33% (95%CI, 3.07−15.60) for fatigue. Compared with symptomatic SARS-CoV-2 infection, asymptomatic infection was associated with a significantly lower risk of developing COVID-19-related sequelae (p < 0.05), with 80% lower risk of developing at least one symptom (OR = 0.20, 95%CI, 0.09−0.45), 81% lower risk of fatigue (OR = 0.19, 95%CI, 0.08−0.49), 90% lower risk of loss of taste/smell (OR = 0.10, 95%CI, 0.02−0.58). Our results suggested that there were long-term effects of asymptomatic SARS-CoV-2 infection, such as loss of taste or smell, fatigue, cough and so on. However, the risk of developing long-term symptoms in asymptomatic SARS-CoV-2 infected persons was significantly lower than those in symptomatic SARS-CoV-2 infection cases.

Association of Infection with Different SARS-CoV-2 Variants during Pregnancy with Maternal and Perinatal Outcomes: A Systematic Review and Meta-Analysis.

The aim of this study is to review the currently available data, and to explore the association of infection with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants during pregnancy with maternal and perinatal outcomes in the real world. Observational cohort studies were analyzed that described the maternal and perinatal outcomes of infection with different SARS-CoV-2 variants during pregnancy. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) for maternal and perinatal outcomes. Random effects were used to estimate the pooled odds ratios (OR) and their 95% CI for different outcomes between Delta and pre-Delta periods, and between Omicron and Delta periods. Eighteen studies, involving a total of 133,058 cases of SARS-CoV-2 infection during pregnancy (99,567 cases of SARS-CoV-2 wild type or pre-variant infection and 33,494 cases of SARS-CoV-2 variant infections), were included in this meta-analysis. Among pregnant women with SARS-CoV-2 infections, the PPs for required respiratory support, severe or critical illness, intensive care unit (ICU) admission, maternal death, and preterm birth <37 weeks were, respectively, 27.24% (95%CI, 20.51−33.97%), 24.96% (95%CI, 15.96−33.96%), 11.31% (95%CI, 4.00−18.61%), 4.20% (95%CI, 1.43−6.97%), and 33.85% (95%CI, 21.54−46.17%) in the Delta period, which were higher than those in the pre-Delta period, while the corresponding PPs were, respectively, 10.74% (95%CI, 6.05−15.46%), 11.99% (95%CI, 6.23−17.74%), 4.17% (95%CI, 1.53−6.80%), 0.63% (95%CI, 0.05−1.20%), and 18.58% (95%CI, 9.52−27.65%). The PPs for required respiratory support, severe or critical illness, and ICU admission were, respectively, 2.63% (95%CI, 0.98−4.28%), 1.11% (95%CI, 0.29−1.94%), and 1.83% (95%CI, 0.85−2.81%) in the Omicron period, which were lower than those in the pre-Delta and Delta periods. These results suggest that Omicron infections are associated with less severe maternal and neonatal adverse outcomes, though maternal ICU admission, the need for respiratory support, and preterm birth did also occur with Omicron infections. Since Omicron is currently the predominant strain globally, and has the highest rates of transmission, it is still important to remain vigilant in protecting the vulnerable populations of mothers and infants. In particular, obstetricians and gynecologists should not ignore the adverse risks of maternal ICU admission, respiratory support, and preterm births in pregnant patients with SARS-CoV-2 infections, in order to protect the health of mothers and infants.

Comparison of Long COVID-19 Caused by Different SARS-CoV-2 Strains: A Systematic Review and Meta-Analysis.

