Prevalence and determinants of persistent symptoms after infection with SARS-CoV-2: protocol for an observational cohort study (LongCOVID-study)

Introduction
A substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnoea. However, knowledge regarding the nature and risk factors for developing persisting symptoms is still limited. Hence, in this study, we aim to determine the prevalence, severity, risk factors and impact on quality of life of persisting symptoms in the first year following acute SARS-CoV-2 infection.

Methods and analysis
The LongCOVID-study is both a prospective and retrospective cohort study being conducted in the Netherlands, with a one year follow-up. Participants aged 5 years and above, with self-reported positive or negative tests for SARS-CoV-2 will be included in the study. The primary outcome is the prevalence and severity of persistent symptoms in participants that tested positive for SARS-CoV-2 compared with controls. Symptom severity will be assessed for fatigue (Checklist Individual Strength (CIS subscale fatigue severity)), pain (Rand-36/SF-36 subscale bodily pain), dyspnoea (Medical Research Council (mMRC)) and cognitive impairment (Cognitive Failure Questionnaire (CFQ)). Secondary outcomes include effect of vaccination prior to infection on persistent symptoms, loss of health-related quality of life (HRQoL) and risk factors for persisting symptoms following infection with SARS-CoV-2.

Ethics and dissemination
The Utrecht Medical Ethics Committee (METC) declared in February 2021 that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study (METC protocol number 21-124/C). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in a peer-reviewed journal.

Leggi
Luglio 2022

Impact of prior SARS-CoV-2 infection and COVID-19 vaccination on the subsequent incidence of COVID-19: a multicentre prospective cohort study among UK healthcare workers – the SIREN (Sarscov2 Immunity & REinfection EvaluatioN) study protocol

Introduction
Understanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infection.

Methods and analysis
This is a prospective cohort study design in staff members working in hospitals in the UK. At enrolment, participants are allocated into cohorts, positive or naïve, dependent on their prior SARS-CoV-2 infection status, as measured by standardised SARS-CoV-2 antibody testing on all baseline serum samples and previous SARS-CoV-2 test results. Participants undergo monthly antibody testing and fortnightly viral RNA testing during follow-up and based on these results may move between cohorts. Any results from testing undertaken for other reasons (eg, symptoms, contact tracing) or prior to study entry will also be captured. Individuals complete enrolment and fortnightly questionnaires on exposures, symptoms and vaccination. Follow-up is 12 months from study entry, with an option to extend follow-up to 24 months.
The primary outcome of interest is infection with SARS-CoV-2 after previous SARS-CoV-2 infection or COVID-19 vaccination during the study period. Secondary outcomes include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres.

Ethics and dissemination
The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12 January 2021. Participants gave informed consent before taking part in the study.
Regular reports to national and international expert advisory groups and peer-reviewed publications ensure timely dissemination of findings to inform decision making.

Trial registration number
ISRCTN11041050.

Leggi
Giugno 2022

Incidence of SARS-CoV-2 reinfection in a paediatric cohort in Kuwait

Objective
Subsequent protection from SARS-CoV-2 infection in paediatrics is not well reported in the literature. We aimed to describe the clinical characteristics and dynamics of SARS-CoV-2 PCR repositivity in children.

Design
This is a population-level retrospective cohort study.

Setting
Patients were identified through multiple national-level electronic COVID-19 databases that cover all primary, secondary and tertiary centres in Kuwait.

Participants
The study included children 12 years and younger between 28 February 2020 and 6 March 2021. SARS-CoV-2 reinfection was defined as having two or more positive SARS-CoV-2 PCR tests done on a respiratory sample, at least 45 days apart. Clinical data were obtained from the Pediatric COVID-19 Registry in Kuwait.

Primary and secondary outcome measures
The primary measure is to estimate SARS-CoV-2 PCR repositivity rate. The secondary objective was to establish average duration between first and subsequent SARS-CoV-2 infection. Descriptive statistics were used to present clinical data for each infection episode. Also, incidence-sensitivity analysis was performed to evaluate 60-day and 90-day PCR repositivity intervals.

Results
Thirty paediatric patients with COVID-19 had SARS-CoV-2 reinfection at an incidence of 1.02 (95% CI 0.71 to 1.45) infection per 100 000 person-days and a median time to reinfection of 83 (IQR 62–128.75) days. The incidence of reinfection decreased to 0.78 (95% CI 0.52 to 1.17) and 0.47 (95% CI 0.28 to 0.79) per person-day when the minimum interval between PCR repositivity was increased to 60 and 90 days, respectively. The mean age of reinfected subjects was 8.5 (IQR 3.7–10.3) years and the majority (70%) were girls. Most children (55.2%) had asymptomatic reinfection. Fever was the most common presentation in symptomatic patients. One immunocompromised experienced two reinfection episodes.

