Validity of prognostic models of critical COVID-19 is variable. A systematic review with external validation.

OBJECTIVES: To identify prognostic models which estimate the risk of critical COVID-19 in hospitalized patients and to assess their validation properties. STUDY DESIGN AND SETTING: We conducted a systematic review in Medline (up to January 2021) of studies developing or updating a model that estimated the risk of critical COVID-19, defined as death, admission to intensive care unit, and/or use of mechanical ventilation during admission. Models were validated in two datasets with different backgrounds (HM [private Spanish hospital network], n = 1,753, and ICS [public Catalan health system], n = 1,104), by assessing discrimination (area under the curve [AUC]) and calibration (plots). RESULTS: We validated 18 prognostic models. Discrimination was good in nine of them (AUCs ≥ 80%) and higher in those predicting mortality (AUCs 65%-87%) than those predicting intensive care unit admission or a composite outcome (AUCs 53%-78%). Calibration was poor in all models providing outcome's probabilities and good in four models providing a point-based score. These four models used mortality as outcome and included age, oxygen saturation, and C-reactive protein among their predictors. CONCLUSION: The validity of models predicting critical COVID-19 by using only routinely collected predictors is variable. Four models showed good discrimination and calibration when externally validated and are recommended for their use.

Residual pulmonary infiltrates, symptoms and diffusion impairment at 1-year after severe COVID-19 infection have different associated factors.

INTRODUCTION: After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year follow-up. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (DLCO ) at 1-year follow-up in patients from the Spanish Registry RECOVID. METHODS: RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits. RESULTS: Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced DLCO . Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO2 /FiO2 <450 or CURB-65 ≥2. Reduced DLCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO2 /FiO2 <450 and CURB-65 ≥2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced DLCO (9.5%), radiological findings (25%) or both (11%). CONCLUSIONS: The factors associated with symptom persistence, incomplete radiological resolution and DLCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced DLCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation.

Relationship sustainability-store equity across segments of retail customers

PurposeThe study of sustainability in retail has experienced an exponential interest in recent years as a result of greater awareness on the part of consumers of the negative effects of the current way of producing and consuming on society and the environment. This work examines the heterogeneous evaluation based on behavioural variables in retail trade and how consumer perceptions towards sustainable practices implemented in stores can influence the overall store equity.Design/methodology/approachThe authors propose a theoretical model based on the literature, tested through a mixed regression model in a sample of 510 customers of food retail establishments.FindingsThe dimensions of sustainability are postulated as driving forces of brand equity towards the retail establishment. Specifically, social sustainability shows a greater impact on consumer perception, being the main factor in the development of the store's brand equity. Furthermore, the analysis of unobserved heterogeneity identifies three latent classes in which the effects of perceptions on sustainable retail activities vary across consumer segments.Originality/valueThe study analyses in a single model the effect of sustainability dimensions on store equity from the consumer's perspective, analysing the differences between these relationships as a consequence of the unobserved heterogeneity of consumers.

Prevalence and factors associated with self-reported anxiety in adults during the COVID-19 pandemic in Argentina, Brazil, Peru, Mexico, and Spain: A cross-sectional Ibero-American study.

The present study evaluated the factors associated with the perception of anxiety during the first wave of covid-19 in Ibero-American countries. This cross-sectional study was carried out with 5.845 participants of both sexes, over 18 years of age, and residents of four Latin American countries-Argentina (16.7%), Brazil (34.5%), Mexico (11.1%), and Peru (17.5%), and one European country-Spain (20.1%). Data were collected in 2020, between April 1st and June 30th in Spain and between July 13th and September 26th in the Latin American countries. We used an online questionnaire with sociodemographic, lifestyle, self-reported anxiety, and covid-19 related questions. The chi-square statistical test and Multivariate logistic regressions were performed to analyze the factors associated with self-reported anxiety. The presence of self-reported anxiety was found in 63.8% of the participants during the isolation period. The association occurred mainly in women (OR:1.52; CI: 1.3-1.7), those aged 18 to 29 years (OR: 1.51; CI: 1.2-1.9) and 30 to 49 years (OR: 1.56; CI: 1.3-1.9), residents of Argentina (OR: 1.55 CI: 1.2-1.9), Brazil (OR: 2.38; CI: 2.0-2.8) and Mexico (OR: 1.52; CI: 1.2-1.9), those who gained weight (OR:1.71 CI: 1.5-1.9) or lost weight (OR: 1.40; CI: 1.2-1.6), and those who reported having slept more (OR: 1.56; CI: 1.3-1.8) or less (OR: 2.89; CI: 2.5-3.4). We conclude that the prevalence of self-reported anxiety in Ibero-American countries was high during the period studied, highlighting a higher likelihood of its occurrence in Brazil, in those who began to sleep less and gained weight.

