Explore the vast range of titles available.

•Vaccination did not reduce symptoms of post-acute sequelae (PASC).•Antibody kinetics did not differ between participants with and without PASC.•Early antibody titers were comparable between participants with and without PASC.•Therapeutic potential of COVID-19 vaccination on PASC seems unlikely. Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC. RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression. Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46–5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183–324) and 181 (147–230) among participants with PASC, and 170 (125–252) and 144 (113–196) among those without PASC, respectively. Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.

Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70–0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79–0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63–0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65–0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence. This meta-analysis demonstrates that people who received COVID-19 vaccination had a lower risk of long COVID compared with those who were unvaccinated during the Omicron era, with booster doses providing additional protection beyond a primary course.

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

BackgroundGovernments used travel bans during the COVID-19 pandemic to limit the introduction of new variant of concern (VoC). In the Netherlands, direct flights from South Africa were banned from 26 November 2021 onwards to curb Omicron (B.1.1.529) importation.ObjectivesThis study retrospectively evaluated the effect of the South African travel ban and the timing of its implementation on subsequent Omicron infections in the Netherlands and, in order to help inform future decision-making, assessed alternative scenarios in which the reproduction number (Re) and volume of indirectly imported cases were varied.DesignDescriptive analysis and modelling study.Outcome measureTime (days) from 26 November 2021 to reach 10 000 cumulative Omicron infections in the Netherlands.MethodsTo benchmark the direct importation rate of Omicron from South Africa, we used the proportion (n/N, %) of passengers arriving on two direct flights from South Africa to the Netherlands on 26 November 2021 with a positive PCR sequencing result for Omicron VoC infection. We scaled the number of directly-imported Omicron infections before and after the travel ban to the incidence in South Africa. We assumed that 10% of all cases continued to arrive via indirect routes, a ‘failure rate’ of 2% (ie, incoming Dutch citizens not adhering to quarantine on arrival) and an effective reproduction number (Re) of Omicron of 1.3. In subsequent analyses, we varied, within plausible limits, the Re (1.1–2.0) and proportion of indirectly-imported cases (0–20%).ResultsCompared with no travel ban, the travel ban achieved a 14-day delay in reaching 10 000 Omicron cases, with an additional day of delay if initiated 2 days earlier. If all indirect importation had been prevented (eg, European-wide travel ban), a 21-day delay could have been achieved. The travel ban’s effect was negligible if Re was ≥2.0 and with a greater volume of ongoing importation.ConclusionsTravel bans can delay the calendar timing of an outbreak but are substantially less effective for pathogens where importation cannot be fully controlled and tracing every imported case is unfeasible. When facing future disease outbreaks, we urge policy-makers to critically weigh up benefits against the known socioeconomic drawbacks of international travel restrictions.

Introduction Point‐of‐care testing for CD4 cell count is considered a promising way of reducing the time to eligibility assessment for antiretroviral therapy (ART) and of increasing retention in care prior to treatment initiation. In this review, we assess the available evidence on the patient and programme impact of point‐of‐care CD4 testing. Methods We searched nine databases and two conference sites (up until 26 October 2013) for studies reporting patient and programme outcomes following the introduction of point‐of‐care CD4 testing. Where appropriate, results were pooled using random‐effects methods. Results Fifteen studies, mainly from sub‐Saharan Africa, were included for review, providing evidence for adults, adolescents, children and pregnant women. Compared to conventional laboratory‐based testing, point‐of‐care CD4 testing increased the likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5–4.9, n=2] and receiving a CD4 result (OR 2.8, 95% CI 1.5–5.6, n=6). Time to being tested was significantly reduced, by a median of nine days; time from CD4 testing to receiving the result was reduced by as much as 17 days. Evidence for increased treatment initiation was mixed. Discussion The results of this review suggest that point‐of‐care CD4 testing can increase retention in care prior to starting treatment and can also reduce time to eligibility assessment, which may result in more eligible patients being initiated on ART.