Conclusion
SARS-CoV-2 reinfection is uncommon in children. Previous confirmed COVID-19 in children seems to result in a milder reinfection.

Leggi
Giugno 2022

Correction: Behavioral factors associated with SARS-CoV-2 infection. Results from a web-based case-control survey in the Capital Region of Denmark

Cajar MD, Tan FCC, Boisen MK, et al. Behavioral factors associated with SARS-CoV-2 infection. Results from a web-based case-control survey in the Capital Region of Denmark. BMJ Open 2022;12:e056393. doi: 10.1136/bmjopen-2021-056393
The article was erroneously published without the full title as Behavioral factors associated with SARS-CoV-2 infection. The title has been amended to Behavioral factors associated with SARS-CoV-2 infection. Results from a web-based case-control survey in the Capital Region of Denmark.

Leggi
Giugno 2022

Correction: Seroprevalence of SARS-CoV-2 virus antibodies and sociodemographic features of pregnant women in Mogadishu, Somalia: a cross-sectional survey study

Sh. Nur MA, Dahie HA, Hassan NA, et al. Seroprevalence of SARS-CoV-2 virus antibodies and sociodemographic features of pregnant women in Mogadishu, Somalia: a cross-sectional survey study. BMJ Open 2022;12:e059617. doi: 10.1136/bmjopen-2021-059617
The published version misspelled co-author’s name as Mohamed Husein Adam Adam. The correct name should be Mohamed Hussein Adam.

Leggi
Giugno 2022

Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2

Objective
To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic.

Design, setting and participants
This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic.

Primary and secondary outcome measures
The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation.

Results
Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was –4.72 mg/dL vs –4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March–April 2020 vs 30.8% in November 2020 to January 2021, p

Leggi
Giugno 2022

cfDNA as a surrogate marker for COVID-19 severity in patients with influenza-like symptoms with and without SARS-CoV-2 infections in general practice: a study protocol for a prospective cohort study

Introduction
The clinical course of patients with a SARS-CoV-2 (COVID-19) infection varies widely, from symptom-free to severe courses that can lead to death. Laboratory values of SARS-CoV-2 patients such as lymphocyte counts or C-reactive protein (CRP) do not allow a prediction of the actual course of the disease. To identify a possible predictive marker for the differentiation and prognosis of illness with influenza-like symptoms with and without SARS-CoV-2 infections in general practice, we will analyse the concentrations of cell-free DNA (cfDNA) levels, laboratory and clinical parameters, temperature, oxygen saturation, breathing rate and concomitant symptoms in patients with flu-like symptoms with and without a SARS-CoV-2 infection.

Methods and analysis
This is a single-centre, two-arm, parallel longitudinal cohort study with a total of 44 patients. 22 patients with flu-like symptoms without a SARS-CoV-2 infection and 22 patients with flu-like symptoms with a SARS-CoV-2 infection will be recruited. The primary objective is to compare cfDNA levels in ambulatory patients in general practice with flu-like symptoms with SARS-CoV-2 infection with those with influenza like symptoms without a SARS-CoV-2 infection during the disease (day 7 and day 14). The secondary objective is to determine whether there is a correlation between cfDNA concentrations on the one hand, and laboratory and clinical parameters on the other hand. cfDNA, differential blood count, high-sensitive CRP and erythrocyte sedimentation rate will be measured in blood samples, concomitant symptoms will be surveyed via a self-assessment questionnaire, and oxygen saturation, breathing rate and examination of the lungs will be reported by treating physicians.

Ethics and dissemination
Ethical approval was issued on 1 March 2021 by the Ethics Committee Essen under the number 21-9916-BO. Findings will be published in peer-reviewed open-access journals and presented at national and international conferences.

Trial registration number
DRKS00024722.

Leggi
Giugno 2022

Perceived stress, trust, safety and severity of SARS-CoV-2 infection among patients discharged from hospital during the COVID-19 pandemics first wave: a PREMs survey

Aim
To investigate experiences of stress, feelings of safety, trust in healthcare staff and perceptions of the severity of a SARS-CoV-2 infection among inpatients discharged from Valais Hospital, Switzerland, during the COVID-19 pandemic’s first wave.

Methods
Discharged patients aged 18 years or more (n=4665), hospitalised between 28 February and 11 May 2020, whether they had been infected by SARS-CoV-2 or not, were asked to complete a self-reporting questionnaire, as were their informal caregivers, if available (n=866). Participants answered questions from Cohen’s Perceived Stress Scale (PSS) (0=no stress, 40=severe stress), Krajewska-Kułak et al’s Trust in Nurses Scale and Anderson and Dedrick’s Trust in Physician Scale (10=no trust, 50=complete trust), the severity of a SARS-CoV-2 infection (1=not serious, 5=very serious), as well as questions on their perceived feelings of safety (0=not safe, 10=extremely safe).

