ABSTRACT
BackgroundBy March 2023, 54 countries, areas and territories (thereafter "CAT") reported over 2.2 million coronavirus disease 2019 (COVID-19) deaths to the World Health Organization (WHO) Regional Office for Europe (1). Here, we estimate how many lives were directly saved by vaccinating adults in the Region, from December 2020 through March 2023. MethodsWe estimated the number of lives directly saved by age-group, vaccine dose and circulating Variant of Concern (VOC) period, both regionally and nationally, using weekly data on COVID-19 mortality and COVID-19 vaccine uptake reported by 34 CAT, and vaccine effectiveness (VE) data from the literature. We calculated the percentage reduction in the number of expected and reported deaths. FindingsWe found that vaccines reduced deaths by 57% overall (CAT range: 15% to 75%), representing [~]1.4 million lives saved in those aged [≥]25 years (range: 0.7 million to 2.6 million): 96% of lives saved were aged [≥]60 years and 52% were aged [≥]80 years; first boosters saved 51%, and 67% were saved during the Omicron period. InterpretationOver nearly 2.5 years, most lives saved by COVID-19 vaccinationwere in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FundingThis work was supported by a US Centers for Disease Control cooperative agreement (Grant number 6 NU511P000936-02-020), who had no role in data analysis or interpretation. DisclaimerThe authors affiliated with the World Health Organization (WHO) are alone responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince first identified in late 2019, COVID-19 has caused disproportionately high mortality rates in older adults. With the rapid development and licensing of novel COVID-19 vaccines, immunization campaigns across the WHO European Region started in late 2020 and early 2021, initially targeting the most vulnerable and exposed populations, including older adults, people with comorbidities and healthcare professionals. Several studies have estimated the number of lives saved by COVID-19 vaccination, both at national and multi-country level in the earlier stages of the pandemic. However, only one multi-country study has assessed the number of lives saved beyond the first year of the pandemic, particularly when the Omicron variant of concern (VOC) circulated, a period when vaccination coverage was high in many countries, areas and territories (CAT), but COVID-19 transmission was at its highest. Added value of this studyHere we quantified the impact of COVID-19 vaccination in adults by age-group, vaccine dose and period of circulation of VOC, across diverse settings, using real world data reported by 34 CAT in the WHO European Region for the period December 2020 to April 2023. We estimated that COVID-19 vaccination programs were associated with a 57% reduction (CAT range: 15% to 75%) in the number of deaths among the [≥]25 years old, representing over 1.5 million lives saved (range: 0.7 million to 2.6 million) in 34 European CAT during the first 2.5 years following vaccine introduction. The first booster savedthe most lives (721,122 / 1,408,967, (57%) of all lives saved). The [≥]60 years old age group accounted for 96% of the total lives saved (1,349,617 / 1,408,967) whereas the [≥]80 years old age group represented 52% of the total lives saved (728,858 / 1,408,967 lives saved) and 67% of all lives were saved during the Omicron period (942,571 / 1,408,967). Implications of all the available evidenceOur results reinforce the importance of up-to-date COVID-19 vaccination, particularly among older age-groups. Communication campaigns supporting COVID-19 vaccination should stress the value of COVID-19 vaccination in saving lives to ensure vulnerable groups are up-to-date with vaccination ahead of periods of potential increased transmission.
Subject(s)
COVID-19ABSTRACT
Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased SARS-CoV-2 testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of newly emerged variants. The Joint WHO Regional Office for Europe and ECDC Infection Severity Working Group was formed to produce and pilot a standardised study protocol to estimate relative variant case-severity in settings with individual-level SARS-CoV-2 testing and COVID-19 outcome data during periods when two variants were co-circulating. To assess feasibility, the study protocol and its associated statistical analysis code was applied by local investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the case-severity of Omicron BA.1 relative to Delta cases. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio [aHR]=0.41, 95% CI 0.31-0.54), ICU admission (aHR=0.12, 95% CI 0.05-0.27), and death (aHR=0.31, 95% CI 0.28-0.35) was lower for Omicron BA.1 compared to Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study has demonstrated the feasibility of conducting variant severity analyses in a multinational collaborative framework. The results add further evidence for the reduced severity of the Omicron BA.1 variant.
Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , DeathABSTRACT
Background There have been no population-based studies of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions across the full paediatric age range. We examine the epidemiology of SARS-CoV-2 in children and young people (CYP) aged <23 years. Methods We used a birth cohort of all children born in Scotland since 1997, constructed via linkage between vital statistics, hospital records and SARS-CoV-2 surveillance data. We calculated risks of tests and PCR-confirmed infections per 1000 CYP-years between August and December 2020, and COVID-19-related hospital admissions per 100,000 CYP-years between February and December 2020. We used Poisson and Cox proportional hazards regression models to determine risk factors. Results Among the 1226855 CYP in the cohort, there were 378402 tests, 19005 PCR confirmed infections and 346 admissions, corresponding to rates of 770.8/1000 (95% confidence interval 768.4-773.3), 179.4 (176.9-182.0) and 29.4/100,000 (26.3-32.8) CYP-years respectively. Infants had the highest COVID-19-related admission rates. Chronic conditions, particularly multiple types of conditions, was strongly associated with COVID-19-related admissions across all ages. The hazard ratio for >1 chronic condition type was 12.2 (7.9-18.82) compared to children with no chronic conditions. 89% of admitted children had no chronic conditions recorded. Conclusions Infants, and CYP with chronic conditions are at highest risk of admission with COVID-19, however the majority of admitted CYP have no chronic conditions. These results provide evidence to support risk/benefit analyses for paediatric COVID-19 vaccination programmes. Studies examining whether maternal vaccine during pregnancy prevents COVID-19 admissions in infants are urgently needed. Funding UK Research and Innovation-Medical Research Council
Subject(s)
COVID-19ABSTRACT
ObjectivesTo investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland. DesignCase-crossover study comparing recent (1-14 days after vaccination) with less recent exposure to vaccination among cases of CVT. SettingNational data for Scotland from 1 December 2020, with diagnosed CVT case ascertainment through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021 and with linkage to vaccination records. Main outcome measurePrimary acute cerebral venous thrombosis ResultsOf 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). The 95% credible interval for the rate ratio associated with recent versus less recent exposure to BNT162b2 (0.6 to 95.8) was too wide for useful inference. ConclusionsThese findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear. What is already known on this topicThe risk of cerebral venous thrombosis (CVT) within 28 days of receiving the AstraZeneca ChAdOx1 vaccine has been estimated as 18 to 25 per million doses in Germany and Scandinavia, but only 5 per million doses in the UK based on the Yellow Card reporting scheme. Risk estimates based on adverse event reporting systems are subject to under-ascertainment and other biases. What this study addsAll diagnosed cases of CVT in Scotland were ascertained by searching neuroimaging studies from December 2020 to May 2021 and linked to national vaccination records. The risk of CVT within 28 days of vaccination with ChAdOx1 was estimated as 3.5 per million doses with an upper bound of 6 per million doses, against a background incidence of about 12 per million adults per year. This indicates that the Yellow Card system has not seriously underestimated the risk in the UK; the explanation for higher risk in other European countries is not clear.
Subject(s)
COVID-19 , Venous ThrombosisABSTRACT
Background: The effect of vaccination for COVID-19 on onward transmission is unknown. Methods: A national record linkage study determined documented COVID-19 cases and hospitalizations in unvaccinated household members of vaccinated and unvaccinated healthcare workers from 8th December 2020 to 3rd March 2021. The primary endpoint was COVID-19 >= 14 days following the first dose. Results: The cohort comprised of 194,362 household members (mean age 31.1 years) and 144,525 healthcare workers (mean age 44.4 years). 113,253 (78.3%) of healthcare workers received at least one dose of the BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine and 36,227 (25.1%) received a second dose. Household members of vaccinated healthcare workers had a lower risk of COVID-19 case compared to household members of unvaccinated healthcare worker (rate per 100 person-years 9.40 versus 5.93; HR 0.70, 95% confidence interval [CI] 0.63-0.78). The effect size for COVID-19 hospitalization was similar, with the confidence interval crossing the null (HR 0.77 [0.53-1.10]). The rate per 100 person years was lower in vaccinated compared to unvaccinated healthcare workers for documented (20.13 versus 8.51; HR 0.45 [0.42-0.49]) and hospitalized COVID-19 (0.97 versus 0.14; HR 0.16 [0.09-0.27]). Compared to the period before the first dose, the risk of documented COVID-19 case was lower at >= 14 days after the second dose for household members (HR 0.46 [0.30-0.70]) and healthcare workers (HR 0.08 [0.04-0.17]). Conclusion: Vaccination of health care workers was associated with a substantial reduction in COVID-19 cases in household contacts consistent with an effect of vaccination on transmission.
