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Introduction: The COVID-19 pandemic worldwide forced governments to undertake intervention measures to encourage social distancing. Meanwhile, traumatic skin lacerations require multiple hospital visits for dressing, changings, and suture removal since they are usually repaired with non-absorbable sutures. In a matter of fact, these visits can be avoided by using absorbable sutures instead. However, absorbable sutures carry the theoretical risk of wound infection. In this study, our aim was to determine whether absorbable sutures are better than non-absorbable sutures in repairing lacerations during the COVID-19 pandemic. The first and second objectives were to assess the rate of infection and the number of postoperative hospital visits. Method(s): A sample of 469 patients with traumatic skin lacerations were analysed during the COVID-19 pandemic in April-July 2020. In the control group, wounds were repaired using non-absorbable sutures, while rapid-onset absorbable sutures were used in the treatment group. By conducting a phone call follow-up after 21 days, several parameters regarding infection signs and hospital visits were compared between both groups. Result(s): No statistically significant difference was observed between both groups regarding wound infection (p-value= 0.623). Using absorbable sutures resulted in fewer postoperative hospital visits than non-absorbable sutures (p-value= 0.001). This study is limited because the assessment of wound infection was subjective to the patient by a phone call follow-up. Conclusion(s): Using absorbable sutures to close traumatic skin lacerations is safe. They should be considered during a pandemic to reduce hospital visits for suture removal, which will subsequently enhance social distancing and relieve hospital load.
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Introduction: Increasing evidence demonstrates the effectiveness of universal masking precautions in reducing the transmission of COVID-19. Whether these precautions have an impact on surgical site infections (SSI), currently remains unknown. This study assesses whether implementation of universal masking precautions altered the rates of SSI. Method(s): We performed a single-institution, retrospective cohort study using the NSQIP database, evaluating all patients undergoing most performed general surgery procedures from June 2018 to December 2021. SSI rates were compared between patients who underwent operation before and after implementation of universal masking precautions at our institution in March 2020. Statistical analyses were performed using Fisher's exact test. Result(s): A total of 1,539 patients were included;721 patients were in the pre-masking cohort, while 818 in post-masking cohort. During this time period, a total of 143 (9.3%) patients developed SSI, 3.6% incisional and 5.7% deep organ space infections (OSI) (p=0.6601). Incisional and OSI rates did not differ significantly between the two groups (incisional 3.47% vs 3.67%, p=0.891;OSI 5.41% vs 5.99%, p=0.6608). Sub-analysis of top 5 procedures (by volume - laparoscopic cholecystectomy, hepatectomy, thromboendarterectomy, colectomy with anastomosis, and colectomy with ileocolostomy) demonstrated a significant decrease in incisional infections (3.7% vs 1.62%, p=0.0354). Conclusion(s): While the incidence of SSI did not differ significantly in the overall cohort after implementation of universal masking precautions, there was a decrease in incisional infections in commonly performed procedures at our institution. Future research is needed to identify whether continued masking precautions may minimize the risk of SSI in specific patient populations.
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Some claims have been made that that Covid vaccination is effective against both infection and mortality, even though the WHO is seeking more evidence to determine how well vaccines stop infection and transmission. On the basis of UK daily data over the period 10 January 2021–6 January 2022, evidence is presented indicating that vaccination is not effective against infection but it is highly effective against mortality. This makes scientific sense because the function of vaccination is to stimulate the production of antibodies that fight off the virus, which does not imply the ability to stop infection.
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Introduction: During the first year of the Covid-19 pandemic we observed a decrease of our shunt revision rate. In order to investigate a possible correlation with an assumingly lower general infection rate in children in times of lock down and homeschooling, we performed a detailed analysis of our shunt and general pediatric patient population. Method(s): Electronic patient charts retrieval for children admitted for shunt revision or infectious diseases was performed for four time periods (study period April 2020 - March 2021, control periods from three previous years). A detailed analysis of all shunt revision and infectious cases including age and season specific evaluation followed. Possible correlations were investigated. Result(s): A total of 318 shunt revision and 13,919 pediatric cases have been evaluated. The shunt revision rate during the study period was 29% less compared to the average rate of three previous years (p 0.061), the number of pediatric cases with main diagnosis infection dropped significantly (p < 0.05), whereas other pediatric admissions remained stable. Significant age or seasonal influences did not exist. The number of shunt revisions in association with a documented systemic infection or a primary shunt infection dropped significantly during the study period (p<0.05 each). This was not the case for underdrainage, overdrainage (p>0.05 each) or other indications. In general, infections of upper and lower airways, the gastrointestinal and nervous system decreased during the pandemic, urinary infection rates remained stable. Conclusion(s): The decreased shunt revision rate during the first year of the pandemic seems correlate with a decrease of the general infection rate in children and adolescents at the same time. Infectionassociated shunt failures showed a significant decrease during this period compared to previous years.
