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Background: Bloodstream Infections (BSIs) that arise secondary to urinary tract infections (UTIs) are frequently encountered in both community and hospital settings and are associated with significant morbidity, mortality, high healthcare costs and prolonged hospital stays Objective: This descriptive review aims to evaluate available information on the relationship of urinary tract infections with healthcare-associated and community-onset bloodstream infections to get a deeper understanding of improved public health interventions and suggest possibilities for future research. Material andMethods: A literature search was conducted using PubMed and Embase. Articles published during the last 10 years (2010 and 2020) were imported into covidence for the initial title and screening. All study s were reviewed by two independent reviewers and were eligible for full-text review if they mentioned urinary tract infection as a source of bloodstream infection. The data obtained were analyzed in Microsoft Excel. Result(s): Out of 65 articles reviewed for full text, 10 studies were selected. In total 6763 BSI cases were reported. We observed 2075 (30.6%) community-acquired (CA) BSIs compared to 1102 (16.2%) healthcare-associated (HCA) BSIs, and 1484 (21.9%) hospital-acquired (HA) BSIs. UTI was a major source of BSIs in community settings followed by HCA BSIs in most studies. Escherichia. coli was the most common pathogen isolated in patients with CA-BSIs. Hospital Acquired and HCA bacterial infections have the most antimicrobial resistance, compared to CA-infections. Conclusion(s): Urinary tract Infections are a major source of developing secondary BSIs. Escherichia. coli is a major pathogen in CA-BSIs. Multidrug-resistant organisms accounted for most of the BSIs, especially in hospital settings and among patients receiving health care.Copyright © 2023, Khyber Medical College. All rights reserved.
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The coronavirus disease-19 pandemic with the characteristics of asymptomatic condition, long incubation period and poor treatment has influenced the entire globe. Coronaviruses are important emergent pathogens, specifically, the recently emerged sever acute respiratory syndrome coronavirus 2, the causative virus of the current COVID-19 pandemic. To mitigate the virus and curtail the infection risk, vaccines are the most hopeful solution. The protein structure and genome sequence of SARS-CoV-2 were processed and provided in record time;providing feasibility to the development of COVID-19 vaccines. In an unprecedented scientific and technological effort, vaccines against SARS-CoV-2 have been developed in less than one year. This review addresses the approaches adopted for SARS-CoV-2 vaccine development and the effectiveness of the currently approved vaccines.Copyright © 2023, Finlay Ediciones. All rights reserved.
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Objective: To compare different treatment strategies for patients of COVID-19 in Pakistan. Study Design: Retrospective longitudinal study. Place and Duration of Study: Abbas Medical Hospital, Muzaffarabad Pakistan, during Apr 2021. Methodology: One hundred and twenty, COVID-19-positive patients between 31-45 years of age were admitted to Abbas hospital after carrying out the rRT-PCR test. Group-A was administered Azithromycin, while Group-B was treated with Azithromycin in combination with Hydroxychloroquine. Group-C was given a combination of oral Ivermectin and Doxycy-cline, and Group-D was treated with Lopinavir. Diagnostic tests include rRT-PCR, blood parameters such as creatinine, random blood sugar, alanine aminotransferase, complete blood count, ECG, chest x-ray and blood biomarkers including procalcitonin, C-reactive protein, lactate dehydrogenase and ferritin were performed at Day 1, 5, 7, 14 and 30. Results: Patients treated with Azithromycin revealed the highest recovery of about (77.80%) among COVID-19 patients, followed by the combination of Azithromycin and Hydroxychloroquine which was (65.56%), the combination of Ivermectin and Doxycycline was (19.63%), and Lopinavir was (9.06%) displayed minimum potency in recovering the COVID-19 positive patients (p-value <0.001). Conclusions: Azithromycin was most effective in helping patients recover from COVID-19, followed by a combination of azithromycin and Hydroxychloroquine. Patients who recovered after treatment with Ivermectin Doxycycline were lower, followed by those who recovered with Lopinavir only. © 2022, Army Medical College. All rights reserved.
