There is a need to establish the effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in reducing COVID-19-related hopitalization of patients in Jordan. As the vaccination program accelerates, it is important to determine whether the vaccines' effectiveness (VE) has successfully reduced the number of acute cases admitted to hospital.n = 536) and unvaccinated (n = 585) individuals across the 2-month period from February 6 to April 6, 2022. The cases were patients who tested positive for SARS-CoV-2 (“case-patients”), whilst the control group were hospital patients who did not test positive for SARS-CoV-2 (“control-patients”).To determine the efficacy of Pfizer-BioNTech and Sinopharm COVID-19 vaccines among Jordanian patients admitted to Prince Hamza hospital, a single center case-control study was performed. The study analyzed the hospitalization rates of vaccinated (p < 0.001), and it was highest in those between the ages of 18 and 28-years-old . For patients with pre-existing conditions, including chronic heart disease, chronic lung disease, and diabetes, VE was higher compared to patients with no comorbidities, though the difference was not statistically significant. Finally, in comparing all vaccinated participants, VE was higher for those who received the Pfizer vaccine   than for those who received the Sinopharm vaccine  ; (p = 0.011).This study found that among 1,121 total participants (561 cases and 560 control), the overall vaccine effectiveness (VE) among the participants was 84% (95% Cl 79–88%). VE was higher in females  than in males  (Overall, Pfizer and Sinopharm vaccines were found to be effective in limiting hospitalizations for acute cases of coronavirus among Jordanian adult's patient's cohort between February 6 and April 6, 2022, especially among patients with comorbidities. In December 2019, the acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in China and rapidly spread across the world, jumpstarting a global pandemic that has persisted . MoreoveMany companies have introduced candidate vaccines, each with various indications, contraindications, and adverse events, but ultimately all providing differing levels of efficacy in preventing infection, acute outcomes, and death as a result of coronavirus infection . TherefoOne of the several studies that have considered explanations for the country's low vaccination population found that misinformation and conspiracy theories, primarily ones that discredit the vaccine's ability to reduce rates of hospitalization, have had a negative impact on vaccine administration among Jordanians . As thisTo consider each vaccine's effectiveness in preventing coronavirus-related hospitalizations among sample of Jordanians patients, this study used a retrospective case-controlled analysis of 1,121 adults over the age of 18 years who were hospitalized at Prince Hamza Hospital in Jordan between February 6 and April 6, 2022. Prince Hamzah Hospital is the main isolation and treatment center for COVID-19 in Jordan. The sample consisted of patients who tested positive for SARS-CoV-2 and had also received either the Pfizer-BioNTech or the Sinopharm vaccination. The control group was comprised of patients who were admitted to the hospital but did not test positive for SARS-CoV-2. Any individuals with immune compromising conditions were excluded from the pool.The pool of hospitalized patients due to coronavirus consisted of individuals who had both a positive test for SARS-CoV-2 within 10 days of symptom onset and a diagnosis of a clinical syndrome that signals an acute case of coronavirus, which includes ≥1 of the following: fever, cough, shortness of breath, loss of smell, requiring respiratory support, or new pulmonary findings on chest imaging consistent with pneumonia. The control group consisted of patients who were hospitalized without an indication of acute coronavirus and who tested negative for SARS-CoV-2.A standardized medical record review provided demographic information including age, gender, medical history, SARS-CoV-2 vaccination status, and other patient characteristics. Specific details of patients' SARS-CoV-2 vaccine administrations, including dates and vaccine suppliers, were supplied through source verification of documents like vaccine cards or hospital records.Patients' vaccination status was categorized based on the number of vaccine doses received before the reference date , (“case-patients”), and the date of hospitalization for coronavirus-negative patients (“control-patients”). All hospitalized patients were determined to be either “fully vaccinated” or “unvaccinated.” Because both Pfizer and Sinopharm SARS-CoV-2 vaccinations were administered as a two-dose series and protective immunity is not expected immediately after the first dose, participants were only considered “fully vaccinated” fourteen days after receipt of the second vaccine dose . SubsequOR, where CIOR is the confidence interval of the odds ratio estimates.By comparing the vaccination status of case patients and control patients, VE was calculated using the following expression: VE = (1–odds ratio) × 100% . The 95%t-test or Wilcoxon rank-sum tests for continuous variables.VE estimates were stratified by age group, designated in 10-year increments , SARS-CoV-2 vaccine supplier (Pfizer-BioNTech or Sinopharm), and the following underlying medical conditions: diabetes mellitus, chronic lung disease, chronic cardiovascular disease, and obesity. Characteristics of cases and controls were compared by employing chi-square tests or Fisher's exact tests for categorical variables and Student's Hashemite University and Prince Hamza Hospital's Ethics Service Committee granted ethical approval for this case study (reference number 5/3/2020/2021).A total of 186 patients, who were hospitalized at Prince Hamza Hospital between February 6 and April 6, 2022, were excluded from this study. Of these, 36 had an immune compromising condition, 66 had received ≥1 vaccine dose other than a Pfizer-BioNTech or Sinopharm vaccine, and 84 did not meet other eligibility criteria. The remaining 1,121 recorded patients included 561 case-patients and 560 control-patients. Overall, 585 (52%) patients were unvaccinated and 536 (47.5%) were vaccinated. Of those who were vaccinated, 205 (18%) were fully vaccinated with the Sinopharm vaccine and 331 (29.5%) were fully vaccinated with the Pfizer-BioNTech vaccine . Demograp > 0.001). The most prevalent underlying conditions reported for both case-patients and control-patients, respectively, were chronic heart disease  and diabetes   . Finallyp = 0.011). Additionally, the risk of coronavirus infection among patients who received the Pfizer-BioNTech was 0.22 compared to 0.36 among those who received the Sinopharm vaccination.The risk of coronavirus infection among vaccinated groups was 0.28 (149/536) while the risk of coronavirus infection among unvaccinated groups was 0.7 (418/585), suggesting a risk ration of 0.4 and odd ration of 0.16 (95% CI 0.12–0.21). VE among hospitalized patients included in the sample was 84% (95 CI 79–88%). In terms of VE by supplier, those who had received the Pfizer-BioNTech vaccine had a higher VE rate   than the Sinopharm vaccine    than any other age range. For those with comorbidities, VE was higher for patients with underlying cardiovascular disease , chronic lung disease , and diabetes mellitus  compared with patients who had no underlying conditions .While the Pfizer-BioNTech vaccine's effectiveness against infection increased only after the first twenty weeks following the vaccination, the Sinopharm vaccine markedly decreased 4 weeks after the final dose was administered .An essential element of managing the COVID-19 pandemic involves vaccines. Our study indicates that two doses of Pfizer-BioNTech or Sinopharm vaccines at least fourteen days after administration provided significant reduction in coronavirus-associated hospitalizations at Prince Hamza Hospital in Jordan. Based upon the hospitalization rates of patients in our patient cohort, it is evident that Sinopharm (VE 92%) is less effective than Pfizer-BioNTech (VE 67%) These results are consistent with previous studies, in particular, those done during the period between March and July, and February and August 2021, which showed the VE of Pfizer-BioNTech and Sinopharm against hospitalization rates to be 86% (95% CI = 82–88%) , 11, andOn the other hand, this study finds that the VE is lower than in some other assessments in preventing hospitalization due to coronavirus. These other case studies, which examined the same vaccination suppliers as this study, suggested that the VE for fully vaccinated individuals to be 96% (95% CI 49–99%) among adults who received Pfizer-BioNTech vaccines and 81% (95% CI 88–93%) among adults who received the Sinopharm vaccines , 14. ThiThe findings of this study revealed that although both vaccines alleviated the risk of being hospitalized, each offered a different level of protection. For instance, patients given the Pfizer-BioNTech formula exhibited comparatively modest attenuation of VE, and they were more protected than their counterparts, whom received the Sinopharm vaccine, but their protection levels fell significantly. Furthermore, it supports other emerging evidence to suggest that, while VE waning is an expected result following the second dose of both Pfizer-BioNTech and Sinopharm vaccines –17, the Our findings can be contextualized against several other studies vaccines' efficiency levels. For instance, an assessment of registries in Sweden indicated a sharp fall in vaccine efficacy against the risk of being hospitalized after 25 weeks . MeanwhiP < 0.001)  .Our study found that the maximum VE occurred in patients aged 18–28-years-old . This finding is similar to those reported by other researchers, who found the antibody response to be greater in younger people than in older people –29. HoweIn a comparison of the sexes, we found VE was greater in females than males; this observation may be attributed to hormonal differences between the sexes. It is recognized that estradiol in females promotes adaptive and innate immune responses, whereas these same responses are dulled by testosterone in males; therefore, the antibody response is greater in females than males . NotarteAn important finding reported by Ma, Hao  is that Limitations of this study include diversity of the sample pool, identification of the virus variant, and antibody measurements. First, this study did not consider children, immune compromised adults, or individuals who tested positive for coronavirus but were not hospitalized. Second, supplier-specific effectiveness among a variety of virus variants could not be determined as variants were largely unknown. Thirdly, our study is disadvantaged by inconsistent serological undertakings at admission. This means we could not assess immune status prior to hospitalization; nor could we quantify vaccine-induced antibody levels to correlate with vaccine effectiveness. This information would have enabled us to develop deeper and broader knowledge about the effectiveness of the vaccines.Further, estimates of vaccine effectiveness could be compounded by certain behavioral measures that were not considered in this study. For example, the use of non-pharmaceutical interventions, including mask use, social distancing, and exposure risks have been found to be useful in preventing coronavirus infection, much apart from one's vaccination status .In conclusion, this study demonstrated that Pfizer-BioNTech and Sinopharm vaccines were effective in reducing the rate of hospitalization among a sample of 1,121 adult Jordanians patients between February 7 and April 7, 2022. Vaccines were found to be particularly effective for patients with comorbidities and younger age groups. In addition, this research emphasizes the importance of monitoring vaccine effectiveness over time, rather than at an isolated moment. It reiterates the useful and increasingly relevant role served by booster doses in restoring high levels of protection that were observed early in the vaccination roll out. Understanding vaccine effectiveness by vaccine supplier can guide individual choices and policy recommendations regarding the continued administration of coronavirus vaccines, as well as subsequent boosters in providing substantial and significant protection against coronavirus hospitalization. Moving forward, this study hopes to add to the ongoing research and increasing information around preventative measures to fight coronavirus. Future research that explores the interdependence of age, comorbidities, serostatus, and sex and the relationships between them with humoral responses is warranted. Also, studies could compare the extent and nature of humoral responses of other COVID-19 vaccines, such as Johnson & Johnson, and Moderna (mRNA 1273), and the vaccines evaluated in this study.