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Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.
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Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.
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BackgroundCoronavirus (COVID-19) pneumonia emerged in Wuhan, China, in December 2019. It was highly contagious spreading all over the world, with a rapid increase in the number of deaths. The reported cases have reached more than 14 million with more than 600,000 deaths around the world. So, the pandemic of COVID-19 became a surpassing healthcare crisis with an intensive load on the healthcare resources.In this study, the aim was to differentiate COVID-19 pneumonia from its mimickers as atypical infection, interstitial lung diseases, and eosinophilic lung diseases based on CT, clinical, and laboratory findings.ResultsThis retrospective study included 260 patients, of which 220 were confirmed as COVID-19 positive by two repeated RT-PCR test and 40 were classified as non-COVID by two repeated negative RT-PCR test or identification of other pathogens, other relevant histories, or clinical findings.In this study, 158 patients were male (60.7 %) and 102 patients were female (39.3%). There was 60.9% of the COVID-19 group were male and 39.1% were female. Patients in the non-COVID group were significantly older (the mean age was 46.4) than those in the confirmed COVID-19 group (35.2y). In the COVID-19 group, there was exposure history to positive cases in 84.1% while positive exposure history was 20% in the non-COVID group.ConclusionThe spectrum of CT imaging findings in COVID-19 pneumonia is wide that could be contributed by many other diseases making the interpretation of chest CTs nowadays challenging to differentiate between different diseases having the same signs and act as deceiving simulators in the era of COVID-19.
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Objective: To analyze data on socio-demographic and clinical characteristics of SARS-CoV-2 infected population whose samples were received from Medical Research Institute, Sri Lanka. Method(s): Laboratory based retrospective study was done on patient samples which were tested positive for SARS-CoV-2 by National Reference Virology Laboratory at the Medical Research Institute, Sri Lanka, from November, 2020 to November, 2021. Data on socio-demographic characteristics and clinical presentation of 13 126 patients were examined. Result(s): The mean age of the study population was (36.0+/-7.2) years and the majority were men (64.0%). The highest number of positive cases were found in the 21-30 years-of-age group. Two distinct peaks were noted in the incidence of SARS-CoV-2 positive individuals. In addition, 42.5% of the positive samples tested positive (42.5%) were from Medical Officer of Health collection centres. Furthermore, 60.6% (7 951) of the infected subjects were asymptomatic whereas the remaining were symptomatic. The highest percentage of symptomatic patients were observed in the 91-100 years-of-age group while the highest asymptomatic subjects were found in the 31-40 years-of-age group. The percentage of asymptomatic children (65.3%) was significantly (P<0.05) higher than that of adults (43.4%). Conclusion(s): The findings of this study aid decision makers to focus on the vulnerable groups, and geographic and temporal distribution of patients in the public health strategies that aim at preventing the spread of the disease and reducinig its mortalities.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.
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The incidence of the new coronavirus infection (COVID-19) remains a global problem worldwide. However, the effect of COVID-19 on the course of pregnancy and the possibility of intrauterine infection are insufficiently investigated. Recent studies suggest the possibility of a transplacental transmission of infection caused by SARS-CoV-2. Goal: To analyze SARS-Cov-2 RNA detection cases in newborns and to study possible factors influencing the infection of newborns from mothers with COVID-19. Materials and methods. From March to August 2020, there were 64 births to women with a confirmed diagnosis of COVID-19 at the Botkin's Infection Disease Hospital. In 15 newborns, the diagnosis of COVID-19 was laboratory confirmed. In this study, the histories of 14 newborns and their mothers were analyzed retrospectively. The diagnosis of COVID-19 was based on the detection of SARS-Cov-2 RNA in a nasopharyngeal swab or in fecal samples. Results. Analysis of the histories of mothers showed that 4 (28.6%) patients had an asymptomatic disease. Three (21.4%) women had a severe course of COVID-19, 7 (50%) patients had a course of moderate severity. Fetal hypoxia was more common in women with severe or moderate course of COVID-19. In 6 (42.7%) newborns, a positive nasopharyngeal swab was obtained within 48 hours after birth. None of the women whose children were RNA-positive in the first two days had a severe form of the disease, and two patients had an asymptomatic disease. Conclusion. 