Decline and uneven recovery from 7 common long-term conditions managed in the Catalan primary care after two pandemic years: an observational retrospective population-based study using primary care electronic health records (preprint)

Background: The incidence of chronic diseases during the COVID-19 pandemic has drastically been reduced worldwide due to disruptions in healthcare systems. The aim of our study is to analyse the trends in the incidence of 7 commonly managed primary care chronic diseases during the last 2 years of the COVID-19 pandemic in Catalonia. Methods We performed an observational retrospective population-based study using data from primary care electronic health records from January 2018 to August 2022 (5.1 million people over 14 years). We divided the study period into two: a pre-pandemic period (before 14 March 2020) and a pandemic period. We performed a segmented regression analysis of daily incidence rates per 100,000 inhabitants of 7 chronic diseases: type 2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD), heart failure (HF), hypertension and hypercholesterolemia. In addition, we compared annual incidence between pandemic years (2020, 2021 and 2022) and 2019. Associated incidence rate ratios (IRR) were also calculated. Finally, we estimated the number of expected diagnoses during the pandemic period using data from 2019 and we compared it with the observed data. Results We analysed 740,820 new chronic diseases’ diagnoses. Daily incidence rates of all 7 chronic diseases were drastically interrupted on 14 March 2020, and a general upward trend was observed during the following months. Reductions in 2020 were around 30% for all conditions except COPD which had greater reductions (IRR: 0.58 [95% CI: 0.57 to 0.6]) and HF with lesser drops (IRR: 0.86 [95% CI: 0.84 to 0.88]). Some of the chronic conditions have returned to pre-pandemic diagnosis levels, except asthma, COPD and IHD. The return to pre-pandemic diagnosis levels compensated for the drops in 2020 for T2DM and HF, but not for hypertension which presented an incomplete recovery. We also observed an excess of hypercholesterolemia diagnoses of 8.5% (95%CI: 1.81–16.15%). Conclusions Although primary care has recovered the pre-pandemic diagnosis levels for some chronic diseases, there are still missing diagnoses of asthma, COPD and IHD that should be addressed.

Multisystem Inflammatory Syndrome in Children and SARS-CoV-2 variants: a two-year ambispective multicentric cohort study in Catalonia, Spain. (preprint)

Purpose Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe disease temporarily related to SARS-CoV-2. We aimed to describe the epidemiological, clinical and laboratory findings of all the MIS-C cases diagnosed in children < 18 years-old in Catalonia (Spain) to study their trend throughout the pandemic.Methods Multicenter ambispective observational cohort study (April 2020-April 2022). Data were obtained from the COVID-19 Catalan surveillance system and from all the hospitals in Catalonia. We analyzed MIS-C cases regarding SARS-CoV-2 variants for demographics, symptoms, severity, monthly MIS-C incidence, ratio between MIS-C and accumulated COVID-19 cases, and associated rate ratios (RR).Results Among 555,848 SARS-CoV-2 infections, 152 children were diagnosed with MIS-C. Monthly MIS-C incidence was 4.1 (95%CI: 3.4–4.8) per 1,000,000 people, and 273 (95%CI: 230–316) per 1,000,000 SARS-CoV-2 infections (i.e., one case per 3,700 SARS-CoV-2 infections). During the Omicron period, MIS-C RR was 8.2 (95%CI: 5.7–11.7) per 1,000,000 SARS-CoV-2 infections, significantly lower (p < 0.001) than for previous variant periods, in all age groups. Median [IQR] age of MIS-C was 8 [4–11] years, 62.5% male, and 80.2% without comorbidities. Common symptoms were gastrointestinal findings (88.2%) and fever > 39oC (81.6%), nearly 40% had an abnormal echocardiography and 7% coronary aneurysm. Clinical manifestations and laboratory data were not different throughout the variant periods (p > 0.05).Conclusions The rate ratio between MIS-C cases and SARS-CoV-2 infections was significantly lower in the Omicron period for all the age groups, including those not vaccinated, suggesting that the variant could be the main factor for this shift in the MISC trend. Regardless of variant type, the patients had similar phenotypes and severity throughout the pandemic.