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Hashemite University and Prince Hamza Hospital's Ethics Service Committee (reference number 5/3/2020/2021). The patients/participants provided their written informed consent to participate in this study.HA-M was responsible for the study design, analyzed data, and wrote the manuscript. KA, EA, YA, and ZA responsible for data collection and co-wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA) are associated with radiological outcome, anti-TNF response and all cause-mortality in RA. RA is associated with cardiovascular (CV) morbidity and mortality, but the increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim of this study was to investigate whether amino acids at positions 11, 71 and 74 of HLA-DRB1 are associated with cardiovascular (CV) mortality in inflammatory polyarthritis (IP).The Norfolk Arthritis Register (NOAR) is an incidence register of IP: recruitment 1990–2007, final follow-up 2011. Two thousand five hundred fourteen patients had available genetic and mortality data. Amino acids at positions 11, 71 and 74 of HLA-DRB1 were determined. Univariate Cox proportional hazard models were applied to assess the association of genetic markers and both all-cause mortality and cardiovascular mortality.Among 2514 participants, 643 (25.6%) died during the study, and 343 (53.3%) of these deaths were attributed to CV causes. One thousand six hundred fifty (65.6%) participants were female, 709 (32.3%) were anti-CCP-positive and the median age of participants was 54.p=0.023). Mediation analysis revealed associations were independent of anti-CCP status.HLA-DRB1 haplotypes associated with susceptibility to rheumatoid arthritis (RA) consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors. Associations were independent of anti-CCP status, which suggests in the future, genetic factors will add to the prediction of risk of cardiovascular mortality beyond serological markers. Positions 11, 71 and 74 of HLA-DRB1 are associated with cardiovascular mortality in inflammatory polyarthritis.Position 11, which has not been previously implicated with cardiovascular mortality, shows the strongest association. This effect is independent of anti-CCP status and CRP at baseline.The findings suggest that genetic factors may to the prediction of risk of cardiovascular mortality beyond traditional cardiovascular risk factors and serological markers.Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality . IdentifRA genetic susceptibility alleles at the HLA-DRB1 gene locus encoding for a conserved amino acid sequence at positions 70–74 are known as “the shared epitope” (SE). The SE alleles, have been found in previous studies to be associated with mortality in RA, a substantial component of which was through CV disease , 7.Recently, amino acids at HLA-DRB1 position 11, outside the SE, were shown to be the strongest genetic predictors of RA susceptibility –11. AddiThe aim of this study was to identify whether this genetic information could add to clinical predictors at baseline, to predict those at the highest risk of cardiovascular mortality.The Norfolk Arthritis Register (NOAR) is a primary care-based inception cohort of patients with IP defined as a minimum of 2 swollen joints for a period of at least 4 weeks . PatientA semiautomated, reverse dot-blot method was used in HLA typing . All samAnticyclic citrullinated peptide antibody positivity (anti-CCP2) was determined with the CCP2 assay; Axis-Shield DIASTA kit , where > 5 U/ml was defined as positive.Data on all-cause mortality and CV mortality was provided by the Office for National Statistics, as described previously, where CV mortality was recognised as CVD mentioned on the death certification, using the International Classification of Diseases Tenth Revision .Univariate Cox proportional hazard models were applied to assess the association of genetic markers and both all-cause mortality and CV mortality. Models for all-cause and CV mortality were adjusted for available CV risk factors: obesity, gender and evidence of hypertension (defined by self-reported co-prescription of antihypertensive agents). These covariates were identified using forward stepwise regression. Variables found to be collinear were not included in the final analysis. These were smoking status, evidence of diabetes (defined as self-reported co-prescription of diabetes medications), age at baseline assessment and statin use. Data on all variables was collected at baseline assessment.Hazard models were firstly applied to the entire cohort of patients with IP and then restricted to patients who fulfilled the 1987 classification criteria for RA. When calculating differences between highest and lowest risk genetic factors, bivariate analysis was used. Results are reported as hazard ratios with 95% confidence intervals.p value was calculated using a linear regression model to determine the association between effect sizes (β coefficients) of susceptibility and CV mortality. All analysis was performed using STATA/IC 14.0.Lastly, a multivariate cox-proportional hazard model was applied to the 3 most frequent haplotypes occurring in the NOAR cohort, defined by an allele frequency of over 12% to test their association with CV mortality. A one-tailed Mediation analysis was performed to determine whether the genetic effects of CV mortality were due to intermediate parameters  . This anTwo thousand five hundred fourteen subjects in NOAR were identified to have genotype and mortality data available. Of these, 643 (25.6%) died during the study and 343 (53.3%) of these deaths were attributed to CV causes. Cohort characteristics are summarised in Table p=0.023) [p=0.01). The analysis was repeated adjusting for anti-CCP status and associations were found to be independent of this serological marker. The association with group 4 haplotypes remained statistically significant after adjustment for anti-CCP status .HLA-DRB1 amino acids, haplotypes, or haplotype groups associated with RA susceptibility are also associated with CV mortality and this association is independent of sex, hypertension and obesity Table . HLA-DRBp=0.023) . The relHLA-DRB1 haplotypes can be ranked according to the magnitude of their association with RA susceptibility, and we have previously shown that this hierarchy is conserved for various measures of disease outcome and overall mortality , 8. Our 11) are shown to be associated with CRP , p=0.003) and in a separate model, with anti-CCP , p=0.000). However, in a model containing both of these factors, Ser11 is no longer associated with CRP (p=0.614), suggesting the association between Ser11 and CRP is fully mediated by anti-CCP status. We found that Ser11 is associated with cardiovascular mortality, and some of this association is independent of anti-CCP and CRP. This is demonstrated in a final model, containing Ser11, CRP and anti-CCP, where Ser11 remained protective . This suggests there is a non-systemic pathway through which genetic markers may exert an effect on CV mortality. These findings are depicted in cyclic diagrams in Fig. We next performed mediation analysis and the results of tstep-by-stepstep analysis are shown in Table It has been shown that CV mortality in RA has, in part, a genetic basis. “The shared epitope” (SE) has been previously shown to be associated with CV mortality, and this association is independent of autoantibody status , 7, 17. Valine at position 11 of HLA-DRB1, outside of the SE, was shown to have the highest association with disease susceptibility, radiological damage and all-cause mortality, whilst serine at this position was most protective –12. In tThere are some possible explanations behind the associations between HLA-DRB1 haplotypes and CV mortality in inflammatory polyarthritis patients. HLA-DRB1 haplotypes increase susceptibility to RA which in turn is well known to increase CV morbidity and mortality. However, when restricting the analysis to those who satisfied criteria for RA only, effect sizes for highest risk haplotype (VKA) and lowest risk (SEA) increase. This suggests that there is a mechanism through which HLA independently influences the risk of CV death in these patients, as opposed to solely through the development of RA.One possible explanation of the influence of HLA-DRB1 haplotypes on this risk is through increased systemic inflammation . In mediAnother possible mechanism behind the association of HLA-DRB1 haplotypes with CV mortality may be as a result of increased disease severity rather than increased susceptibility. Those with severe disease are more likely to carry risk haplotypes as previously demonstrated . If thosThe exact mechanism of action underlying the association of HLA-DRB1 haplotypes with susceptibility to and outcome of RA remains a matter of debate. However, mounting evidence suggests that haplotypes associated with high susceptibility and more severe outcomes carry amino acids within their peptide-binding groove which will increase affinity to autoantigenic peptides . The preTo our knowledge, there are no other studies looking specifically at CV mortality and HLA-DRB1 haplotypes defined by positions 11, 71 and 74. However, there is a study involving a male-predominant cohort of US veterans, which explored the association with these haplotypes and all-cause mortality . AlthougA particular strength of this study is that NOAR is a large inception cohort of patients with inflammatory polyarthritis with the availability of genetic and mortality data. There are some limitations to this study: information on CV mortality was derived from death certification, which may be inaccurate. The data on covariates was collected at baseline, and it is possible that the status of these may change through the course of follow-up. However, the aim of this study was to informthe prediction of those at highest risk at disease onset, making this a greater representation of a clinical setting. Clearly, replication of these findings in independent cohorts would be required to confirm these findings and to determine the role of patients’ HLA typing in the assessment of CV risk in RA.Treatment of RA has changed considerably since the conception of NOAR, and there is evidence that effective treatment of disease activity reduces the risk of premature cardiovascular death. Further investigation would be required to evaluate whether this also modulates the association between HLA-DRB1 haplotypes and CV mortality.CV disease and mortality remain a significant challenge in the management of RA. Understanding the mechanisms underpinning genetic associations of mortality in RA could help enable risk stratification of patients from disease presentation. Our findings show HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors. Notably, associations were persistent after adjustment of anti-CCP status. This suggests in the future that genetic factors will add to the prediction of the risk of cardiovascular mortality beyond serological markers. The clinical utility of whether HLA typing in informing management of cardiovascular risk remains to be explored, but would likely form part of a larger tool including clinical and serological predictors.