1. The frequency of detection of SARS-CoV-2 RNA in newborns from mothers with COVID-19 (under mother-child separation) was 21.9%. 2. Infection of a newborn with SARS-CoV-2 is possible both with a severe course of the disease in the mother and with an asymptomatic course. 3. A caesarean section does not exclude the possibility of a newborn infection with SARS-CoV-2. 4. In newborns, in most cases, an asymptomatic course of COVID-19 is observed.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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The incidence of the new coronavirus infection (COVID-19) remains a global problem worldwide. However, the effect of COVID-19 on the course of pregnancy and the possibility of intrauterine infection are insufficiently investigated. Recent studies suggest the possibility of a transplacental transmission of infection caused by SARS-CoV-2. Goal: To analyze SARS-Cov-2 RNA detection cases in newborns and to study possible factors influencing the infection of newborns from mothers with COVID-19. Materials and methods. From March to August 2020, there were 64 births to women with a confirmed diagnosis of COVID-19 at the Botkin's Infection Disease Hospital. In 15 newborns, the diagnosis of COVID-19 was laboratory confirmed. In this study, the histories of 14 newborns and their mothers were analyzed retrospectively. The diagnosis of COVID-19 was based on the detection of SARS-Cov-2 RNA in a nasopharyngeal swab or in fecal samples. Results. Analysis of the histories of mothers showed that 4 (28.6%) patients had an asymptomatic disease. Three (21.4%) women had a severe course of COVID-19, 7 (50%) patients had a course of moderate severity. Fetal hypoxia was more common in women with severe or moderate course of COVID-19. In 6 (42.7%) newborns, a positive nasopharyngeal swab was obtained within 48 hours after birth. None of the women whose children were RNA-positive in the first two days had a severe form of the disease, and two patients had an asymptomatic disease. Conclusion. 1. The frequency of detection of SARS-CoV-2 RNA in newborns from mothers with COVID-19 (under mother-child separation) was 21.9%. 2. Infection of a newborn with SARS-CoV-2 is possible both with a severe course of the disease in the mother and with an asymptomatic course. 3. A caesarean section does not exclude the possibility of a newborn infection with SARS-CoV-2. 4. In newborns, in most cases, an asymptomatic course of COVID-19 is observed.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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BackgroundCT chest severity score (CTSS) is a semi-quantitative measure done to correlate the severity of the pulmonary involvement on the CT with the severity of the disease.The objectives of this study are to describe chest CT criteria and CTSS of the COVID-19 infection in pediatric oncology patients, to find a cut-off value of CTSS that can differentiate mild COVID-19 cases that can be managed at home and moderate to severe cases that need hospital care.A retrospective cohort study was conducted on 64 pediatric oncology patients with confirmed COVID-19 infection between 1 April and 30 November 2020. They were classified clinically into mild, moderate, and severe groups. CT findings were evaluated for lung involvement and CTSS was calculated and range from 0 (clear lung) to 20 (all lung lobes were affected).ResultsOverall, 89% of patients had hematological malignancies and 92% were under active oncology treatment. The main CT findings were ground-glass opacity (70%) and consolidation patches (62.5%). In total, 85% of patients had bilateral lung involvement, ROC curve showed that the area under the curve of CTSS for diagnosing severe type was 0.842 (95% CI 0.737–0.948). The CTSS cut-off of 6.5 had 90.9% sensitivity and 69% specificity, with 41.7% positive predictive value (PPV) and 96.9% negative predictive value (NPV). According to the Kaplan–Meier analysis, mortality risk was higher in patients with CT score > 7 than in those with CTSS < 7.ConclusionPediatric oncology patients, especially those with hematological malignancies, are more vulnerable to COVID-19 infection. Chest CT severity score > 6.5 (about 35% lung involvement) can be used as a predictor of the need for hospitalization.
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It has been recommended that patients with leukaemias and lymphomas undergo universal screening for SARS-COV-2 using RT-qPCR before each treatment on the grounds of their high risk of experiencing severe forms of COVID-19. This raises a conflict with different recommendations which prioritise testing symptomatic patients. We found that among 56 RT-qPCR obtained in asymptomatic patients with hematologic neoplasms before chemotherapy administration, 2 (3.5%) were positive. A negative result did not exclude SARS-COV-2 infection in 1 patient (1.8%). It is unclear what the benefit of screening for SARS-COV-2 using RT-qPCR in patients with hematologic neoplasms who receive chemotherapy is.