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Introduction: Enhanced recovery after operation and surgical site infection (SSI) bundles have been implemented in hospital systems nationwide to mitigate complications after colorectal operation. These quality improvement bundles (QIB) aim to improve patient safety and should decrease healthcare costs. This study identifies the impact of QIB on SSI rate and hospital costs. Method(s): Vizient and SSI reporting data was queried from 2016- 2021, for all colorectal resections tracked by the National Healthcare Safety Network across the enterprise. The operations were linked to a financial database. Data was analyzed quarterly to identify a relationship between SSI rate, hospital cost, and implementation of SSI mitigation elements. Result(s): 4,163 patients were identified during the study period. SSIs peaked in quarter 2 of 2018 at 5.3%, after which SSI mitigation efforts were announced. A steady decrease is seen in SSI rates, until quarter 3 of 2020, when our hospital system experienced its first COVID wave. With adjustment for procedure type, hospital costs increased by 15.8% per case from 2018-Q3 forward on average with the sharpest elevation observed in quarter 3 of 2019, due to medication startup costs for our SSI bundle. Conclusion(s): We successfully reduced colon SSIs with implementation of an ERAS bundle but incurred 16% greater costs compared with pre implementation, especially during the early implementation period.
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This study was undertaken in the college of the Dentistry-University of Basra, Oral and maxillofacial surgery Department. This survey assessed protective measures regarding COVID-19 infection and aimed to evaluation the evidence on the affiliation between use of preventive measures and COVID-19 infection among dental students in Basra. The questionnaires were designed and assembled into two domains as follows: 1-Personal data including age, sex, and academic stage. 2-Analytical data including questions regarding infection rate among dental students and their commitment of COVID-19 preventive measures. An explanation for the aim of this study was coupled to the questionnaire, and the members were asked to sign an online informed permission. The questionnaires were directed toward 1000 dental students and only 875 were responding to the survey and included in the databank. The duration of study approximately takes 10 days, the questionnaire was conducted to students on February, 12th 2020 and the documents collecting were closed at (February, 22nd 2020). On the topic of preventive measures follow in order to avoid the dispersion of COVID-19 infection, an endemic feature of Corona virus disease has led to the deaths of thousands of individuals across several countries. For the prevention of the extent of the disease and its mortality, several preventive measures have been recommended. Conversely, the level of acquaintance and the implementation of such protective measures against COVID-19 among dental students in Basra which constitute vulnerable group are yet to be evaluated. Eight-hundred and seventy-fife questionnaires were analysed. Out of the 875 participants, (250) were males, and (675) were females. Two hundred and sixty-one (29.8%) participants had been infected with covid-19, and six hundred and fourteen (70%) were not being infected. Regarding the correlation between the infection with COVID-19 and the sex and college stage, consequently, no substantial statistical differences were detected between the males and females amongst COVID infected students. This survey demonstrated that the terms of self-protective means in addition to community disaffection will be considerably drops the statistics of dental student's COVID infections.Copyright © RJPT. All right reserved.