Although many studies of long COVID-19 were reported, there was a lack of systematic research which assessed the differences of long COVID-19 in regard to what unique SARS-CoV-2 strains caused it. As such, this systematic review and meta-analysis aims to evaluate the characteristics of long COVID-19 that is caused by different SARS-CoV-2 strains. We systematically searched the PubMed, EMBASE, and ScienceDirect databases in order to find cohort studies of long COVID-19 as defined by the WHO (Geneva, Switzerland). The main outcomes were in determining the percentages of long COVID-19 among patients who were infected with different SARS-CoV-2 strains. Further, this study was registered in PROSPERO (CRD42022339964). A total of 51 studies with 33,573 patients was included, of which three studies possessed the Alpha and Delta variants, and five studies possessed the Omicron variant. The highest pooled estimate of long COVID-19 was found in the CT abnormalities (60.5%; 95% CI: 40.4%, 80.6%) for the wild-type strain; fatigue (66.1%; 95% CI: 42.2%, 89.9%) for the Alpha variant; and ≥1 general symptoms (28.4%; 95% CI: 7.9%, 49.0%) for the Omicron variant. The pooled estimates of ≥1 general symptoms (65.8%; 95% CI: 47.7%, 83.9%) and fatigue were the highest symptoms found among patients infected with the Alpha variant, followed by the wild-type strain, and then the Omicron variant. The pooled estimate of myalgia was highest among patients infected with the Omicron variant (11.7%; 95%: 8.3%, 15.1%), compared with those infected with the wild-type strain (9.4%; 95%: 6.3%, 12.5%). The pooled estimate of sleep difficulty was lowest among the patients infected with the Delta variant (2.5%; 95%: 0.2%, 4.9%) when compared with those infected with the wild-type strain (24.5%; 95%: 17.5%, 31.5%) and the Omicron variant (18.7%; 95%: 1.0%, 36.5%). The findings of this study suggest that there is no significant difference between long COVID-19 that has been caused by different strains, except in certain general symptoms (i.e., in the Alpha or Omicron variant) and in sleep difficulty (i.e., the wild-type strain). In the context of the ongoing COVID-19 pandemic and its emerging variants, directing more attention to long COVID-19 that is caused by unique strains, as well as implementing targeted intervention measures to address it are vital.

Conducting a supportive oncology clinical trial during the COVID-19 pandemic: challenges and strategies.

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT03030859). Registered on 22 January 2017.

Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75.

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.

The Mental Health Impact of the COVID-19 Pandemic on Older Adults in China: A Systematic Review.

Considered at a high risk during the COVID-19 pandemic, older adults in China not only face the disadvantages caused by their relatively low immune systems, but also the challenges brought about by the complex psychological environment in which they spend this special period of their life. However, a thorough study on the impact of the pandemic on older adults' mental health in China remains scant. Hence, this research aimed to investigate the question: What are the mental health outcomes and associated risk factors of the COVID-19 pandemic on older adults in China? Two Chinese academic databases (China National Knowledge Infrastructure and WANFANG DATA) as well as six English academic databases (PubMed, Scopus, Web of Science, MEDLINE, Social Science, and Google Scholar) were searched while following PRISMA guidelines. Studies were selected according to the predetermined inclusion criteria. Further, relatively high detective rates of mental health disorders, including anxiety symptoms (4.9% to 48.6%), depression symptoms (13.8% to 58.7%), hypochondria (11.9%), suicidal ideation (4.1%), along with worries and fear (55.7%) were all reported. The COVID-19 pandemic has presented a threat to not only the physical, but also the psychological health of Chinese older adults. The most common risk factors of psychological distress among Chinese older adults were found in female gender, living in rural areas, coexisting chronic diseases, and insufficient knowledge about the COVID pandemic. As a result, government policy and psychological guidelines that are created in order to alleviate the adverse effects of COVID-19 on older adults' mental health, need to be further developed.

Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76 and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared to BA.5, remain unclear. Here we show BA.2.75 exhibits substantially higher affinity for host receptor ACE2 than BA.5 and other variants. Structural analyses of BA.2.75 Spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the “up” conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma, but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct neutralizing antibody escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations. Graphical SARS-CoV-2 BA.2.75 is growing rapidly and globally. Cao et al. solved the structure of BA.2.75 spike and show it has stronger binding to human ACE2 than previous variants. BA.2.75 also exhibited distinct antigenicity compared to BA.5, escaping neutralizing antibodies targeting various epitopes and evading convalescent plasma from BA.5 breakthrough infections.

Comparison of the Effectiveness and Safety of Heterologous Booster Doses with Homologous Booster Doses for SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis.