Subject(s)
COVID-19 , Hematologic Neoplasms , Leukemia , Humans , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , Sensitivity and SpecificityABSTRACT
The coronavirus disease-19 (COVID-19) is an infectious disease caused by the enveloped RNA beta-severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2). The COVID-19 may have a variable presentation, from an asymptomatic disease to acute respiratory distress syndrome (ARDS) and multi-organ failure. Impairment of endocrine systems may also occur in COVID-19 patients and thyroid gland involvement was reported in a not negligible number of patients, as documented in several studies since the pandemic outbreak. Abnormal thyroid function tests (TSH and/or thyroid hormones) are frequently reported in COVID-19 patients with variable prevalence and mild to moderate severity in available studies. Keys for understanding this dilemma are introduced in this overview. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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The novel coronavirus pandemic highlighted the importance of discussing and monitoring emerging diseases to scientific society, particularly in the case of zoonotic diseases. Diseases emerge in nature and infect living beings current on all continents, even in the current scenario of biomedical research evolution. Among the most studied emerging animal diseases are the swine viral diseases, due to their high occurrence and severity. Added to this, is the economic impact on the health of pigs and in some cases on human health. The challenges of swine health include endemic diseases, foodborne and transboundary diseases. Idiopathic vesicular diseases and subclinical diseases have also been identified, either alone or in combination with other infections. Several factors have contributed to these phenomena, but failures in biosecurity, biocontainment, and herd immunity imbalances are critical and must be addressed. Viruses evolve naturally, through mutation, rearrangement, or recombination, either to become more virulent or more transmissible, or not. This review will discuss the broad field of emerging swine viral infections, how monitoring the evolution of these viral agents is of supreme importance. Also, when should a new disease or emerging agent is considered a risk to swine production? Although the evolution of pork production systems is admirable, animal diseases continue to account for 20% of the losses. Therefore, international organizations work with member countries to prevent animal diseases, ensure food supply, maintain household income, health, and preserve the future. One Health is not just a concept, but an action of surveillance and control that all countries must implement. Copyright © 2023 Universidade Federal de Goias. All rights reserved.
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Introduction: Within the last year, cases with multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) associated with SARS-CoV-2-vaccination have been published worldwide. It remains unclear, whether the clinical onset in these patients is either causal and denovo or, alternatively, the initial manifestation of a preexisting demyelinating disease and thus a coincidence in time. Objective(s): We therefore compared clinical, laboratory and neuroimaging data of MS patients with clinical onset after SARSCoV- 2-vaccination (MSpostvacc) with a MS cohort without association to the vaccination (MSreference), respectively, with a single case of MOGAD following SARS-CoV-2-vaccination (MOGADpostvacc). Aim(s): To determine whether there is evidence of a preexisting, chronic inflammatory disease at clinical onset in MSpostvacc and MOGADpostvacc patients. Method(s): We included patients with clinical manifestation of MS or MOGAD <=30 days following SARS-CoV-2-vaccination and analysed clinical, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) data. The MSpostvacc characteristics were compared to an age- and gender- matched MS cohort recruited at our neuroimmunological outpatient clinic. Result(s): In 5 patients (3 female) the initial diagnosis of MS was made in association to SARS-CoV-2-vaccination (4 after BNT162b2 vaccine;mean clinical onset after 8 days). CSFspecific oligoclonal bands and indications of a preexisting inflammatory process were detectable on MRI and OCT in all MSpostvacc patients. Their analysed parameters (clinical, CSF, MRI, OCT) were assimilable to those of the MSreference cohort. One woman with onset of MOGAD after ChAdOx1 nCoV-19 vaccination was identified. Here, CSF analysis revealed an acute inflammatory profile (106 cells per mul;no CSF-specific OCB). After treatment with high-dose corticosteroids, the initial cerebral and cerebellar lesions resolved on follow-up MRI. Conclusion(s): Since we found CSF-specific oligoclonal bands, chronic inflammatory lesions on MRI and retinal neuroaxonal damage on OCT a denovo disease seems unlikely for the MSpostvacc cohort. Our data point to the hypothesis that the MSpostvacc patients described had a subclinical disease that first manifested coincidentally with the SARS-CoV-2-vaccination. However, this cannot be assumed for the MOGADpostvacc patient.
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OBJECTIVE: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID. DESIGN: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages. SETTING: Israeli general practice. SUBJECTS: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and ,936 without a history of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms. RESULTS: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness. CONCLUSION: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.Key PointsLong-COVID has emerged as a significant health problem with a serious impact on normal daily function⢠Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.⢠Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.⢠Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.
