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The Lancet. Microbe Apr 2023The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy.
METHODS
We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238.
FINDINGS
28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies.
INTERPRETATION
The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues.
FUNDING
Shenzhen Science and Technology Programs.
Topics: Humans; COVID-19 Vaccines; Asymptomatic Infections; COVID-19; SARS-CoV-2; Immunoglobulin G; Randomized Controlled Trials as Topic
PubMed: 36868258
DOI: 10.1016/S2666-5247(22)00390-1 -
International Journal of Environmental... Feb 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection has brought new challenges to the global prevention and control of coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Humans; SARS-CoV-2; COVID-19; Reinfection; Health Education; Hospitalization
PubMed: 36834029
DOI: 10.3390/ijerph20043335 -
The Pediatric Infectious Disease Journal Mar 2023Asymptomatic SARS-CoV-2 infections have raised concerns for public health policies to manage epidemics. This systematic review and meta-analysis aimed to estimate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asymptomatic SARS-CoV-2 infections have raised concerns for public health policies to manage epidemics. This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons globally by year of age.
METHODS
We searched PubMed, Embase, medRxiv and Google Scholar on September 10, 2020, and March 1, 2021. We included studies conducted during January to December 2020, before routine vaccination against COVID-19. Because we expected the relationship between the asymptomatic proportion and age to be nonlinear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age.
RESULTS
A total of 38 studies were included in the meta-analysis. In total, 6556 of 14,850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14,850, 95% CI: 43.3%-45.0%). The predicted asymptomatic proportion peaked in children (36.2%, 95% CI: 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95% CI: 3.4%-12.7%).
CONCLUSIONS
Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.
Topics: Child; Adolescent; Young Adult; Humans; COVID-19; SARS-CoV-2; Epidemics; Public Health; Asymptomatic Infections
PubMed: 36730054
DOI: 10.1097/INF.0000000000003791 -
International Journal of Environmental... Jan 2023Little 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Humans; COVID-19; SARS-CoV-2; Ageusia; Asymptomatic Infections; Fatigue
PubMed: 36674367
DOI: 10.3390/ijerph20021613 -
Open Forum Infectious Diseases Jan 2023Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment...
BACKGROUND
Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment but are often labor intensive, and thus an automated means of reducing unnecessary urine testing is preferred. In this systematic review and meta-analysis, we sought to identify studies describing interventions utilizing clinical decision support (CDS) to optimize UTI diagnosis and to characterize the effectiveness of these interventions.
METHODS
We conducted a comprehensive electronic search and manual reference list review for peer-reviewed articles published before July 2, 2021. Publications describing an intervention intending to enhance UTI diagnosis via CDS were included. The primary outcome was urine culture test rate.
RESULTS
The electronic search identified 5013 studies for screening. After screening and full-text review, 9 studies met criteria for inclusion, and a manual reference list review identified 5 additional studies, yielding a total of 14 studies included in the systematic review. The most common CDS intervention was urinalysis with reflex to urine culture based on prespecified urinalysis parameters. All 9 studies that provided statistical comparisons reported a decreased urine culture rate postintervention, 8 of which were statistically significant. A meta-analysis including 4 studies identified a pooled urine culture incidence rate ratio of 0.56 (95% confidence interval, .52-.60) favoring the postintervention versus preintervention group.
CONCLUSIONS
In this systematic review and meta-analysis, CDS appeared to be effective in decreasing urine culture rates. Prospective trials are needed to confirm these findings and to evaluate their impact on antimicrobial prescribing, patient-relevant outcomes, and potential adverse effects.
PubMed: 36632418
DOI: 10.1093/ofid/ofac691 -
Vaccines Dec 2022Background: Monkeypox is a global public health concern, given the recent outbreaks in non-endemic countries where little scientific evidence exists on the disease.... (Review)
Review
Background: Monkeypox is a global public health concern, given the recent outbreaks in non-endemic countries where little scientific evidence exists on the disease. Specifically, there is a lack of data on asymptomatic monkeypox virus infection. This study aims to evaluate the overall prevalence of asymptomatic monkeypox virus infection. Methods: In this systematic review and meta-analysis, we performed an extensive literature search in PubMed, Scopus, Web of Science, ProQuest, EMBASE, EBSCOHost, Cochrane, and preprint servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN, and SSRN) and assessed all published articles till September 2022. Primary studies reporting monkeypox infections among asymptomatic participants were included after quality assessment. The characteristics of the study and information on the number of cases and symptomatic status were extracted from the included studies. The heterogeneity between studies was assessed using the I2 statistic. Publication bias was analyzed using funnel plots and Egger regression tests. The primary outcome was the pooled prevalence of asymptomatic infections within the examined population. Results: A total of 16 studies were included for qualitative synthesis, while five studies, including 645 individuals, were included for quantitative synthesis. There was substantial heterogeneity between studies (I2 = 94.86%; p < 0.01), with a pooled percentage of asymptomatic infections in the studied population of 10.2% (95%CI, 2.5−17.9%). Conclusion: This meta-analysis suggests that many people infected with the monkeypox virus are asymptomatic and difficult to detect. Therefore, prompt detection of these cases of monkeypox virus and appropriate subsequent management is of utmost importance to global public health.