As vaccine resources were distributed unevenly worldwide, sometimes there might have been shortages or delays in vaccine supply; therefore, considering the use of heterogeneous booster doses for Coronavirus disease 2019 (COVID-19) might be an alternative strategy. Therefore, we aimed to review the data available to evaluate and compare the effectiveness and safety of heterologous booster doses with homologous booster doses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We searched relevant studies up to 27 April 2022. Random-effects inverse variance models were used to evaluate the vaccine effectiveness (VE) and its 95% confidence interval (CI) of COVID-19 outcomes and odds ratio (OR) and its CI of safety events. The Newcastle-Ottawa quality assessment scale and Cochrane Collaboration's tool were used to assess the quality of the included cohort studies. A total of 23 studies involving 1,726,506 inoculation cases of homologous booster dose and 5,343,580 inoculation cases of heterologous booster dose was included. The VE of heterologous booster for the prevention of SARS-CoV-2 infection (VEheterologous = 96.10%, VEhomologous = 84.00%), symptomatic COVID-19 (VEheterologous = 56.80%, VEhomologous = 17.30%), and COVID-19-related hospital admissions (VEheterologous = 97.40%, VEhomologous = 93.20%) was higher than homologous booster. Compared with homologous booster group, there was a higher risk of fever (OR = 1.930, 95% CI, 1.199-3.107), myalgia (OR = 1.825, 95% CI, 1.079-3.089), and malaise or fatigue (OR = 1.745, 95% CI, 1.047-2.906) within 7 days after boosting, and a higher risk of malaise or fatigue (OR = 4.140, 95% CI, 1.729-9.916) within 28 days after boosting in heterologous booster group. Compared with homologous booster group, geometric mean neutralizing titers (GMTs) of neutralizing antibody for different SARS-CoV-2 variants and response rate of antibody and gama interferon were higher in heterologous booster group. Our findings suggested that both homologous and heterologous COVID-19 booster doses had great effectiveness, immunogenicity, and acceptable safety, and a heterologous booster dose was more effective, which would help make appropriate public health decisions and reduce public hesitancy in vaccination.

Post-vaccination infection rates and modification of COVID-19 symptoms in vaccinated UK school-aged children and adolescents: A prospective longitudinal cohort study.

Background: We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and adolescents (CA) in the UK during periods of Delta and Omicron variant predominance. Methods: In this prospective longitudinal cohort study, we analysed data from 115,775 CA aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CA with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CA, and post-vaccination side-effects. Findings: Between August 5, 2021 and February 14, 2022, 25,971 UK CA aged 12-17 years received one dose of BNT162b2 vaccine. The probability of testing positive for infection diverged soon after vaccination, and was lower in CA with prior SARS-CoV-2 infection. Vaccination reduced proxy-reported infection risk (-80·4% (95% CI -0·82 -0·78) and -53·7% (95% CI -0·62 -0·43) at 14-30 days with Delta and Omicron variants respectively, and -61·5% (95% CI -0·74 -0·44) and -63·7% (95% CI -0·68 -0.59) after 61-90 days). Vaccinated CA who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CA; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CA. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved within few days (3 days in most cases). Interpretation: One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CA aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CA also had generally mild disease. Overall, vaccination was well-tolerated. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimer's Society, and ZOE Limited.

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study.

The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants.

Long-Term Consequences of COVID-19 at 6 Months and Above: A Systematic Review and Meta-Analysis.

