scholarly journals Using secondary cases to characterize the severity of an emerging or re-emerging infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tim K. Tsang ◽  
Can Wang ◽  
Bingyi Yang ◽  
Simon Cauchemez ◽  
Benjamin J. Cowling
Keyword(s):  
Infectious Disease ◽  
Systematic Review ◽  
Statistical Model ◽  
Disease Severity ◽  
Severe Disease ◽  
Clinical Severity ◽  
Contact Tracing ◽  
Emerging Infection ◽  
Index Cases ◽  
Extract Information

AbstractThe methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. Here, we conducted a systematic review to extract information on disease severity among index cases and secondary cases identified by contact tracing of index cases for COVID-19. We identified 38 studies to extract information on measures of clinical severity. The proportion of index cases with fever was 43% higher than for secondary cases. The proportion of symptomatic, hospitalized, and fatal illnesses among index cases were 12%, 126%, and 179% higher than for secondary cases, respectively. We developed a statistical model to utilize the severity difference, and estimate 55% of index cases were missed in Wuhan, China. Information on disease severity in secondary cases should be less susceptible to ascertainment bias and could inform estimates of disease severity and the proportion of missed index cases.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Hayley A Thompson ◽  
Andria Mousa ◽  
Amy Dighe ◽  
Han Fu ◽  
Alberto Arnedo-Pena ◽  
...  
Keyword(s):  
Systematic Review ◽  
Severe Acute Respiratory Syndrome ◽  
Negative Binomial ◽  
Meta Analysis ◽  
Contact Tracing ◽  
Binomial Model ◽  
Transmission Potential ◽  
Transmission Rates ◽  
Symptom Status ◽  
Index Cases

Abstract Background Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited. Methods We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs. Results Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4–24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings. Conclusions Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings.

scholarly journals Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Flook ◽  
C. Jackson ◽  
E. Vasileiou ◽  
C. R. Simpson ◽  
M. D. Muckian ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Systematic Review ◽  
At Risk ◽  
Risk Factor ◽  
Disease Severity ◽  
Severe Disease ◽  
Public Health Response ◽  
Wide Range ◽  
Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

scholarly journals Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis

2021 ◽  
Author(s):  
Panagiotis Paliogiannis ◽  
Arduino Aleksander Mangoni ◽  
Michela Cangemi ◽  
Alessandro Giuseppe Fois ◽  
Ciriaco Carru ◽  
...  
Keyword(s):  
Systematic Review ◽  
Serum Albumin ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Geographic Area ◽  
Adverse Outcomes ◽  
Poor Outcome ◽  
Standard Mean Difference ◽  
Meta Regression Analysis

AbstractCoronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t =  − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t =  − 2.77, p = 0.008) and C-reactive protein (t =  − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

scholarly journals Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis

2021 ◽  
pp. archdischild-2020-321385
Author(s):  
Omar Irfan ◽  
Fiona Muttalib ◽  
Kun Tang ◽  
Li Jiang ◽  
Zohra S Lassi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
World Bank ◽  
Low Income ◽  
Meta Analysis ◽  
Severe Disease ◽  
Income Level ◽  
Clinical Findings ◽  
Middle Income ◽  
Middle Income Countries

ObjectiveCompare paediatric COVID-19 disease characteristics, management and outcomes according to World Bank country income level and disease severity.DesignSystematic review and meta-analysis.SettingBetween 1 December 2019 and 8 January 2021, 3350 articles were identified. Two reviewers conducted study screening, data abstraction and quality assessment independently and in duplicate. Observational studies describing laboratory-confirmed paediatric (0–19 years old) COVID-19 were considered for inclusion.Main outcomes and measuresThe pooled proportions of clinical findings, treatment and outcomes were compared according to World Bank country income level and reported disease severity.Results129 studies were included from 31 countries comprising 10 251 children of which 57.4% were hospitalised. Mean age was 7.0 years (SD 3.6), and 27.1% had a comorbidity. Fever (63.3%) and cough (33.7%) were common. Of 3670 cases, 44.1% had radiographic abnormalities. The majority of cases recovered (88.9%); however, 96 hospitalised children died. Compared with high-income countries, in low-income and middle-income countries, a lower proportion of cases were admitted to intensive care units (ICUs) (9.9% vs 26.0%) yet pooled proportion of deaths among hospitalised children was higher (relative risk 2.14, 95% CI 1.43 to 3.20). Children with severe disease received antimicrobials, inotropes and anti-inflammatory agents more frequently than those with non-severe disease. Subgroup analyses showed that a higher proportion of children with multisystem inflammatory syndrome (MIS-C) were admitted to ICU (47.1% vs 22.9%) and a higher proportion of hospitalised children with MIS-C died (4.8% vs 3.6%) compared with the overall sample.ConclusionPaediatric COVID-19 has a favourable prognosis. Further severe disease characterisation in children is needed globally.