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Currently, 640 million cases of coronavirus disease 2019 (COVID-19) and 6.6 million deaths have been reported world-wide. Risk factors for severe COVID-19 are known, including those with compromised immunity. Among patients with inborn errors of immunity (IEI), early reports of severe outcomes lead to strict masking and social distancing measures. While this resulted in relatively low infection rates among those with IEI, real-world data describing the clinical course of COVID-19 in this patient population have remained limited. We performed a retrospective study of adult IEI patients followed by our center in which a positive test (rapid antigen or PCR) for COVID-19 was determined between November 2021-November 2022. Medical charts were reviewed, and patient interviews conducted. All patients provided informed consent. Twenty-nine patients were enrolled (22 females, 7 males), aged between 18-69 years (median: 20-29 years). The cohort included those with antibody deficiencies (41.37%), combined immunodeficiencies (34.48%;HIES, CARD11, STAT1-GOF), immune dysregulation disorders (20.69%;LRBA deficiency, AIRE deficiency) and phagocyte defect (3.45%;CGD). The duration of symptoms ranged between 3 days-4 weeks (median: < 1 week). Upper respiratory symptoms (including sore throat, congestion) were reported in 97% while fever was present in 41% of patients. Prior to infection, 14 (48%) patients had underlying asthma or bronchiectasis - 2 subsequently experienced shortness of breath and were treated with inhalers or Sotrovimab, respectively. No treatment was required in 65.5% of cases. The remaining received Paxlovid (10.3%), Sotrovimab (13.79%), or antibiotics (10.3%). Of the 2 patients with STAT1-GOF, one tested positive during a repeat episode of febrile neutropenia which required hospitalization. No other patients were hospitalized or needed ICU admission. No deaths were recorded. In light of these favourable outcomes, patients with IEI can gradually and safely return to normal activities.Copyright © 2023 Elsevier Inc.
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Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26-35, 36-45, 46-55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.
Subject(s)
COVID-19 , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/prevention & control , Papillomavirus Infections/prevention & control , Human Papillomavirus Viruses , Pandemics , Prevalence , Early Detection of Cancer , COVID-19/epidemiology , SARS-CoV-2/genetics , Genotype , Papillomaviridae/genetics , Human papillomavirus 16/genetics , China/epidemiologyABSTRACT
Background: More than a year has passed since the first coronavirus vaccines were widely used. However, some healthcare workers are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite full vaccination. The immune effect of SARSCoV- 2 vaccines attenuates in a few months in contrast to other universal vaccines, such as the hepatitis B vaccine, which have an immune effect that lasts for a longer time. In addition, the neutralizing antibody (Ab) titers can be measured only in limited medical institutions. In this study, we aimed to investigate the factors that predict SARS-CoV-2 infection in healthcare workers after vaccination. Method(s): In this study, we enrolled one thousand one hundred and thirty-three healthcare workers (826 women, 307 men) after second inoculation of the BNT162b2 vaccine (Pfizer /BioNTech) in February- April 2021. Medical checkups and self-reported questionnaires were used to collect medical histories and demographic characteristics. The Alinity SARS-CoV-2 IgG II Quant (Abbott) quantitative IgG spike protein serology assay was examined in a cohort of participants 1, 4, 6 months after the second vaccination, and 1 month after the third vaccination of the BNT162b vaccine. Lower Ab titers were defined under median at each time point. The relationships between SARS-CoV-2 infection and these factors were analyzed. Result(s): The mean observation period was four hundred and fortyeight days. The median titers at 1, 4, 6 months after the second vaccination were 9293 U/mL (interquartile range [IQR], 5840-14392 U/mL), 1658 U/mL (IQR, 999-2676) and 832 U/mL (IQR, 523-1300), respectively. The risk factors for lower Ab titers were age (60 years older, odds ratio [OR], 2.08), presence of current illness (OR 1.52), smoking habit (OR 2.36), and no fever after the second vaccination (OR 2.44). The median titers at 1 month after the third vaccination was 13780 U/mL (IQR, 9085-22722), and the risk factor for lower Ab titers was hepatitis B surface Ab (HBsAb) negative (OR 1.38). The total 1-year cumulative infection rate was 4.9%. The median infection period was three hundred and twenty days (IQR, 298-365) after the second vaccination. The risk factors of infection were age (30 s and 40 s), and HBsAb negative. The 1-year cumulative infection rate of 30-40 s and other ages were 6.6% and 3.7%, respectively (p<0.01). The 1-year cumulative infection rate of HBsAb negative participants with 30-40 s and other age were 7.7% and 4.9%, respectively (p = 0.064), while that of HBsAb positive participants with 30-40 s and other age were 6.7% and 1.7%, respectively (p<0.01). Conclusion(s): HBsAb and age can become prognostic factors to be infected with SARS-CoV-2 after vaccination. Especially, HBsAb negative people under 50 years old should pay attention to SARSCoV- 2 infection even after second vaccination.
