What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis  were analysed as independent variables.Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS  included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables . The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI  and cryoglobulins  were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables . The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests , DAS-ESSDAI  and cryoglobulins  were independent predictors of SjS-related death.The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.10.13039/100004336Novartis. Sjögren syndrome (SjS) is a systemic autoimmune disease for which it remains uncertain whether it has a reduced life expectancy. We searched PubMed for studies published from 1998 to January 31, 2023, with the terms “Sjögren syndrome” AND “mortality risk factors”. We also included publications cited in the documents when relevant. We did not use any restrictions for the language of the published studies. The criteria used to include or exclude studies consisted of the fulfilment of the current classification criteria , and a statistical approach mainly based on Cox-Proportional Hazard models.These studies have been centered on analysing the predictors of all-cause and SjS-related causes of death in populations of less than 1000 people, yielding that the number of events of interest  is too low, ranging between 30 and 50. These small samples limit the reliability of identifying mortality risk factors and prevent detailed analysis of different causes of death when stratified. Additionally, all these studies, except for one, did not classify systemic activity using the ESSDAI definitions and scoring and did not study predictors for specific causes of death.The study identified all-cause and SjS-related death predictors in the largest cohort  with the broadest international representation (27 countries from 5 continents). Baseline predictors included positive cryoglobulins (identified as an independent variable in the five multivariate-adjusted CPH models), high systemic activity (identified in three models), and abnormal results in oral tests (identified in two models), conferring an increased risk of death of 1.7–1.9 for all-cause death and 1.4–2.6 for SjS-related death. Although it was not the objective of this study, high systemic activity at diagnosis was also related to poor survival due to infections and cardiovascular disease.The findings support the mandatory measurement at SjS diagnosis of systemic activity using the ESSDAI score and cryoglobulin testing to anticipate better which patients may have poor outcomes and will require closer follow-up.,Sjögren syndrome (SjS) is a systemic autoimmune disease that primarily affects women between the fourth and sixth decades of life, but it also can be diagnosed at any age.,,,,What baseline predictors would be involved in mortality in people with SjS remains uncertain.The Sjögren Big Data Consortium,The Sjögren Big Data Consortium is an international, multicentre registry established in 2014 to provide a real-world understanding of the phenotypes and outcomes of individuals with primary SjS through the cooperative merging of existing individual databases from leading centres in SjS clinical research. Inclusion criteria for the registry consisted of a clinical diagnosis of primary SjS based on fulfilling 2002/2016 classification criteria.,,The database consisted of a minimum basic data set (MBDS) of variables considered essential for characterizing the disease phenotype at the time of diagnosis: age, sex, ethnicity, country of residence, ocular and oral dryness, ocular and oral tests, salivary gland biopsy, global clinical ESSDAI scores (clinESSDAI), antinuclear antibodies, rheumatoid factor, anti-Ro and anti-La antibodies, C3 and C4 levels, and cryoglobulins. Diagnostic tests for SjS  were conducted according to the recommendations of 2002/2016 criteria.To harmonize databases from each centre, we applied specific pre-processing techniques such as detecting and treating outliers, influential observations, errors in naming standards, and other errors, and excluding observations with missing data for mandatory variables . The study was approved by the Ethics Committee of the coordinating centre, and live participants provided written/oral informed consent. . The study adhered to the STROBE reporting guidelines.,,A statistical approach was designed using a directed acyclic graph (DAG) . The pri,Descriptive data are presented as mean and standard deviation (SD) for continuous variables and numbers and percentages (%) for categorical variables. The effect of phenotypic determinants at diagnosis on mortality was assessed using univariate Cox proportional hazards (CPH) regression analysis. Variables corresponding to disease determinants were dichotomized; the value considered as a prognostic factor was defined according to the results obtained in previous studies.The start of the follow-up time for each patient was defined according to the date when the physician responsible for the patient's follow-up confirmed criteria fulfillment. The end of the follow-up time for each patient was defined according to the last recorded National Healthcare System visit. Patients with less than six months of follow-up after criteria fulfillment were excluded. We restricted the Kaplan–Meier analysis to 20-year follow-up. The Log Rank-Mantel-Cox test was used to compare the survival curves between patients with and without the determinants. All studies were conducted using the R software package (R version 4.2.3).We carried out the following post-hoc sensitivity analyses: 1) Stratification of systemic activity according to the systemic disease activity states (DAS) using a univariate CPH model: no activity , low activity , moderate activity  and high activity The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. MRC, PBZ & AFC has directly accessed and verified the merged data. MRC was responsible for the decision to submit the manuscript.Among the 15,654 patients available in the Big Data Registry by April 2022, 2852 cases were excluded from the survival analysis due to a lack of follow-up, and 1430 due to a follow-up period of fewer than six months. Therefore, we analysed the data from 11,372 cases ; 229 (2%) fulfilled the 2002 classification criteria only (positive anti-La in the absence of anti-Ro antibodies). Baseline features are summarized in Patients were followed for a mean of 8.6 years (SD 7.12 years), and 876 (7.7%) deaths were recorded. The overall cumulative risk of all-cause death in the entire cohort was 4.95%  at 5 years, 9.74%  at 10 years, 18.50%  at 20 years, and 25.69%  at 30 years, respectively.Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables  with a P-value <0.1 . In the Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS (0.8% at any follow-up time); other causes of death included infection (28%), cardiovascular diseases (27%), solid malignancies (18%) and other (14%) .Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables  with a P-value <0.1 . In the In the multivariate-adjusted, competing risks CPH regression model, oral tests , DAS-ESSDAI  and cryoglobulins  were independent predictors of SjS-related death , Fig. 2.The sensitivity analysis stratifying systemic activity according to the DAS states showed that those patients presenting with a high DAS-ESSDAI at diagnosis had significantly worse survival compared to those with moderate or low DAS-ESSDAI . The strUnivariate and multivariate-adjusted analyses of prognostic factors for the leading causes of death unrelated to systemic Sjögren  are summarized in We present the data on mortality in primary SJS in the largest study conducted to date, including nearly 12,000 individuals who were followed for an average of 9 years, with almost 900 deaths identified. These figures are 15–30 times higher than those reported in previous studies,,,We found that epidemiological profile and disease-related phenotype at diagnosis modulate the survival of people affected by the disease. The epidemiological profile played a significant role in the adjusted multivariate models, driven mainly by the age at which the disease is diagnosed; these are expected findings considering not only the influence of aging on the risk of death but also their recognized influence on the clinical and immunological phenotype of SjS.,Among disease-related determinants of mortality, systemic activity scored according to the ESSDAI and cryoglobulinaemia were the two key baseline predictors of all-cause and Sjögren-related death. Firstly, high systemic activity at diagnosis (more than 14 points according to the DAS-ESSDAI classification) was associated with a 1.7-fold increased risk of all-cause death and a 1.6-fold increased risk of SjS-related death in the competing risk multivariate analysis. These results confirm a previous study conducted in 1045 Spanish patients, which first linked systemic activity defined according to the ESSDAI with systemic-cause mortality in SjS.,,The key SjS-related mortality risk factor identified in all the multivariate CPH models was cryoglobulinaemia, which has been reported by several studies conducted in smaller European cohorts from Spain, Italy, Hungary, and Greece.,,From a practical view, it is also helpful to highlight what SjS-related features at diagnosis do not influence survival. Glandular involvement has no impact, not only considering dryness symptoms but also on diagnostic tests, including ocular tests and salivary gland biopsy, confirming the results of previous studies.The study results can be interpreted after considering the potential limitations of their design and methodology. The predominant presence of European patients may limit the generalization of the results beyond this ethnicity. In addition, the participant centres are mainly tertiary university hospitals that are considered the referral centre in their corresponding cities , contributing to a potential selection bias favoring the collection of individuals with a more severe clinical phenotype. The retrospective design in a real-world scenario allowed for missing information in some diagnostic variables. This is a fact to be considered when the results obtained from multivariate-adjusted models are interpreted, especially for cryoglobulins tested only in half the patients' total cohort. Another source of heterogeneity may be the availability of some diagnostic tests in all participating centres and their significant influence on the multivariate models concerning missing values. Information about the use of immunosuppressive therapies at diagnosis was not collected for several reasons, including the lack of previous studies linking their use with mortality in adjusted models, the lower frequency of their use in comparison with other systemic autoimmune diseases,The key methodological strength of this study is its large sample size, with nearly 12,000 patients  and the broadest international representation (27 countries from 5 continents). Previous studies have analysed SjS populations of less than 1000 patients, and most mortality rates are below 10% . Therefore, the sample size of the dependent variable (people who died) was too low, ranging between 30 and 50, affecting the reliability of their results. We consider that the results obtained after analysing a cohort of nearly 12,000 patients will be more