Results
Of our 1341 respondents, 141 had been infected with SARS-CoV-2. Median PSS score was 24 (IQR1–3=19–29), median trust in healthcare staff was 33 (IQR1–3=31–36), median perceived severity of a SARS-CoV-2 infection was 4 (IQR1–3=3–4) and the median feelings of safety score was 8 (IQR1–3=8–10). Significant differences were found between males and females for PSS scores (p

Leggi
Giugno 2022

SARS-CoV-2 infection and antibody seroprevalence in routine surveillance patients, healthcare workers and general population in Kita region, Mali: an observational study 2020-2021

Objective
To estimate the degree of SARS-CoV-2 transmission among healthcare workers (HCWs) and general population in Kita region of Mali.

Design
Routine surveillance in 12 health facilities, HCWs serosurvey in five health facilities and community serosurvey in 16 villages in or near Kita town, Mali.

Setting
Kita region, western Mali; local health centres around the central (regional) referral health centre.

Participants
Patients in routine surveillance, HCWs in local health centres and community members of all ages in populations associated with study health centres.

Main outcome measures
Seropositivity of ELISA test detecting SARS-CoV-2-specific total antibodies and real-time RT-PCR confirmed SARS-CoV-2 infection.

Results
From 2392 routine surveillance samples, 68 (2.8%, 95% CI: 2.2% to 3.6%) tested positive for SARS-CoV-2 by RT-PCR. The monthly positivity rate was 0% in June–August 2020 and gradually increased to 6% by December 2020 and 6.2% by January 2021, then declined to 5.5%, 3.3%, 3.6% and 0.8% in February, March, April and May 2021, respectively. From 397 serum samples collected from 113 HCWs, 175 (44.1%, 95% CI: 39.1% to 49.1%) were positive for SARS-CoV-2 antibodies. The monthly seroprevalence was around 10% from September to November 2020 and increased to over 40% from December 2020 to May 2021. For community serosurvey in December 2020, overall seroprevalence of SARS-CoV-2 antibodies was 27.7%. The highest age-stratified seroprevalence was observed in participants aged 60–69 years (45.5%, 95% CI: 32.3% to 58.6%). The lowest was in children aged 0–9 years (14.0%, 95% CI: 7.4% to 20.6%).

Conclusions
SARS-CoV-2 in rural Mali is much more widespread than assumed by national testing data and particularly in the older population and frontline HCWs. The observation is contrary to the widely expressed view, based on limited data, that COVID-19 infection rates were lower in 2020–2021 in West Africa than in other settings.

Leggi
Giugno 2022

Protocol for a prospective quasi-experimental study on SARS-CoV-2 transmission during outdoor sports events in France: the COVID-ESO project

Introduction
The spread of SARS-CoV-2 and its variants in the community remains a major concern despite the application of control measures including the banning of mass sporting events. The circulation of SARS-CoV-2 within the general population, and potentially within the population practicing outdoor sports activities, suggests contexts conducive to the transmission of the virus. We hypothesise that outdoor sports events (OSEs) do not present a higher risk of SARS-CoV-2 contamination. The objective of the COVID-ESO project is to measure if individuals participating in OSE present a similar risk of SARS-CoV-2 transmission compared with individuals not participating in OSE, in France.

Methods and analysis
The COVID-ESO project is a prospective, quasi-experimental study to be conducted in volunteer individuals likely to participate in OSE. Six events are targeted across France to be included. Three sport trials will be eligible for the study: running, cycling and triathlon. Each individual participating in the OSE will choose one of his or her usual training partner to be eligible for the unexposed control group. Individuals will be matched (1:1) on age, sex and the district of residence. Individuals assigned to the exposed group will participate in the OSE, whereas individuals assigned to the unexposed group will not participate in the OSE. All individuals will be asked to perform saliva tests on the day of the event and 7 days after the event. A questionnaire including sociodemographic, clinical and exposure data to SARS-CoV-2 will be sent by email for both groups on the day before the event and 7 days after the event. Differences in SARS-CoV-2 infection rates between the exposed versus the unexposed group will be analysed by fitting a conditional logistic regression model, adjusted for potential confounders. As the sport events unfold, data will be analyzed by performing sequential meta-analyses.

Ethics and dissemination
This protocol has been approved by the ethical committee. Ethical approval has been obtained for the Clinical research and committee of South West of France, 10 June 2021. COMITE DE PROTECTION DES PERSONNES DU SUD-OUEST ET OUTRE-MER 4 under the reference number 21.03.23.71737/CPP2021-04-045 a COVID/2021-A00845-36. Findings generated from this study will be shared to national health and sport authorities.