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Intro: The emergence of SARS-CoV-2 was accompanied by great uncertainty regarding the main epidemiological characteristics of the transmission. In a context where epidemiological surveillance was mainly targeted on symptomatic patients, we assessed the extent of SARS-CoV-2 transmission in French Guiana conducting an intra-household transmission study and population-based seroprevalence surveys repeated over time. Method(s): Household monitoring included virological and clinical follow-up for all household members for the first 28 days after the date of confirmation of the index case and serological follow-up over a 12-month period. Three seroprevalence surveys were conducted in July and September 2020 and in September 2021. Finding(s): A total of 57 dwellings including 245 individuals were included in the intra-household study. The average time between the date of onset of symptoms and the date of confirmation of diagnosis and inclusion in the study was 4.2 days and 7.2 days respectively. Secondary transmission was found in three quarters of households with a secondary infection rate of 35%. The highest transmission rate were observed in the most disadvantaged populations, within couples and from adults to children. Population-based seroprevalence studies have made it possible to monitor seroprevalence rates, which have varied from 15% at the time of the epidemic peak of the first epidemic wave to 65% of the population at the beginning of the fourth wave, despite the low impact of vaccination in French Guiana. Conclusion(s): The results obtained highlighted a high transmission of the virus in French Guiana associated with a low severity rate linked to the structure of the particularly young population. The project has provided health authorities with useful data to support prevention and control strategies and has allowed to evaluate the impact of interventions implemented during the pandemic.Copyright © 2023
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Background/Aims To assess the incidence and vulnerability of rheumatology patients to COVID-19 infection in early stages of pandemic. Methods Self completed questionnaire was posted to patients. Results Patients diagnosed with rheumatic diseases were categorised as people at high risk of infection with COVID-19 (pharmacologically immunosuppressed) and with possible worsening outcomes than the general population. This study was a self-completed questionnaire which was sent to all patients registered under a National Health Services specialist rheumatology department in the UK, between May 2020 and May 2021. A total of 610 responses were received and data was analysed statistically. The aim from this survey was to assess COVID19 infection prevalence amongst rheumatology patients under the care of this department, and to examine the profiles of patients with reported COVID-19 infection, their comorbidities, rheumatoidrelated medications and infection severity and outcome. Of 610 responders diagnosed with rheumatoid diseases, 12 patients (1.96%) received a diagnosis of COVID-19 based on their clinical presentation. However, when patients undertaken a Polymerase Chain Reaction test, only 2 patients (16.6%) returned positive results. In both the COVID-19 and non-COVID groups 60% were shielding (n=361). In our sample infection rate was around 30 times (1 in 50 rheumatoid patients, 2% in the sample population) the prevailing rate for the general population in the region (75 in 100,000, 0.075% in the general population). Negative testing did not preclude the presence of disease, but this may reflect poor efficacy and reliability of testing in the early days of the pandemic. The sample means and SD+/- were 63.96/ 13.23 for age and 27.76/5.79 for BMI. Sample population characteristics presented in Table 1. Conclusion This patient group were more vulnerable to COVID-19 infection compared to the general population but appear not to be at greater risk of severe disease.