Low rates of heart failure (HF) hospitalizations were observed during the 2020 peak of the COVID-19 pandemic. Additionally, posthospitalization follow-up transitioned to a predominantly telemedicine model. It is unknown whether the shift to telemedicine impacted disparities in posthospitalization follow-up or HF readmissions.The aim of this paper is to determine whether the shift to telemedicine impacted racial and ethnic as well as socioeconomic disparities in acute decompensated heart failure (ADHF) follow-up and HF readmissions. We additionally sought to investigate the impact of the COVID-19 pandemic on the severity of ADHF hospitalizations.This was a retrospective cohort study of HF admissions across 8 participating hospitals during the initial peak of the COVID-19 pandemic , compared to the same time frame in 2019. Patients were stratified by race, ethnicity, and median neighborhood income. Hospital and intensive care unit (ICU) admission rates, inpatient mortality, 7-day follow-up, and 30-day readmissions were assessed.P<.001). Patients in 2020 had higher rates of ICU admission, compared with 2019 . This trend was seen across all subgroups and was significant for patients from the highest income quartile . While there was a trend toward higher inpatient mortality in 2020 versus 2019 , no difference was seen among different racial and socioeconomic groups. Telemedicine comprised 81.6% of 7-day follow-up in 2020, with improvement in 7-day follow-up rates . Inequities in 7-day follow-up for patients from non-Hispanic Black racial backgrounds compared to those from non-Hispanic White backgrounds decreased during the pandemic. Additionally, those with telemedicine follow-up were less likely to be readmitted in 30 days when compared to no follow-up .From March 15, 2019, to June 1, 2020, there were 1162 hospitalizations for ADHF included in the study. There were significantly fewer admissions for ADHF in 2020, compared with 2019 (442 vs 720; There were no major differences in HF ICU admissions or inpatient mortality for different racial and socioeconomic groups during the COVID-19 pandemic. Inequalities in 7-day follow-up were reduced with the advent of telemedicine and decreased 30-day readmission rates for those who had telemedicine follow-up. Acute decompensated heart failure (ADHF) is the leading hospital discharge diagnosis in the United States . HoweverWhile the COVID-19 pandemic has had many different effects on the health care system, one constant thread has been the disproportionate toll the virus has had on patients who self-identify with racial and ethnic minority groups, as well as patients who live in lower-income neighborhoods . In ChicThis was a retrospective cohort study derived from patients who were hospitalized for ADHF within the Northwestern Memorial Healthcare (NMHC) system. The NMHC system comprises over 200 sites and 10 hospitals that provide health care to a varying and diverse population throughout the city of Chicago and the surrounding metropolitan area. Overall, 8 hospitals were included that collected data on patients who were hospitalized in 2019 and 2020. Two hospitals that did not collect data in 2019 were excluded.Patient data were obtained via the Northwestern Medicine Enterprise Data Warehouse. The latter provides a single comprehensive repository of all clinical and research data across all NMHC facilities. Included in this retrospective cohort study were adults aged 18 years and older who were hospitalized with the International Classification of Diseases (ICD), ninth revision  or tenth revision, ICD-10  primary diagnosis of ADHF . PatientThe primary objective of this study was to investigate the effect of the COVID-19 pandemic on both acuity of ADHF hospitalizations as well as changes in posthospitalization follow-up after the implementation of telemedicine. The endpoints assessed included the rate of inpatient mortality, predicted inpatient mortality calculated by validated risk scores, incidence of intensive care unit (ICU) admission, posthospitalization follow-up within 7 days, and 30-day readmission rates. Predicted in-hospital mortality was determined using Get With the Guidelines—Heart Failure (GWTG-HF) as well as the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) risk scores. Both the GWTG-HF score and the OPTIMIZE-HF score are successful predictors of in-hospital mortality for both patients with reduced HF and preserved left ventricular ejection fraction ,14. GWTGResults were stratified by race and ethnicity as well as median neighborhood income quartile. Patients were divided into income quartiles based on their zip code’s median household income using data from the US Census Bureau American Community Survey 2010-2014. Income quartile 1 represents the lowest median household income while income quartile 4 represents the highest.t tests and χ2 tests where appropriate. P<.05 (2‐sided test) was considered significant. All statistical tests and analyses were performed with Stata, version 16 (StataCorp).Data are presented as mean values with SD if normally distributed and median with interquartile range if skewed. Categorical data are presented as frequencies and percentages. Baseline characteristics and outcomes were compared between the 2019 historical control cohort and the 2020 peak COVID-19 pandemic cohort, using Student This study was approved by the institutional review board at Northwestern University , and the procedures followed were in accordance with the with the Helsinki Declaration of 1975, as revised in 2000. All patient data included within the study have been deidentified.P<.001). Baseline patient characteristics are presented in Overall, there were 1162 hospitalizations for ADHF between the 2 cohorts. There were significantly fewer admissions for ADHF in 2020 compared with 2019  and had a higher percentage admitted from income quartile 3  as well as fewer from income quartile 2 . There were significantly more patients with non-Hispanic White racial backgrounds  admitted in 2020 with a coinciding decrease in non-Hispanic Black admissions .Patients admitted in 2020 were more likely to have chronic obstructive pulmonary disease . Patients from income quartile 4  had greater rates of ICU admissions in 2020 compared to 2019. Though not statistically significant, there was a trend toward higher mortality for those admitted in 2020 compared to 2019 . There was no difference in predicted inpatient mortality between the 2019 and 2020 cohorts or any of the racial or socioeconomic subgroups.A greater proportion of patients were admitted to the ICU in 2020 compared to 2019 . Moreover, 142 (97.2%) of the telemedicine follow-up encounters were conducted via phone while only 4 (2.8%) were conducted by video. A greater proportion of patients had successful 7-day follow-up in 2020 compared to 2019 . All racial, ethnic, and socioeconomic groups saw a trend toward improved 7-day follow-up with patients who had non-Hispanic Black racial backgrounds  meeting statistical significance as well as those from income quartiles 3  and 4 . Female patients also saw significant improvements in follow-up with the implementation of telemedicine as compared to 2019 . In 2020, patients who received follow-up within 7 days of hospital discharge were significantly less likely to be readmitted in 30 days when compared to those who had no follow-up . Patients who received 7-day follow-up via telemedicine  were also less likely to be readmitted in 30 days when compared to no follow-up.In 2020, 81.6% of 7-day follow up was conducted via telemedicine as compared to 0% in 2019  were more likely to be admitted to the ICU, though there were no major differences in ICU admission rates among different racial and ethnic minorities or neighborhood income levels; (2) had lower rates of 30-day readmissions with telemedicine follow-up within 7 days of discharge; and (3), perhaps most importantly, had a reduction in follow-up rate disparities and increased rates of 7-day follow-up with the advent of telemedicine. Though previous studies have reported on ADHF admissions and outcomes during the COVID-19 pandemic, to our knowledge, our study is the first to investigate racial, ethnic, and socioeconomic differences for patients with HF during the acute hospitalization. It is also the first study to assess the impact of telemedicine on disparities in ADHF posthospitalization follow-up and 30-day readmission rates.Our study supports prior findings of reduced admissions for ADHF seen throughout the United States and Europe with the onset of the COVID-19 pandemic -6. This The COVID-19 pandemic has had an unequal toll on patients from racial and ethnic minorities and those from lower income neighborhoods. Self-identified Black patients and those from poorer neighborhoods who contracted SARS-CoV-2 were more likely to be hospitalized and have worse inpatient outcomes when compared to White patients and those from more affluent areas ,16. RegaPrevious reports have differed on whether there have been higher rates of ICU admission or inpatient mortality during the COVID-19 pandemic for ADHF ,6,19,20.decreased during the pandemic period. Whereas in 2019, the gap was 36.6% of non-Hispanic White patients getting 7-day follow-up visits compared to 17.0% of non-Hispanic Black patients, in 2020, this gap narrowed to 43.6% of non-Hispanic White patients, as compared to 33% of non-Hispanic Black patients getting follow-up care. This disparity has been well reported, with Black race being associated with lower odds of early physician follow-up for not only HF but other chronic conditions as well [Lack of follow-up after hospitalization for ADHF is associated with an increased risk of rehospitalization for patients of racial and ethnic minorities, and those from lower socioeconomic backgrounds ,22-24. I as well -29. It iWe found a striking reduction in readmission rates for patients with telemedicine follow-up compared to no follow-up. The reason for this association is not clear. It is possible that this association is confounded by an omitted variable, and that patients who can conduct a telemedicine appointment have other factors that also mitigate risk of readmission. It is also possible that during a period with limited in-person appointments, patients selected for in-person follow-up were sicker and were more likely to need readmission. However, this finding is promising, and further prospective studies should be pursued to assess if telemedicine may be a feasible option in reducing 30-day HF readmissions.Our study has important limitations. While median neighborhood household income can help estimate a patient’s financial and social situation, it does not fully capture each patient’s individual socioeconomic status. Additionally, our cohort consisted of patients admitted with a primary diagnosis of ADHF, but we cannot rule out that some