Acute pulmonary embolism in times of SARS-CoV-2: Diagnostic and therapeutic management / Tromboembolismo pulmonar agudo en tiempos de SARS-CoV-2: diagnóstico y tratamiento

There is a clear association between novel coronavirus 2 infection and the diagnosis of venous thromboembolic disease, as a cosequence of the development of a systemic inflammatory response syndrome due to the activation of the coagulation cascade. It occurs in 90% of patients with severe forms of the infection, evidencing the presence of pulmonary endovascular micro and macro thrombosis. This suggests a possible clinical benefit of thromboprophylaxis according to the patient's clinical risk. The suspicion of venous thromboembolic disease in the context of this pandemic represents a diagnostic challenge due to the co-existence of similarities between both conditions in several different aspects. It should be noted that the diagnosis of acute pulmonary embolism does not exclude the possibility of simultaneous viral infection. The evaluation of patients with suspected acute pulmonary embolism in the context of the pandemic should be optimized in order to implement a rapid diagnosis and treatment to reduce the associated morbidity and mortality. This will help reducing infectious risk for health-care professionals and other patients.

Existe una clara relación entre la infección por el nuevo coronavirus 2 y el diagnóstico de enfermedad tromboembólica venosa, como consecuencia del desarrollo de un síndrome de respuesta inflamatoria sistémica debido a la activación de la cascada de la coagulación. Se presenta en el 90% de los pacientes con formas graves de la infección, lo que revela la presencia de microtrombosis y macrotrombosis intravascular pulmonar. Esto sugiere un posible beneficio clínico de la aplicación de una tromboprofilaxis adecuada al riesgo clínico de cada paciente. Asimismo, la sospecha de enfermedad tromboembólica venosa en el contexto de esta pandemia representa un reto diagnóstico debido a la existencia de similitudes entre ambas alteraciones en varios aspectos. Debe tenerse en cuenta que el diagnóstico de tromboembolismo pulmonar agudo no excluye la posibilidad de infección viral. La valoración de pacientes con sospecha de tromboembolismo pulmonar agudo en el contexto de la pandemia debe ser eficaz para establecer un diagnóstico y tratamiento con rapidez, a fin de reducir la morbilidad y mortalidad adjuntas, sin que ello eleve el riesgo de infección para los profesionales de la salud y otros pacientes.

Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study.

Background: The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample. Methods: 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05. Results: We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue. Conclusion: There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial 'U1111-1237-8231'. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

Patient information videos on SACT to improve patient experience and access to information: A North/NE London collaboration

Background: Prior to the COVID-19 pandemic, oncology patients attended in-person educational sessions to understand the practicalities and side-effects of their planned systemic anti-cancer treatments (SACT). These were halted during the pandemic to minimise hospital attendances. Moreover, patients were unable to bring family or friends for support at consultations. Providing this key treatment information in a digital format using videos was proposed with these aims: 1. Improve accessibility of information. 2. Improve patient experience. 3. Improve staff experience and efficiency. Method(s): A network collaboration with the Royal Free London and North East London Cancer Alliance enabled consistency of information and increased exposure of the videos. A patient-centred approach was taken in developing the videos: 1. A baseline patient survey assessed current and proposed methods of communicating: patients received written and verbal information, but some felt they had been given 'too much' or 'not enough' information and 33% of patients reported a video would be helpful. 2. A patient focus group guided content: cannulation, real patient experiences and images of staff/facilities were identified as important. 3. The videos were translated into four languages to meet the needs of the local patient population. A multiprofessional team of doctors, nurses, managers and communications staff were involved in the development and production of the videos. Between November 2020 and September 2021, several Plan Do Study ACT (PDSA) cycles were undertaken to create, edit and review content in the production process, with patient and production team feedback throughout. Intervention(s): Three videos were produced covering an overview of treatment and the side-effects of chemotherapy and immunotherapy. These were disseminated via trust websites, YouTube and QR codes on posters. Learning outcomes of the videos were assessed by separate patient and staff feedback surveys. Result(s): 15 patients were approached prior to starting SACT to complete a questionnaire prior to and after watching the videos. Prior to watching the videos, 60% of patients felt they had not received enough SACT information, 73% were anxious about treatment. After watching the videos, 100% reported understanding of the common side-effects of treatment and how to contact the hospital for advice. 87% would recommend the videos to others, 73% would watch them again. 100% of staff surveyed agreed that the videos improved accessibility to key patient information. The videos answered common questions patients asked staff prior to starting treatment. Over six months, there have been >300 YouTube views. [Formula presented] Conclusion(s): Multilingual patient information videos are an effective way to deliver key information about SACT, improve patient experience and reduce anxiety. Next steps are to intensify signposting by increasing stakeholder exposure, and consider adapting the videos for national use. YouTube views will be counted to continue to monitor the use and sustainability of this intervention. Keywords: systemic anti-cancer therapy, digital, videos, patient education, patient experience, patient information, multilingual, staff experience, network collaboration, SACT, chemotherapy, immunotherapy Copyright © 2022

Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study

Background The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample. Methods 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05. Results We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue. Conclusion There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial ‘U1111-1237-8231’. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

Corrigendum: The effects of COVID-19 on the placenta during pregnancy.

[This corrects the article DOI: 10.3389/fimmu.2021.743022.].

Mitochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damage.

BACKGROUND AND PURPOSE: Mitochondria play a central role in the host response to viral infection and immunity, being key to antiviral signaling and exacerbating inflammatory processes. Mitochondria and Toll-like receptor (TLR) have been suggested as potential targets in SARS-CoV-2 infection. However, the involvement of TLR9 in SARS-Cov-2-induced endothelial dysfunction and potential contribution to cardiovascular complications in COVID-19 have not been demonstrated. This study determined whether infection of endothelial cells by SARS-CoV-2 affects mitochondrial function and induces mitochondrial DNA (mtDNA) release. We also questioned whether TLR9 signaling mediates the inflammatory responses induced by SARS-CoV-2 in endothelial cells. EXPERIMENTAL APPROACH: Human umbilical vein endothelial cells (HUVECs) were infected by SARS-CoV-2 and immunofluorescence was used to confirm the infection. Mitochondrial function was analyzed by specific probes and mtDNA levels by real-time polymerase chain reaction (RT-PCR). Inflammatory markers were measured by ELISA, protein expression by western blot, intracellular calcium (Ca2+) by FLUOR-4, and vascular reactivity with a myography. KEY RESULTS: SARS-CoV-2 infected HUVECs, which express ACE2 and TMPRSS2 proteins, and promoted mitochondrial dysfunction, i.e. it increased mitochondria-derived superoxide anion, mitochondrial membrane potential, and mtDNA release, leading to activation of TLR9 and NF-kB, and release of cytokines. SARS-CoV-2 also decreased nitric oxide synthase (eNOS) expression and inhibited Ca2+ responses in endothelial cells. TLR9 blockade reduced SARS-CoV-2-induced IL-6 release and prevented decreased eNOS expression. mtDNA increased vascular reactivity to endothelin-1 (ET-1) in arteries from wild type, but not TLR9 knockout mice. These events were recapitulated in serum samples from COVID-19 patients, that exhibited increased levels of mtDNA compared to sex- and age-matched healthy subjects and patients with comorbidities. CONCLUSION AND APPLICATIONS: SARS-CoV-2 infection impairs mitochondrial function and activates TLR9 signaling in endothelial cells. TLR9 triggers inflammatory responses that lead to endothelial cell dysfunction, potentially contributing to the severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathways may help to define novel therapeutic strategies for COVID-19.

Evaluation of chlorhexidine sensitization amongst healthcare workers.

BACKGROUND: Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers (HCWs). AIMS: To evaluate the prevalence of sensitization to chlorhexidine amongst HCWs at a large tertiary hospital to assess the potential allergic safety risks associated with chlorhexidine exposure to staff. METHODS: Sensitization to chlorhexidine was evaluated by measurement of serum-specific immunoglobulin E (IgE) in samples collected from staff assessed after a sharps-injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitization was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products because of infection control procedures and the coronavirus disease 2019 pandemic. RESULTS: A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2%. Prevalence of sensitization in samples collected before and after increased chlorhexidine exposure was 1% and 3%. This did not represent a statistically significant difference. CONCLUSIONS: The prevalence figures for chlorhexidine sensitization in this study are higher than have been estimated previously for similar HCW cohorts. Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitization in this group. Given the risk of severe reactions in sensitized individuals, this study indicates that evaluation of chlorhexidine allergy is important when investigating occupational allergy in HCWs.

COVID-19 crisis monitor: assessing the effectiveness of exit strategies in the State of São Paulo, Brazil.