Increase of scabies infestations during the COVID-19 pandemic in Catalonia (preprint)

During the COVID-19 pandemic, several clinicians in Spain reported an increase in scabies diagnoses. We performed a time-series analysis with data from 2014 to 2022 to quantify this increase. We found an increasing trend during late 2020 and 2021, peaking in March 2022 with an almost 4.5-fold incidence than expected, especially in those aged between 16 and 30 years. Although scabies is more frequent in most socioeconomic deprived areas, the observed rise occurs in all the areas. We recommend increasing surveillance among other countries to detect unexpected increases in scabies outbreaks.

Cancer diagnosis in primary care after second pandemic year in Catalonia: a time-series analysis of primary care electronic health records covering about five million people (preprint)

Background During COVID-19 pandemic, incidence of chronic disease had drastically been reduced due to health care interruptions. The aim of this study is to analyze cancer diagnosis during the two years of the COVID-19 pandemic. Methods Time-series study of malignant neoplasms, using data from the primary care electronic health records from January 2014 to December 2021. We obtained the expected monthly incidence using a temporary regression adjusted by trend and seasonality. We additionally compared cancer incidence in 2019 with those of 2020 and 2021 using the T-Test. We performed analysis globally, by sex and by type of cancer. Results During 2020, the incidence of cancer had reduced by -21% compared to 2019 (p-value <0.05). Greater reductions were observed during lockdown in early 2020 (>40%) and with some types of cancers, especially prostate and skin cancers (−29.6% and -26.9% respectively, p-value<0.05). Lung cancers presented statistically non-significant reductions in both years. Cancer diagnosis returned to expected around March 2021, and incidence in 2021 was similar to that of 2019 (overall difference of 0.21%, p=0.967). However, -11% reduction still was found when comparing pandemic months of 2020-2021 with pre-pandemic months (2019-2020) Conclusions Although primary care cancer diagnostic capacity in 2021 has returned to pre-pandemic levels, missing diagnoses during the last two years have not been fully recovered. Key messages Cancer diagnoses have dramatically dropped during 2020 worldwide. We observe a -21% decline in 2020, but a return to pre-pandemic diagnosis capacity in 2021. A -11% outstanding drop was still found comparing pre-pandemic to pandemic months. Reductions were greater during the lockdown (>40%). Lung and breast cancers presented fewer reductions while prostate and skin cancers had greater drops. Missing diagnoses during the last two years have not been fully recovered

Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2: a cohort analysis (preprint)

Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. We used linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 238 (1.7%) in the heterologous and 389 (2.7%) in the homologous groups developed COVID-19 between 1st June 2021 and 11th October 2021. The resulting hazard ratio (95% confidence interval) was 0.61 [ 0.52-0.71 ], favouring heterologous vaccination, with a Number Needed to Treat of 94.9 [ 71.8 - 139.8 ]. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirmed these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials.

Sexually Transmitted Infections, the Epidemic That Persists After the COVID-19 Pandemic: a Time-series Analysis of the Primary Care Electronic Health Records Covering About 5 Million People in Catalonia (preprint)

Background: The COVID-19 pandemic and related control measures have affected the diagnosis of other diseases, including sexually transmitted infections (STI). Our aim is to analyse the impact of the COVID-19 pandemic on the incidence of STI diagnosed in primary care. Methods: : Time-series study of STI, using data from primary care electronic health records in Catalonia (Spain) from January 2016 to March 2021. We obtained the monthly expected incidence of STI using a temporary regression, where the response variable was the incidence of STI from 2016 to 2019 and the adjustment variables were the trend and seasonality of the time series. Excess or reduction of STI were defined as the number of observed minus the expected cases, globally and stratified by age, sexe, type of STI and socioeconomic status. Results: : Between March 2020 and March 2021 we observed a reduction of 20.2% (95% CI: 13.0% to 25.8%) on STI diagnoses compared to the expected. This reduction was greater during the lockdown period (-39%), in women (-26.5%), in people aged under 60 years (up to -22.4% in people aged 30-59 years), less deprived areas (-24%) and some types of STI, specially chlamydia (-32%), gonorrhea (-30.7%) and HIV (-21.5%). Conversely, syphilis and non-specific STI were those with lesser reductions with -3.6% and -7.2%, respectively, Conclusions: : The COVID-19 pandemic has impacted on STI incidence, reducing the number of diagnoses performed in primary care and raising concerns about future evolution of STI trends. Those STI that are less symptomatic or diagnosed through screening will deserve special attention regarding potential diagnostic delays.