Background It is important to gain insight into the burden of COVID-19 at city district level to develop targeted prevention strategies. We examined COVID-19 related hospitalisations by city district and migration background in the municipality of Amsterdam, the Netherlands. Methods We used surveillance data on all PCR-confirmed SARS-CoV-2 hospitalisations in Amsterdam until 31 May 2020, matched to municipal registration data on migration background. We calculated directly standardised (age, sex) rates (DSR) of hospitalisations, as a proxy of COVID-19 burden, per 100,000 population by city district and migration background. We calculated standardised rate differences (RD) and rate ratios (RR) to compare hospitalisations between city districts of varying socio-economic and health status and between migration backgrounds. We evaluated the effects of city district and migration background on hospitalisation after adjusting for age and sex using Poisson regression. Results Between 29 February and 31 May 2020, 2326 cases (median age 57 years [IQR = 37–74]) were notified in Amsterdam, of which 596 (25.6%) hospitalisations and 287 (12.3%) deaths. 526/596 (88.2%) hospitalisations could be matched to the registration database. DSR were higher in individuals living in peripheral (South-East/New-West/North) city districts with lower economic and health status, compared to central districts (Centre/West/South/East) (RD = 36.87,95%CI = 25.79–47.96;RR = 1.82,95%CI = 1.65–1.99), and among individuals with a non-Western migration background compared to ethnic-Dutch individuals (RD = 57.05,95%CI = 43.34–70.75; RR = 2.36,95%CI = 2.17–2.54). City district and migration background were independently associated with hospitalisation. Conclusion City districts with lower economic and health status and those with a non-Western migration background had the highest burden of COVID-19 during the first wave of COVID-19 in Amsterdam.

Evidence on long COVID remains limited in sub-Saharan countries. This study explored the occurrence of COVID-19-related symptoms and factors affecting recovery and long COVID severity in Nairobi, Kenya. A prospective cohort of individuals testing positive for SARS-CoV-2 between February 2022 and February 2023 was followed until June 2023. COVID-19-related symptoms were assessed every three months. Time to recovery was analyzed using survival analysis, while factors affecting recovery factors and long COVID severity using Cox proportional hazard and Poisson regression, respectively. Among 291 participants (median age 34, 59.1% female), 42 (14%) had severe/critical infection. At 6 and 12 months post-positive PCR, 53.1% and 33.5% had ≥ 1 COVID-19-related symptoms, respectively. Fatigue (40.2%), pain (36.8%), sore throat (36.8%), headaches (36.4%), and loss of strength (31.6%) were most common. Median time to recovery was longer for severe/critical cases than mild/moderate (234 vs 206 days,  = 0.016). Participants aged 40-64 years experienced slower recovery than those aged < 40 years (aHR = 0.635 [95%CI, 0.429;0.941]). Participants with tertiary education recovered faster than those with primary education (aHR = 1.869 [95%CI, 1.050;3.327]). Long COVID severity was associated with female sex (aIRR = 1.418 [95%CI; 1.078;1.864]), tertiary education (aIRR, 0.489 [95%CI, 0.415;0.576]), and ≥ 1 comorbidity (aIRR = 2.415 [95%CI, 1.639;3.559]). Six months post-infection, half had lingering symptoms, with a third still affected after a year. Recovery was faster in younger, educated individuals, while severe long COVID was more common in women, those with low education and pre-existing conditions. The burden of long COVID in Kenya requires support for vulnerable groups.

IntroductionAcute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.Methods and analysisThis is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.Ethics and disseminationResults will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).Trial registration numberInternational Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).

Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231-556] and 214 [95% CI 153-299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11-30] and 14 [95% CI 8-25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02-0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data. Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC. RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (D.sub.LCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects. 186/349 (53%) participants had [greater than or equal to]2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNF[alpha] at 24 weeks. Early (0-4 week) IL-1[beta] and BMI at COVID-19 onset were predictive of PASC at 24 weeks. Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1[beta] shows promise as a predictor of PASC.