As COVID-19-related health indicators improve after restrictive measures were set in place in different parts of the world, governments are expected to guide how to ease interventions while minimizing the risk of resurgent outbreaks. Whereas epidemiologists track the progress of the disease using daily indicators to understand the pandemic better, economic activity indicators are usually available at a lower frequency and with considerable time lags. We propose and implement a timely trade-based regional economic activity indicator (EAI) that uses high-frequency traffic data to monitor daily sectoral economic activity in different sectors for the Brazilian State of São Paulo, a highly impacted region, overcoming the challenge of real-time assessment of the economy amid the COVID-19 outbreak. We then use this novel set of information combined with hospitalization rates to provide a first assessment of the São Paulo Plan, the COVID-19 exit strategy designed to gradually lifting interventions introduced to control the outbreak in the State. Available data show that, in its first 60 days, the phased strategy pursued in São Paulo has been effective in gradually reactivating economic activity while maintaining the adequate responsiveness of the healthcare system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00168-021-01085-8.

Evaluation of chlorhexidine sensitisation amongst healthcare workers with reference to hand hygiene procedures and infection control during the COVID-19 pandemic

Background: Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. While severe reactions have been reported predominantly in patients in perioperative situations, some small case reports have indicated significant reactions in healthcare workers exposed to chlorhexidine in the workplace. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers. We sought to evaluate the prevalence of sensitisation to chlorhexidine amongst healthcare workers at a large tertiary hospital in order to assess the potential allergic safety risks associated with chlorhexidine exposure amongst staff. Method: Sensitisation to chlorhexidine was evaluated by measurement of serum specific IgE in samples collected from staff assessed after a sharps injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitisation was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products as a result of infection control procedures and the COVID-19 pandemic. Results: A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2.1%. Prevalence of sensitisation in samples collected prior to onset of the COVID-19 pandemic was 1.4% and 2.8% in samples collected post onset. This did not represent a statistically significant difference. Conclusions: Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitisation in this study. However, the prevalence figures for chlorhexidine sensitisation are higher than estimated for similar cohorts in previous studies. This highlights the importance of testing for chlorhexidine allergy when investigating occupational allergy, particularly given the risk of severe reactions in sensitised individuals.

Rapid transition of patients on intravenous immunoglobulin replacement to subcutaneous immunoglobulin replacement is feasible and leads to improved health economics

Background: The onset of the COVID-19 pandemic facilitated a rapid acceleration of the Subcutaneous Immunoglobulin in the Community Program (SCIg Program) in the Northern Sydney Local Health District (NSLHD) due to clinical need. SCIg may be administered at home, whilst IVIg is an intravenous infusion of 6 hours' duration administered monthly in the Day Procedure Unit. Methods: Between 1 March and 30 June 2020, all patients receiving IVIg under the supervision of our immunologists were enrolled in the SCIg Program. An allergy/immunology Clinical Nurse Specialist or Registered Nurse Year 8 provided the first training session to all patients, encompassing instruction on product inspection, draw-up, needle insertion, administration via push and pump methods, standard infection control precautions, waste/sharps disposal, record-keeping, storage, adverse event recognition, product and consumable pick-up, product reconciliation, and contact portals. Subsequent training sessions were provided by CSL Behring in the community. All product, consumables and support were funded by the NSLHD. Health economic data was obtained for the cost of IVIg and SCIg delivery. Results: Sixty-two patients were enrolled. Seven refused SCIg training citing needle phobia (n = 4), and lifestyle reasons (n = 3). Fifty-five completed training in 1 to 3 weekly training sessions. The age range of patients was 18 to 90. Four patients reverted to IVIg in the 12-month follow-up period because of lifestyle (n = 3) or inadequate manual dexterity (n = 1). There was no change in the number of infections in the 12-month period before and after SCIG transition. The cost of IVIg in the preceding 12-month period was $179,982. The cost of SCIg for 12 months was $46,019, with a cost saving of $133,963. Discussion: Fifty-five patients completed training over a 3-month period. SCIg has been shown to be an effective alternative to IVIg in preventing bacterial infection in all patients, and is associated with significant improvement to health economics.