Subject(s)
COVID-19ABSTRACT
Background: The QCovid algorithm is a risk prediction tool for COVID-19 hospitalisation and mortality that can be used to stratify patients by risk into vulnerability groups . We carried out an external validation of the QCovid algorithm in Scotland.Methods: We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription polymerase chain reaction (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisation and deaths in our dataset for two time periods: 1 March, 2020 to 30 April, 2020, and 1 May, 2020 to 30 June, 2020.Findings: Our dataset comprised 5,384,819 individuals, representing 99% of the estimated population (5,463,300) resident in Scotland in 2020. The algorithm showed excellent calibration in both time periods with close correspondence between observed and predicted risks. Harrell ’s C for deaths in males and females in the first period was 0.946 (95% CI: 0.941 - 0.951) and 0.925 (95% CI: 0.919 - 0.931) respectively. Harrell’s C for hospitalisations in males and females in the first period was 0.809 (95% CI: 0.801 - 0.817) and 0.816 (95% CI: 0.808 - 0.823) respectively.Interpretation: The QCovid algorithm shows high levels of external validity in predicting the risk of COVID- 19 hospitalisation and death in the population of Scotland.Funding: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK.Declaration of Interests: Dr. Hippisley-Cox reports grants from MRC, grants from Wellcome Trrust, grants from NIHR, during the conduct of the study; other from ClinRisk Ltd, outside the submitted work. Dr. Sheikh reports grants from NIHR, grants from MRC, grants from HRR UK, during the conduct of the study. All other authors report no conflict of interest.Ethics Approval Statement: Ethical permission for this study was granted from South East Scotland Research Ethics Committee 02 [12/SS/0201]. The Public Benefit and Privacy Panel Committee of Public Health Scotland, approved the linkage and analysis of the de-identified datasets for this project [1920-0279].
Subject(s)
COVID-19ABSTRACT
* Objectives - To investigate:(1) the risk of severe COVID-19 in those eligible for shielding, and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population. * Design - Matched case-control study (REACT-SCOT). * Setting - Population of Scotland from 1 March 2020 to 28 January 2021. * Participants - All 160307 diagnosed cases of COVID-19 and 1564782 controls matched for age, sex and primary care practice, linked with all 204913 individuals identified as eligible for shielding by Public Health Scotland. * Main outcome measure - Severe COVID-19, defined as cases that entered critical care or were fatal. * Results - With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 5.3 (95% CI 5.0 to 5.7, p=4 x 10-527) in those with moderate risk conditions and 7.6 (95% CI 7.1 to 8.3, p=1 x 10-527) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.6 (95% CI 9.6 to 19.2, p=8 x 10-50). In both the shielded and the general population, the risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.6 (95% CI 11.7 to 13.6, p=2 x 10-989) overall. In a case-crossover analysis with less recent exposure only (15 to 24 days before first testing positive) as reference category, the rate ratio associated with recent exposure only was 6.3 (95% CI 3.6 to 11.1, p=2 x 10-10). Among those eligible for shielding, the population attributable risk fraction (PARF) of severe cases for recent exposure to hospital was 36%. In the general population the PARF for recent exposure to hospital peaked at 46% in May 2020 and again at 64% in December 2020. * Conclusions - The effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. For solid organ transplant recipients, in whom the efficacy of vaccines is uncertain, these results support a policy of offering vaccination to household contacts. Mitigating the impact of the epidemic requires control of nosocomial transmission.