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STATEMENT OF PROBLEM/QUESTION: Chagas disease (CD) is a lifelong protozoan parasitic infection that if left untreated can result in cardiomyopathy in a third of cases;a screening program can identify individuals with chronic asymptomatic disease. DESCRIPTION OF PROGRAM/INTERVENTION: Elmhurst Hospital is a public safety net hospital in Queens serving a diverse community with many immigrants from Mexico, Central and South America. An estimated 8 million people in Latin America and 300,000 in the US are living with CD. We implemented a Chagas screening program in the Elmhurst adult primary care clinic. Our electronic health record (EHR), Epic, captures patient diversity by including 200 ethnic background options;we used this field to identify at-risk patients. Patients waiting for their appointment were brought into a private area and educated about CD by a Spanish-speaking volunteer. They were asked their country of origin, their ability to recognize the Reduviid bug, and the type of house they grew up in. Written educational materials about CD in Spanish provided by CDC website were given to patients. Once a patient accepted screening the provider received a secure chat in the EHR instructing them to order the Chagas serology. All patients have been kept on a secure list, and all are called for follow-up regardless of their results. Patients who test positive receive a follow-up plan that includes cardiac testing and referral to the Infectious Diseases (ID) clinic. Education about immigrant health and CD was provided to faculty, nurses and residents by ID specialists. MEASURES OF SUCCESS: The number of patients accepted and screened for CD. FINDINGS TO DATE: From June to November 2021, 340 patients in the Elmhurst medicine clinic were approached about their risk for CD. Of these migrants 36% were from Mexico, 51% were from S. America and 13% were from Central America. 23% of these patients grew up in an adobe house and 26% recognized the reduviid bug from a picture. Of 324 at-risk individuals asked about previous Chagas knowledge, only 7% were familiar with CD. 203 patients were tested with final results, 18 refused testing, 37 tests are pending for the next visit, and 82 were not ordered. 2 were positive on the screening ELISA with confirmation pending;CDC has suspended testing during the COVID-19 pandemic. Family members will be screened if confirmatory testing is positive. KEY LESSONS FOR DISSEMINATION: For practices serving large atrisk populations, a Chagas screening program can help to address a healthcare disparity. Partnership with ID specialists is essential for this process to succeed. Having an EHR that captures diverse demographic information identifies atrisk patients and is critical to the success of such a program. Challenges include having to obtain confirmatory testing at CDC which involves a patient returning for a follow-up visit and another blood draw. PCP champions can be a useful resource to sustain CD screening in the future. Low awareness of CD in our patient population suggests that community outreach to at-risk individuals is needed to increase awareness.
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sars-cov-2 infections appear to affect children less frequently and severely than adults. Children are frequently asymptomatic or have less severe symptoms and, therefore, less tested. objective. To determine prevalence and epidemiological characterization of sars-cov-2 in children from Chaco, Argentina. material and method. Descriptive, observational study. Once authorized by the Ethics Committee, the Chaco Epidemiology Computerized Database was reviewed, laboratory confirmed pediatric patients with sars-cov-2 infection of both sexes were included, aged between 30 days of life and under 13 years and 11 months of age, from March to September 2020. results. 320 pediatric patients (170 men and 150 women) were admitted. The ages between one and 13 years;average of seven years. The provenance mostly from Resistencia. Regarding morbidities, 86.8% did not present any type and 13.1% did. The most frequent comorbidity was asthma. Regarding the signs and symptoms of presentation: 285 (89%) presented signs-symptoms and 35 (10.9%) asymptomatic. The most frequent signs and symptoms were: fever 106 (37.1%);cough 61 (21.4%);odynophagia 47 (16.4%). conclusions. In the studied population, a higher prevalence of symptomatic was found;being fever and cough, the most prevalent symptoms, however they cannot be considered characteristic of sars-cov-2 in children, requiring further studies.