The 134-year-old problem meets the 1-year-old problem: Lessons learned in managing acute appendicitis during the COVID era

Introduction: The Right Iliac Fossa Pain Treatment (RIFT) study highlighted the rate of negative appendicectomies in the UK as one third of all procedures. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID) pandemic has changed surgical practice. New practices in the COVID era have changed the rate of negative appendicectomies. Methods: A retrospective analysis was conducted of patients admitted with appendicitis from March 2020 to June 2020. Patient Demographics: 58 patients were identified, 43 (74%) were adults and 15 (26%) were children. The median age of the adults was 33 (range 18-80) and the median American Society of Anaesthetists (ASA) grading was 1. The median age of children was 11 (range 4-17) and all were ASA grade 1. Results: 73.8% (31) of adult patients had a Computerised Tomography (CT) scan as part of their workup. 40% of paediatric patients underwent an ultrasound scan of the abdomen whilst the remaining 60% were diagnosed clinically. The open approach was favoured in both cohorts (39.5% and 46.7% respectively). No negative appendicectomies were performed. Conclusion: COVID19 has changed practice resulting in better outcomes for colorectal units. Further studies (COVID SURG and COVID HAREM) are needed to fully assess the role of imaging in reducing the number of negative appendicectomies.

The Effects of COVID-19 on the Placenta During Pregnancy.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.

Prior Immunosuppressive Therapy and Severe Illness Among Patients Diagnosed with SARS-CoV-2: a Community-Based Study.

BACKGROUND: An estimated 10 million people in the USA are immunocompromised, a risk factor for severe COVID-19. Data informing whether immune-mediated medications lead to more severe infection are sparse. OBJECTIVE: Determine whether outpatient immunosuppressive therapies that treat autoimmune inflammatory disease or prevent solid organ transplant rejection are associated with severe illness after diagnosis with SARS-CoV-2 DESIGN: Retrospective cohort study PARTICIPANTS: Adults with a positive PCR nasal swab for SARS-CoV-2 from February 25 to September 9, 2020, cared for within a large integrated health care organization MAIN MEASURES: Exposure was defined as an outpatient fill of prednisone, immunomodulator, small-molecule, or biologic therapy in the 105 days prior to a positive SARS-CoV-2 PCR test. The main outcome was either hospitalization, ICU admission, or death within 45 days after diagnosis of SARS-CoV-2. Multivariable logistic regression models were adjusted for age, race, gender, body mass index, comorbidities, and autoimmune disease. KEY RESULTS: A total of 39,686 adults had a positive PCR test. In the primary analysis, prior prednisone use was associated with severe illness after diagnosis with SARS-CoV-2 (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.08-1.60); however, immunomodulator (OR 0.88; 95% CI 0.57-1.34) and biologic/small-molecule therapy (OR 1.26; 95% CI 0.79-2.00) were not. Secondary analyses showed variable risk among therapies: Janus-kinase inhibitors had an increased odds of severe illness (OR 3.35; 95% CI 1.16-9.67), thiopurines/conventionaldisease-modifying antirheumatic drugs had a reduced odds (OR 0.53; 95% CI 0.32-0.88), and tumor necrosis factor inhibitors were not associated (OR 0.45; 95% CI 0.18-1.08). CONCLUSIONS AND RELEVANCE: Outpatient use of prednisone is associated with severe illness after diagnosis of SARS-CoV-2. Immunomodulator and biologic/small-molecule therapy were not associated, but different risk subgroups were identified. Our findings can inform risk-benefit discussions in the clinic and risk-based recommendations for patients on these therapies.

Advent of the virtual multidisciplinary team meeting: do remote meetings work?

The multidisciplinary team (MDT) is key to the management and decision-making process for head and neck cancer. The sudden shift to virtual meetings due to the COVID-19 pandemic has been arguably the most dramatic change since inception of the MDT, and we know of no studies that have evaluated the head and neck MDT since this change in working. A preliminary questionnaire was designed and trialled, based on guidance on MDT qualities and measurable outcomes as per published national guidelines. A questionnaire was then distributed to all head and neck MDTs in the UK. We obtained 97 individual responses, from 27 units. Our results indicated that most clinicians (70.1%) felt that decision making was unchanged. Most (84.5%) also felt that technology resources were satisfactory and that some aspects of communication (viewing of images and slides) were as good or improved (76.3%). However, there were notable deficiencies with remote working. In particular, the majority of respondents perceived that engagement (43.9%), teamworking (69.1%), and training (47.7%) were worse since they moved to remote meetings. Our study suggests mixed opinions of virtual meetings. Our results demonstrate that despite remote working, head and neck MDT participants feel that they have largely been able to perform in most indicators. However, we should consider solutions to the perceived deficiencies in engagement, training, teamworking, and communication. To our knowledge, this is the first study to evaluate virtual head and neck MDT meetings, and the largest study of virtual MDTs and remote working within healthcare.