Subject(s)
COVID-19ABSTRACT
Objectives To estimate the real-world effectiveness of the Pfizer/BioNTech BNT162b2 vaccine and Astrazeneca ChAdOx1 vaccine against Confirmed COVID-19, hospitalisations and deaths. To estimate effectiveness on the UK variant of concern. Design Test negative case control design Setting Community COVID-19 PCR testing in England Participants All adults in England aged 70 years and older (over 7.5 million). All COVID-19 testing in the community among eligible individuals who reported symptoms between 8 th December 2020 and 19 th February 2021 was included in the analysis. Interventions One and two doses of BNT162b2 vaccine. One dose of ChAdOx1 vaccine. Main outcome measures Symptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19. Results Individuals aged >=80 years vaccinated with BNT162b2 prior to 4 th January, had a higher odds of testing positive in the first 9 days after vaccination (odds ratio up to 1.48, 95%CI 1.23-1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore estimated relative to the baseline post-vaccination period. Vaccine effects were noted from 10-13 days after vaccination, reaching an effectiveness of 70% (95% CI 59-78%) from 28-34 days, then plateauing. From 14 days after the second dose a vaccine effectiveness of 89% (95%CI: 85-93%) was seen. Individuals aged >=70 years vaccinated from 4 th January had a similar underlying risk of COVID-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (95%CI 51-69%) from 28-34 days after vaccination then plateaued. With the ChAdOx1 vaccine, vaccine effects were seen from 14-20 days after vaccination reaching an effectiveness of 60% (95%CI 41-73%) from 28-34 days and further increasing to 73% (95%CI 27-90%) from day 35 onwards. On top of the protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death. Cases who had been vaccinated with one dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation. There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout of this vaccine. Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 is 85% effective at preventing death with COVID-19. Conclusion Vaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease. Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.
Subject(s)
COVID-19ABSTRACT
Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%; 95% CI 65 to 90 at 28-34 days post-vaccination).Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Health Data Research UK.Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).
Subject(s)
COVID-19 , EmergenciesABSTRACT
Background: Households appear to be the highest risk setting for transmission of COVID-19. Large household transmission studies were reported in the early stages of the pandemic in Asia with secondary attack rates ranging from 5-30% but few large scale household transmission studies have been conducted outside of Asia. Methods: A prospective case ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. Household secondary attack rates and serial intervals were estimated. Individual and household basic reproduction numbers were also estimated. The incubation period was estimated using known point source exposures that resulted in secondary cases. Results: A total of 233 households with two or more people were included with a total of 472 contacts. The overall household SAR was 37% (95% CI 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. We find lower secondary attack rates in larger households. SARs were highest when the primary case was a child. We estimate a mean incubation period of around 4.5 days. Conclusions: High rates of household transmission of COVID-19 were found in the UK emphasising the need for preventative measures in this setting. Careful monitoring of schools reopening is needed to monitor transmission from children.
Subject(s)
COVID-19ABSTRACT
ObjectiveMany healthcare staff work in high-risk settings for contracting and transmitting Severe Acute Respiratory Syndrome Coronavirus 2. Their risk of hospitalisation for coronavirus disease 2019 (COVID-19), and that of their households, is poorly understood. Design and settings and participantsDuring the peak period for COVID-19 infection in Scotland (1st March 2020 to 6th June 2020) we conducted a national record linkage study to compare the risk of COVID-19 hospitalisation among healthcare workers (age: 18-65 years), their households and other members of the general population. Main outcomeHospitalisation with COVID-19 ResultsThe cohort comprised 158,445 healthcare workers, the majority being patient facing (90,733 / 158,445; 57.3%), and 229,905 household members. Of all COVID-19 hospitalisations in the working age population (18-65-year-old), 17.2% (360 / 2,097) were in healthcare workers or their households. Adjusting for age, sex, ethnicity, socio-economic deprivation and comorbidity, the risk of COVID-19 hospitalisation in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazards ratio [HR] 0.81; 95%CI 0.52-1.26 and 0.86; 95%CI 0.49-1.51 respectively). In models adjusting for the same covariates however, patient facing healthcare workers, compared to non-patient facing healthcare workers, were at higher risk (HR 3.30; 95%CI 2.13-5.13); so too were household members of patient facing healthcare workers (HR 1.79; 95%CI 1.10-2.91). On sub-dividing patient-facing healthcare workers into those who worked in front-door, intensive care and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (HR 2.09; 95%CI 1.49-2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of COVID-19 hospitalisation was less than 0.5% but was 1% and above in older men with comorbidity. ConclusionsHealthcare workers and their households contribute a sixth of hospitalised COVID-19 cases. Whilst the absolute risk of hospitalisation was low overall, patient facing healthcare workers and their households had 3- and 2-fold increased risks of COVID-19 hospitalisation.