representative of the worldwide SjS population.In conclusion, the key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring nearly two times increased risk of all-cause and Sjögren-related death. The risk increased to five times for all-cause death and up to ten times for Sjögren-systemic death in individuals presenting with severe multiorgan disease (at least two organs or systems involved and scored as highly active at diagnosis). Systemic involvement was directly involved in 14% of deaths in individuals with SjS, in more than half the cases due to haematological malignancies. These findings support the mandatory measurement of systemic activity and cryoglobulin testing at SjS diagnosis to anticipate better which patients will require closer follow-up. Further studies are needed to investigate the potential association between the SjS phenotype at diagnosis and the risk of dying due to causes unrelated to systemic disease, mainly cardiovascular events and infections.All co-authors contributed to the manuscript . MRC did the statistical analysis. PBZ and AFC wrote the first draft of the report with input from MRC. MRC, PBZ & AFC has directly accessed to and verified the merged data. MRC was responsible for the decision to submit the manuscript.Data available on request due to privacy/ethical restrictions: The data that support the findings of this study are available on request from the corresponding author [MRC]. The data are not publicly available due to restrictions (information that could compromise the privacy of research participants).AR and ADF received the following Grant sor Contracts: R01 DE018209/DE/NIDCR NIH HHS/United States; U54 GM104938/GM/NIGMS NIH HHS/United States; P30 AR053483/AR/NIAMS NIH HHS/United States; P50 AR060804/AR/NIAMS NIH HHS/United States; R01 AR065953/AR/NIAMS NIH HHS/United States.ADF received the following Grants: R01 AR074310/NIAMS NIH HHS/United States; Janssen Research and Development, LLC.ADF reported the following patent: Antibody Tests for Identifying Ro Negative Sjögren's Syndrome and Use as Biomarkers for Dysregulated B Cell Responses, B Cell Lymphoma, Tissue Fibrosis and Salivary Gland Dysfunction. U.S. Patent application 17/797,619, filed August 4, 2022, European Patent application 21750408.3, filed September 14, 2022 and Canadian Patent application, filed September 14, 2022.FA received Grants from Pfizer & Novartis, payments or honoraria from Abbvie, Pfizer, Galapagos, Novartis, BMS, Boeringher, Janssen, and participated on Safety/Advisory Boards of Janssen and Boeringher.MR participated on Safety/Advisory Boards by Janssen and in clinical trials .PO participated on Safety/Advisory Boards by Fresenius Kabi, Novartis & Boehringer Ingelheim.RG received Grants from Pfizer and Abbvie, payments/honoraria from Abbvie, Pfizer, MSD, Novartis, BMS and Boeringher, and participated on Safety/Advisory Boards by Abbvie, Pfizer, and Boeringher.SR participated on Safety/Advisory Boards by Janssen.TM declared that is working as medical advisor for UCB Pharma Sweden.VCR declared that is working as medical advisor for UCB Pharma Sweden.All other authors declare no competing interests.


Background: Understanding and addressing coronavirus disease 2019 (COVID-19) vaccine hesitancy is crucial to informing vaccination outreach strategies and achieving high vaccination coverage. Marin County, California, United States, has a history of vaccine hesitancy regarding childhood vaccinations required for school entry.Objectives: We aimed to describe and address COVID-19 vaccine hesitancy in Marin County to inform outreach and messaging. Our objectives were to identify subgroups with high COVID-19 vaccine hesitancy early in distribution, better understand local concerns and feedback about the COVID-19 vaccine distribution process, and inform tailored vaccine messaging to increase vaccination confidence and coverage.Methods: The survey, which was administered from January 3 to May 10, 2021, queried demographics, vaccine acceptance, reasons for hesitancy, and reasons for acceptance. Open-ended questions were used for respondents to report additional reasons for hesitancy and for general feedback about the vaccine distribution process. We conducted quantitative and qualitative analyses stratified by COVID-19 vaccine acceptance to identify subgroups with high hesitancy. Results were shared weekly in real-time with leadership and key community partners working on vaccine outreach.Results: Among the 5,618 survey responses, there were differences in vaccine hesitancy by sociodemographic characteristics with the highest hesitancy reported among subgroups identifying as Black/African American and young adult, and within the lowest family income grouping. The most common reason for vaccine hesitancy was “uncertain about the side effects of the vaccine” (67.3% endorsement) and responses varied by race and ethnicity. Qualitative data revealed equity-related, vaccine distribution, and vaccine access themes that were not present in structured responses. Vaccine hesitancy survey results were paired with vaccination coverage and COVID-19 case data to inform tailored outreach strategies and priorities week-to-week.Conclusions: Marin County had some of the highest COVID-19 vaccination rates in the United States during the pandemic and met equity goals aimed at ensuring vulnerable populations received vaccinations. Presenting real-time survey findings with leadership and key community partners informed a timely and tailored COVID-19 vaccine outreach and delivery strategy. Marin County, population 259,943, is located in California’s San Francisco Bay Area . While MMarin has a history of vaccine hesitancy with the highest rates of Personal Belief Exemptions from school-required vaccinations among Bay Area counties in 2015 . In the Access to the COVID-19 vaccine was impeded by the pandemic conditions of the time and pervasive mistrust of public health and medical institutions . ResearcSurvey designWe developed a survey to be conducted among people who lived or worked in Marin County. Survey questions included race, ethnicity, age, educational attainment, household income, occupation, geography, and acceptance of the COVID-19 vaccine. Validated items were included when possible. Respondents were classified as hesitant (“No” or “Unsure”) or accepting (“Yes”) based on their response to “Are you open to receiving the COVID-19 vaccine?” For those who were hesitant, we posed structured questions regarding reasons for hesitancy and what might lead them to receive the vaccine. For those who were accepting, we asked reasons for acceptance. Open-ended questions probed additional reasons for hesitancy, what would make them comfortable receiving the vaccine, reasons for acceptance, and other comments. The University of Washington Internal Review Board’s policy asks that researchers self-determine that a project does not meet criteria for human subjects research and is thus exempt from IRB review. Their self-determination tool indicated that this project did not meet criteria for human subjects research.Survey administrationSurvey responses were collected electronically via Google Forms  from January 3 to May 10, 2021. Responses were solicited through email, text, community partners, town hall presentations, the County COVID-19 website, and an in-person event conducted orally in Spanish. The survey was available in English and Spanish.Quantitative analysisWe compared the survey sample’s demographic distribution with Marin’s general adult population 18+ years). We used proportions and chi-square tests to analyze responses by race/ethnicity, age, household income, educational attainment, city of residence, and occupation. Subgroups with fewer than 30 respondents were combined or excluded from analyses. We compared endorsement of reasons for COVID-19 vaccine hesitancy by racial and ethnic subgroups. All data were analyzed using Stata/SE 16.0  [+ years. Qualitative analysisQualitative methodology was used to identify COVID-19 vaccine perceptions that had not been anticipated and were not included in structured response options. We used a modified grounded theory approach to identify main themes present in the open-ended, free-text survey responses [Sharing findings to inform vaccination strategyCOVID-19 vaccine distribution began in Marin County in January 2021 and continued throughout the year  and census tract to inform real-time vaccine outreach strategies countywide and for the community response teams  in English and 189 (3.4%) in Spanish. Non-Hispanic White individuals were overrepresented among respondents (76.6%) when compared with Marin’s adult population (69.0%). There were significant differences (p < 0.05) in COVID-19 vaccine hesitancy by race/ethnicity, age, educational attainment, household income, and city of residence  and “I feel the vaccine approval process was too quick” (57.7%). These endorsements varied by racial and ethnic subgroup. Eighty-one percent of White vaccine-hesitant respondents were uncertain about the side effects of the vaccine while 66% of their Hispanic/Latino/a/x counterparts endorsed this reason. Sixty-eight percent of respondents who identified as Black/African American felt the vaccine approval process was too quick compared to 61% among White and 50% among Asian vaccine-hesitant respondents.When asked when hesitant individuals would be more comfortable receiving the vaccine, the most endorsed responses were “I know more about the vaccine’s side effects” (50.5%), and “More time passing” (50.2%). Among respondents who did not identify as vaccine hesitant, the two reasons for vaccine acceptance with the highest endorsement were “I want to protect myself from getting COVID-19” (87.1%), and “I want to protect my family and community from getting COVID-19” (86.0%). Among the 62 open-ended responses to other reasons for vaccine hesitancy, leading themes identified were distrust in institutions (n=12), concerns over long-term reactions to vaccines (n=10), the vaccine being too new or approved too quickly (n=10), and general feelings of fear (n=10). An additional important theme identified was mistrust of governmental institutions for fear of harming people of color (n=2), which was supported by Black/African American and American Indian/Alaskan Native respondents.The conceptual model developed from open-ended responses shows the spectrum of vaccine hesitancy to acceptance, highlighting factors that might influence hesitant individuals to accept the vaccine and affect vaccine access Figure . Some paSeveral open-ended responses supported themes around challenging logistics that made it difficult for people to get the COVID-19 vaccine. These themes included requests for more information and outreach, a desire for more transparency on vaccine distribution, difficulty finding vaccine appointments, and comments about who was eligible to receive the vaccine during early vaccine delivery. Lastly, several respondents supported equity-related themes such as accessibility to technology, for older adults, and those living with disabilities, and more support for non-English speakers.Findings were shared in the weekly Vaccination Strategy Meetings that included County leadership, healthcare partners, and other community-based organizations participating in COVID-19 vaccine outreach  were more vaccine hesitant than older age groups. Similar patterns were seen in other populations -8,11,15.Much like in other studies, concerns about side effects, the novelty of the vaccine, and distrust of institutions were apparent in our quantitative and qualitative findings -13,18-19This study emphasizes the importance of Marin County HHS continuing to build trust with the community by integrating local data into public health strategy. Other research supports the importance of identifying and addressing community concerns about the COVID-19 vaccine early in vaccine distribution ,21. SurvStrengths and limitationsAn asset of this project was the utility of the data for timely public health and healthcare action. The communication of survey findings through several formats early in COVID-19 vaccine delivery allowed decision-makers to easily digest and incorporate community perspectives into vaccine strategy. Perhaps in part due to its proactive and innovative uses of data for public health action like this survey, Marin County had the highest COVID-19 vaccination rates in California during the summer of 2021 -23.Another strength of this survey was the use of qualitative data. Because the survey was administered early in COVID-19 vaccine delivery, there was little known about the reasons for vaccine hesitancy and acceptance. Therefore, structured response options designed in December 2020 did not necessarily capture the concerns that would change and arise over time. Through analyzing open-ended responses with a modified grounded theory approach, we learned important, new local perspectives that were incorporated into vaccine outreach materials and dialogue. The conceptual framework highlighted important factors among respondents whose confidence in the vaccine grew and allowed us to address hesitancy as it related to race and ethnicity (Figure The timeframe in which we conducted the survey was both beneficial because of its pivotal position in early vaccine delivery during a surge in COVID-19 infections, and impacted the design of the survey and the interpretation of our findings. During survey development, COVID-19 vaccine perspectives were not widely available and attitudes were likely to change over time. Therefore, the reasons for hesitancy and acceptance were anticipated based on limited information. While open-ended responses helped gather opinions not in structured response options, we may have missed or underestimated local concerns in the later stages of the pandemic, such as those related to distrust. Due to political, demographic, and cultural factors, COVID-19 vaccine perceptions may differ greatly by community. While these local data informed practice in Marin County, generalizing these findings to other settings should be done with caution. This emphasizes the value of collecting data locally in order to drive effective public health efforts.Another limitation of the study was the sampling approach. Emailing the survey link to healthcare employees when they were eligible for vaccination and posting it on the County’s COVID-19 vaccine website were two administration methods that could have resulted in an overrepresentation of survey respondents who were more likely to be highly educated or more digitally literate than the general population. We may have failed to reach key populations, such as those who speak languages other than English or Spanish, live with disabilities, or lack computer access. These groups could have different concerns about the COVID-19 vaccine than survey respondents. To capture responses from additional subpopulations, we hosted an in-person interview event and advertised the survey in a town hall. Even with these efforts, our survey distribution did not yield a sample representative of the Marin population by important characteristics such as race and ethnicity.The Marin COVID-19 Vaccine Perceptions Survey was an example of using local, timely, community-generated data to iteratively shape public health approaches during a pandemic. Survey responses allowed us to identify subgroups with higher hesitancy and understand local concerns through structured and unstructured data during a pivotal time in which the novel vaccine was being distributed. The data were used in near real-time to inform vaccination strategy and messaging. These data were paired with vaccination coverage and COVID-19 incidence data to acknowledge hesitancy as well as access, infection risk, and coverage during vaccine distribution. This applied approach may have contributed to an exceptionally high COVID-19 vaccination coverage in Marin County, despite its history of vaccine hesitancy. Marin County will continue to shape public health strategy and build community trust through learnings from local data.


Most symptomatic SARS-CoV-2 infections produce mild to moderate symptoms. Although most patients are managed in the outpatient setting, little is known about the effect of general practitioners’ (GP) management strategies on the outcomes of COVID-19 outpatients in Italy.Describe the management of Italian GPs of SARS-CoV-2 infected adult patients and explore whether GP active care and monitoring are associated with reducing hospitalisation and death.Retrospective observational study of SARS-CoV-2 infected adult outpatients managed by GPs in Modena  from March 2020 to April 2021. Information on management and monitoring strategies, patients’ socio-demographic characteristics, comorbidities, and outcomes  were retrieved through an electronic medical record review and analysed descriptively and through multiple logistic regression.Out of the 5340 patients from 46 GPs included in the study, 3014 (56%) received remote monitoring, and 840 (16%) had at least one home visit. More than 85% of severe or critical patients were actively monitored (73% daily) and 52% were visited at home. Changes over time in patients’ therapeutic management were observed in concordance with the guidelines’ release. Active daily remote monitoring and home visits were strongly associated with reduced hospitalisation rate .GPs effectively managed an increasing number of outpatients during the first waves of the pandemic. Active monitoring and home visits were associated with reduced hospitalisation in COVID-19 outpatients. KEY MESSAGESThis practice-based research network study from Northern Italy demonstrates the importance of primary care management of patients with COVID-19.GPs effectively treated a large - and increasing - number of patients outside the hospital.Active monitoring and home visits by GPs were associated with fewer hospital admissions for COVID-19.Since February 2020, the Coronavirus disease 2019 (COVID-19) . In mostItalian GPs faced several challenges and difficulties managing patients during the first wave of the COVID-19 pandemic . The lacSupport for GPs was provided mainly by the GP-Out-of-Hour (OoH) service and by COVID-19 special units of continuity care . These new working units were dedicated to home visits and initial assessment of infected patients .To date, little is known about the management strategies used by Italian GPs for SARS-CoV-2 patients and their impact on COVID-19-related hospitalisations and mortality. First, this study aimed to describe the clinical characteristics of infected patients and the management strategies used by their GPs during the first and subsequent waves of the pandemic. Second, it aimed to explore the association between active monitoring by GPs and COVID-19-related hospitalisations and mortality in adult patients in the Province of Modena .The MAGMA study is a retrospective cohort study of SARS-CoV-2 positive subjects based on the review of electronic medical records (EMRs) provided by 46 GPs of the Province of Modena . See the acknowledgement section for insights on the name MAGMA chosen for this study.n = 462) were invited via e-mail to attend a study presentation webinar. During the webinar, GPs were asked to collaborate on the study. They were eligible if they recorded patient data using the software MILLEWIN®.Between March and April 2021, all GPs practising in the province of Modena (n = 46) were provided with Structured Query Language (SQL) to perform EMR data extraction independently. SQL-based data extraction is routinely used by GPs in the local health service of Modena for audit purposes. Nevertheless, prior to the study, GPs received additional training on data wrangling to standardise activities and improve data quality. Data was checked for completeness and consistency by each GP, who manually added information on the severity of the disease and the monitoring strategies. We included in the analysis patients with a positive SARS-CoV-2 real-time polymerase chain reaction test performed between 01/03/2020 and 30/04/2021.Participating GPs  monitoring, 4 options were possible: (a) no monitoring, (b) passive monitoring (i.e. monitoring performed only upon the patient’s request); (c) irregular active monitoring (not daily); and (d) active daily or twice daily monitoring. There were also 4 options for home visits: (a) no home visits, (b) only USCA/OoH service visit; (c) only GP visit, or (d) both USCA/OoH service and GP visit. These options were then grouped into a summary variable to describe the overall GP monitoring strategy as follows: (a) none or low-level monitoring ; (b) only active daily or twice daily remote monitoring; or (c) home visits .The patient’s socio-demographic characteristics, lifestyle and clinical features were collected: age, gender, number of comorbidities, severe obesity BMI > 35), smoking habits, place of residence (home/nursing home), socio-economic deprivation   and COVID-19-related deaths (yes/no). Outcome-related variables were automatically registered in the patient’s electronic medical record. A complete description of the variables and their level definitions, the data sources and possible sources of bias are provided as T-student test or Mann–Whitney U-test was used to analyse numeric variables depending on their distribution. Multiple logistic regression models were built to explore the association of GPs´ monitoring strategies on hospitalisation or death due to COVID-19. The summary variable ‘GP monitoring strategy’ was used as the primary exposure variable in the model. To control for potential confounders and to evaluate their role, covariates were also included in the model. Associations are reported as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). SPSS Statistics®, version 27[Categorical variables were summarised by absolute and relative frequencies. Mean and Standard Deviation (SD) or median and interquartile range (IQR) were used to summarise continuous variables according to their distribution. Pearson’s chi-square test or Fisher’s exact test was used to compare categorical variables. ersion 27 and ExceThis study was reported according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines .A total of 46 GPs  agreed to participate. They were younger, predominantly female, working in an urban setting and group practices. Enrolled GPs served a population of 64,763 people, with an average of 1408  patients received no pharmacological treatment. Significant prescription changes in in the subsequent waves over the first one were observed . AntibioOverall, 3014 (56%) patients received remote monitoring, either irregularly (9%), daily (24%) or twice daily (6%) . Remote Overall, 840 patients (16%) were visited at home. Their proportion significantly increased with the increase