Health and economic benefits of achieving contraceptive and maternal health targets in Small Island Developing States in the Pacific and Caribbean.

INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M-US$15.9M) over 2020-2030 for the five Pacific countries (15% more than US$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M-US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M-US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US$426.2M (US$138.6M-US$745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Impact of COVID-19 Restrictions in Childbirth and Puerperium: A Cross-Sectional Study.

Introduction (1): The COVID-19 pandemic led to changes in healthcare during pregnancy, childbirth and puerperium. The objective of this study was to know the impact of visit restrictions, PCR performance and use of masks on delivery and puerperium care. Methods (2): A descriptive cross-sectional study was carried out. A survey was used to assess the impact of COVID-19-related measures on women who had given birth in hospitals in the Region of Murcia, Spain, between March 2020 and February 2022. Results (3): The final sample size was 434 women. The average scores were 4.27 for dimension 1 (Visit restrictions), 4.15 for dimension 2 (PCR testing) and 3.98 for dimension 3 (Mask use). More specifically, we found that the restriction of visits was considered a positive measure for the establishment of the mother-newborn bond (mean score 4.37) and that the use of masks at the time of delivery should have been made more flexible (mean score 4.7). Conclusions (4): The policy of restricting hospital visits during the pandemic caused by COVID-19 has been considered beneficial by mothers, who expressed that they did not feel lonely during their hospital stay.

Leisure Time Physical Activity and SARS-CoV-2 Infection among ELSA-Brasil Participants.

The regular practice of physical activity (PA) can reduce the chance of aggravation of the disease and lower rates of hospitalization and mortality from COVID-19, but few studies have analyzed the association of PA with the risk of infection by SARS-CoV-2. The aim of the study was to analyze the association between PA and self-reported SARS-CoV-2 infection. A longitudinal study was conducted with data from 4476 ELSA-Brasil participants who had their PA analyzed twice, once in 2016-2018 and again in 2020. PA was identified using the IPAQ at both follow-up moments and categorized into four groups: (a) remained physically inactive (reference); (b) remained physically active; (c) became physically active in the second moment; and (d) became physically inactive in the second moment. The variables of age, sex, obesity, hypertension, diabetes and specific protective practices against COVID-19 were tested as possible confounders. Data were analyzed by logistic regression. A 95% confidence interval (CI) was used. Remaining physically active was associated with a 43% reduction in the risk of SARS-CoV-2 infection only among those who used specific practices to protect against COVID-19, OR = 0.57 and CI = 0.32-0.99. The results suggested that regular practice of PA can reduce the risk of SARS-CoV-2 infection, especially among those who have used specific practices to protect against COVID-19 during the pandemic.

Working from home, work-time control and mental health: Results from the Brazilian longitudinal study of adult health (ELSA-Brasil).

This cross-sectional study investigated the association between work-time control (WTC), independently and in combination with hours worked (HW), and four mental health outcomes among 2,318 participants of the Longitudinal Study of Adult Health (ELSA-Brasil) who worked from home during the COVID-19 pandemic. WTC was assessed by the WTC Scale, and mental health outcomes included depression, anxiety, stress (measured by the Depression, Anxiety and Stress Scale, DASS-21), and self-rated mental health. Logistic regression models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs). Among women, long HW were associated with stress (OR = 1.56; 95% CI = 1.11-2.20) and poor self-rated mental health (OR = 1.64; 95% CI = 1.13-2.38), whereas they were protective against anxiety among men (OR = 0.59; 95% CI = 0.37-0.93). In both sexes, weak WTC was associated with all mental health outcomes. Among women, the long HW/weak WTC combination was associated with all mental health outcomes, and short HW/weak WTC was associated with anxiety and stress. Among men, long HW/strong WTC was protective against depression and stress, while short HW/strong WTC and short HW/weak WTC was associated with all mental health outcomes. In both sexes, weak WTC, independently and in combination with HW, was associated with all mental health outcomes. WTC can improve working conditions, protect against mental distress, and fosterwork-life balance for those who work from home.

Patient-reported outcomes measures (PROMs) and patient-reported experience measures (PREMs) of COVID-19 telerehabilitation: Prospective pilot program.

Telemedicine is proving to be a useful tool in the telemonitoring of respiratory patients and telerehabilitation programs. The use of telemedicine has been proposed by the main medical societies because of the limited resources and the healthcare workers infection risk in the Coronavirus Disease 2019 (COVID-19) pandemic. The aim of this pilot program is to evaluate the feasibility of COVID-19 telerehabilitation program from the hospital to the home with clinical, functional and patient satisfaction outcomes. Rehabilitation was initiated in the hospital by a physiotherapist and complemented by "Estoi" (a mobile application), which was continued at home with telemonitoring and messaging with the medical team. Patients' habitual use of smartphones was not queried for inclusion. Sixteen patients were consecutively enrolled, 47% women with a mean age of 63 years old. 50% of patients completed ≥15 rehabilitation sessions. In total, 88% of patients referred that the mobile application incentive them to do more physical therapy, and 63% would choose telerehabilitation instead of center-based rehabilitation for new rehabilitation programs. Patient satisfaction (0-10) for the mobile application was 8.4 and 8.9 for the telerehabilitation program. Beginning telerehabilitation in the hospital could increase the efficacy and efficiency of physical therapy, which is safe for patients and healthcare workers. Following at home, this telerehabilitation program seems to encourage and empower patients who have reported high satisfaction. Further randomized studies with larger numbers of patients and multicenter studies are required to evaluate these results.