We aimed to review the data available to evaluate the long-term consequences of coronavirus disease 2019 (COVID-19) at 6 months and above. We searched relevant observational cohort studies up to 9 February 2022 in Pubmed, Embase, and Web of Science. Random-effects inverse-variance models were used to evaluate the Pooled Prevalence (PP) and its 95% confidence interval (CI) of long-term consequences. The Newcastle-Ottawa quality assessment scale was used to assess the quality of the included cohort studies. A total of 40 studies involving 10,945 cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were included. Of the patients, 63.87% had at least one consequence at the 6 month follow-up, which decreased to 58.89% at 12 months. The most common symptoms were fatigue or muscle weakness (PP 6-12 m = 54.21%, PP ≥ 12 m = 34.22%) and mild dyspnea (Modified Medical Research Council Dyspnea Scale, mMRC = 0, PP 6-12 m = 74.60%, PP ≥ 12 m = 80.64%). Abnormal computerized tomography (CT; PP 6-12 m = 55.68%, PP ≥ 12 m = 43.76%) and lung diffuse function impairment, i.e., a carbon monoxide diffusing capacity (DLCO) of < 80% were common (PP 6-12 m = 49.10%, PP ≥ 12 m = 31.80%). Anxiety and depression (PP 6-12 m = 33.49%, PP ≥ 12 m = 35.40%) and pain or discomfort (PP 6-12 m = 33.26%, PP ≥ 12 m = 35.31%) were the most common problems that affected patients' quality of life. Our findings suggest a significant long-term impact on health and quality of life due to COVID-19, and as waves of ASRS-CoV-2 infections emerge, the long-term effects of COVID-19 will not only increase the difficulty of care for COVID-19 survivors and the setting of public health policy but also might lead to another public health crisis following the current pandemic, which would also increase the global long-term burden of disease.

mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern.

In order to overcome the pandemic of COVID-19, messenger RNA (mRNA)-based vaccine has been extensively researched as a rapid and versatile strategy. Herein, we described the immunogenicity of mRNA-based vaccines for Beta and the most recent Omicron variants. The homologous mRNA-Beta and mRNA-Omicron and heterologous Ad5-nCoV plus mRNA vaccine exhibited high-level cross-reactive neutralization for Beta, original, Delta, and Omicron variants. It indicated that the COVID-19 mRNA vaccines have great potential in the clinical use against different SARS-CoV-2 variants.

Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. METHODS: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. RESULTS: 694 (276 younger (5-11 years), 418 older (12-17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2-9.75) with Alpha, 5 days (IQR 2-9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2-5) symptoms with Alpha, 4 (IQR 2-7) with Delta; in older children, 5 (IQR 3-8) symptoms with Alpha, 6 (IQR 3-9) with Delta infection ). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. CONCLUSIONS: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

Effectiveness and Safety of COVID-19 Vaccine among Pregnant Women in Real-World Studies: A Systematic Review and Meta-Analysis.

We aimed to assess the effectiveness and safety of coronavirus disease 2019 (COVID-19) vaccines for pregnant women in real-world studies. We searched for observational studies about the effectiveness and safety of COVID-19 vaccines among vaccinated pregnant women from inception to 6 November 2021. A total of 6 studies were included. We found that vaccination prevented pregnant women from SARS-CoV-2 infection (OR = 0.50, 95% CI, 0.35-0.79) and COVID-19-related hospitalization (OR = 0.50, 95% CI, 0.31-0.82). Messenger-RNA vaccines could reduce the risk of infection in pregnant women (OR = 0.13, 95% CI, 0.03-0.57). No adverse events of COVID-19 vaccination were found on pregnant, fetal, or neonatal outcomes. Our analysis confirmed the effectiveness and safety of COVID-19 vaccines for pregnant women. Policy makers should formulate targeted strategies to improve vaccine coverage in pregnant women.

Disentangling post-vaccination symptoms from early COVID-19.

BACKGROUND: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. METHODS: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria. FINDINGS: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). INTERPRETATION: Post-vaccination symptoms per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. FUNDING: UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.

Accessible data curation and analytics for international-scale citizen science datasets.

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. As of May 23rd, 2021, over 5 million participants have collectively logged over 360 million self-assessment reports since its introduction in March 2020. The success of the Covid Symptom Study creates significant technical challenges around effective data curation. The primary issue is scale. The size of the dataset means that it can no longer be readily processed using standard Python-based data analytics software such as Pandas on commodity hardware. Alternative technologies exist but carry a higher technical complexity and are less accessible to many researchers. We present ExeTera, a Python-based open source software package designed to provide Pandas-like data analytics on datasets that approach terabyte scales. We present its design and capabilities, and show how it is a critical component of a data curation pipeline that enables reproducible research across an international research group for the Covid Symptom Study.

Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2.

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.