Vaccines against Covid-19, venous thromboembolism, and thrombocytopenia. A population-based retrospective cohort study (preprint)

BackgroundWe aimed at estimating the risk of venous thromboembolism (VTE), thrombocytopenia (TCP), and VTE associated with TCP, by age and sex, after the first dose of both adenovirus vector-based and mRNA-based Covid-19 vaccines, and after the second dose of m-RNA vaccines. MethodsIn this population-based retrospective cohort study in the national health care databases in Catalonia, we examined three groups: 1 662 719 people 10 years of age and over vaccinated with the first dose of a Covid-19 vaccine, 622 778 with the second dose, and 190 616 diagnosed of Covid-19 in the same period (between1 January 2021 and 18 April 2021). The rates of various clinical presentations of VTE and TCP were compared with those in the reference population (7 013 040 people served by the health care system in 2019). The two primary outcomes were the observed 21 day rate of a composite variable of cerebral venous sinus thrombosis, mesenteric thrombosis, portal vein thrombosis, or any venous thromboembolism (VTE) associated with thrombocytopenia (TCP), and the rate of any VTE associated with TCP (VTE+TCP). Analyses were standardised by age and sex. ResultsThe 21 day rate per 100 000 of the primary composite variable was 2.15 in the reference population, 5.65 following the first vaccine dose (standardised difference, 2.53 (95% CI [CI], 1.04 to 4.00), and 7.23 following the second dose (standardised difference, 4.07 (95% CI, 1.43 to 6.70). The event rates of VTE+TCP and of all the secondary variables showed the same patterns. Excess event rates were higher in men than in women, and they were not especially increased in any particular age group. All Covid-19 vaccines were associated with increased rates of the outcome variables. Excess event rates were much higher in the Covid-19 cohort (35.60 per 100 000 (95% CI, 26.15 to 45.06). ConclusionsWe observed increases of rates of venous thromboembolism in usual and unusual anatomical sites and of thrombocytopenia in recipients of both adenovirus vector and mRNA vaccines against Covid-19. Excess rates were higher in men than in women and they were not particularly elevated in any specific age group.

Non-differential risk of SARS-CoV-2 infection for members of polling stations on Catalan parliament voting day (preprint)

We aimed to assess the risk of SARS-CoV-2 infection for polling station members during the Catalan elections in February 2021. We compared the incidence 14 days after the elections between a cohort of polling station members (N= 18,304) and a control cohort paired by age, sex and place of residence. A total of 37 COVID-19 cases (0.2%) were confirmed in the members of the polling stations and 43 (0.23%) in the control group (p-value 0.576). Our study suggests that there was no greater risk of infection for the members of the polling stations.

Effects of BNT162b2 mRNA Vaccination on COVID-19 Disease, Hospitalisation and Mortality in Nursing Homes and Healthcare Workers: A Prospective Cohort Study Including 28,594 Nursing Home Residents, 26,238 Nursing Home Staff, and 61,951 Healthcare Workers in Catalonia (preprint)

Background: Spain began vaccinating priority groups against COVID-19 with BNT162b2 in late December 2020. We report associations of vaccination with COVID-19 infection, hospitalisation, and mortality among nursing home residents, nursing home staff, and healthcare workers. Methods: We analysed three cohorts of all nursing home residents, nursing home staff, and healthcare workers in Catalonia on 27 December 2020. Data were obtained from linked primary care, RT-PCR and lateral flow test, hospital, and mortality records. Those with a pre-study COVID-19 diagnosis or no linked electronic medical records were excluded. Two doses of BNT162b2 were administered 3 weeks apart. Participants were followed until the earliest of an outcome (confirmed COVID-19 infection, hospitalisation, and mortality) or 5 March 2021. Participants could contribute data to the unvaccinated, one-dose, and two-dose groups. Analyses were conducted using time-varying Cox regression. Multivariable adjustment for imbalances in socio-demographics, comorbidity, and polypharmacy. Findings: We included 28,594 nursing home residents, 26,238 nursing home staff, and 61,951 healthcare workers, of whom 2,405, 1,584, and 2,672 received COVID-19 diagnoses; 383, 35, and 76 were hospitalised; and 409, 0, and 1 died. The adjusted hazard ratio (HR) (95% confidence interval) for COVID-19 infection after two-dose vaccination was 0·08 (0·07-0·09) for nursing home residents, 0·12 (0·10-0·15) for nursing home staff, and 0·05 (0·04-0·07) for healthcare workers. The adjusted HRs for hospitalisation and mortality after two-dose vaccination were 0·03 (0·02-0·05) and 0·02 (0·01-0·03), respectively, for nursing home residents. Nursing home staff and healthcare workers recorded insufficient events for mortality analysis. Interpretation Vaccination was associated with 85%-96% reduction in SARS-CoV-2 infection in all three cohorts, and bigger reductions in hospitalisations and mortality amongst nursing home residents for up to two months. More data are needed on the long-term effects of COVID-19 vaccines. Funding: Partially supported by National Institute of Health Research UK, We do not have any other funding acknowledgements.Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Clinical Research Ethics Committee of the IDIAP Jordi Gol with reference number 21/045-PCV.