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Background/Aims It is recognised that immunosuppressive medications, often relied upon in the management of autoimmune rheumatic disease, inhibit vaccine-induced immunity against the SARS-CoV-2 virus. A key challenge for rheumatologists is maximising immunity provided by the vaccine in their patients. Recent data has implicated methotrexate (MXT), a commonly used disease modifying anti-rheumatic drug (DMARD), in reducing patients' vaccine-induced immunity against the virus and studies have demonstrated the effectiveness of pausing MXT medication for 2-weeks after receiving the vaccine in boosting patients' immunity. There is a lack of data exploring the impact of concurrent biologic-DMARD (b-DMARD) use with MXT on COVID-19 infection rates in vaccinated individuals. This analysis forms part of a larger programme of research (clinicaltrials.gov NCT04542031) exploring COVID-19 in patients with rheumatic disease. Here we provide a comparative analysis of COVID-19 infection rates between patients taking MXT either with or without b-DMARD therapy and those on no immunosuppression. Methods We distributed two web-based questionnaires via SMS-messaging in April 2020 and December 2021 and two interim monitoring questionnaires in December 2020 and June 2021. All rheumatology patients with a valid mobile telephone number under follow up at the Royal Wolverhampton Trust were invited to participate in the study;those that consented received follow up questionnaires. We collected information on demographics, rheumatology diagnosis and treatment, vaccination status, and COVID-19 infection rates. Data were collected 7-days following questionnaire distribution. Results Initial questionnaires were sent to 7911 active follow up patients, 1636/ 7911 (21%) responded and consented to further follow up;906/1636 (55.4%) provided a complete response to the final survey which was subsequently linked to survey one enabling analysis. Responders were female (622/906, 68.7%), white (865, 95.5%), 60 years or above (519, 57.3%), and vaccinated (898/906;99.1%). Of those vaccinated significantly more patients that were on any immunosuppressive therapy compared to those on no immunosuppression (92/530 (17.4%) vs. 26/368 (7.1%);p<0.001), and more in the MXT monotherapy group compared to no immunosuppression (33/222 (14.9%) vs. 26/368 (7.1%);p=0.001) contracted COVID-19. Similar numbers in the MTX and b-DMARD and b-DMARD without MXT groups (23/140 (16.4%) vs. 36/168 (21.4%);p=0.23) contracted COVID-19. Conclusion Recent trial data from the VROOM study has demonstrated that omitting a patients MXT therapy for a 2-week period following administration of the COVID-19 vaccine doubles their antibody response. This data highlights that the risk of COVID-19 infection in vaccinated rheumatology patients is doubled in patients on any immunosuppressive medication compared to those on no immunosuppression, while there is no significant difference in infection rates between patients on MXT and a b-DMARD and b-DMARD therapy without MXT. Further work exploring the impact of different types of immunosuppression on COVID-19 vaccine-induced immunity and simple interventions to maximise this immunity in immunosuppressed individuals is required.
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Introduction: Intensive care outcomes in patients with cirrhosis are relatively poor. The comparison between outcomes, especially related to infections, remains unclear in those with and without cirrhosis. With the emergence of resistant and fungal organisms, the changes in infection profiles over time are important to analyze. The aim of this study is to determine the impact of cirrhosis and infections on inpatient death over time in a qSOFA-matched cohort of patients with and without cirrhosis. Method(s): Inpatients admitted to ICUs throughout 2015-2021 were analyzed. Patients with cirrhosis were matched 1:1 by age, gender, and admission qSOFA to patients without;COVID-positive patients were excluded. Admission demographics, labs, the reasons for ICU transfer, infections, and inpatient death or hospice referral were obtained for each patient. Comparisons were made between patients with and without cirrhosis and those who died/referred to hospice versus not. Logistic regression for death/hospice was performed. In patients with cirrhosis, the culture results were compared over the years. Result(s): 1669 patients;833 cirrhosis and 836 non-cirrhosis patients were included. Patients with cirrhosis had higher rates of infection, positive culture, abdominal infection, and bacteremia. They also had higher gram-positive and fungal infections with a higher rate of VRE. They showed a greater organ failure load, death, and hospice referral compared to patients without cirrhosis. Logistic regression showed that cirrhosis (OR 4.0, p< 0.0001), admission qSOFA (1.60, p< 0.0001), WBC (1.02, p=0.003), reasons for ICU (altered mental status 1.69, hypotension 1.79, renal support 2.77, respiratory failure 1.79, CVA 1.96, all p< 0.0001) with Infection (1.77, p< 0.0001, >1 microbe isolated 1.86, p=0.05) were risk factors for death/hospice. The infection trend in the cirrhosis group showed a significant decrease in positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time. Conclusion(s): Despite matching for demographics and qSOFA, patients with cirrhosis had higher risks of death and organ failures. They were more likely to develop gram-positive and fungal infections with multiple organisms and VRE. Time trends in cirrhosis showed lower rates of positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time, which should encourage re-evaluation of diagnostic and prophylactic strategies in cirrhosis-related infections. (Figure Presented).