Leggi
Giugno 2022

Seroprevalence of SARS-CoV-2 virus antibodies and sociodemographic features of pregnant women in Mogadishu, Somalia: a cross-sectional survey study

Objective
Recent investigations have revealed that COVID-19 during pregnancy substantially increases the risk of harmful outcomes for mothers and neonates, including preterm death and stillbirth as well as severe maternal morbidity and mortality. Hence, the urgent need to understand the prevalence rate and level of awareness about COVID-19 (SARS-CoV-2 virus infection) and the practice of preventive measures against the disease among pregnant women in Somalia. This study aims to determine the prevalence of COVID-19 among pregnant women seeking antenatal care in the Benadir region (Mogadishu) of Somalia and to assess their knowledge and preventive practices towards COVID-19.

Setting
A hospital-based cross-sectional study involving two major referral maternity hospitals in Mogadishu, Somalia.

Participants
Pregnant women seeking antenatal services were included in our study.

Methods
A total of 477 blood samples were collected from pregnant women attending the two referral hospitals in Mogadishu and screened for COVID-19. The participants were subjected to questionnaire interviews where their detailed history and practice of prevention against COVID-19 were evaluated.

Results
The results showed that 175 (36.7%) were positive while 302 (63.3%) samples were negative for SARS-CoV-2 virus antibodies. Also, out of the 141 pregnant women who had two children or less, 19.4% were positive for IgG/IgM antibodies. Participants who had close contact with patients with COVID-19 were significantly associated for testing positive with a p value 0.0001. Students, teachers, employed people and individuals reported COVID-19 like symptoms were all associated with COVID-19 seropositivity outcomes.

Conclusion
Pregnant women and those with commorbidies should be given special preventive care and health education about COVID-19 transmission.

Leggi
Giugno 2022

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach

Objectives
We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW).

Design, setting and participants
Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil.

Outcome measures
The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test.

Results
We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34).

Conclusions
This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Leggi
Giugno 2022

Behavioral factors associated with SARS-CoV-2 infection. Results from a web-based case-control survey in the Capital Region of Denmark

Objective
To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection.

Design
Case–control web-based questionnaire study.

Setting
Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly.

Participants
8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality.

Exposure
Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic.

Main outcomes and measures
SARS-CoV-2 infection incidence rate ratios (IRR).

Results
Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52; UC: 0.63) and outdoor sports activities (NC: 0.75; UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79; UC: 0.98), physical distancing (NC: 0.79; UC: 0.82) and avoiding handshakes (NC: 0.74; UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection.

Conclusions
In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

Leggi
Giugno 2022

Rapid antigen testing by community health workers for detection of SARS-CoV-2 in Dhaka, Bangladesh: a cross-sectional study

Objective
To evaluate the diagnostic performance and feasibility of rapid antigen testing for SARS-CoV-2 detection in low-income communities.

Design
We conducted a cross-sectional community-based diagnostic accuracy study. Community health workers, who were trained and supervised by medical technicians, performed rapid antigen tests on symptomatic individuals, and up to two additional household members in their households and diagnostic results were calibrated against the gold standard RT-PCR.

Setting
Low-income communities in Dhaka, Bangladesh.

Participants
Between 19 May 2021 and 11 July 2021, 1240 nasal and saliva samples were collected from symptomatic individuals and 993 samples from additional household members (up to two from one household).

Results
The sensitivity of rapid antigen tests was 0.68 on nasal samples (95% CI 0.62 to 0.73) and 0.41 on saliva (95% CI 0.35 to 0.46), with specificity also higher on nasal samples (0.98, 95% CI 0.97 to 0.99) than saliva (0.87, 95% CI 0.85 to 0.90). Testing up to two additional household members increased sensitivity to 0.71 on nasal samples (95% CI 0.65 to 0.76), but reduced specificity (0.96, 95% CI 0.94 to 0.97). Sensitivity on saliva rose to 0.48 (95% CI 0.42 to 0.54) with two additional household members tested but remained lower than sensitivity on nasal samples. During the study period, testing in these low-income communities increased fourfold through the mobilisation of community health workers for sample collection.

Conclusions
Rapid antigen testing on nasal swabs can be effectively performed by community health workers yielding equivalent sensitivity and specificity to the literature. Household testing by community health workers in low-resource settings is an inexpensive approach that can increase testing capacity, accessibility and the effectiveness of control measures through immediately actionable results.

Leggi
Giugno 2022

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic

Stroke, Ahead of Print. BACKGROUND:Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2.METHODS:We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients

Leggi
Aprile 2022