Subject(s)
COVID-19ABSTRACT
Objectives -- To investigate the relation of severe COVID-19 to prior drug prescribing. Design -- Matched case-control study (REACT-SCOT) based on record linkage to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. Setting -- Scottish population. Main outcome measure -- Severe COVID-19, defined by entry to critical care or fatal outcome. Participants -- All 4272 cases of severe COVID-19 in Scotland since the start of the epidemic, with 36948 controls matched for age, sex and primary care practice. Results -- Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in care homes, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.7, 13.2), and was not accounted for by treatment of conditions designated as conferring increased risk. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19. The largest effect was for antipsychotic agents: rate ratio 4.14 (3.39, 5.07). Other drug classes with large effects included proton pump inhibitors (rate rato 2.19 (1.70, 2.80) for >= 2 defined daily doses/day), opioids (3.62 (2.65, 4.94) for >= 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates, and were stronger with recent than with non-recent exposure. Conclusions -- Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression or dyskinesia, have anticholinergic effects or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Although the evidence for causality is not conclusive, these results support existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy as a potential means of reducing COVID-19 risk. Registration -- ENCEPP number EUPAS35558
Subject(s)
COVID-19 , Dyskinesia, Drug-Induced , Respiratory InsufficiencyABSTRACT
Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poorly quantified. Methods: We identified as cases all those in Scotland with a positive SARS-CoV-2 nucleic acid test in the national laboratory database and anyone else with a death certificate mentioning COVID-19. Seven controls matched for age, sex and general practice were selected per case. Data were linked to the national diabetes register, hospitalisation and critical care unit (CCU) databases. Analyses focused on those with COVID-19 requiring critical care or dying. Analyses were by conditional and unconditional logistic regression. Findings: 0.3% (n=845) of those with diabetes had developed severe or fatal COVID-19, representing rate ratios of 3.86 (2.74, 5.45) in type 1 and 1.69 (1.56, 1.84) in type 2 diabetes. Rates were almost threefold in the most versus least socioeconomically deprived quintiles of the population. Most (77%) cases had another recognised co-morbidity such as heart or lung disease (OR 2.6). Diabetes specific factors associated with increased risk included; HbA1c odds ratio (OR) >85 mmol/mol versus <53: 1.96(1.55,2.48);p-value <0.001, prior diabetic ketoacidosis: OR 2.44(1.41,4.20);p-value 0.001 and hypoglycaemia hospitalisations: OR 3.28(2.41,4.46);p-value <0.001. Chronic retinal and renal complications were also associated with increased risk. A cross-validated predictive model of severe or fatal disease had a C-statistic of 0.83. Interpretations: Relative risks of severe or fatal COVID-19 are substantially elevated in both types of diabetes. Risk scores based on prior clinical history should be useful for identifying those with diabetes needing tailored protective measures.Funding Statement: There was no specific funder for this study.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: This research was conducted with approval from the Public Benefit Privacy Protection Panel (PBPP ref. 1617- 0147), originally set up under PAC 33/11, with approval from the Scotland A Research Ethics Committee (ref. 11/AL/0225). All datasets were de-identified before analysis.