scholarly journals Factors Associated with Disease Severity and Mortality among Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Vignesh Chidambaram ◽  
Nyan Lynn Tun ◽  
Waqas Haque ◽  
Marie Gilbert Majella ◽  
Ranjith Kumar Sivakumar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
English Language ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Data Extraction ◽  
Meta Analysis ◽  
Severe Disease ◽  
Factors Associated ◽  
Risk Of Mortality

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45; 95%CI 1.23,1.71), dyspnea (RR 2.55; 95%CI 1.88,2.46), diabetes (RR 1.59; 95%CI 1.41,1.78), hypertension (RR 1.90; 95%CI 1.69,2.15). Congestive heart failure (OR 4.76; 95%CI 1.34,16.97), hilar lymphadenopathy (OR 8.34; 95%CI 2.57,27.08), bilateral lung involvement (OR 4.86; 95%CI 3.19,7.39) and reticular pattern (OR 5.54; 95%CI 1.24,24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

scholarly journals SARS-CoV-2 circulation in the school setting: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Chiara Martinoli ◽  
Carlo La Vecchia ◽  
Sara Raimondi ◽  
Federica Bellerba ◽  
Clementina Sasso ◽  
...  
Keyword(s):  
Systematic Review ◽  
Odds Ratio ◽  
Meta Analysis ◽  
School Setting ◽  
Viral Transmission ◽  
Contact Tracing ◽  
Random Effects Models ◽  
Viral Spread ◽  
Literature Searches ◽  
Index Cases

Background. The contribution of children to viral spread in schools is still under debate. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Methods: Literature searches from April, 2021 and repeated on May, 15th 2021 yielded a total of 1088 publications: screening, contact tracing and seroprevalence studies. MOOSE guidelines were followed and data analyzed using random-effects models. Results: From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% Confidence Interval [CI] 0.05-0.81%) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%; 95%CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (Odds Ratio [OR]=0.26; 95%CI 0.11-0.63) and were less susceptible to infection (OR=0.60; 95% CI 0.25-1.47). Finally, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children are 43% significantly less likely than adults to test positive for antibodies (OR=0.57; 95%CI: 0.49-0.68). In conclusion, testing all subjects in schools, independently of symptoms, students less likely than adults favor viral spread and SARS-CoV-2 circulation in schools was found to be limited.

scholarly journals Laboratory Tests and Outcome for Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 5 (5) ◽  
pp. 1038-1049 ◽  
Author(s):  
Anne Alnor ◽  
Maria B Sandberg ◽  
Charlotte Gils ◽  
Pernille J Vinholt
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Laboratory Tests ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Routine Laboratory ◽  
Standard Mean Difference

Abstract Background Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. Content PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Summary 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p &lt; 0.001. Furthermore, low lymphocyte count (MD −0.32 × 109/L), platelet count (MD −22.4 × 109/L), and hemoglobin (MD, −4.1 g/L); all p &lt; 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

scholarly journals Contact Tracing of COVID-19 in Karnataka, India: Superspreading and Determinants of Infectiousness and Symptomaticity

2020 ◽  
Author(s):  
Mohak Gupta ◽  
Giridara G Parameswaran ◽  
Manraj S Sra ◽  
Rishika Mohanta ◽  
Devarsh Patel ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Attack Rate ◽  
Clinical Severity ◽  
Contact Tracing ◽  
Significant Heterogeneity ◽  
Symptomatic Infection ◽  
Individual Level ◽  
Serial Interval ◽  
Index Cases ◽  
Degree Of Heterogeneity