Predictors and changes of physical activity in idiopathic pulmonary fibrosis.

BACKGROUND: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. METHODS: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. RESULTS: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]. CONCLUSION: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.

Outcomes of COVID-19 Patients Admitted to the Intermediate Respiratory Care Unit: Non-Invasive Respiratory Therapy in a Sequential Protocol.

The intermediate respiratory care units (IRCUs) have a pivotal role managing escalation and de-escalation between the general wards and the intensive care units (ICUs). Since the COVID-19 pandemic began, the early detection of patients that could improve on non-invasive respiratory therapies (NRTs) in IRCUs without invasive approaches is crucial to ensure proper medical management and optimize limiting ICU resources. The aim of this study was to assess factors associated with survival, ICU admission and intubation likelihood in COVID-19 patients admitted to IRCUs. Observational retrospective study in consecutive patients admitted to the IRCU of a tertiary hospital from March 2020 to April 2021. Inclusion criteria: hypoxemic respiratory failure (SpO2 ≤ 94% and/or respiratory rate ≥ 25 rpm with FiO2 > 50% supplementary oxygen) due to acute COVID-19 infection. Demographic, comorbidities, clinical and analytical data, and medical and NRT data were collected at IRCU admission. Multivariate logistic regression models assessed factors associated with survival, ICU admission, and intubation. From 679 patients, 79 patients (12%) had an order to not do intubation. From the remaining 600 (88%), 81% survived, 41% needed ICU admission and 37% required intubation. In the IRCU, 51% required non-invasive ventilation (NIV group) and 49% did not (non-NIV group). Older age and lack of corticosteroid treatment were associated with higher mortality and intubation risk in the scheme, which could be more beneficial in severe forms. Initial NIV does not always mean worse outcomes.

Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia.

BACKGROUND: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases. METHODS: We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir. The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir. DISCUSSION: A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days. CONCLUSIONS: Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.

Remdesivir en pacientes trasplantados renales con neumonía por SARS-CoV-2 Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia

Background Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases. Methods We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir. The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir. Discussion A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days. Conclusions Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.

COVID-19 in patients with Pulmonary Alveolar Proteinosis A European multicenter study

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) signaling is essential in both alveolar macrophages (AMs) differentiation and activation of lung immune cells [1]. Differentiated AMs are crucial in both the elimination of alveolar microbes and surfactant clearance. The disruption of the GM-CSF axis in alveolar macrophages leads to the development of pulmonary alveolar proteinosis (PAP) [1]. In the majority of patients this relates to the presence of autoantibodies against GM-CSF autoimmune (a)PAP but there are multiple other causes [1, 2, 3]. GM-CSF deficient animals may have impaired lung inflammatory response to commensal microbes and humans with PAP may occasionally develop opportunistic lung infections [4]. The mainstay of pharmacological treatment in aPAP is inhaled GM-CSF which is off-label but increasingly used worldwide [5, 6, 7, 8, 9].

Mapping tourism and hospitality research on information and communication technology: a bibliometric and scientific approach

Technology and information and communication technology (ICT) have been gaining importance in tourism and hospitality with a booming research interest during the last years and specifically recently due to the disruptions of the COVID-19 crisis. Hence it is useful to structure the existing knowledge in this field to better guide directions for future research. To that end, this study synthesizes the academic literature about ‘technology and ICT’ in tourism and hospitality by carrying out a bibliometric analysis. The study identified 2424 documents, including the words ‘technolog*’ and/or ‘ICT’ combined with ‘touris*’, ‘hospitality’, ‘hotel’, and/or ‘travel’ that were published in the period 1988–2021 and collected from tourism and hospitality journals indexed in the Web of Science (WOS) and SCOPUS databases. The analysis was carried out by using SciMAT software, which offers different bibliometric tools and methods in order to achieve consistent results through a keyword co-occurrence analysis and an evolution map. The findings revealed the major research themes, including technology acceptance model, electronic word-of-mouth, user-generated content, self-services technologies, robotics, smart tourism, virtual reality, and trust in technology. The study concludes by identifying and discussing a future research agenda.

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease.

BACKGROUND: Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. METHODS: 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. RESULTS: Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. CONCLUSIONS: Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.

BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.