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Coronavirus disease (COVID-19) is a potentially fatal infectious disease caused by the SARS-CoV-2 virus, a virus of zoonotic origin (1). It has been observed that clinical manifestations of SARS-CoV-2 infection range from asymptomatic disease to severe viral pneumonia accompanied by severe respiratory failure and may result in death (2). The most common initial symptoms of COVID-19 disease are fever, cough, and fatigue. Transmission primarily occurs through direct contact or droplets spread from an infected person (1). The binding of a receptor expressed by host cells is the first step of viral infection. Lung epithelial cells are thought to be the primary target of the virus. Most of the used drugs are drugs used in the treatment of other diseases, and their effectiveness in the treatment of COVID-19 is still at the research level. Specific anti-infection drugs are under development for potential treatment in humans (1). Veklury (Remdesivir) is the first treatment for COVID-19 to receive FDA approval. It is used in adults and pediatric patients [12 years and older and at least 40 kilograms] for the treatment of COVID-19 requiring hospitalization (3). The treatment of COVID-19 in our country is carried out by the recommendations of the Ministry of Health's Guide 'COVID-19 (SARS-CoV-2 infection)' prepared by the recommendations of the Coronavirus Science Council and updated by the developments (4). All of the drugs recommended in the manual are used under the approval of the Ministry of Health within the framework of non-indication drug use. In this pandemic, where new waves are constantly coming, scientists have succeeded in developing a large number of COVID-19 vaccine types in a short time as a result of intensive studies. The mRNA-based Pfizer-BioNTech COVID-19 vaccine is the first FDA-approved vaccine [23.08.2021] (5). The information about the COVID-19 disease, which is spreading rapidly around the world, is increasing with new researches day by day. Thrombophilia is a hypercoagulable condition that predisposes patients to thrombosis. It is a multifactorial condition that can result from genetic factors, acquired factors, or a combination of both. The prothrombin gene (F2), factor V Leiden (F5), and PAI-1 are important biomarkers of thrombophilia. Patients with multiple gene defects have a high risk of thrombosis (6). It is known that thromboembolic events can develop in patients with COVID-19 and the incidence of death increases accordingly. Studies have shown that VTE can be induced in patients with COVID-19 and severe pneumonia, and the incidence of VTE in COVID-19 patients hospitalized in the intensive care unit due to severe pneumonia has been reported to be high (7). The risk of thrombosis and arterial and venous thromboembolic complications seen in 30% of hospitalized subjects due to Novel Coronavirus pneumonia has been reported in many studies, which can be explained by the prolonged inflammatory response, decreased physical activity during infection, and reduced oxygen levels in the circulation (6). Thrombotic and microangiopathic effects of the SARS-CoV-2 virus have been reported in COVID-19 patients (8). Circulatory disorders in the toes of COVID-19 patients are also reported as 'Covid toe (acro ischemia)' (9). Although it is reported that the disease progresses more severely in the elderly, patients with sub-diseases, and smoking history, it is also observed that the clinical course is severe and patient losses are experienced in young patients who do not have any underlying disease. The mechanisms of the development of thromboembolic events are the binding of the virus to the ACE-2 receptor and/or direct endothelial damage, activation of inflammatory and microthrombotic pathways as a result of endothelial damage by complement activation as in sepsis, and stasis due to hospitalization and immobility (10). DIC clinic may develop in patients with severe clinical course. The pathophysiology of DIC is reported to be complex and multifactorial, involving the interaction between the hemostatic system and components of the innate immune response to the infecting pathogen (11). However, there is no comprehensive research on inherited thrombophilia factors that may affect the hemostatic system. Severe clinical course in young patients, a similar clinical course in individuals from the same family even though they are in different cities, elderly patients recovering from the clinic safely and being discharged, VTE in different locations in COVID-19 patients, microangiopathic thrombus, etc. monitoring of the findings, the use of anticoagulants due to their positive contributions in treatment are included in the observations in this process. In the light of all this information, it is aimed to examine and reveal the possible relationship between the genetic variations evaluated in the thrombophilia panel and COVID-19 and presented with the literature data findings and recent studies. Gralinski et al. suggested that PAI-1 plays a protective role against infection in the viral pathogenesis studies of SARS-coronavirus disease (12). In another study, no statistically significant difference in thrombophilia polymorphic biomarkers between the severely ill COVID-19 group and the healthy population was found (6). Various studies that will provide new information on the subject are also actively continuing. In conclusion, thrombosis is frequently seen in severe COVID-19 patients. Essentially, the determination of the thrombophilia profile can assist in determining bleeding risk, mortality, ARDS incidence, and admission to the ICU. Latent genetic risk factors for thrombotic events may affect the outcome of COVID-19. Therefore, the identification of these factors may be useful for understanding the various COVID-19 outcomes and assessing COVID-19 patients' risk of thrombosis, severe disease, and vaccination policies.