Subject(s)
Diabetic Ketoacidosis , Lung Diseases , Diabetes Mellitus, Type 2 , Diabetes Mellitus , COVID-19 , Multiple MyelomaABSTRACT
BackgroundThe objectives of this study were to identify risk factors for severe COVID-19 and to lay the basis for risk stratification based on demographic data and health records. Methods and FindingsThe design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for SARS-CoV-2 in the national database followed by entry to a critical care unit or death within 28 days, or a death certificate with COVID-19 as underlying cause. Up to ten controls per case matched for sex, age and primary care practice were selected from the population register. All diagnostic codes from the past five years of hospitalisation records and all drug codes from prescriptions dispensed during the past nine months were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. There were 4272 severe cases. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio (95% CI) 21.4 (19.1, 23.9). Univariate rate ratios (95% CIs) for conditions listed by public health agencies as conferring high risk were 2.75 (1.96, 3.88) for Type 1 diabetes, 1.60 (1.48, 1.74) for Type 2 diabetes, 1.49 (1.37, 1.61) for ischemic heart disease, 2.23 (2.08, 2.39) for other heart disease, 1.96 (1.83, 2.10) for chronic lower respiratory tract disease, 4.06 (3.15, 5.23) for chronic kidney disease, 5.4 (4.9, 5.8) for neurological disease, 3.61 (2.60, 5.00) for chronic liver disease and 2.66 (1.86, 3.79) for immune deficiency or suppression. 78% of cases and 52% of controls had at least one listed condition (NA of cases and NA of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past nine months and with at least one hospital admission in the past five years [rate ratios 3.10 (2.59, 3.71)] and 2.75 (2.53, 2.99) respectively] even after adjusting for the listed conditions. In those without listed conditions significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses and prescriptions provided an additional 1.25 bits (C-statistic 0.825). A limitation of this study is that records from primary care were not available. ConclusionsAlong with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over. Author summaryMost people infected with the SARS-CoV-2 coronavirus do not become seriously ill. It is The risk of severe or fatal illness is higher in older than in younger people, and is higher in people with conditions such as asthma and diabetes than in people without these conditions. Using Scotlands capability for linking electronic health records, we report the first systematic study of the relation of severe or fatal COVID-19 to pre-existing health conditions and other risk factors. We show that the strongest risk factor, apart from age, is residence in a care home. The conditions associated with increased risk include not only those already designated by public health agencies - asthma, diabetes, heart disease, disabling neurological disease, kidney disease - but many other diagnoses, associated with frailty and poor health. This lays a basis for constructing risk scores based on electronic health records that can be used to advise people at high risk of severe disease to shield themselves when there cases in their neighbourhood.
Subject(s)
COVID-19ABSTRACT
Objectives: Following detection of the first virologically-confirmed cases of COVID-19 in Great Britain, an enhanced surveillance study was initiated by Public Health England to describe the clinical presentation, course of disease and identify risk factors for infection of the first few hundred cases. Methods: Information was collected on the first COVID-19 cases according to the First Few X WHO protocol. Case-control analyses of the sensitivity, specificity and predictive value of symptoms and risk factors for infection were conducted. Point prevalences of underlying health conditions among the UK general population were presented. Findings: The majority of FF100 cases were imported (51.4%), of which the majority had recent travel to Italy (71.4%). 24.7% were secondary cases acquired mainly through household contact (40.4%). Children had lower odds of COVID-19 infection compared with the general population. The clinical presentation of cases was dominated by cough, fever and fatigue. Non-linear relationships with age were observed for fever, and sensitivity and specificity of symptoms varied by age. Conditions associated with higher odds of COVID-19 infection (after adjusting for age and sex) were chronic heart disease, immunosuppression and multimorbidity. Conclusion: This study presents the first epidemiological and clinical summary of COVID-19 cases in Great Britain. The FFX study design enabled systematic data collection. The study was able to characterize the risk factors for infection with population prevalence estimates setting these relative risks into a public health context. It also provides important evidence for generating case definitions to support public health risk assessment, clinical triage and diagnostic algorithms.
Subject(s)
COVID-19 , Heart Diseases , Fever , FatigueABSTRACT
Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.