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Background: Serious infections are more frequently seen in patients with infam-matory rheumatic diseases, being treated with immunosuppressive or biologic disease-modifying antirheumatic drugs (b-DMARDs). Potential harmful effects of immunosuppressive drugs as well as b-DMARDs were a major concern during the early phases of the Coronavirus disease 2019 (COVID-19) pandemic, and preliminary data documented the worse outcome of COVID-19 associated with B cell depleting treatments (1). On the other hand, limited information has been shared about the course of COVID-19 in patients with monogenic autoinfamma-tory disorders using IL-1 inhibitors. Objectives: We herein aimed to evaluate the course of COVID-19 in adult patients with the most common form of infammasomopathy, Familial Mediterranean Fever (FMF), who were on biologic agents. Methods: In this cross-sectionally study, FMF patients were evaluated by screening their clinical and electronic records in our database in October 2021. The FMF patients with a record of PCR-confrmed COVID-19 were investigated in more detail in our hospital. Characteristics of FMF fndings as well as clinical and laboratory fndings associated with COVID-19 were recorded from the outpatient follow-up cards. Results: We identified 184 FMF patients using biologic agents, and their baseline characteristics are summarized in Table 1. Among them, 36 had PCR-confirmed COVID-19;32 of them were currently on b-DMARD along with colchicine (31 anti-IL-1, 1 anti-TNF), and 4 of them had a previous history of b-DMARD treatment. Data about the course of COVID-19 could be reached in 34 patients. Four (11%) patients had an asymptomatic course. Remaining patients with symptomatic COVID-19 had the following symptoms: cough (50%), headache (47.2%), fever (44.4%), loss of taste and smell (41.6%), myalgia (0.6%), dyspnoea (27.8%), diarrhea (25%) abdominal pain (5.6%). Thorax computed tomography was performed in 10 patients, and findings of pneumonia were documented in 6 (16.7%). The mean values of the laboratory parameters were as follows: C-reactive protein 99.48 ± 112.66 mg/L;ferritin 316 ± 208.3;D-Dimer 2445 ± 3917, Lactate Dehydroge-nase 253 ± 61, troponin T 26 ± 20, procalcitonin 0.348 ± 0.53. Lymphopenia was detected in 5 (13.9%) patients;mean lymphocyte count was 1080 ± 363. Data about the treatment could be reached in 34 patients. Antiviral therapy was prescribed in 25 (69.4%) patients (favipiravir, n=22;and oseltamivir, n=3). Antibiotics were given to 6 (16.7%) patients, and 6 (16.7%) received hydroxychloroquine. Parenteral steroids were administered to 2 patients during the hospitalization. Six (16.7%) patients required hospitalization, and 2 (5.6%) required oxygen support, non-invasive mechanical ventilation, and one of them followed in the intensive care unit. Twenty-two patients were on anakinra treatment, and none of them required additional dose. Only 1 patient, a 61-year-old male patient with a history of lung lobectomy and renal transplantation, received tocilizumab due to macrophage activation syndrome, and he later died of sepsis. This patient was on anakinra until 2 years before, and it was discontinued due to an allergic reaction. Only 4 patients had a history of vaccination before COVID-19, and none of them developed pneumonia and required hospitalization. Six patients had FMF attacks after recovering from COVID-19. None of the patients developed thromboembo-lism and secondary bacterial infections. Conclusion: This survey identified 36 biologic b-DMARD receiving FMF patients, who had COVID-19. All but 1 patient had complete recovery, and b-DMARD usage did not negatively affect the COVID-19 course. None of the patients currently on anti-IL-1 or anti-TNF had a worse outcome. Based on these observations, it can be suggested that refractory FMF patients can continue their b-DMARD treatments when they had COVID-19.