patients may have contracted the SARS-CoV-2 virus as an additional contributor to the higher morbidity and mortality seen during the pandemic. We did not exclude patients with SARS-CoV-2 infection because this would inaccurately reflect the true burden of HF admissions during the pandemic. Additionally, the inclusion of these patients allowed greater accuracy in assessing 7-day follow-up and 30-day readmission rates. Finally, while our hospital system has locations throughout the Chicago metropolitan area, we were unable to capture 30-day readmissions for patients who were admitted to medical centers outside of the NMHC system.Patients admitted for ADHF during the COVID-19 pandemic had higher rates of ICU admissions and a trend toward higher inpatient mortality; however, there were no major differences seen in rates between different racial, ethnic, and socioeconomic groups. Additionally, as the use of telemedicine became more ubiquitous, 7-day follow-up after hospital discharge increased for all patients and decreased disparities in follow-up. Patients who had 7-day follow-up, including telemedicine follow-up, were also less likely to be readmitted in 30 days. These findings suggest that telemedicine acts as a digital bridge rather than a digital divide in improving early follow-up, decreasing disparities in follow-up, and reducing 30-day readmissions. Future prospective randomized trials are needed to assess whether telemedicine may be a feasible tool in reducing HF readmission rates and improving access to follow-up, especially for those from marginalized communities. Further work is needed to assess whether telemedicine should remain as a viable option for the delivery of care to patients with HF during and beyond the pandemic.


SARS-CoV-2 reinfections are a public health concern because of the potential for transmission and clinical disease, and because of our limited understanding of whether and how well an infection confers protection against subsequent infections. Despite the public health importance, few studies have reported rigorous estimates of reinfection risk.Leveraging Indiana University’s comprehensive testing program to identify both asymptomatic and symptomatic SARS-CoV-2 cases, we estimated the incidence of SARS-CoV-2 reinfection among students, faculty, and staff across the 2020–2021 academic year. We contextualized the reinfection data with information on key covariates: age, sex, Greek organization membership, student vs faculty/staff affiliation, and testing type.Among 12,272 people with primary infections, we found a low level of SARS-CoV-2 reinfections . We observed higher risk for SARS-CoV-2 reinfections in Greek-affiliated students.We found evidence for low levels of SARS-CoV-2 reinfection in a large multi-campus university population during a time-period prior to widespread COVID-19 vaccination.The online version contains supplementary material available at 10.1186/s12879-022-07578-x. The first global case of SARS-CoV-2 reinfection was documented in August 2020 , with adDespite the public health importance, few studies have reported rigorous estimates of reinfection risk. However, those that exist have confirmed that reinfections are relatively rare. General population estimates from Qatar, Denmark, Mexico, and the United States all found reinfection risk < 1% –11. One In the current study we estimated the incidence of SARS-CoV-2 reinfection among students, faculty, and staff at Indiana University (IU) across the 2020–2021 academic year. We also contextualized the observed reinfections with demographic and infection data.This study was conducted using data from IU, a large, public university with nine campuses throughout Indiana. In total, IU serves over 71,000 undergraduate and 19,000 graduate students, with over 21,000 affiliated faculty and staff. The largest enrollments are at the two core campuses of IU-Bloomington  and IUPUI . IU-Bloomington is the flagship campus located in south-central Indiana, while IUPUI is an urban campus in downtown Indianapolis. The seven additional campuses are spread across the state of Indiana . During the 2020–2021 academic year, surveillance testing accounted for the vast majority of all tests recorded in the IU database , while maintaining random selection within groups. The full population of IU affiliates was categorized by campus and by type of affiliation . Students were further subdivided into undergraduate and graduate students, into those with on-campus vs. off-campus residences, and into those with affiliations  that may have placed them at heightened risk for transmission. Each week, each group was assigned a probability of being selected for testing, based on their risk profile and the total testing capacity available. Generally, undergraduate students, residential students, and students affiliated with Greek organizations were assigned a higher probability of being selected for testing than other groups. However, with few exceptions (e.g. fully remote workers or students with no campus interaction), all IU affiliates were in the sampling frame for random surveillance testing each week.Results for all SARS-CoV-2 tests, either university administered or self-reported by individuals, were recorded in an administrative database. Additional file Our primary outcome of interest was incident SARS-CoV-2 reinfection. We defined this outcome as any positive SARS-CoV-2 test at least 12 weeks after a first positive test. As a point of comparison, we also calculated the rates of first infection, defined as the first positive SARS-CoV-2 test under observation.We contextualized the reinfection data with information on key covariates: age , sex , Greek organization membership (yes/no), and type of IU affiliation (student/faculty/staff). We also categorized by testing type (asymptomatic/symptomatic) to make some inference about the symptomology of first infections relative to reinfections. Finally, we calculated the median date of infection for those with single infections and those with reinfections (separately for 1st and 2nd infections).We calculated incidence rates and 95% confidence intervals for reinfections and first infections directly. We produced a Kaplan–Meier survival curve for the reinfection cohort to visually represent the timing of reinfections. The Kaplan–Meier survival curve graphs the probability of remaining free from reinfections over the course of follow-up. We compared the profiles of people with single infections vs. reinfections using Chi-square tests for the categorical socio-demographic variables and Mann–Whitney U tests for the continuous date and time interval variables.Overall, 83,878 IU affiliates contributed at least one RT-PCR test in the 2020–2021 academic year ] was low relative to the incidence rate for first infections . The median date of infection for single infections  was significantly later than the median date of first infection for those who later experienced a reinfection . The median time interval between 1st and 2nd infections was 124 days (IQR: 98–172).Those who experienced reinfections differed from those with single infections in some notable ways. People with reinfections were significantly more likely to be members of Greek organizations. Greek members made up 8% of the total study population, 26% of the single infections, and 43% of the total reinfections . There were no statistically significant differences by sex, age, or type of IU affiliation. The first and second infections for people with reinfections were identified more than half of the time via an asymptomatic testing mechanism (55%), higher than observed for people with single infections (46%), though not statistically significantly different .We found that reinfections were rare but not absent in a large population of IU students, faculty, and staff in the 2020–2021 academic year. Reinfection risk was higher in Greek-affiliated students. Because we restricted to the 2020–2021 academic year during which vaccine availability was limited, and because we censored individuals at vaccination, our results reflect reinfections in the context of natural immunity.Our findings closely align with the few existing estimates of reinfection risk, despite the varied settings and designs used. In datasets with limited asymptomatic testing in Qatar, Denmark, Mexico, and the US, the reinfection risk ranged from 0 to 0.65%, with variable follow-up time ranging from 5 to 10 months –11, 14. The observed higher risk of reinfection among Greek-affiliated students deserves special attention. This finding may reflect a true increased risk underlying a population that has been characterized by high levels of alcohol consumption, large social events, and congregate living. Early evidence suggests high-risk alcohol consumption is associated with SARS-CoV-2 infections , with plThere are several aspects of our data that warrant caution in interpreting our findings. Importantly, given the rarity of the reinfection outcomes, many of our estimates were measured imprecisely. This is true even given the very large total population  that underpins these estimates. Future studies should consider pooling data across universities with similar testing schemes to maximize statistical power. Also, it is possible that some reinfections were misclassified. To address this concern, we included a 12-week wash-out period between positive tests to determine reinfection status. However, we did not require laboratory-confirmed negative RT-PCR results between infections, or otherwise determine distinct infections with phylogenetic analyses. Thus, it is possible for viral remnants to account for some of the reinfections, though unlikely given the length of washout period we applied. In the other direction, our testing system did not test every IU affiliate at regular, frequent intervals, nor did we collect complete information on positive tests prior to August 2020. Thus, some true reinfections could have been misclassified as single infections. However, this concern is somewhat alleviated by the fact that the time period under observation was fairly early in the pandemic, and by data from a serological study among IU-Bloomington undergraduates revealing low seropositivity (4.6%) at the beginning of the study period .In sum, we found evidence for low levels of SARS-CoV-2 reinfection in a large multi-campus university population during a time-period prior to widespread COVID-19 vaccination. These findings suggest that prior infections should not exempt people from surveillance and mitigation efforts, and that people with prior infections should not rely on natural immunity to protect against subsequent infection. Instead, given the strong evidence that full vaccination does protect against reinfection , people Additional file 1: Table S1. Distribution of Indiana University SARS-CoV-2 tests by type, August 2020–May 2021.