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Purpose of Study In the spring of 2020, the coronavirus pandemic brought new challenges to healthcare systems as the rising demand for protective equipment led to product and resource inequalities around the globe. The inability to safeguard workers led to increased infection rates and deaths of healthcare professionals worldwide. The purpose of this study is to evaluate the response of an in-house innovation committee to meet the unforeseen needs faced by healthcare systems during an acute medical crisis. Methods Used Housed directly within the University of Utah's health system (U Health), The Center for Medical Innovation (CMI) teamed up with the hospital's administration, BME, COVID task force, and occupational health to create an innovative think-tank to tackle the challenges brought in by the coronavirus pandemic, with the purpose of stratifying clinical needs based upon acuity, frequency, and urgency. While prioritizing equipment needs, CMI used human-centered design to analyze common industry practices, engineer comparable solutions from commercially available materials, test reimagined products against known gold-standards, and create open-source assembly guides that allowed others facing similar shortages to do the same. Summary of Results The close-working relationship between CMI and U Health allowed for the rapid identification, innovation, and engineering of products that met the needs of healthcare workers during the months following the COVID pandemic. Many of these were directly adopted in clinical settings, including aerosol containment tents, powered air-purifying respirators, and self-testing stations. Additionally, CMI identified and engineered 20 additional readily producible, rapid-response products in anticipation of future needs, such as a bubble CPAP, containment boxes, and re-usable PPE. From these, dozens of open source, 'Improvised Personal Protective Equipment' manuals were shared with global partners to address the inequality of medical equipment in lowresource settings. Conclusions The rapid development of easily-producible, lowcost solutions for acute clinical needs-especially those faced by the equipment shortages seen during a pandemic-is improved via the partnership between health systems and a center for medical innovation.
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SARS-like coronaviruses, including SARS-CoV and SARS-CoV-2, encode spike proteins that bind human ACE2 protein on the cell surface to enter target cells and cause infection. The efficiency of virus entry depends on ACE2 sequence and expression levels in target cells. A small fraction of humans encodes variants of ACE2, thus altering the biochemical properties at the protein interaction interface. All humans possess cells with vastly differing amounts of ACE2 on the cell surface, ranging from cell types with high expression in the gut and lungs to lower expression in the liver and pancreas. Mastering our understanding of spike-ACE2 interaction and infection requires experiments precisely perturbing both variables. Thus, we developed a synthetic cell engineering approach compatible with high throughput assays for pseudo-typed virus infection. Our assay system is capable of assessing both variables individually and in combination. We adapted an engineered HEK293T DNA recombinase landing pad cell line capable of expressing transgenic ACE2 sequences at highly precise levels. Infection with lentiviruses pseudotyped with the spikes of SARS-like coronaviruses revealed that high ACE2 abundance could mask the effects of impaired binding thereby making it challenging to know the role of affinity altering mutations during infection. We limited the ACE2 abundance on the cell surface by expressing transgenic ACE2 behind a suboptimal Kozak sequence, thereby altering its protein translation rate. This allowed us to understand how ACE2 sequence could impact its interaction with coronavirus spike proteins as two human ACE2 variants at the binding interface, K31D and D355N, exhibited reduced infection. Our experiments suggested that we need to better understand how ACE2 expression determines the susceptibility of cells for SARS-like coronavirus binding and infection. We thus created an ACE2 Kozak library consisting of ~4,096 Kozak variants, each conferring a different ACE2 protein translation rate thus resulting in a range of ACE2 steady-state abundances. Combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) revealed the library to span two orders of magnitude of ACE2 abundance. Challenging this library of cells with spike pseudotyped lentiviruses revealed how ACE2 abundance correlated with infection rate. The library-based experiments yielded a dynamic range wider than traditional single sample infection assay, likely more representative of infection dynamics in vivo. Now that we have characterized the impacts of ACE2 abundance on infectivity in engineered cells, our next goal is to expand the comparison to physiologically relevant cells with endogenously expressed proteins. Modulating protein abundance levels will be key to creating maximally informative functional assays for any protein in cell-based assays, and we have laid the groundwork for being able to simultaneously test the impacts of protein abundance and sequence in combination for proteins involved in diverse cellular processes. This research was supported by a National Institute of Health (NIH) grant GM142886 (KAM).