PubMed: 36560493
DOI: 10.3390/vaccines10122083 -
Journal of Evidence-based Medicine Dec 2022Contact tracing plays an essential role in mitigating the impact of an epidemic. During the COVID-19 pandemic, studies of those who have been in close contact with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Contact tracing plays an essential role in mitigating the impact of an epidemic. During the COVID-19 pandemic, studies of those who have been in close contact with confirmed cases offer critical insights to understand the epidemiological characteristics of SARS-CoV-2 better. This study conducts a meta-analysis of existing studies' infection rates and affecting factors.
METHODS
We searched PubMed, Web of Science and CNKI from the inception to April 30 2022 to identify systematic reviews. Two reviewers independently extracted the data and assessed risk of bias. Meta-analyses were conducted to calculate pooled estimates by using Stata/SE 15.1 software.
RESULTS
There were 47 studies in the meta-analysis. Among COVID-19 close contacts, older age (RR = 1.94, 95% CI: 1.70, 2.21), contacts in households (RR = 2.83, 95% CI: 2.20, 3.65), and people in close contact with symptomatic infections (RR = 3.62, 95% CI: 1.88, 6.96) were associated with higher infection rates.
CONCLUSION
On average, each primary infection corresponded to 5.8 close contacts. Among COVID-19 close contacts, older age and contacts in households were associated with higher infection rates, and people in close contact with symptomatic infections had three times higher risk of infection compared to people in close contact with asymptomatic infections. In general, there are significantly more studies from China about close contacts, and the infection rate among close contacts was lower compared to other countries.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; Contact Tracing; China
PubMed: 36513958
DOI: 10.1111/jebm.12508 -
Ultrasound in Obstetrics & Gynecology :... Apr 2023Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection.
METHODS
MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy.
RESULTS
Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low.
CONCLUSIONS
Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Cytomegalovirus Infections; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Prenatal Care; Valacyclovir
PubMed: 36484439
DOI: 10.1002/uog.26136 -
World Journal of Methodology Nov 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Various...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Various researchers have worked to elucidate the pathogenic mechanisms underlying these variable presentations. Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors, including sex steroid hormones. Transgender men or non-binary individuals who undergo gender-affirming hormone therapy (GAHT) are a unique population of interest for exploring the androgen-mediated coronavirus disease 2019 (COVID-19) hypothesis. As the search for reliable and effective COVID-19 treatments continues, understanding the risks and benefits of GAHT may mitigate COVID-19 related morbidity and mortality in this patient population.
AIM
To investigate the potential role of GAHT in the development of COVID-19 infections and complications.
METHODS
This systematic review implemented an algorithmic approach using PRISMA guidelines. PubMed, Scopus, Google Scholar top 100 results, and archives of was on January 12, 2022 using the key words "gender" AND "hormone" AND "therapy" AND "COVID-19" as well as associated terms. Non-English articles, articles published prior to 2019 (prior to COVID-19), and manuscripts in the form of reviews, commentaries, or letters were excluded. References of the selected publications were screened as well.
RESULTS
The database search resulted in the final inclusion of 14 studies related to GAHT COVID-19. Of the included studies, only two studies directly involved and reported on COVID-19 in transgender patients. Several clinical trials looked at the relationship between testosterone, estrogen, and progesterone in COVID-19 infected cis-gender men and women. It has been proposed that androgens may facilitate initial COVID-19 infection, however, once this occurs, testosterone may have a protective effect. Multiple clinical studies have shown that low baseline testosterone levels in men with COVID-19 are associated with worsening outcomes. The role of female sex hormones, including estrogen and progesterone have also been proposed as potential protective factors in COVID-19 infection. This was exemplified in multiple studies investigating different outcomes in pre- and post-menopausal women as well as those taking hormone replacement therapy. Two studies related specifically to transgender patients and GAHT found that estrogen and progesterone could help protect men against COVID-19, and that testosterone hormone therapy may increase the risk of contracting COVID-19.
CONCLUSION
Few studies were found related to the role of GAHT in COVID-19 infections. Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.
PubMed: 36479311
DOI: 10.5662/wjm.v12.i6.465 -
Malaria Journal Dec 2022In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those... (Review)
Review
BACKGROUND
In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those performing forest-related work. Furthermore, asymptomatic cases of P. knowlesi malaria have been reported including among women and children.
METHODS
Pubmed, Scopus and the Web of Science databases for literature describing asymptomatic P. knowlesi malaria published between 2010 and 2020 were searched. A systematic literature review was conducted to identify studies reporting the prevalence and incidence of laboratory confirmed asymptomatic P. knowlesi cases in humans, their clinical and demographic characteristics, and methods used to diagnose these cases.
RESULTS
By analysing over 102 papers, thirteen were eligible for this review. Asymptomatic P. knowlesi infections have been detected in 0.03%-4.0% of the population depending on region, and infections have been described in children as young as 2 years old. Various different diagnostic methods were used to detect P. knowlesi cases and there were differing definitions of asymptomatic cases in these studies. The literature indicates that regionally-differing immune-related mechanisms may play a part on the prevalence of asymptomatic P. knowlesi.
CONCLUSION
Differing epidemiological characteristics of asymptomatic P. knowlesi malaria in different regions reinforces the need to further investigate disease transmission mechanics. Effective public health responses to changes in P. knowlesi epidemiology require proactive intervention and multisectoral collaboration.
Topics: Child; Humans; Female; Child, Preschool; Plasmodium knowlesi; Communicable Diseases, Emerging
PubMed: 36474243
DOI: 10.1186/s12936-022-04339-8