While bariatric surgery restults in significant long-term weight loss for most patients with obesity, post-surgical weight gain affects a considerable percentage of patients to varying degrees of severity. Furthermore, a small but significant percentage of patients experience inadequate post-surgical weight loss. Although many studies have examined the role of anti-obesity medications to address post-operative weight regain, an evidence-based consensus has not yet been achieved because of the heterogeneity of populations studied and the studies themselves. Observational studies in the post-bariatric surgery population consistently demonstrate the benefit of medical weight management after bariatric surgery, with most evidence highlighting liraglutide, topiramate, and phentermine/topiramate. New anti-obesity medications are anticipated to be helpful for post-surgical weight optimization given their efficacy in the non-surgical population. Bariatric surgery has been demonstrated to achieve significant weight loss in patients with obesity. The sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have historically been the most popular bariatric surgical procedures in the US and remained so in 2019 at 61.4% and 17.0% respectively, with bariatric revision of a prior procedure ranking 3rd most common at 16.7%  prospective observational study examined 1406 individuals after RYGB who were followed up for 5 years or longer and found that weight regain (WR) occurred as early as within one year of RYGB after the nadir weight was achieved, with patients regaining a median of 26.8% of maximum weight loss at 5 years after surgery, or a median weight regain of 9.7% relative to their presurgical weight at 5 years after surgery , 4. The The LABS, SOS and Baig et al. studies highlight that WR following bariatric surgery is not uncommon and affects patients to varying degrees of severity depending on the type of bariatric surgery performed. WR can be a distressing experience for patients, and excess weight regain is associated with many diseases, such as diabetes, hypertension, hyperlipidemia, asthma, arthritis, depression, coronary heart disease, and various malignancies . Therefo2 or greater and for individuals with a BMI of 27 kg/m2 plus comorbidities  of 30 kg/mbidities . CurrentOrlistat is an intestinal lipase inhibitor that reduces fat absorption by approximately 30%  FDA-apprvia central neural pathways  and is FDA-approved for type 2 diabetes as liraglutide 1.8mg and for obesity as liraglutide 3.0mg. Benefit of liraglutide in the post-bariatric surgery setting is supported by a randomized controlled trial  and multNaltrexone is an opioid receptor antagonist that inhibits the auto-inhibition of anorexigenic neurons in the hypothalamus . BupropiSemaglutide is a GLP-1-RA that is FDA-approved for type 2 diabetes as semaglutide 2.0mg and for obesity as semaglutide 2.4mg. There are no studies evaluating semaglutide specifically in the post-bariatric surgery population. Several phase 3 randomized controlled trials, which excluded individuals with a history of bariatric surgery, proved superior weight loss with semaglutide 2.4mg compared to placebo in individuals with obesity or metabolically complicated overweight: 12.4% in general , 11.1% iTirzepatide is a dual GLP-1-RA and gastric inhibitory peptide receptor agonist (GIP-RA). It is FDA-approved for the treatment of type 2 diabetes. There are no studies evaluating tirzepatide specifically in the post-bariatric surgery population. However, a recent phase 3 trial, which excluded individuals with a history of bariatric surgery, demonstrated weight loss efficacy approaching that of some bariatric surgeries. In a double-blind, randomized, controlled trial of 2539 adults with obesity (BMI ≥ 30) or medically complicated overweight (BMI ≥ 27), tirzepatide 15mg weekly resulted in 20.9% weight loss over 72 weeks compared to 3.1% weight loss with placebo . More thRetrospective studies have investigated weight loss associated with obesity pharmacotherapy in general among patients with a history of bariatric surgery without identifying specific AOM monotherapies or AOM combination therapies. A trend toward greater weight loss has been observed with two or more AOMs compared to patients taking zero or one AOM . GLP-1-ROther studies identified factors associated with greater weight loss in the population of patients with medically managed obesity after bariatric surgery. Greater weight loss results were observed with use of AOMs for patients with a history of laparoscopic adjustable gastric band vs. SG  and RYGBThere are no official guidelines on perioperative weight optimization in patients undergoing bariatric surgery, and there is no consensus on the pharmacologic management of weight regain, inadequate weight loss, or weight loss plateau after bariatric surgery. Whether initiation of AOM preoperatively has long-term benefits to mitigate these post-operative weight issues is unknown. When initiated post-operatively, the choice of which AOM to use for weight optimization is an important component in the long-term care of patients with obesity.There is a paucity of data available to guide pharmacotherapeutic weight management decisions before bariatric surgery and whether this impacts the sustainability of clinically significant weight loss post-operatively. Weight loss in the pre-operative period has proven benefits, including a reduction in the likelihood of post-operative complications after RYGB , 42 but Weight regain after bariatric surgery most often begins 1-2 years post-operatively . PatientOf all AOMs, liraglutide, topiramate, and phentermine/topiramate are the pharmacologic agents best supported with current observational studies. Use of GLP-1-RAs for weight optimization after bariatric surgery will likely gain popularity given evidence in the post-surgical population  and the Medical co-morbidities may influence the choice of on- or off-label AOM used for weight optimization after bariatric surgery. In addition to significant weight loss, semaglutide has proven systemic benefits in the non-surgical population –50, wherContraindications should also inform the choice of AOM used for weight optimization after bariatric surgery. Topiramate or phentermine/topiramate are options in patients who have a contraindication to GLP-1-RAs  or who have poorly controlled gastroesophageal reflux disease, which is a common concern after sleeve gastrectomy. For patients who are not candidates for GLP-1-RAs and have a contraindication to topiramate  and/or phentermine , monotherapy bupropion or bupropion/naltrexone might be considered, though little data exists regarding its efficacy after bariatric surgery.The use of an AOM may not be appropriate or effective for all patients with weight regain, inadequate weight loss, or WLP following bariatric surgery. If a patient’s unexpected post-operative weight trajectory is due to an anatomic etiology, surgical or endoscopic revision may be indicated. After SG and RYGB, revisional bariatric surgery has become the third most common type of bariatric surgery performed in the Unites States , with weIn patients with a history of bariatric surgery, the presentations of weight regain, weight loss plateau, or inadequate weight loss are opportunities for weight optimization. Observational studies have consistently demonstrated the effectiveness of AOMs in treating these post-operative weight issues, with liraglutide, topiramate, and phentermine/topiramate having the best supporting evidence among all AOMs. The future of perioperative weight optimization in patients undergoing bariatric surgery is an increasingly empowered field due to the availability of on- and off-label AOMs, evolution of gut peptide modulators as pharmacotherapy, and the development of endoscopic interventions.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.EL: Created first draft and performed edits according to feedback from senior authors OS: Contributed to second draft, primarily within Expect Opinion and Conclusion sections BT: Provided feedback and guidance on all drafts LA: Provided feedback and guidance on all drafts. All authors contributed to the article and approved the submitted version.