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Introduction: Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies, especially under therapy with monoclonal antibodies targeting B-cells. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with chronic lymphocytic leukemia (CLL), Non-Hodgkin Lymphoma (NHL) and Hodgkin's Lymphoma (HL) after vaccination with the mRNA BNT162b2 vaccine, up to 50 days post their first vaccine dose. Methods: This is a large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy subjects and patients with hematological malignancies. We report here the results in CLL, NHL and HL patients in comparison to age- and gender-matched controls who were vaccinated at the same time period (January to May 2021). After vein puncture, the serum of both patients and controls was collected on day 1 (D1;before the first BNT162b2 dose), on day 22 (D22;before the second dose of the BNT162b2) and on day 50 (D50;3 weeks post second dose of the BNT162b2). Serum was separated within 4 hours from blood collection and stored at -80°C until the day of measurement. NAbs against SARS-CoV-2 were measured using FDA approved methodology (ELISA, cPass™ SARS-CoV-2 NAbs Detection Kit;GenScript, Piscataway, NJ, USA) on the abovementioned timepoints. A NAb titer of at least 30% is considered as positive, according to manufacturer, whereas a NAb titer of at least 50% has been associated with clinically relevant viral inhibition [Walsh et al. N Engl J Med 2020, 383, 2439-50]. Samples of the same individual were measured in the same ELISA plate. Results: We evaluated 132 patients with CLL/Lymphomas after vaccination with the BNT162b2. Patient population included 53 with CLL, 57 with NHL and 22 with HL, while 214 healthy controls, of similar age and gender, were also studied. At the time of vaccination, 30% (n=40) of patients had asymptomatic disease and out of 92 symptomatic patients, 49% (n=45) were on active treatment. Vaccination with two doses of the BNT162b2 led to lower production of NAbs against SARS-CoV-2 in patients compared with controls, both on day 22 and on day 50 (P<0.001 for all comparisons) for all subgroups. After the first dose of the vaccine, on D22, the patient group had lower NAb titers compared with controls: the median NAb inhibition titer was 18% (IQR: 8.5-29%) for patients versus 41.6% (IQR: 25.3-59%) for controls;p<0.001. On D50, the median NAb inhibition titer was 32.5% (IQR: 13.5-93%) for patients versus 94.7% (IQR: 89-97%) for controls;p<0.001. More specifically, only 50.8% (67/132) of the patients versus 98.1% (210/214) of the controls developed NAb titers ≥30% and 43.9% (58/132) of patients versus 95.3% (204/214) titers ≥50% (high protective titers) at day 50 (p<0.0001 for all comparisons;Figure-left part). Importantly, active treatment (which included anti-CD antibodies, Bruton's tyrosine kinase inhibitors, a combination of the above, chemotherapy-only regimens or Bcl-2 inhibitors) was an independent prognostic factor for suboptimal antibody response at day 50 (<50%) in the patient subgroup (p<0.001). Rituximab administration in the last 12 months correlated with decreased antibody response at day 50 (p<0.01). Patients with HL were more likely to achieve humoral responses (>50% at day 50) compared to other disease types (p<0.05;Figure-right part). Disease-related immune dysregulation and therapy-related immunosuppression were therefore involved in the low humoral responses seen in patients. Regarding adverse events, 9% and 9.8% patients reported mild reactions after the first and second dose of the BNT162b2 vaccine, respectively. Conclusion: Patients with CLL/NHL/HL have a low humoral response following SARS-CoV-2 vaccination, particularly patients who are on active treatment with rituximab or BTK inhibitors. These patient subgroups therefore should continue utilizing protective measures against SARS-CoV-2 (masks, social distancing, etc) as they re at high risk for COVID-19. Further studies on the kinetics of immune subpopulations following COVID-19 vaccination will elucidate the underlying immune landscape and determine the potential need for additional booster vaccine doses or protective administration of antibodies against SARS-CoV-2 in CLL/NHL/HL patients with poor response after full vaccination. [Formula presented] Disclosures: Terpos: Sanofi: Consultancy, Honoraria, Research Funding;Novartis: Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Janssen-Cilag: Consultancy, Honoraria, Research Funding;GSK: Honoraria, Research Funding;Genesis: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;BMS: Honoraria;Amgen: Consultancy, Honoraria, Research Funding. Gavriatopoulou: Janssen: Honoraria;GSK: Honoraria;Genesis: Honoraria;Takeda: Honoraria;Sanofi: Honoraria;Amgen: Honoraria;Karyopharm: Honoraria. Baltadakis: Amgen: Honoraria;Bristol-Myers Squibb: Honoraria;Alexion: Honoraria;Astellas: Honoraria;Pfizer: Honoraria, Other: Travel Grants;Gilead: Honoraria;Novartis: Honoraria;Abbvie: Honoraria;Genesis Pharma: Other: Travel Grants;Gilead: Other: Travel Grants;WinMedica: Other: Travel Grants;Baxalta Hellas: Other: Travel Grants. Dimopoulos: BMS: Honoraria;Amgen: Honoraria;Janssen: Honoraria;Takeda: Honoraria;Beigene: Honoraria.