Brief AbstractWe analysed SARS-CoV-2 surveillance and contact tracing data from Karnataka, India up to 21 July 2020. We estimated metrics of infectiousness and the tendency for superspreading (overdispersion), and evaluated potential determinants of infectiousness and symptomaticity in COVID-19 cases. Among 956 cases confirmed to be forward-traced, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases, suggesting significant heterogeneity in individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in underlying number of contacts. Secondary attack rate was 3.6% among 16715 close contacts. Transmission was higher when index case was aged >18 years, or was symptomatic (adjusted risk ratio, aRR 3.63), or was lab-confirmed ≥4 days after symptom onset (aRR 3.01). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 times more likely to generate symptomatic secondaries. This could potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are suggested to confirm this. Mean serial interval was 5.4 days. Adding backward contact tracing and targeting control measures to curb super-spreading may be prudent. Due to low symptomaticity and infectivity, interventions aimed at children might have a relatively small impact on reducing transmission.Structured AbstractBackgroundIndia has experienced the second largest outbreak of COVID-19 globally, yet there is a paucity of studies analysing contact tracing data in the region. Such studies can elucidate essential transmission metrics which can help optimize disease control policies.MethodsWe analysed contact tracing data collected under the Integrated Disease Surveillance Programme from Karnataka, India between 9 March and 21 July 2020. We estimated metrics of disease transmission including the reproduction number (R), overdispersion (k), secondary attack rate (SAR), and serial interval. R and k were jointly estimated using a Bayesian Markov Chain Monte Carlo approach. We evaluated the effect of age and other factors on the risk of transmitting the infection, probability of asymptomatic infection, and mortality due to COVID-19.FindingsUp to 21 July, we found 111 index cases that crossed the super-spreading threshold of ≥8 secondary cases. R and k were most reliably estimated at R 0.75 (95% CI, 0.62-0.91) and k 0.12 (0.11-0.15) for confirmed traced cases (n=956); and R 0.91 (0.72-1.15) and k 0.22 (0.17-0.27) from the three largest clusters (n=394). Among 956 confirmed traced cases, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases. Among 16715 contacts, overall SAR was 3.6% (3.4-3.9) and symptomatic cases were more infectious than asymptomatic cases (SAR 7.7% vs 2.0%; aRR 3.63 [3.04-4.34]). As compared to infectors aged 19-44 years, children were less infectious (aRR 0.21 [0.07-0.66] for 0-5 years and 0.47 [0.32-0.68] for 6-18 years). Infectors who were confirmed ≥4 days after symptom onset were associated with higher infectiousness (aRR 3.01 [2.11-4.31]). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 (3.29-20.24) times more likely to generate symptomatic secondaries. Serial interval had a mean of 5.4 (4.4-6.4) days with a Weibull distribution. Overall case fatality rate was 2.5% (2.4-2.7) which increased with age.ConclusionWe found significant heterogeneity in the individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in the underlying number of contacts. To strengthen contact tracing in over-dispersed outbreaks, testing and tracing delays should be minimised, retrospective contact tracing should be considered, and contact tracing performance metrics should be utilised. Targeted measures to reduce potential superspreading events should be implemented. Interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission owing to their low symptomaticity and infectivity. There is some evidence that symptomatic cases produce secondary cases that are more likely to be symptomatic themselves which may potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are needed to confirm this finding.FundingGiridhara R Babu is funded by an Intermediate Fellowship by the Wellcome Trust DBT India Alliance (Clinical and Public Health Research Fellowship); grant number: IA/CPHI/14/1/501499.

scholarly journals Differential Association of Viral Dynamics With Disease Severity Depending on Patients’ Age Group in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuri Kim ◽  
Shinhyea Cheon ◽  
Hyeongseok Jeong ◽  
Uni Park ◽  
Na-Young Ha ◽  
...  
Keyword(s):  
Viral Load ◽  
Elderly Patients ◽  
Disease Severity ◽  
Acute Phase ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Clinical Severity ◽  
Younger Patients

Despite a clear association of patient’s age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of viral load dynamics with patient’s age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients’ plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.

scholarly journals D Dimer – Prognostic indicator for disease severity in patients hospitalised with COVID 19

2021 ◽  
Vol 8 (4) ◽  
pp. 461-464
Author(s):  
Vineet Banga ◽  
Stuti Jain
Keyword(s):  
Retrospective Study ◽  
Disease Severity ◽  
Severe Disease ◽  
Prognostic Indicator ◽  
Clinical Severity ◽  
Care Hospital ◽  
Severity Of Disease ◽  
Management Protocol ◽  
Severity Levels ◽  
D Dimer

Patients of Covid 19 infections present with different severity. Levels of D Dimer in these patients can be correlated with disease severity for management and prognosis. To evaluate the usefulness of D-Dimer levels in blood to correlate with disease severity in COVID 19 patients. Retrospective study was done in Department of Pathology of Secondary Care hospital that became designated covid hospital from May 2021 to June 2021 on 60 COVID 19 positive admitted patients. D dimer levels were analysed and correlated with clinical severity of disease. Out of total 60 patients, 33 were in mild, 23 in moderate and 4 were in severe category. In mild cases D Dimer varies from 43 ng/ml to 183 ng/ml. In moderate cases D Dimer varies from 270 ng/ml to 991 ng/ml. In severe cases D Dimer varies from 1043 ng/ml to 2463 ng/ml. The study suggests cut off levels for D Dimer as up to 200 ng/ml for mild, 200-1000 ng/ml for moderate and more than 1000 ng/ml for severe category in COVID 19 patients. D dimer helps in identifying severe disease and can be used as an essential biomarker in developing the management protocol for COVID 19 patients.

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