This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8–16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs . Participants with NCDs were more likely than those without to have depressive symptom , especially among those who need to refill their medication during the COVID-19 lockdown . Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown. In China, a total of 1,210,601 cases have been confirmed, including 15,372 deaths1. Between February and March 2020, China issued a two-month lockdown due to COVID-19 pandemic, mandating all individuals (unless authorized otherwise) to stay at home and stop outdoor activity and social gathering2. During the lockdown period, people’s lives changed drastically, and depressive symptom is likely to be triggered5.Since 2020, Coronavirus Disease 2019 (COVID-19) has been diagnosed in over 500 million individuals and caused over six million deaths worldwide as of May 4th, 20227. Therefore, patients with NCDs may experience more psychological burden during the COVID-19 pandemic or COVID-19 lockdown. It is estimated that 244.5 million people have been diagnosed with hypertension8, 92.4 million with diabetes9, and 94 million with cardiovascular disease in China10. These patients generally have a much higher risk of COVID-related morbidity and mortality, and even without COVID infection, their treatment for NCD and quality of life can be affected during the pandemic lockdown due to the impact of health care access and medication refill. Few studies have investigated the impact of COVID-19 lockdown on NCD patients in a community setting.COVID-19 patients who died were generally older, with a history of noncommunicable diseases (NCDs)Within the WELL China cohort that has collected baseline data 8–16 months before COVID-19, we incorporated a survey one month after the COVID-19 lockdown to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among 3327 cohort members in the Gongshu District, Hangzhou, China.Table Figure Figure Table In this large population-based survey, we showed that during the COVID-19 lockdown in China, the prevalence of low physical activity and depressive symptom increased, while the prevalence of current smoking, drinking, and poor sleep quality decreased. Younger age (< 45 years) and the need for medication refill were associated with a higher risk of having incident depressive symptom during the lockdown, whereas maintaining moderate to vigorous physical activity was associated with lower risk of having depressive symptom during COVID-19 lockdown.11. In contrast, reduced alcohol drinking and smoking, and improved sleep quality are positive changes related to health and well-being during this lockdown period. It is possible that NCDs patients may benefit from the lockdown by reducing risky behaviors and improved sleep. Follow up and further research should investigate the short-term benefits of these behavior changes in patients with NCDs and whether these improvements in healthy lifestyle remain after the lockdown period.Our finding on lifestyle behavior changes during the lockdown period in China provides information on the impact of the COVID-19 pandemic. The lockdown prohibited people from going out and exercising outdoors, likely resulting in the higher prevalence of low physical activity and excessive sitting, which may translate to increased risk of chronic diseases12. Given the extent of the COVID-19 lockdown worldwide, this high prevalence of depressive symptom suggests that millions of individuals may experience mental health stress during the COVID-19 lockdown. Traditional psychological crisis intervention, e.g., face-to-face contact with qualified mental health professionals, is not likely to be readily available to all who need it. Psychological service system should thus be, and is being re-formed to incorporate novel strategies  to better tackle psychological problem during the COVID-19 epidemic14.Depressive symptom increased from 13.7% at baseline (before lockdown) to 20.7% during lockdown, suggesting an adverse impact of lockdown on mental health. This results in consistent with previous findings on general population15. Collectively, these data suggest the importance of providing adequate clinical support, either through telemedicine or special arrangements , for high-risk individuals, such as patients with chronic diseases during future outbreaks or lockdown to minimize mortality. In addition, mental health of patients with chronic disease needs to be taken into account to minimize anxiety and mental breakdown to minimize the deterioration of the underlying conditions.Lack of medical support may also lead to newly emerged depressive symptom among NCDs patients since they were not able to visit the clinic in person for follow up, in particular for imaging or examinations that need in-person service. In addition, in our study, the need to refill medication was associated with a higher risk of having incident depressive symptom during COVID-19 lockdown, suggesting that lack of medication for their chronic conditions may result in concerns and anxiety, leading to depressive symptoms. This concern is further highlighted by the fact that over 70% of patients with chronic diseases have reported inadequate availability of medicine during COVID-19 lockdownThe key strength of our study is having longitudinal data on the same individuals before and during COVD-19 in a large population-based study. Limitation of the study should be noted. First, all our data are self-reported, thereby some misclassification is possible. Second, the follow up survey was carried out one month after the lockdown already completed, thereby some recall issues may contribute to misclassification of information. Third, generalizability of our results is limited as access to health care and support vary greatly in different country.In conclusion, in this community-based study, we found that COVID-19 lockdown significant impact lifestyle and quality of life among individuals with chronic diseases. These results provide the basis for targeted prevention to better prepare NCD patients, community, and healthcare system to meet the challenge in future outbreaks or lockdown.20. Briefly, WELL-China is a population-based cohort for the investigation of well-being in Hangzhou, Zhejiang province, China. In this COVID-19 Study, we surveyed the 4144 WELL-China participants who completed their baseline survey in Gongshu District, Hangzhou, China, between October 2018 and May 2019, which is 8–16 months before the COVID-19-related nationwide lockdown.Subjects were a subset of the Wellness Living Laboratory (WELL)-China study. Details of the WELL-China cohort are Described elsewhereFor the COVID-19 survey, we conducted a telephone survey in April 2020, around one month after the lockdown, to collect information on lifestyle, mental health and medical access during the 2-month lockdown  period. Of the 4144 participants at baseline, 3356 responded to the telephone survey (81% response rate). We excluded 27 participants who did not report their baseline NCDs conditions, leaving 3329 for the final analysis.The WELL-China project was approved by the ethics review board at both Zhejiang University (No. ZGL201507-3) in China and Stanford University (IRB-35020) in USA. All participants provided written informed consent. The follow-up telephone interview was further approved by the ethics review board at Zhejiang University (No. ZGL202004-01). We conducted this study in accordance with the latest revised ethical guidelines of the Declaration of Helsinki.21.During 2018–2019, face-to-face interviews were performed to collect baseline characteristics before the COVID-19 outbreak. Information on noncommunicable diseases (NCDs) was assessed and included self-reported history of diagnosed diabetes, hypertension, cardiovascular disease, cancer, endocrine and metabolic diseases, osteoarthritis, digestive system diseases, respiratory system diseases, mental diseases, urinary system diseases, nervous system diseases, immune diseases, and allergies at baseline. Smoking status and alcohol consumption were categorized as never, former, or current. Sleep quality was self-reported as very good, fairly good, fairly bad, or very bad. Eating behavior was categorized into not regular, mostly regular, or very regular. Physical activity was measured using the short version of the International Physical Activity Questionnaire, and were classified into three categories: low; moderate; and vigorousWe used telephone follow-up survey to collect the same information on lifestyles and WHO-5 as well as medication refill during the lockdown period. Participants who reported moderate to vigorous physical activity both at baseline and during follow-up survey was defined as maintaining moderate to vigorous physical activity.22.The WHO-Five Well-being Index (WHO-5) was used to assess depressive symptom. The WHO-5 tool is a five-item self-report instrument that assesses well-being  over the past two weeks on a 6-point Likert scale . Scores on the WHO-5 range from 0 to 25, and higher scores indicate greater well-being. The WHO-5 has demonstrated good reliability and validity and the ability to identify adults experiencing depression in medical settings in several countries across Africa, Asia, Australia, Europe, North America, and South America22. Depressive symptom was then defined as the participants has answered 0 (at no time) to 1 (some of the time) to any of the five items or if the WHO-5 raw score below 1323.The five items included: (1) “I have felt calm and relaxed”, (2) “I have felt cheerful and in good spirits”, (3) “I have felt active and vigorous”, (4) “My daily life has been filled with things that interest me” and (5) “I woke up feeling fresh and rested”Participants who were classified to have depressive symptom in 2020 during the COVID-19 lockdown but not at baseline (2018–2019) were classified as having incident depressive symptom.Chi-square tests were used to assess whether baseline characteristics differed between participants with and without NCDs. McNemar's tests were used to investigate the change in lifestyle and mental health between before and during the COVID19 lockdown.Univariable and multivariable logistic regressions were used to investigate the association between baseline characteristics and incident depressive symptom during COVID-19 lockdown, among participants with and without NCDs.We used STATA, version 13 , for all the analyses. All statistical tests were two-sided, and statistical significance was defined as P < 0.05.