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Background: A hyperinfammatory response compatible with features of macrophage activation syndrome (MAS) contributes to this worse outcome in patients with Coronavirus Disease 2019 (COVID-19). Glucocorticoids have become the standard of care for those requiring oxygen support or mechanical ventilation. More targeted anti-infammatory treatments with tocilizumab and anakinra have also been shown to be effective. Objectives: More studies are being awaited to clarify the features of patients who would beneft more, and we investigated the characteristics of the surviving and dead patients who received anakinra. Methods: The records of hospitalized adult patients between March 2020 and May 2021 in a tertiary referral center were evaluated. Diagnosis of COVID-19-re-lated MAS was based on the expert opinion and preliminary criteria developed by our group that patients with a score of ≥45 were accepted COVID-19-related MAS.1 Patients who received anakinra constituted the study group. Anakinra dose was determined according to the clinical and infammatory parameters;and doses varied between daily 100-300 mg SC to 400-800 mg IV. Laboratory data of surviving and died patients were comparatively analyzed by using the ANCOVA method on the relevant days (baseline, anakinra-onset day, frst response to anakinra treatment, and discharge or death). The temporal variation (drug onset day-frst response day, drug onset day-discharge, or death day) was evaluated using the ANOVA method. A 50% reduction of CRP compared to the anakinra start day was accepted as the frst response to the treatment. Results: Out of 1080 hospitalized patients, 218 (151 male, 67 female, mean age 60.0±14.1) who received anakinra were identifed. Among them, 125 (57.3%) patients were followed in the ward, 21 (9.6%) did not need oxygen treatment during the hospitalization;69 (31.6%) patients were followed at ICU, 40 of them were intubated, 30 (13.7%) died in ICU. Anakinra had been started in a mean of 4.8 days of hospitalization. Twenty had tocilizumab initially and then received anak-inra because of ongoing infammatory parameters. The majority (83.5%) received steroid treatment (79.5% methylprednisolone, 5% of dexamethasone), and 6 received one IV pulse 250 mg of methylprednisolone;36 (16.5%) were followed before September 2020 and received anakinra without steroids because of the standard of care at that period. Only CRP was different between the alive and dead patients for the baseline parameters (p=0.05). On the frst day of drug treatment, CRP and procalcitonin values were signifcantly higher in dead patients (Table 1). A 50% decrease in CRP level was achieved in 3.1 days in survivors and 4.7 days in dead patients. D-dimer (p=0.018), CRP (p=0.006), LDH (p=0.003), procalcitonin (p=0.005), creatinine kinase (p=0.001), and fbrinogen levels (p=0.05) were significantly different between the surviving and dead patients when the measurements between the frst drug administration day and response day were compared. Neu-trophil, lymphocyte count, ferritin, D-dimer, CRP, LDH, AST, procalcitonin, creati-nine kinase, and fbrinogen levels were signifcantly different between the patients when the parameters between the frst drug administration day and discharge/death day were compared. Dead patients had higher CRP values and they did not show a continuing CRP decrease with the steroids and anakinra (Figure 1). Conclusion: Retrospective analysis of 218 patients suggests that starting anakinra earlier in hospitalized patients may provide better results, and a decrease in CRP, ferritin, D-dimer values, as well as an increase in lymphocyte count, are associated with favorable outcomes. Increasing values of D-dimer and troponin during treatment are associated with worse outcomes, possibly indicating cardiovascular and thrombotic pathologies not responding to anakinra. Changes in the CRP values are found to help monitor the response to anakinra. Other infammatory pathways could be targeted in those who are not responding to appropriate doses of anakinra within 5 days.
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Background: Several anti-inflammatory drugs which were targeted different mechanisms and investigated for both prevention and treatment for COVID-19. Objectives: The current study aimed to investigate whether patients regularly using colchicine or hydroxychloroquine (HCQ) have an advantage of protection from COVID-19 or developing less severe disease. Methods: Patients who were taking colchicine or HCQ regularly for a rheumatic disease including Familial Mediterranean Fever, Behçet's syndrome, Systemic Lupus Erythematosus, Rheumatoid Arthritis and Sjogren's syndrome as well as their healthy household contacts as the control group were included into the study. The clinical data regarding COVID-19 were collected using a standard form, and serum samples were analyzed for anti-SARS-COV-2 nucleocapsid IgG. Patients treated with any biologic or immunosuppressive treatments were not included into the study. Results: A total of 635 regular colchicine users with their 643 household contacts and 317 regular HCQ users with their 333 household contacts were analyzed. Anti-SARS-Cov2 IgG was positive in 43 (6.8%) regular colchicine users and 35 (5.4%) household contacts (OR=1.3;95% CI:0.8-2;p=0.3) (Table 1). COVID-19 related symptoms were described by 29 (67.4%) of the patients and 17 (48.6%) household contacts (OR=2.2;95% CI:0.9-5.5;p=0.09), and hospital admission was observed in five (11.6%) and one (2.9%) of these subjects (OR=4.5;95% CI:0.5-40.2;p=0.1), respectively (Figure 1). Seropositive subjects were observed in 22 (6.9%) regular HCQ users and 24 (7.2%) household contacts (OR=1.1;CI:0.6-1.9;p=0.8) (Table 1). COVID-19-related symptoms occurred in 16 (72.7%) of the 22 patients and 12 (50%) of 24 household contacts (OR=2.7;95% CI:0.8-9.1;p=0.1). Three patients (13.6%) were admitted to hospital, while one household contact (4.2%) was hospitalized (OR=3.6;95% CI:0.3-37.8;p=0.2) (Figure 1). Disease-specific analyses disclosed that there was no significant difference in terms of COVID-19 frequency and severity between a particular disease subset and household contacts (Table 1). Univariate logistic regression analysis showed no effect of age and gender on the SARS-CoV-2 seroprevalence rate among regular colchicine or HCQ users and household contacts (p=0.2 and p=0.7, respectively for colchi-cine users versus contacts, p=0.7 and p=0.3, respectively for HCQ users versus contacts). Conclusion: Being on a regular treatment of colchicine or HCQ was not resulted in the prevention of COVID-19 or amelioration of its manifestations.