Reduction of respiratory syncytial virus burden of disease observed in primary care diagnosis of children under 5 years old during the COVID-19 pandemic: a time-series analysis using routinely collected data from primary care electronic health records in Catalonia (Spain). (preprint)

Background: Great reductions of respiratory syncytial virus (RSV) in children were observed during the 2020 Southern hemisphere winter. Aim: To describe trends of RSV related disease in children in the Northern hemisphere and to propose a low cost clinical surveillance system based on primary care electronic health records (EHR). Methods: Time series analysis of RSV-related disease and virus laboratory-confirmations in children under 5 years old from 1 September 2009 to 16 January 2021. We collected RSV diagnoses from primary care EHR in Catalonia (Spain). We compared the trend of RSV in the season 2020-2021 with that in the previous seasons. We estimated the expected RSV cases with data from 2009 to 2018 using a time series regression adjusted by seasonality. We used the same method to estimate the expected RSV laboratory-confirmations as a sensitivity analysis. Results: In previous seasons, RSV-related disease peaks in Catalonia during the weeks 52 and 53. However in the 2020-2021 period, we observed a reduction of 87.6% (95% CI: 82.7% to 90.3%) in RSV-related disease from october 2020 compared to the expected. Only 1 RSV case was laboratory-confirmed during the 2020-2021 season until mid-January. Conclusions: We observed a nearly absence of RSV-related disease and laboratory-confirmations during the weeks when RSV usually peaks in Catalonia. The use of primary care EHR could be a low-cost surveillance system to monitorize trends of RSV the coming months.

Divergences on expected pneumonia cases during the COVID-19 epidemic in Catalonia: A time-series analysis of primary care electronic health records covering about 6 million people. (preprint)

BackgroundPneumonia is one of the complications of COVID-19. Primary care electronic health records (EHR) have shown the utility as a surveillance system. AimTo analyze the trends of pneumonia during two waves of COVID-19 pandemic in order to use it as a clinical surveillance system and an early indicator of severity. MethodsTime series analysis of pneumonia cases, January 2014-December 2020. We collected pneumonia diagnoses from primary care EHR, covering >6 million people in Catalonia (Spain). We compared the trend of pneumonia in the season 2019-2020 with that in the previous years. We estimated the expected pneumonia cases with data from 2014 to 2018 using a time series regression adjusted by seasonality and influenza epidemics. ResultsBetween 4 March and 5 May 2020, 11,704 excess pneumonia cases (95% CI: 9,909 to 13,498) were identified. We observed a second excess pneumonia period from 22 october to 15 november of 1,377 excess cases (95% CI: 665 to 2,089). In contrast, we observed two great periods with reductions of pneumonia cases in children, accounting for 131 days and 3,534 less pneumonia cases (95% CI: 1,005 to 6,064) from March to July; and 54 days and 1,960 less pneumonia cases (95% CI 917 to 3,002) from October to December. ConclusionsDiagnoses of pneumonia from the EHR could be used as an early and low cost surveillance system to monitor the spread of COVID-19.