Plasmodium falciparum has prompted questions over whether it could improve the diagnosis of malaria in pregnancy and pregnancy outcomes in malaria endemic areas.Rapid diagnostic tests (RDTs) are effective tools to diagnose and inform the treatment of malaria in adults and children. The recent development of a highly sensitive rapid diagnostic test (HS-RDT) for This landscape review collates studies addressing the clinical performance of the HS-RDT. Thirteen studies were identified comparing the HS-RDT and conventional RDT (co-RDT) to molecular methods to detect malaria in pregnancy. Using data from five completed studies, the association of epidemiological and pregnancy-related factors on the sensitivity of HS-RDT, and comparisons with co-RDT were investigated. The studies were conducted in 4 countries over a range of transmission intensities in largely asymptomatic women.Sensitivity of both RDTs varied widely  yet HS-RDT detected individuals with similar parasite densities across all the studies including different geographies and transmission areas [geometric mean parasitaemia around 100 parasites per µL (p/µL)]. HS-RDTs were capable of detecting low-density parasitaemias and in one study detected around 30% of infections with parasite densities of 0–2 p/µL compared to the co-RDT in the same study which detected around 15%.P. falciparum diagnosis, if storage conditions can be adhered to.The HS-RDT has a slightly higher analytical sensitivity to detect malaria infections in pregnancy than co-RDT but this mostly translates to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity. The analysis presented here highlights the need for larger and more studies to evaluate incremental improvements in RDTs. The HS-RDT could be used in any situation where co-RDT are currently used for The online version contains supplementary material available at 10.1186/s12936-023-04445-1. Malaria in pregnancy (MiP) is associated with increased risk of poor maternal and infant health outcomes, including fetal loss, maternal anaemia, pre-term birth, low birthweight and intrauterine growth retardation, which in turn increase the risk of infant morbidity and mortality . ModelleWHO has reviewed different ‘Test and Treat’ strategies in the context of MiP, such as Intermittent Screening and Treatment (ISTp) at the first antenatal care (ANC) visit . AlthougPlasmodium falciparum are commonly asymptomatic and have low density infections [IPTp is contra-indicated in the first trimester of pregnancy, yet a high proportion of women are infected in the first trimester , which cfections , and inffections . An impofections . A modelfections . It alsofections . ImproveP. falciparum infections below the detection limit of co-RDTs. The HS-RDTs enable point-of-care testing with an analytical sensitivity (limit of detection (LOD)) that is ten-fold lower than that reported for current best-in-class co-RDTs, at 80 pg of HRP2 per mL of blood [A highly sensitive RDT (HS-RDT) based on detection of Histidine-Rich Protein 2 (HRP2) was developed  to improve the identification of of blood  comparedof blood  as testeof blood –18.e.g. transmission intensities, target populations). This review compiles all existing evidence to date on the performance and use case scenarios of the HS-RDT in the context of pregnancy to inform policy makers and the research community on existing evidence and knowledge gaps.In June 2018, the WHO Global Malaria Programme convened a technical consultation to identify the evidence required to develop recommendations on the use of the HS-RDT in different contexts including the detection of MiP . The lacThis evidence review encompassed both published articles in peer-reviewed journals as well as other grey literature such as technical reports or presentations at scientific conferences.Information was gathered on completed and ongoing research projects or grants reported between January 2017 to December 2020 in the following databases: MEDLINE–Pubmed Central, Malaria in Pregnancy Library , Cochrane Library, MESA Track database, Conference books , ClinicalTrials.gov, WHO–International Clinical Trials Registry Platform, ICH GCP–Clinical Trials Registry, Grantome.com, Europe PMC Grant Finder, National Institutes of Health (NIH). The keywords used for the project search were: malaria, pregnant/pregnancy, RDT, diagnostic, (highly/ultra)-sensitive, HS-RDT, hsRDT, uRDT, Alere.Experts and stakeholders were contacted to further identify ongoing studies. This included 25 active researchers in the field of MiP or malaria diagnostics, as well as focal persons in international organizations working in these fields. Each contact was also asked to name other experts in the field who were then contacted. All Principal Investigators of identified eligible studies were contacted in order to confirm their study details and the accuracy of the data included in the comparative analyses presented in this review.P. falciparum detection using any reference assay.Prospective studies of any design were eligible if they included pregnant women during pregnancy (any trimester) or at delivery, used the NxTek™ Eliminate malaria Pf RDT by Abbott Diagnostics ), and reported The product disclosure statements were assessed for all co-RDTs used in the trials and all were assessed to be of high quality. All studies used the recommended 5 µL of blood to perform the RDT. The molecular reference standards used in the completed studies were quantitative PCR , quantitative Reverse Transcription PCR , Photo-induced-electron-transfer PCR , nested PCR  and a composite qPCR + Loop-mediated isothermal DNA amplification . The equivalent volume of blood from which DNA was extracted and used for the molecular methods varied and was not known for most studies, however the Benin study used 1.7 µL blood equivalent. LOD or limit of quantification (LOQ) were used as determined and reported in the study where possible, or based on the reference for the technique.Quantitative and qualitative data from all the eligible studies were collected in multiple Excel spreadsheets. Figures were prepared with Graphpad Prism 8.1. , and additional test performance analyses (i.e. not provided in published articles) of Pearson and Spearman correlations and paired t-test were conducted with STATA version 11 software . Efforts were made to perform meta-analyses, but the heterogeneity of the studies was too great to provide meaningful results.A total of 13 studies addressing HS-RDT use in pregnancy were identified as of December 2020  and at delivery (3/8) and from symptomatic and asymptomatic individuals  and medium , to high  > 5 per year). Malaria transmission was determined by Data sets for five of the eight completed studies were available and included in this review. The sample size of the five studies ranged from 270 to 942, with the Benin study  samplingThe studies included high malaria infection prevalence areas  and Kenya showed decreasing sensitivity with increasing gravidity, and the study in Benin showed an increasing difference in sensitivity between the HS-RDT and co-RDT with increasing gravidity Fig. .Fig. 6SeP. falciparum prevalence reported in the studies , nor with the LOD of the reference method .HS-RDT sensitivity was not associated with Clinical outcomes were investigated only in the Benin study, where the effect of the RDT used on maternal and birth outcomes was evaluated. The results from this single study investigating clinical outcomes indicated that infections detected with the HS-RDT but not with the co-RDT were associated with maternal anaemia, suggesting that testing based on the HS-RDT might be clinically relevant in this specific context and provide a direct health benefit for the pregnant women.Different use cases were investigated in studies in Benin, Colombia and Malawi where the HS-RDT was used to detect placental infections from either placental or peripheral blood at delivery. The sensitivity of HS-RDT compared to co-RDT to detect infections from peripheral blood compared to placental blood was significantly higher in Benin, but both tests showed poor sensitivity in Colombia to detect parasites in placental blood . The study in Benin calculated the parasitaemia level at which samples were HS-RDT positive and co-RDT negative (N = 28) to have a mean density of 20.7 p/µL with HRP2 levels at a mean of 1049 pg/mL.P. falciparum malaria in pregnancy. In the reported studies HS-RDT does detect some very low parasitaemias, with the lowest density detected being ~ 2 parasite/μL. In the two studies with available data on parasitaemia the HS-RDT detected lower parasitaemias than the co-RDT. Overall, the detection of parasites is consistent across studies (~ 100 parasite/μL), therefore the variability in HS-RDT sensitivity is likely due to variations in epidemiological context such as parasite density distributions. Sensitivity of HS-RDTs ranged widely from 20 to 86% compared to molecular methods. The HS-RDT showed a slightly higher analytical sensitivity than the co-RDT in most studies but this difference was only statistically significant in the study from Benin.This paper describes the evidence landscape of HS-RDT performance compared with co-RDTs to diagnose The five studies with available data were heterogenous both geographically and by transmission intensity, aiding generalizability of the results. A key assumption is that molecular testing of peripheral blood can detect placental malaria, making these data comparable between sites . DespiteAnother source of variability in sensitivity is likely to be the samples used: although the RDTs are intended for use with fresh blood, the studies in Benin, Colombia (1), and Indonesia all used thawed blood, which may affect RDT performance. The study in Indonesia used thawed red blood cell pellets (stored: ~ 1 year), reconstituted with plasma to 30% haematocrit. This off-label use might account for the very low sensitivity of both the co-RDT and HS-RDT in this study. A further source of variation in sensitivity could be the reference standard used and its associated LOD. LODs ranged from ~ 0.02–6 parasite/μL. Across the five studies included in this analysis however, there was no trend for sensitivity to be associated with reference assay LOD.Both RDTs tended to have higher sensitivity in febrile women compared with afebrile women, as expected. Prevalence of malaria infection is known to be highest at first ANC visit, and declines with gravidity by both PCR and co-RDT , 8. The Another reason for minimal differences between HS-RDT and co-RDT could be that co-RDTs have a lower LOD than expected. While the criteria of detection of at least 200 parasite/μL is required for pre-qualification by WHO, the exact LOD is unknown and for some may approach the LOD of HS-RDT . The SD Bioline Pf co-RDT was tested against the HS-RDT by Das et. al  and was The main limitation of this evidence review is the difficulty of pooling data due to the heterogeneity of the studies, difference in reference assays and reporting formats, and small numbers of studies included. In turn, this heterogeneity is also a benefit to describe the potential advantages of the HS-RDTs in different situations. The main goal of diagnosing MiP is to reduce adverse clinical outcomes for women and their children. The study in Benin  identifihrp2/hrp3 deletion parasites that escape detection [Using HS-RDT in a similar manner to co-RDTs is supported, for example, using HS-RDT instead of co-RDT at ANC visits to assess community malaria transmission will provide more accurate prevalence estimates. However, other factors to consider in procurement include that HS-RDT has limited temperature stability and shelf-life claims compared to most co-RDT, and the costs of tests. Both tests will be limited in impact by the emergence of etection .Overall, the studies confirmed that the HS-RDT has a slightly higher analytical sensitivity than co-RDTs in various MiP epidemiological contexts. The use of the HS-RDT could be recommended in all cases where co-RDTs are currently used in ANC settings, although factors other than analytical sensitivity must be weighed in each context.Additional file 1:Table S1. Testing characteristics of the completed studies evaluating the use of the HS-RDT for the detection of MiP. Table S2. True and False positives and negatives by study. Figure S1. Sensitivity of the HS-RDT and parasite density of the maternal infections detected by the reference standard in each study. Densities represented as geometrical mean + confidence interval (p/μL). Figure S2. Sensitivity of HS-RDT at delivery in peripheral and placental blood.