ABSTRACT
Introduction: Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with multiple myeloma (MM), especially under treatment. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in non-vaccinated MM patients who were diagnosed with COVID-19 compared to MM patients after full vaccination with the mRNA BNT162b2 vaccine. Methods: The analysis was performed in the context of an ongoing large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination. We evaluated MM patients diagnosed with COVID-19, confirmed by PCR, matched for age, gender, line of treatment, type of myeloma, type of treatment and response with vaccinated MM patients during the same time period (January - May 2021). Major exclusion criteria for both COVID-19 and vaccine MM groups included the presence of: (i) autoimmune disorder under immunosuppressive therapy or other active cancer;(ii) active HIV, hepatitis B and C infection, and (iii) end-stage renal disease. Serum was collected at 4 th week post confirmed diagnosis for the COVID-19 MM group and at 4 th week post the second BNT162b2 dose for the vaccine MM group. NAbs against SARS-CoV-2 were measured using an FDA approved methodology (cPass™ SARS-CoV-2 NAbs Detection Kit, GenScript, Piscataway, NJ, USA). Results: We evaluated 35 patients with MM and COVID-19 (6 had smoldering MM and 29 symptomatic MM), along with 35 matched MM patients who received the BNT162b2 vaccine. Among COVID-19 MM patients, 13 were diagnosed with mild, 12 with moderate and 10 with severe disease;22/35 patients were hospitalized and 10/35 were intubated. Seven (20%) patients died due to COVID-19. During the disease course 21 patients (60%) were treated with dexamethasone. Type of treatment was not different between COVID-19 positive and vaccinated MM patients. Between the two patient groups, there was no difference in terms of age [median (IQR) 65 (59) for COVID-19 positive versus 66 (74) for COVID-19 vaccinated, respectively, p=0.76], gender [males: 19/35 (54.3%) versus 16/35 (45.7%), respectively, p=0.47), BMI (median 27 versus 26kg/m 2, respectively, p=0.56), asymptomatic disease [6/35 (18.2%) in both groups, p=1], prior lines of treatment [range: 1 to 7 versus 1 to 6, respectively, p=0.99], and type of treatment (p=0.87). Among the COVID-19 MM patients, 6 (20.7%) were in sCR/CR, 6 (20.7%) in VGPR, 12 (41.4%) patients in PR, 2 (6.9%) in MR/SD and one (3.5%) in PD at the time of confirmed infection. Among the vaccinated MM group, 10 (34.5%) patientswere in sCR/CR, 4 (13.8%) in VGPR, 11 (37.9%) in PR, one (3.5%) in MR/SD and one (3.5%) in PD at the time of vaccination (p-value=0.93 for the comparison between COVID-19 and vaccinated MM groups). No differences between COVID-19 and vaccinated MM patients were also noted regarding the median lymphocyte count (1200/μl versus 1400/μl, respectively, p=0.08) and the median immunoglobulin values (IgG 732 mg/dl versus 747 mg/dl, respectively, p=0.29;IgA 9 mg/dl versus 61 mg/dl, respectively, p=0.7;IgM 26 mg/dl versus 25 mg/dl, p=0.97). The incidence of comorbidities was also similar between the two groups (cardiovascular diseases 55.2% versus 44.8%, respectively, p=0.47;diabetes mellitus 66.7% versus 33.3%, p=0.28;chronic pulmonary disease 50% each, p=1.0). Interestingly, patients with MM and COVID-19 showed a superior humoral response compared with vaccinated MM patients. The median (IQR) NAb titers were 87.6% (IQR: 71.6-94) and 58.7% (21.4-91.8) for COVID-19 and for vaccinated MM patients, respectively (p=0.01). In both groups, 27 out of 35 patients were receiving active treatment for MM at the time of NAb evaluation. The median NAb titer was 88% (IQR 71.6%-96.3%) for COVID-19 MM patients and 35.4% (IQR 17.5%-85.5%) for vaccinated MM patients who received anti-myeloma therapy (p=0.001). Importantly, there was no difference in NAb production between COVID-19 and vaccinated MM patients who did not receive any treatment (median NAb titers, 85.1% versus 91 7%, p=0.14). Conclusion: Patients with MM and COVID-19 present a superior NAb response against SARS-CoV-2 compared with fully vaccinated patients with the BNT162b2 vaccine. This finding was more pronounced among patients receiving active treatment for MM. In this context, additional booster doses may be considered for MM patients with poor humoral response after the BNT162b2 vaccine. [Formula presented] Disclosures: Gavriatopoulou: Genesis: Honoraria;Karyopharm: Honoraria;Takeda: Honoraria;Janssen: Honoraria;Sanofi: Honoraria;GSK: Honoraria;Amgen: Honoraria. Terpos: BMS: Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Janssen-Cilag: Consultancy, Honoraria, Research Funding;GSK: Honoraria, Research Funding;Novartis: Honoraria;Genesis: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding. Kastritis: Amgen: Consultancy, Honoraria, Research Funding;Genesis Pharma: Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria, Research Funding;Takeda: Honoraria. Dimopoulos: Amgen: Honoraria;BMS: Honoraria;Janssen: Honoraria;Takeda: Honoraria;BeiGene: Honoraria.