The impact of the COVID-19 pandemic and related control measures on cancer diagnosis in Catalonia:A time-series analysis of primary care electronic health records covering about 5 million people. (preprint)

ObjectivesCancer care has been disrupted by the response of health systems to the COVID-19 pandemic, especially during lockdowns. The aim of our study is to analyse the impact of the pandemic on the incidence of cancer diagnosed in primary care. DesignTime-series study of malignant neoplasm and diagnostic procedures, using data from the primary care electronic health records from January 2014 to September 2020. SettingPrimary care, Catalonia, Spain ParticipantsPeople older than 14 years and assigned in one of the primary care practices of the Catalan Institute of Health with a new diagnosis of malignant neoplasm. Main outcome measuresWe obtained the monthly expected incidence of malignant neoplasms using a temporary regression, where the response variable was the incidence of cancer from 2014 to 2018 and the adjustment variables were the trend and seasonality of the time series. Excess or lack of malignant neoplasms were defined as the number of observed minus expected cases, globally and stratified by sex, age, type of cancer, and socioeconomic status. ResultsBetween March and September 2020 we observed 8,766 (95% CI: 4,135 to 13,397) less malignant neoplasm diagnoses, representing a reduction of 34% (95% CI: 19.5% to 44.1%) compared to the expected. This underdiagnosis was greater in individuals aged more than 64 years, men, and in some types of cancers (skin, colorectal, prostate). Although the reduction was predominantly focused during the lockdown, expected figures have not yet been reached (40.5% reduction during the lockdown and 24.3% reduction after that). ConclusionsReduction on cancer incidences has been observed during and after the lockdown. Urgent policy interventions are necessary to mitigate the indirect effects of COVID-19 pandemic and related control measures on other diseases and some strategies must be designed in order to reduce the underdiagnosis of cancer. What is already know in this topic- The COVID-19 pandemic and related control measures have significantly affected medical care worldwide, with effects on cancer diagnosis. - Non-COVID elective services (healthcare consultations, services, cancer screening programmes) were suspended and have been associated with a reduction in incidence of cancer. - Skin non-melanoma cancers has been more affected than other type of cancers What this study adds?- Provides data from a primary care perspective in a population about 5 million people. - Underdiagnosis of cancer occurred during the lockdown. However, this reduction extended beyond the end of the lockdown, especially for people older than 64 years, men, and some types of cancer. - Least deprived areas had greater reductions in cancer diagnoses during the lockdown, but after the lockdown the most deprived areas were those with more underdiagnosis.

Hospitalization and 30-day fatality in 121,263 COVID-19 outpatient cases (preprint)

Background: To date, characterisation studies of COVID-19 have focussed on hospitalised or intensive care patients. We report for the first time on the natural history of COVID-19 disease from first diagnosis, including both outpatient and hospital care. Methods: Data was obtained from SIDIAP, a primary care records database covering >6 million people (>80% of the population of Catalonia), linked to COVID-19 RT-PCR tests, hospital emergency and inpatient, and mortality registers. All participants >=15 years, diagnosed with COVID-19 in outpatient between 15th March and 24th April 2020 (10th April for outcome studies) were included. Baseline characteristics, testing, and 30-day outcomes (hospitalisation for COVID-19 and all-cause fatality) were analysed. Results: A total of 121,263 and 95,467 COVID-19 patients were identified for characterisation and outcome studies, respectively. Women (57.8%) and age 45-54 (20.2%) were predominant. 44,709 were tested, with 32,976 (73.8%) PCR+. From 95,467 cases, a 14.6% [14.4-14.9] were hospitalised in the month after diagnosis, with male predominance (19.2% vs 11.3%), peaking at age 75-84. Overall 30-day fatality was 4.0% [95%CI 3.9%-4.2%], higher in men (4.8%) than women (3.4%), increasing with age, and highest in those residing in nursing homes (25.3% [24.2% to 26.4%]). Conclusions: COVID-19 is seen in all age-sex strata, but severe forms of disease cluster in older men and nursing home residents. Although initially managed in primary care, 15% of cases require hospitalization within a month, with overall fatality of 4%.

Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia (preprint)

ObjectivesThere is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia. DesignTime-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020. SettingPrimary care, Catalonia, Spain. ParticipantsPeople registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population. Main outcome measuresWeekly new cases of influenza and COVID-19 diagnosed in primary care. AnalysesDaily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases. ResultsFour influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group. ConclusionsCOVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.