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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Background: The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection remains unclear. Method(s): Using anti-SARS-CoV-2 mAbs with a range of neutralisation potencies and binding specificities, we performed a detailed assessment of mAb-mediated infection of monocytes/macrophages. THP-1 cells were used as a model system, with results confirmed in primary macrophages. Result(s): Infection of THP-1 cells was seen via mAbs targeting the spike RBD, but not with those targeting the NTD or S2 subunit. mAbs with the most consistent potential to mediate infection targeted a conserved region of the RBD (group 1/class IV). No infection was seen with the same quantity of virus but in the absence of antibody, and pre-treating the cells with FcgammaRI and -II blocking antibodies inhibited infection. Thus, antibody-FcR interactions are able to expand the tropism of SARS-CoV-2. Time-course studies demonstrated high-level and productive infection. Studies performed in human iPSC-derived macrophages and primary monocyte-derived macrophages paralleled results seen in THP-1 cells but with lower infection levels. Up to 2% of macrophages were infected, with infected cells appearing multinucleated and syncytial. Addition of ruxolitinib, an inhibitor of JAK1/2 signalling, increased infection up to 10-fold, indicating limitation of infection through innate immune mechanisms. Sera from primary infections (n=80) mediated rare infection events, with a minority of samples (n=3) promoting significant infection. Competition assays confirmed results seen in sera, with the addition of neutralising mAbs diminishing the infection seen with infection-mediating mAbs. Thus, the presence of antibodies with potential to mediate infection is not sufficient to predict myeloid cell infection, rather, the context in which the antibodies are produced is key. Conclusion(s): We hypothesise that a nascent antibody response during peak viral replication in primary infection presents a window of opportunity for myeloid cells to become infected, while establishment of a robust polyclonal response via vaccination or prior infection reduces the likelihood of this occurring. Infection via antibody-FcR interactions could contribute to pathogenesis in primary infection, systemic virus spread or persistent infection.
ABSTRACT
The COVID-19 pandemic is an unprecedented global public health crisis with respect to its effects on economic, physical and mental health. While early lockdown guidelines may have been effective for reducing viral transmission, prolonged quarantine and physical distancing measures may have augmented the disparities underlying the determinants of health. The aggregate effects of rapid and significant economic downturn, as well as physical and mental morbidity and mortality, are reported to increase the risk of suicide. Furthermore, students, females and individuals with pre-existing mental health illness(es) are at an increased risk for poor mental health outcomes as a result of decreased social support and gaps in healthcare access. Individuals with a mood disorder are at a greater risk for COVID-19 hospitalisation. Additionally, international collaboration addressing underlying social and economic inequities across high-, middle-and low-income countries is critical for managing infection rates. Taken together, public health policies should target upstream factors that affect the determinants of ill health.Copyright © ERS 2021.
ABSTRACT
Introduction: As of 29 July 2022, SARS-CoV-2 has infected 4.7 million Malaysians. Reinfection, defined as a new infection 90 days from initial infection is now rising due to the emergence of new variants. Studies have shown that healthcare workers (HCW) are 3.4 times more likely to test positive for COVID-19. This study aims to describe the reinfection rate of COVID-19 and protection effectiveness (PE) from past infection among HCWs in public hospitals in Malaysia. Method(s): A prospective cohort study was conducted from March 2021. HCWs were followed up to determine the post BNT162b2 vaccination humoral response to SARS-CoV-2. Additionally, participants were prompted to self-report a positive COVID-19 result. Reinfection rates were calculated using the total number of patients who had a prior infection as denominator. Infection rates were analysed at a predetermined period throughout our follow-up. Protection offered by prior infection was calculated as one minus the ratio of infection rate for COVID-19 positive patients and COVID-19 naive patients (1 - RR x 100%). Result(s): In this cohort, the cumulative incidence rate for SARS-CoV-2 is 44.6% (246/551). Reinfection rate is 6.5% (16/246). The PE at 3 and 6 months were 100% respectively while the PE at 9 and 12 months were 72.1% and 56.2%. Conclusion(s): Past infection offers 100% protection against reinfection up to 6 months but this protection steadily declines with the emergence of Omicron variant, even among vaccinated and boosted individuals. As variant-specific vaccines are still in development, reducing exposure and compliance to COVID-19 prevention guidelines are imperative to avoid infection.