of disease severity and in the subsequent pandemic waves .A similar trend was observed for the variable summarising the overall GP monitoring strategies.p < .001). In the subsequent waves, the hospitalisation rate was lower regardless of the disease stage, as reported in Overall, 521 patients (10%) were hospitalised , with a Most hospital admissions concerned patients with the severe or critical disease , over 70 years (54%) or with at least one comorbidity (68%).p < .001) and occurred mainly in stage 4 . However, the mortality rate in critically ill patients decreased significantly in the subsequent waves compared to the first wave  due to COVID-19. Deaths were more frequent during the first wave than in the subsequent ones , in those with 2 or more comorbidities (60%) and in males (56%). GPs managed twenty-seven deaths (24%) in an outpatient setting: 12 occurred at home upon the patient’s or caregiver’s request and 15 in nursing homes.As shown in via telephone or at home. In the following waves of the pandemic, the use of LMWH and oxygen increased in more severely ill patients, whereas the use of NSAIDs increased in the case of milder disease. As to the effects of GPs´ monitoring strategies, our analysis suggests that patients who get actively monitored or are home-visited are half less likely to be hospitalised than non-monitored patients.This is the first study to describe the management strategies of GPs in a northern province of Italy in caring for SARS-CoV-2 infected patients. More than 85% of patients with the severe or critical disease were remotely monitored, 73% daily, and 52% received a home evaluation. In the subsequent waves, despite the exponential increase of COVID-19 cases to be managed, GPs increased the percentage of patients they could monitor Our study has several strengths. First, we included a large sample of patients obtained thanks to the broad collaboration of local GPs . Second,The main limitation is the retrospective nature of our study, not allowing us to establish causality. Second, we had no information on the timing of therapy or GP monitoring. This limited insights into patients’ management and disease pathways. Third, GPs participated voluntarily, so that, selection bias may affect generalisability. The differences observed between MAGMA GPs and those who did not may affect our results’ generalisability in the Province of Modena. Unfortunately, the lack of data on GP’s characteristics in Italy does not allow us to compare our GP sample nationally. Nevertheless, the characteristics of SARS-CoV-2 infected patients in terms of age, sex and clinical features in the first and subsequent waves reflect national data , so we bDuring the first wave shortage of diagnostic tests , reserveFurther, therapeutic and monitoring strategies vary significantly between the first and next waves, consistently with the improved knowledge on the management of COVID-19 and the publication of guidelines from the Ministry of Health and the Italian regulatory agency (AIFA) ,21. CompOur study shows the benefits of proactive and integrated territorial management (both for remote monitoring and for home visits) on COVID-19 hospitalisation and the results are consistent with current literature . Russo ePotential protective effects of the different remote monitoring strategies, in place of or in addition to the in-person visits, need to be further investigated to draw guidelines to effectively relieve hospital pressure and costs.GPs ability to adjust quickly in the face of a new pandemic may prove effective in helping the management of this and future epidemics. In these contexts, it is warranted that networks of primary care physicians and independent primary care practice-based research are strengthened, as they could promptly provide the much-needed evidence to implement rational patient management policies.Our findings described how GP responded to the first waves of the pandemic and suggest that active monitoring of COVID-19 outpatients performed by primary care physicians may reduce hospitalisations substantially.Click here for additional data file.


Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality  or improved 28-day secondary outcomes, such as hospital discharge , ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI  and RR = 1.06, 95% CI , respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care . Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions)  based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era. At the end of 2019, a surge of pneumonia cases in Wuhan, a city in the Hubei Province of China, led to the identification of a novel coronavirus as the cause. Its rapid spread resulted in an epidemic throughout China, followed by an increasing number of cases around the world. On 11 March 2020, the World Health Organization declared the novel coronavirus outbreak a pandemic. The disease associated with it was designated as COVID-19, which stands for coronavirus disease 2019, and the virus that caused it was designated as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)  or score-related outcomes  . The ICUFurthermore, a subgroup analysis was conducted according to the levels of anti-SARS-CoV-2 antibodies in the CP. Studies were grouped as “high-titer” or “non-high-titer” as per the latest EUA/FDA guideline cut-offs. The subgroup analysis for the titer level did not reveal any statistically significant associations . However, when analyzing by geographic region, studies carried out in Europe  showed a statistically significant association between convalescent plasma therapy and ICU-related outcomes .The subanalysis on hospitalization outcomes  was also statistically significant, showing that outpatients treated with convalescent plasma had a 26% less risk of needing hospital care than those treated with the standard of care .In total, 10 studies were included in the overall meta-analysis for the 14-day cohort. The effect outcome for 14-day mortality was not statistically significant  . There wA meta-analysis for the secondary clinical outcomes showed no statistically significant association between convalescent plasma therapy and hospital discharge  . A subgrThe post hoc meta-regression aimed to assess whether gender, age, time from symptom onset to intervention or total cp dose modified the association between convalescent plasma treatment and each reported outcome. This analysis yielded no statistically significant associations . It was All included studies were randomized control trials, blinded or open label. For the evaluation of quality and risk of bias of each one, the RoB:2 tool by Cochrane was used . Table 1Six studies (17.7%) raised some concerns on their randomization process, mostly due to lack of information on allocation concealment;Five studies (14.7%) raised some concerns on whether there were deviations from the intended interventions;Only one study raised concerns on potential selection of the reported result;One study had a high risk of bias due to vital randomization process concerns.In total, 23/34 studies (67.7%) were assessed as having a low risk of bias, 10/34 studies (29.4%) raised some concerns and only one was deemed to have a high risk of bias . More spA publication bias assessment was performed on outcomes reported in 10 or more studies with the use of Egger’s test ,15. Thesp-value for the bias coefficient generated by Egger’s regression test for small-study effects was p = 0.247 ], showing that convalescent plasma treatment was beneficial in protecting patients from ICU-related disease progression. Specifically, patients treated with convalescent plasma had an 8% less risk of presenting an ICU-related outcome , when compared to those treated with the standard of care or supportive care (with or without placebo/standard plasma infusion). While this result is interesting and significant, it can largely be attributed to the contribution of the weight of the Avendaño-Solá (2021) study . MoreoveCarrying out a subgroup analysis for titer levels (high-titer vs. non-high titer) was challenging, as each study used different antibody measurements and cut-off levels for high-titer labeling. Moreover, achieving in-study heterogeneity among the titers of the plasma units administered was also significant. These led to a statistically nonsignificant and mostly inconclusive result. There was a scarcity of outcome data regarding secondary clinical outcomes, such as hospital discharge (9/34 studies), hospitalization (6/34 studies) and score-related outcomes (6/34 studies). The plasma titer between studies varied and so did COVID-19 disease severity at randomization and study size. Serostatus at the time of treatment was not possible to assess and analyze, as only a percentage of studies provided robust and uniform data for it. Furthermore, records were extracted solely from the PubMed database.In addition, the RECOVERY trial  has raised some concerns during our risk of bias assessment and is worth mentioning, as its weight skewed the results. This is due to the fact that it failed to completely adhere to its design, as 9% of the patients did not receive the allocated intervention (plasma infusion). While this raises questions about the robustness of the results, the aforementioned population percentage was excluded from the comparison analysis between the convalescent plasma group and the control group.2 = 0.0%, p = 0.709) and 14-day  cohorts. In the statistically significant ICU-related European subgroup, heterogeneity was also low and not significant . Overall heterogeneity was 49.8% for the hospitalization outcomes subanalysis, but it was marginally not statistically significant (p = 0.076). While region, sex, age, time from symptom onset to intervention and total convalescent plasma dose can be considerable sources of heterogeneity, subgroup analyses and meta-regression showed no statistically significant association between them and treatment effectiveness. The extensive abstraction and analysis of separate and discrete clinical outcomes and thorough risk of bias assessment are also parts of this study’s strengths. Contrary to other meta-analyses [Despite the aforementioned notable limitations, the present work possesses a plethora of important strengths. Overall heterogeneity was low and not significant both in the 28-day  are similar. Axfors et al. conducted a systematic review and meta-analysis on 33 published and unpublished trial papers and showed a non-statistically significant association as well . Other pFinally, subgroup analyses on immunocompromised patients were not feasible due to the scarcity of available data from randomized studies in the field. A recently published randomized controlled trial by Dekinger et al.  evaluateConvalescent plasma treatment was not associated with a statistically significant reduced risk of overall 28-day or 14-mortality or any other clinical outcome. It was associated, though, with a statistically significant beneficial effect on 28-day ICU-related outcomes in the European study cohort and 28-day hospitalization. The aforementioned evidence hints against the use of convalescent plasma for the treatment of COVID-19 in the general population, but it highlights potential clinical benefits when studying subpopulations . As such, further study on specific subpopulations and outcomes could establish consensus on determining the clinical benefits of convalescent plasma therapy.


To reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed.We fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012–2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022–2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels.We found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70–90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70–90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection.These results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses.The online version contains supplementary material available at 10.1186/s12879-023-08224-w. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in the United States in January 2020. A variety of national and state level non-pharmaceutical interventions (NPIs) such as social distancing, mask wearing, and improved hand hygiene were implemented to curb SARS-CoV-2 incidence and hospitalizations. Federal social distancing guidelines were announced March 16, 2020, and included limiting gatherings to fewer than 10 people, avoiding eating and drinking in bars and restaurants, and avoiding unnecessary travel. These federal guidelines remained in effect through the end of April 2020 .These NPIs also reduced the transmission of enteric pathogens, with a > 80% in incidence of reported norovirus outbreaks in the United States from April to July 2020 , 5. ThisNorovirus is an endemic enteric virus with no current vaccination or specific treatment options. Globally, one out of every five cases of acute gastroenteritis that leads to diarrhea and vomiting is caused by norovirus . NorovirRotavirus is the leading cause of severe diarrhea, hospitalization, and diarrhea- related deaths globally in infants and children < 5 years old . Prior tWe aimed to assess changes in population susceptibility and community incidence of norovirus and rotavirus gastroenteritis episodes that resulted from the COVID-19 pandemic, and project the future trends in incidence as contacts resume and other NPIs are relaxed. We developed pathogen-specific transmission models to reflect their natural history and, for rotavirus, vaccination, and fitted the models to surveillance data up to December 2019. We then made predictions for trends in norovirus and rotavirus disease trends until 2030 under different scenarios of contact patterns informed by mobility data.Our overall analytic approach was to develop pathogen-specific models for norovirus and rotavirus, to fit those models using likelihood to Centers for Disease Control and Prevention (CDC) surveillance data using time-varying contact rates, and then to project the fitted models into the future under different scenarios of increasing contacts. Two separate models were developed to capture the differences in natural history of norovirus and rotavirus and vaccination (in the case of rotavirus). For both models, U.S. birth rates were informed by the CDC Wonder database . We assuWe fitted the models to a weekly time series of norovirus outbreak-cases and rotavirus case reports to CDC. Cases were used for model fitting and the model with the best fit based on maximum likelihood was used for prediction by forward simulation. For norovirus, the total number of norovirus outbreak-associated cases occurring August 2012–December 2019 and reported to the National Outbreak Reporting System (NORS) by states participating in the Norovirus Sentinel Testing and Tracking network (NoroSTAT). NORS is a web-based platform used by states to report data on all foodborne, waterborne, and enteric disease outbreaks spread by person-to-person or animal contact, contact with contaminated environmental surfaces, or by an unknown mode of transmission. The twelve states participating in NoroSTAT report all epidemiologically suspected and laboratory-confirmed norovirus outbreaks to NORS within 7 business days of identification and provide minimum outbreak data elements including the setting and number of cases for each outbreak . Data weFor rotavirus we used data on rotavirus cases reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) during January 2012–December 2019. Laboratories participating in NREVSS voluntarily report to CDC the total aggregate number of weekly tests performed and number of positive tests for various pathogens, including rotavirus. We used the number of aggregate positive tests to indicate the number of cases. Data were extracted on November 22, 2021.13, at which point individuals moved from the recovered class back to the susceptible class, denoted as rate ω [A deterministic susceptible-infected-recovered-susceptible (SIRS) model was developed for norovirus, drawing on our previous studies , 22, 23  periods , 26. UpoA deterministic susceptible-infected-recovered-vaccinated (SIRV) model was developed for rotavirus in the United States population under 5 years, since it primarily a childhood illness, transmission to adult contacts is low, and repeat infections in adulthood are generally not severe , seasonality parameters , and reported fraction (r) for norovirus and rotavirus models using maximum likelihood estimation. The calculated parameters that minimized the negative-log-likelihood were used for forward projections.We estimated transmission parameters  to April 2021, there was a substantial reduction in norovirus cases (90.4% compared to the April 2019-April 2020 time period) and rotavirus cases (81.2% compared to the April 2018-April 2019 time period) in the NORS and NREVSS surveillance data we analyzed. This period corresponds to a reduction in mobility ranging from 18–53%.The maximum likelihood models of norovirus and rotavirus captured key features including seasonality, post-vaccine biennial pattern for rotavirus, and reasonable parameter estimates  Table . The modWe calculated a ratio of the population susceptible relative to the pre-pandemic average. According to the best-fit model, the population susceptibility began to change around August 2020, when it began to increase and peaked in October 2021 at 1.07, representing a 7% increase from the pre-pandemic year because of waning immunity and decreased infections. Following the population susceptibility high of 1.07, the population susceptibility was projected to dip to 0.94 in December 2022 and then reach pre-pandemic equilibrium in 2024 . Our modeled population susceptibility increased and peaked at a high of 1.06 in November 2021. Following November 2021, the population susceptibility was projected to dip at 0.87 in May 2022  and rotavirus (right) compartmental model structure. Supplementary Figure 2. Mobility estimates as the reduction in mobility on a scale from 0 (no mobility reduction) to 1 (100% mobility reduction) from February 4th, 2020.


SARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech’s COMIRNATY (BNT162b2 mRNA) and Moderna’s mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population. The emergence and spread of the SARS-CoV-2 infection in early 2020 had a profound impact on both the healthcare and economic systems. In Italy, the high number of reported cases and deaths  highlighted the significant public health challenge posed by this pandemic .To address these challenges, on January 2, 2021, the Italian Ministry implemented measures to prevent SARS-CoV-2, including a strategic national vaccine program . In thisThe optimal timing of vaccination in relation to cytotoxic chemotherapy or immunotherapy has not been definitively established. However, it is generally recommended to administer the vaccine toward the end of the therapy cycle to minimize the risk of overlapping with periods of low blood cell count. Vaccine administration should not cause delays in chemotherapy and should avoid coinciding with the nadir period induced by chemotherapy. However, limited information is available regarding the recommended intervals between vaccination and treatment, as well as the impact on hematological parameters following vaccination –12.Our study aims to gather data and information from real-world clinical practice to evaluate the use of SARS-CoV-2 vaccines in cancer patients. Real-world data has proven valuable in uncovering factors that may have been underestimated in clinical studies, despite its limitations. Given the unique nature of mRNA-based SARS-CoV-2 vaccines, which were rapidly developed in response to the pandemic, post-marketing surveillance is highly recommended and expected.To this end, we conducted a retrospective analysis of hematological parameters following vaccine administration and their potential impact on the scheduling of anticancer intravenous infusions. Additionally, unlike many trials focusing on seroconversion based on anti-Spike (S) antibody titers, we collected data on anti-nucleocapsid (N) COVID-19 antibodies, which are specifically associated with SARS-CoV-2 infection. In summary, our investigation aims to evaluate clinical and hematological parameters in a real-world dataset of cancer patients receiving SARS-CoV-2 vaccines during oncological treatments.From January 2021 onwards, all patients with cancer undergoing treatment in our institution were offered two doses of the BNT162b2 mRNA vaccine, administered at a 21-day interval as recommended. Patients with a previous SARS-CoV-2 infection within the past 6 months were excluded from the vaccination program. The timing of vaccine administration was carefully coordinated with the patients’ oncological treatments, taking into consideration optimal intervals to avoid the nadir period induced by chemotherapy. All chemo-, immune- and chemo-immunotherapy protocols were used according to oncological guidelines. Patients were required to have a prednisone dosage lower than 10 mg at least seven days before and after the scheduled vaccine administration.A retrospective review of data was conducted on patients who received the vaccine between March and June 2021 in the Medical Oncology Unit of S.Maria delle Grazie Hospital. Prior informed consent was obtained from all patients, and their personal data were anonymized in the database. The study protocol was reviewed and approved by the Campania Centro Ethical Committee . Out of the 220 screened patients, 136 were included in the analysis after excluding those with missing data, completed oncological treatment before vaccine administration, vaccine administration outside the anticancer treatment schedule, or patient refusal.Table SARS-CoV-2 detection was performed using the Elecsys® Anti-SARS-CoV-2 assay, which measures total antibodies against the nucleocapsid protein of SARS-CoV-2. IgG and IgM antibodies against SARS-CoV-2 were measured in human serum and plasma. The assay allowed for differentiation between asymptomatic or oligosymptomatic patients and aided in directing them toward confirmatory testing. Data on seroconversion, neutralizing antibodies, and previous values were collected at four-time points: before vaccination, one, three, and six months after vaccination.Statistical analyses were conducted using descriptive statistics for quantitative and categorical variables. Differences between pre-vaccine and post-vaccine measures were assessed using Student’s t-test for paired samples. Linear regression models were used to investigate predictive factors for significant differences in the WBC count. A significance level of alpha = 0.05 was applied for all analyses, which were performed using R statistical software version 4.0.3.Our cohort consisted of 136 enrolled cases, with the majority being breast cancer patients, followed by gastrointestinal, lung, and genitourinary malignancies. Metastatic disease was present in 86% of the patients. Females accounted for 64% of the total patient population. The median age was 66 years (IQR 31–86). Most patients (over 80%) had a normal or overweight classification based on BMI. Comorbidities were present in 65% of cases, with cardiovascular diseases being the most commonly reported. Approximately 50% of patients received chemotherapy, while the remaining 25% received immune therapy or chemo-immunotherapy.White cell growth factors were administered to 22 out of 136 patients (16%). Regular growth factors were used in only one case, while pegylated growth factors were preferred in the others. In three cases, growth factor support was only provided with one vaccine dose.Vaccine administration did not result in major side effects in our patient series. The most frequently reported effects (approximately 60% of cases) were local, including a sore arm and local skin reactions. Systemic effects such as fatigue and muscle pain were reported in less than 20% of cases. No grade 3–4 toxicity was recorded.There were no significant differences in hematologic parameters between baseline, post-vax 1 (after the first vaccine dose), and post-vax 2 (after the second vaccine dose) in all patients Table , but notThe immune-mediated diseases associated with cancer in our patient series included neurologic syndromes such as Lambert-Eaton and multiple sclerosis, inflammatory bowel diseases like Crohn’s disease, rheumatic polymyalgia, and systemic lupus erythematosus.Only the subgroup of patients treated with chemo-immunotherapy showed a significantly lower WBC value (P = 0.02427*) between the baseline and the second vaccine dose Table . Once agThere was no significant association between the use of growth factors and white blood cell counts before and after vaccine administration Table . Among tBaseline anti-N antibody titers were available for 111 out of 136 patients, and at least two measurements were available for 105 patients. In our cohort, 17 patients  patients, primarily due to neutropenia (7 out of 9 patients) . HoweverA recent study specifically focused on hematological abnormalities following the administration of inactivated whole-virion SARS-CoV-2 vaccine  and the mRNA vaccine BNT162b2 in healthy subjects reported an increased risk of leukopenia shortly after the second dose of BNT162b2 . SimilarThe variations in peripheral blood cell counts can be influenced by various factors, including the concurrent use of medications such as antiretrovirals, corticosteroids, antibiotics, and the presence of concomitant viral infections. In cancer patients undergoing chemotherapy, the use of granulocyte growth factors can also affect these variations. In our study, corticosteroids were gradually reduced before vaccination to potentially enhance seroconversion. White blood cell growth factors were used according to guidelines for high neutropenic regimens. However, the use of growth factors did not prevent the decrease in white blood cell counts, as two out of nine patients with treatment delays received pegylated factors.Lymphocytopenia, a reduction in lymphocyte counts, is commonly observed during SARS-CoV-2 infection and is considered a poor prognostic factor , 25. TheConsidering the significantly low leukocyte counts observed in patients receiving chemo- and chemo-immunotherapy, it is plausible to hypothesize that the vaccine and administered treatment have at least an additive effect. Previous studies have also highlighted a reciprocal bidirectional effect exerted by vaccination and immunotherapy . The immGuidelines in oncology have recommended the use of growth factors to reduce the risk of febrile neutropenia when the risk exceeds 20% . While mSerological testing provides valuable information about the immune response to SARS-CoV-2 following natural infection and vaccination. Most studies have used antigen S tests for assessing vaccine-induced immune response , 8. On tThe S1 viral subunit plays a crucial role in binding to functional ACE2 receptors on susceptible human cells, enabling the virus to enter these cells. Blocking the virus’s entry through anti-spike antibodies significantly contributes to virus neutralization. Traditionally, higher levels of neutralizing antibodies targeting the spike protein of SARS-CoV-2 have been associated with greater vaccine-induced protection. However, with the increasing prevalence of spike protein mutations in variants, the induction of neutralizing antibodies against the N-protein may also be relevant for maintaining protection. The role of anti-N antibodies in conferring long-term immunity in individuals infected with the virus is still unknown . Due to In conclusion, although our study is limited by a relatively small sample size, it provides insights into the hematological changes following mRNA vaccines in patients with solid cancers undergoing active oncological treatments. Importantly, our findings suggest that the administration of mRNA vaccines does not compromise the scheduled delivery of oncological treatments. Despite its limitations, this study contributes to the growing body of evidence supporting the safe and effective use of mRNA vaccines in this specific patient population.


Patients with cancer demonstrate an increased vulnerability for infection and severe disease by SARS-CoV-2, the causative agent of COVID-19. Risk factors for severe COVID-19 include comorbidities, uncontrolled disease, and current line of treatment. Although COVID-19 vaccines have afforded some level of protection against infection and severe disease among patients with solid tumors and hematologic malignancies, decreased immunogenicity and real-world effectiveness have been observed among this population compared with healthy individuals. Characterizing and understanding the immune response to increasing doses or differing schedules of COVID-19 vaccines among patients with cancer is important to inform clinical and public health practices. In this article, we review SARS-CoV-2 susceptibility and immune responses to COVID-19 vaccination in patients with solid tumors, hematologic malignancies, and those receiving hematopoietic stem cell transplant or chimeric-antigen receptor T-cell therapy. Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the literature has demonstrated an increased vulnerability for infection and severe disease among patients with cancer . From a The emergence of COVID-19 vaccines has afforded some level of protection against infection and severe disease among patients with cancer; however, decreased immunogenicity and real-world effectiveness was observed among patients with solid tumors and hematologic malignancies , 15–17. Analyses from the National Center for Advancing Translational Sciences National COVID Cohort Collaborative identified 398 579 adult patients with cancer in the United States, 63 413 (15.9%) of whom had a COVID-19 diagnosis between January 1, 2020 and March 25, 2021  . COVID-1Among patients with cancer, a current diagnosis of COVID-19 is associated with increased risk of mortality. A cohort study characterized COVID-19 outcomes in patients with active or previous malignancy from the COVID-19 and Cancer Consortium (CCC19) database between March 17 and April 16, 2020, and identified 928 patients, 26% of whom had severe COVID-19 illness and 13% died . PatientBreakthrough infections and severe outcomes are more likely to occur in COVID-19–vaccinated patients with cancer than in vaccinated individuals without cancer, with the highest risk in patients with hematologic malignancies and those receiving systemic antineoplastic agents  , 24. WidMany studies have focused on SARS-CoV-2 antibody response to the receptor binding domain (RBD) or spike protein and have demonstrated that patients with cancer have lower COVID-19 vaccine seropositivity rates than the general adult population . AlthougSpecifically, in studies of patients with solid tumors, seropositivity ranged from 75% to 100% after 2 doses of COVID-19 vaccines that received emergency use authorization from the World Health Organization, including those who received mRNA vaccination (mRNA-1273 or BNT162b2) . A wide range of seropositivity rates were reported, but most studies demonstrated that ≥40% of patients with cancer who did not respond to 2 vaccine doses, achieved seropositivity after an additional dose . Note that a delayed interval dosing has been evaluated in a few studies of healthcare workers but not in cancer populations. Studies in healthcare workers found that extending the standard 3- to 6-week interval between the first and second doses of BNT162b2 to 6 to 14 weeks or 8 to 16 weeks significantly increased anti-RBD antibody titers, improved nAb responses to ancestral, alpha, beta, and delta strains, and enriched the CD4response , 67.+ and CD8+ T-cell responses, providing a robust and durable immune response [Use of a heterologous vaccine regimen can enhance humoral and cellular response in patients with cancer as well as healthy individuals. In particular, in patients with solid tumors who received a heterologous regimen of CoronaVac/ChAdOx1 vaccines for doses 1 and 2 followed by a third dose with an mRNA vaccine, seroresponse increased from 16% after dose 2 to 91% after dose 3 with significant increases in anti-RBD antibodies observed . A studyresponse . These sCareful consideration should be used when determining the number of doses, the interval between doses, and the type of vaccine administered regarding both the primary series (doses 1 and 2) as well as any subsequent additional doses (dose 3 and beyond). The development and availability of variant-updated booster vaccines can potentially expand the protection against SARS-CoV-2 VOC. The bivalent vaccines combining ancestral and an omicron variant strain have yet to be robustly evaluated in patients with cancer.Although patients with cancer generally develop a less robust immune response after vaccination against COVID-19 compared to individuals without cancer , the risConsistent with observations in the general population, VE against VOCs have also decreased progressively in patients with cancer, although the reduction has been most prominent in patients with hematologic malignancies . A studyAlthough patients with cancer were not included as the majority targeted population in the original registry trials of COVID-19 vaccines, the safety profile of these vaccines in immunocompromised populations has since been established . At thisAs COVID-19 continues to evolve, it is important to continually evaluate the immune response and real-world effectiveness of vaccination among immunocompromised individuals. Patients with cancer typically develop a less robust immune response after COVID-19 vaccination than individuals without cancer, resulting in higher risk for SARS-CoV-2 infection and severe COVID-19 . In geneIn most severely immunocompromised patients, a 3-dose primary series of an mRNA vaccine is recommended followed by additional booster doses. Recommendations for bivalent vaccines vary by country and region. Administration of additional doses may induce stronger humoral and/or cellular responses in these vulnerable populations with preliminary evidence of translation to real-world effectiveness . AlthougAdverse event rates related to vaccination are generally low in patients with cancer, demonstrating that these individuals can be safely vaccinated during active therapy . FurtherFuture studies should focus on identifying correlates of protection for vaccinated individuals, especially among those with poor humoral responses. In addition, improved reporting of cellular responses in patients with cancer is needed to better understand the immune responses observed in this population. It would also be important to examine whether the immune response recovers during remission and to what extent. Finally, more data are needed on heterologous vaccination schedules and varied dosing intervals in immunocompromised populations. This review was limited in focus on the immunologic and clinical responses to COVID-19 vaccination in patients with solid tumors and hematologic malignancies. Additional studies on the immune response after variant-updated bivalent vaccines and vaccination in combination with COVID-19 therapeutics or other types of pre-exposure prophylaxis are needed in patients with cancer.


This survey study evaluates the factors associated with knowledge and experience of self-managed abortion among patients seeking care at 49 US abortion clinics in 29 states. How commonly do US patients seeking an abortion consider or attempt self-managed abortion before attending a clinic, and what factors are associated with self-management behavior?In this survey study of 19 830 patients attending 49 abortion clinics in 29 states, 1 in 8 considered self-managing before attending the clinic, and of these, 1 in 3 attempted to do so. Individual-level factors, including experiencing clinic access barriers and preferring at-home care, were associated with self-management behavior.These findings suggest that considering self-managed abortion is a common part of the path to accessing care in a clinic, and those on the margins of clinic access or who prefer at-home care are more likely to self-manage. Patients attending US abortion clinics may consider or try self-managing their abortion before coming to the clinic, yet little is known about the factors associated with self-management behavior.To examine the prevalence and factors associated with considering or attempting a self-managed abortion before attending a clinic.This survey study included patients obtaining an abortion at 49 independent, Planned Parenthood, and academic-affiliated clinics chosen to maximize diversity in geographic, state policy, and demographic context in 29 states between December 2018 and May 2020. Data were analyzed from December 2020 to July 2021.Obtaining an abortion at a clinic.Knowledge of medications used to self-manage an abortion, having considered medication self-management before attending the clinic, having considered any method of self-management before attending the clinic, and having tried any method of self-management before attending the clinic.The study included 19 830 patients, of which 99.6.% (17 823 patients) identified as female; 60.9% (11 834 patients) were aged 20 to 29 years; 29.6% (5824 patients) identified as Black, 19.3% (3799 patients) as Hispanic, and 36.0% (7095 patients) as non-Hispanic White; 44.1% (8252 patients) received social services; and 78.3% (15 197 patients) were 10 weeks pregnant or less. Approximately 1 in 3 (34%) knew about self-managed medication abortion, and among this subsample of 6750 patients, 1 in 6 (1079 patients [16.1%]) had considered using medications to self-manage before attending the clinic. Among the full sample, 1 in 8 (11.7%) considered self-managing using any method before clinic attendance, and among this subsample of 2328 patients, almost 1 in 3 (670 patients [28.8%]) attempted to do so. Preference for at-home abortion care was associated with considering medication self-management , considering any method of self-management , and attempting any method of self-management . Experiencing clinic access barriers was also associated with considering medication self-management  and considering any method of self-management .In this survey study, considering self-managed abortion was common before accessing in-clinic care, particularly among those on the margins of access or with a preference for at-home care. These findings suggest a need for expanded access to telemedicine and other decentralized abortion care models. Dobbs v. Jackson Women’s Health Organization Supreme Court decision, which overturned the constitutional right to choose abortion established in Roe v. Wade.1 In many states, access to clinical abortion care was already limited before the Dobbs decision. However, now state-level total or near-total bans have created large areas of the country where abortion in a clinic is unavailable.2 In this new policy climate, self-managed abortion has become an increasingly important component of access.3 A self-managed abortion is one that occurs outside the formal health care setting and comprises a spectrum of methods, including abortion medications (mifepristone and/or misoprostol), herbs and botanicals, and self-harm.4 Although people have self-managed their abortions throughout history, increased access to abortion medications via online pharmacies and telemedicine services such Aid Access means that more people may now self-manage using pills.5Access to in-clinic abortion care in the US has changed profoundly following the 6 while a 2019 study showed that abortion clinic patients in Texas considered or attempted self-management before attending the clinic because they were unsure whether they would be able to overcome access barriers or because they would have preferred to self-manage but were ultimately unable to find an acceptable method.7Although self-managed abortion is often viewed solely as a mutually exclusive alternative to in-clinic care, research suggests that it may be considered or attempted by those who ultimately do access a clinic as part of the path to securing an accessible and acceptable option. A 2014 study showed that 1.2% of US abortion clinic patients had ever attempted to self-manage using misoprostol,Dobbs, and 12 more are expected to enact similar bans or other types of severe restrictions.8 With these new laws in place, knowledge of the factors that motivate self-management behavior among those attending clinics is important; groups who were already more likely to consider or attempt self-management before attending a clinic before Dobbs may also be more likely to self-manage when no clinics are available. Knowledge of these specific groups could allow public health practitioners to ensure that information on safe and effective self-management reaches vulnerable groups and could allow physicians in ERs, primary care settings, and OBGYN offices to be prepared to encounter more patients seeking advice or follow-up care for self-management. Using a survey of abortion patients from a sample of clinics across the US, the objectives of our study are to (1) assess knowledge of, interest in, and experiences with self-managed abortion among patients attending clinics in diverse policy, geographic, and sociodemographic contexts; and (2) examine the association of individual-level factors  and clinic-level factors (such as geography and state policy climate) with self-management knowledge, interest, and experiences.Very little is known, however, about how considering or attempting self-managed abortion before accessing in-clinic care may vary by state and local context or by individual circumstances. To date, 12 states have implemented total or near-total abortion bans after AAPOR) reporting guideline.9Between January 2019 and May 2020, we conducted a survey of abortion patients in 46 independent, Planned Parenthood, and academic-affiliated clinics located in 28 states across the contiguous US. Three clinics located in Texas participated in a pilot study in 2018 to test the feasibility of data collection and are included for a final sample of 49 clinics in 29 states. The institutional review board at the University of Texas at Austin approved the study and participants provided anonymous informed consent. This study followed the American Association for Public Opinion Research  state abortion policy context, defined according to the 2018 Guttmacher Classification according to state legislation either restricting or supporting abortion access11; (3) distance from an international border (either Mexico or Canada), defined using the Google Maps Application Programming Interface; and (4) racial and ethnic diversity according to US Census data12 and later confirmed