ABSTRACT
Background The ChAdOx1 nCoV-19 vaccine has been shown to induce Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT), a syndrome that shares clinical features with heparin-induced thrombocytopenia (HIT). The mechanism of thrombocytopenia and thrombosis in these disorders appears to be related to the development of pathologic anti-PF4/heparin antibodies, some of which could activate complement. Interestingly, we and others have found that complement activation is vital when both pediatric and adult patients have severe respiratory illness from SARS-CoV-2 virus (COVID-19) or in the post-infectious multisystem inflammatory syndrome in children (MIS-C). We hypothesized that patients with severe COVID-19 or MIS-C develop similar anti-PF4/heparin antibodies, which lead to endothelial complement activation that drive the inflammatory responses seen in these diseases. Methods Our cohort included 30 pediatric patients with positive SARS-CoV-2 RT-PCRs: 10 each of severe COVID-19 (“Severe”, MIS-C, and mild/asymptomatic (“Mild”) infection. Using ELISA, we evaluated the levels of antibodies to various platelet-related proteins including PF4, PF4-heparin, and NAP2;in addition, we examined the ability of plasma from each patient to activate complement. The antibody levels were compared to control samples including samples from adult patients with VITT and HIT. Statistical analyses with ANOVA were performed to evaluate differences. Results Patients with MIS-C have a significantly higher anti-PF4 antibody concentration (as measured by mean optical density [OD]) than patients with either mild/asymptomatic disease, or severe COVID-19: Severe 0.5 +/- 0.14;Mild 0.3 +/- 0.12;MIS-C 0.77 +/- 0.35, p=0.003 MIS-C vs. Mild);Similar results were seen for anti-PF4/heparin antibodies: Severe 0.4 +/- 0.14;Mild 0.35 +/- 0.12;MIS-C 0.64 +/- 0.3, p=0.003 MIS-C vs. Mild;p=0.034 MIS-C vs. Severe). These were similar to values obtained for the HIT sample (Figure). Conclusion Patients with MIS-C and severe COVID19 have significant detectable anti-PF4 and PF4/heparin antibodies in contrast to those patients with mild/asymptomatic disease. Our previous studies have shown that patients with MIS-C and COVID-19 have evidence of endovascular complement activation in the form of elevated soluble membrane attack complex (sC5-b9). We have also previously demonstrated that VITT anti-PF4 and anti-PF4/heparin antibodies activate complement and result in endothelial cell activation. These antibodies in pediatric SARS-CoV-2 infection may be involved in the development of more severe disease manifestations. Ongoing investigations will identify if this is due to endothelial complement activation and inflammatory responses that accompany severe disease. This is the first demonstration of the role of anti-PF4 and PF4/heparin antibodies in pediatric SARS-CoV-2. [Formula presented] Disclosures: Bassiri: Guidepoint Global: Consultancy;Kriya Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company. Teachey: Janssen: Consultancy;NeoImmune Tech: Research Funding;Sobi: Consultancy;BEAM Therapeutics: Consultancy, Research Funding. Lambert: ClinGen, ISTH, ASH, GW University: Honoraria;Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bayer: Consultancy;Dova: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Shionogi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Astra Zeneca: Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Sysmex: Research Funding;PDSA: Research Funding;Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Fundi g.