The COVID-19 pandemic strained healthcare workers but the individual challenges varied in relation to actual work and changes in work. We investigated changes in healthcare workers’ mental health under prolonging COVID-19 pandemic conditions, and heterogeneity in the mental-health trajectories.n = 4804) between 4th June 2020 to 28th May 2021. Pandemic-related potentially traumatic events (PTEs), work characteristics , local COVID-19 incidence, and demographic covariates were used to predict Mental Health Index-5 (MHI-5) and Insomnia Severity Index (ISI) in generalized multilevel and latent-class mixed model regressions.A monthly survey over a full year was conducted for employees of the HUS Helsinki University Hospital , directly caring for COVID-19 patients  and PTEs  were all independently associated with psychological distress, when  adjusting for age, sex, profession, and calendar time. Effects of COVID-19 incidence on mental health were dissociable from calendar time  whereas those on sleep were not. Latent mental-health trajectories were characterized by a large class of “stable mental health” (62% of employees) and minority classes for “early shock, improving” (14%) and “early resilience, deteriorating” mental health (24%). The minority classes, especially “early shock, improving”, were more likely to live alone and be exposed to PTEs than the others.Healthcare workers faced changing and heterogeneous mental-health challenges as the COVID-19 pandemic prolonged. Adversity and mental ill-being may have accumulated in some employees, and factors like living arrangements may have played a role. Knowledge on employees’ demographic and socioeconomic background, as well as further research on the factors affecting employees’ resilience, may help in maintaining healthy and efficient workforce in the face of a prolonging pandemic.The online version contains supplementary material available at 10.1186/s12888-022-04389-x. The COVID-19 pandemic represents a global threat to mental health. In the general population and among healthcare personnel, that threat has manifested in relatively high rates of symptoms of anxiety, depression, psychological distress, and post-traumatic stress disorder . In the Many healthcare workers may have experienced a double burden of stress from COVID-19 compared to the general population, given their similar or higher risk to own health and the additional work stress from treating surges of patients with an infectious disease . It has Various mental-health trajectories during the COVID-19 pandemic have been observed amongst the general population, depending on factors like local lockdowns, personal financial difficulties, pre-existing conditions, and contracting the infection , 19. As Although some studies have monitored healthcare workers mental health during the COVID-19 pandemic either at frequent intervals or over long periods of time e.g., , 22), fe, fe22]),n = 25,494) was invited to participate in a baseline online survey during a difficult early phase of COVID-19 pandemic in June 2020, with 4804 employees (19%) answering [The entirety of the personnel of the HUS Helsinki University Hospital  in psychological distress. First, it is important to know how the overall mental health of healthcare workers changes upon prolongation of a pandemic e.g. because accumulating stressful working conditions may reduce quality of care and lead to sickness absences –27 and bThe HUS Helsinki University Hospital serves the 26 municipalities in the region of Uusimaa in Finland, a population of 1.7 million. The region includes the capital city of Helsinki, many smaller cities, and sub-urban and rural areas. Before COVID-19 and subsequent economic and political turbulence, in 2019, the human development index of Uusimaa region was 0.958 , which in = 4804) contained nursing staff (62%), medical doctors (9%), special personnel such as psychologists and social workers (8%), and other non-healthcare personnel (21%), and overall predominantly (88%) females [This study was approved by the HUS Ethical Committee. Permission to conduct the study was obtained from the HUS Joint Resources. After our initial publications on the baseline data and the half-year follow up , 24, thi females . Average females  for a fursonnel 2%, and ovAn e-mail invitation pertaining to an electronic survey delivered both in Finnish and in Swedish languages was sent to all 25,494 employees of HUS. Besides this initial invitation, an open-access link was available in the personnel’s internal website to capture additional employees undergoing work changes or turnover. The survey consisted of demographic background questions, five symptom rating scales , and questions pertaining to changes in daily work, adjustment to those changes, attitudes towards COVID-19 patients, and open questions on possible need for psychological support. The survey took about ten to fifteen minutes to answer. The 4804 employees (19% of the HUS personnel) who participated in the initial June 2020 electronic survey, have received invitations to participate also in the monthly follow-up rounds. Although the pressure of dealing with COVID-19 likely limited representativeness of the initial cross-sectional sample, altogether 82% of participants were at least partly retained in follow ups.https://sampo.thl.fi/pivot/prod/en/epirapo/covid19case/). Hence, prevailing incidence rate could be matched to persons’ responses with a one week accuracy.In addition to the employee-level survey data dated by the time of responding, weekly COVID-19 incidence rates in Uusimaa region were drawn from an open data repository of the Finnish Institute of Health and Welfare  the five-item Mental Health Index (MHI-5), which is the mental-health subscale of the RAND-36 (SF-36) self-report questionnaire of health-related quality of life . MHI-5 rBesides the abovementioned validated measures, we used the following simple tailored questions on potentially traumatic events related to COVID-19: (1) Has your work with suspected or confirmed COVID-19 patients included exceptionally disturbing or distressing assignments; (2) have you had strong anxiety due to your own or close one’s risk of contracting serious illness for your work with suspected or confirmed COVID-19 patients; (3) have you or your close one contracted a severe COVID-19 that required hospital care; and (4) has a close one to you died of COVID-19? If any of 1-4 was endorsed, the employee was considered as having experienced a COVID-19 related PTE. In addition to the PTE questions, we asked whether the employees’ daily work had changed due to COVID-19, whether they had directly provided care to a patient with confirmed or suspected COVID-19 infection during the last week, whether they were members of the nursing staff, and their age and gender .We drew boxplots and local regression lines to illustrate the data to the reader. We then modeled the associations between risk factors and time-varying outcomes with multilevel (mixed-effects) logistic regression models, using a random intercept to model employee-specific risks that are constant over the repeated monthly measurements , 37. Allr to log(r + 1) for regression modeling to linearize the generally exponential growth rate of infection transmission.To understand the overall risk of psychological distress or sleep problems, multiple regression models were fitted with different combinations of covariates in order to adjust their effects on each other in a controlled manner. The effects of calendar time in these models were taken in account via two routes: with polynomials of standardized calendar dates and/or with time-specific local COVID-19 log-incidence per week. More specifically, we strived to first exhaust the effects of simple calendar time by adding polynomials of time until a non-significant higher order polynomial was encountered. Furthermore, we transformed the incidence rate defined as weekly number of new cases To understand possible latent classes (clusters) of risk, we modeled such latent heterogeneity in mental health trajectories using latent class mixed models . In an aThe survey waves approximately reflect the time the participants answered the online questionnaire, with some variation within the waves. Besides large variation between individuals Fig. a, a meanp = 0.105 for interaction). The differential risk of psychological distress between professions did not withstand adjusting for PTEs  latent class  showed relatively stable trajectories with less fluctuation compared to the other classes  . Indeed,In all our models, experiencing a PTE consistently associated with four- to five-fold risk of psychological distress, but these experiences did not distribute uniformly in time. Although Finland was less affected by the first COVID-19 waves than many other European countries , health We examined both psychological distress and sleep problems as outcomes of pandemic working conditions. Sleep problems are a common first psychiatric symptom in prolonged stress and reciprocal relations between insomnia and perceived work stress have been previously established . More geHere, we found both similarities and differences for sleep problems and psychological distress in the hospital employees. Both treating COVID-19 patients and experiencing PTEs were risk factors for both psychological distress and sleep problems, but treating COVID-19 patients had an effect of a comparable magnitude on these outcomes whereas PTEs had almost two times higher effect on psychological distress compared to sleep problems. Furthermore, COVID-19 incidence had an independent effect on psychological distress even after adjusting for calendar time, whereas it did not have such an effect on sleep problems. Notably, the local incidence varied in time but was the same for all the employees. The same was true for the fifth degree polynomial expansion of time already in the model. Thus, the observation of partial independence between incidence and time in predicting psychological distress specifically suggests that novel kinds of incidence effects on psychological distress, but not on sleep, emerged over time. Why might direct patient burden have more prominent time-evolving influence on psychological distress than on sleep problems? Whereas earlier COVID-19 studies have highlighted sleep problems , 5 and mWe also found evidence for the existence of latent sub-groups amongst the healthcare workers, or latent classes, in which the average trajectories through the pandemic differed across the sub-groups. Employees in the class “early shock, improving” , which could pertain to difficulties in reaching employees with an electronic survey in the middle of pandemic work. Our ability to keep this initial sample through the follow up was comparatively better, however. Therein, our relatively dense (monthly) follow-up sampling may have been a strength, as many who did not fill in the first follow-up survey nevertheless did have a chance to participate in some of the later surveys (47% re-participated to the first follow up but 82% to at least one of the follow ups). The published 2020 personnel composition differed from our baseline sample  that may affect how the employees cope with pandemic working conditions. However, one would expect many of such factors to change slowly relative to stressors during a year of pandemic conditions, and therefore our densely sampling surveys are likely to provide a good overall picture on how the respondents and the employee-population they represent responded to the investigated time-dependent mental-health risk factors.As the pandemic conditions exceeded a full year, healthcare workers transient stress reactions as indexed by sleep problems showed both similarities and differences in their correlates compared to general psychological distress. Effects of PTEs and local COVID-19 incidence on psychological distress were visible and changed in time. Furthermore, the mental-health trajectories of the employees under the pandemic year clustered to three distinguishable classes, suggesting latent sources of heterogeneity in how they fared. Hence, while important, meta-analytic work combining cross-sectional estimates in the field risks diluting important sources of mental health. Exposure to direct pandemic patient work, potentially traumatic events related to it, and local burden of transmission may all have influenced employee mental well-being throughout a year of COVID-19 pandemic conditions. However, in addition to controlling such established exposures, continuously following how individual employees cope with the pandemic and assessing need for psychosocial support may be important for both research and human resources if we are unable to rid ourselves from COVID-19 entirely or when future infectious diseases arise.Additional file 1. Supplementary Material. Healthcare workers’ heterogeneous mental-health responses to prolonging Covid-19 pandemic: A full year of monthly follow up in Finland. Supplementary data on a Logistic regression mixed model and on the latent class mixture models.