by selected clinics. Among our sample of 49 clinics, 12% were located in the Northeast, 22% in the Midwest, 29% in the West, and, 37% in the South. Fifty-five percent were in states with a hostile or extremely hostile abortion policy climate, while 45% were in states with a neutral or supportive policy climate. Forty-three percent of clinics were within 200 miles of either the Canadian or Mexican border, and 61% served primarily racial and ethnic minority groups. Participating clinics were offered $2000 in compensation for staff time.We compiled a list of clinics cross-referenced from multiple sources and selected sites using a statistical algorithm designed to maximize sample diversity across 4 key clinic-level variables: (1) geographic region, defined according to the US Census categorization of regions and subregionsWe aimed to survey 500 patients per clinic, with the exception of 14 clinics with smaller than average monthly patient volume, where our goal was 250 patients. Calculations from our pilot study demonstrated that these sample sizes would provide us with 80% power to detect even fairly small differences in average outcomes between sites at an α level of .05. Our final target sample size was 20 850 patients.All patients presenting for abortion care at each clinic were eligible to participate, except in states with parental consent laws for minors, where we implemented a minimum age requirement of 18 years. No compensation was offered for participation. Clinic staff informed patients about the survey and provided those interested with an iPad displaying information about the study as well as a consent form where patients provided anonymous informed consent. The survey was fielded using REDCap software and data were stored on a protected server. The survey was available in both English and Spanish and no identifying information was collected.13 Detailed survey information can be found in eTable in The survey included questions about patients’ knowledge of self-managed abortion, whether they had considered self-managing before coming to the clinic, and whether they had attempted to self-manage, both with respect to abortion pills and nonmedication methods of self-management. Further details on question sequence are shown in eFigure 1 in 14 to each of the 4 outcomes. Within-between models allowed us to account for the hierarchical nature of the survey data, where multiple respondents were surveyed within each participating clinic, and to eliminate bias resulting from between-clinic differences in respondent-level covariate associations. Although fixed-effects models with clinic dummy variables are also an option for dealing with such bias, these eliminate distinctive clinic characteristics, which are also of interest in our study.We calculated the prevalence of knowledge, consideration, and use of medication self-management, as well as having considered or tried any method of self-management before coming to the clinic. We then conducted regression analyses to examine the individual and clinic-level factors associated with each of 4 binary outcomes of interest: (1) knowledge of medication self-management; (2) having considered medication self-management before visiting the clinic; (3) having considered any method of self-management before visiting the clinic; (4) having tried any method of self-management before visiting the clinic. We fit separate within-between logistic regression modelsFor each regression model, we examined 3 categories of covariates. First, variables summarizing individual-level abortion perspectives and experiences, including whether respondents faced barriers to clinic access, knew somebody who self-managed using pills, preferred a nonclinic model of care, or had previously had an abortion. Second, individual-level demographic characteristics, including whether a respondent was born outside the US; had 1 or more children; identified as Black, Hispanic, non-Hispanic White, or another racial or ethnic group; and received any social services. Third, clinic-level characteristics, including proximity to an international border, serving a predominantly racial and ethnic minority population, and state policy context. We evaluated odds ratios (ORs) using α = .05 to assess statistical significance. We used R version 4.0.2  to conduct all statistical analyses and the package panelr to fit our models. Data were analyzed from December 2020 to July 2021.9 Missing data for each variable are listed in Overall, 19 830 patients participated in the survey, and 99.6.% (17 823 patients) identified as female, 60.9% (11 834 patients) were aged between 20 and 29 years, 43.6% (7796 patients) had attended some college, and 27.6% (4947 patients) had graduated high school only . A totalIndividual-level abortion perspectives and experiences are shown in Among the full sample of 19 830 participants, 1 in 3 (6750 patients [34.1%]) knew about pills they could self-source and use to self-manage an abortion . The mosAmong the 6750 participants who knew about pills they could use to self-manage, 1 in 6 (1079 patients [16.1%]) had considered using them before attending the clinic . The mosAmong the full sample of 19 830 participants, 1 in 8 (2328 patients [11.7%]) considered self-managing using any method before attending the clinic. A total of 46.3% (1079 patients) considered using abortion pills, 34.7% (807 patients) considered vitamin C, and 30.7% (715 patients) considered herbs or botanicals . Their mRegression models examining the associations of individual and clinic-level factors with knowledge of medication self-management (19 830 patients); consideration of medication self-management (6750 patients); consideration of any method of self-management (19 830 patients); and attempting any method of self-management (2328 patients) are shown in Individual-level demographics showed some smaller associations with self-management behavior. Identifying as Black was associated with knowledge of medication self-management , while identifying as Hispanic was associated with having tried any method of self-management . Receiving any form of social services was associated with both knowledge of pills  and having considered any method of self-management . Being a parent was negatively associated with having considered  or tried any method of self-management .At the clinic level, location close to the Mexican or Canadian border showed a small positive association with knowledge of medication self-management  but a negative association with having tried any method of self-management . None of the other clinic-level characteristics were significantly associated with any of the 4 outcomes.In this study of 19 830 patients seeking abortion care in 49 US clinics, we found that knowledge of medication self-management is prevalent and that considering self-managed abortion is a common part of the path to accessing in-clinic abortion care. Considering self-management is associated with both clinic access barriers and a preference for at-home abortion care, and these individual-level factors show larger associations with self-management behavior than clinic-level contextual factors or individual-level demographic factors.15 restrictions on public spending, and because private insurance rarely covers abortion.16 In 2020, the national median self-pay price for medication abortion was $560.17 Abortion clinics across the country continue to unify efforts to provide abortion care to nearby populations affected by abortion restrictions, and these efforts will become even more important as more people travel to access abortion care out-of-state.18 However, our findings suggest that many of those who considered self-managed abortion before ultimately attending a clinic did so because they were already on the margins of clinic access. It thus seems likely that greater costs and travel distances following the Dobbs decision will make self-managed abortion a more realistic option than out-of-state travel. Additionally, as self-management becomes more prevalent, the number of people who know someone who has self-managed will increase, perhaps influencing their own behavior, as our results suggest.The larger association of individual-level (as opposed to clinic-level) access barriers suggests that although abortion restrictions in some states no doubt make access challenging, the cost and logistics of in-clinic care can be obstacles for patients everywhere. Most people pay out-of-pocket for their abortions due to the Hyde Amendment,19 Additionally, the recent FDA decision to allow mifepristone to be dispensed by pharmacists following prescription by a physician may further increase remote care options.20 Future pharmacist-only provision models and over-the-counter status for abortion medications could further increase access and meet patient preferences.22 However, these models are unlikely to profoundly change access for people living in states with total or near-total abortion bans, further increasing the importance of self-management in these states. Although one-third of our sample knew that they could self-source abortion pills and use them to self-manage, specific knowledge about exactly which types pills they might use and where they might acquire them was relatively low. This finding suggests that access to accurate information about medication self-management and trustworthy sources of pills is now an important focus for public health, in line with insights from prior work examining the concerns and priorities of people in the US seeking abortion medications online.24 In addition, the associations we found between race and ethnicity, receipt of social services, and self-management behavior demonstrate a need to ensure equitable access to accurate, unbiased, and culturally competent information.The prominent association of individual-level preferences for at-home abortion with self-management behavior suggests that service delivery models designed to allow patients to choose medication abortion without an ultrasound or in-person consultation fill an important gap in patient-centered care. No-touch telemedicine provision for medication abortion following the FDA’s decision to end the in-person dispensing requirement on mifepristone is likely already meeting some of this demand in the states where it is available.The main limitation of our study is that data are self-reported and could be subject to patient discomfort or concerns about sharing self-managed abortion experiences. However, survey self-administration and anonymity likely reduced reporting bias. A key strength is our large sample, designed to explore diversity in individual and clinic context. Although results are not necessarily generalizable to the national population, our aim was to explore differences between clinics with different geographical and policy environments and between individuals with different personal experiences and circumstances.26 We extend this literature to show that rather than being solely a mutually exclusive alternative to in-clinic care, considering self-managed abortion is also a common part of the path to accessing care in the clinic setting. For those who consider or attempt self-management due to a preference for at-home abortion care, new service delivery models that recenter patient desires will help to fill the gap in states where they can be implemented. For those who consider or attempt self-management due to clinic access barriers, safe, effective, and supported options for self-care have become an even more important component of the US abortion care landscape now that Roe is overturned. Public health practitioners will need to consider how to design and disseminate accessible, quality information about safe and effective self-management, while clinicians will need to be ready to encounter those seeking advice about self-management and those seeking safe, medically appropriate, and nonjudgmental aftercare.In this survey study of 19 830 patients attending 49 abortion clinics in the US, we found that knowledge of medication self-management is prevalent and that considering self-managed abortion is a common part of the path to accessing in-clinic abortion care. Our study mirrors the findings of prior work that has demonstrated significant access barriers to US abortion care as well as emerging insights on patients’ preferred care models.