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Objective: Severe acute respiratory syndrome (SARS) coronavirus 2 (SaRS-Cov-2) associated respiratory disease (COVID-19), announced as a pandemic, is a multisystem syndrome. SARS-CoV-2 directly infects and damages vascular endothelial cells, which leads to microvascular dysfunction and promotes a procoagulant state. Dipyridamole (DP) acts as a reversible phosphodiesterase inhibitor and is used mainly as an antiplatelet agent. It is hypothetised that it has possible activities in COVID-19. Design and Methodology: We report our retrospective, real-world results of DP added to low-molecular weight heparin (LMWH) in the treatment of 462 clinically diagnosed and hospitalized COVID-19 patients. We compared anticoagulation with and without DP addition with no administration of anticoagulation in the same time frame. The primary outcome was proven or highly suspected coagulopathy within 30 days of hospitalization. Results: Definitive coagulopathy has been diagnosed in 3 (3.5%) of 85 LMWH administered patients and 7 (2.13%) of 328 DP + LMWH received patients (P=0.456). Five cases with definitive coagulopathy were not initiated any anticoagulation at the time of the event. The multivariate analysis showed that DP addition to the anticoagulant approach did not have any impact on the risk of demonstrated coagulopathy and highly-suspected coagulopathy. Conclusion: We think that our clinical experience is valuable in showing the real-life results of DP + LMWH treatment in COVID-19. This approach did not affect the coagulopathy rate. Our data did also not document an additive effect of DP in the COVID-19 outcome. Prospective controlled trials would give more convincing results regarding the role of DP in COVID-19 endothelial dysfunction and clinical outcome.
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The COVID-19 outbreak has prevented students from contributing towards the economic growth of Pakistan. It first disrupted the education system in China and later entered Pakistan to close all levels of educational institutions/sectors since the middle of March 2020. This study aims to highlight the COVID-19 outbreak's effects on educational sector in Pakistan. Pakistan's overall public sector expenditure as a percentage of GDP before the pandemic was already low as compared to regional level, but due to the pandemic, it has dropped down significantly. This study seeks to answer two important questions: (1) What are the impacts of COVID-19 outbreak on Pakistan? (2) Will the closure of educational institutions impact the economic growth of Pakistan? According to empirical and theoretical findings, the results show that the lack of school education for a long period of time will contribute towards unskilled human capital. The COVID-19 outbreak has impacted student learning activities, which may increase the dropout rates, loss of mental health, and consequently, may impact the economic growth of Pakistan later. © 2021, IGI Global.
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In this brief communication, we have highlighted the challenges confronted by Ophthalmologists during COVID-19 pandemic and formulated steps to develop a comprehensive strategy towards minimizing risk of infection transmission between health care workers and patients. To reduce the risk of cross infection, screening and triaging of the patients was done at very initial stage with only high risk patients (red category) were seen directly on slit lamp biomicroscope with PPE. Green and yellow category (low risk) patients were seen via teaching aids or LCDS and telemedicine methods. Elective surgeries were postponed. Less number of attendants were allowed with the patients. Continued teaching services for undergraduate and post graduate students were done by online methods like zoom or Microsoft teams meeting. Departmental meetings were planned via video conferencing (zoom or Microsoft teams). Recommendations are made in this article to ensure safe access to specialized health care in face of COVID-19 pandemic. © 2021, Ophthalmological Society of Pakistan. All rights reserved.
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Objective: To determine association of ABO and Rh blood groups with COVID-19 RT-PCR positive status. Study Design: Case control study. Place and Duration of the Study: Department of Pathology, Margalla Hospital Taxila, from Apr 2020 to Dec 2020. Methodology: The sample comprised of 436 cases and 500 controls. Out of 3936 RT-PCR done during the study duration, 436 RT-PCR positives were enrolled in study as cases. 500 age and gender matched controls were selected from same population. Study variables (age, gender, blood groups, RT-PCR result) were obtained from Hospital data (HIMS). Data was analyzed using SPSS version 25. Mean and SD was calculated for age. Frequencies were calculated for categorical variables. p-value calculated applying chi square test. Odds ratios calculated to determine association. Results: The mean age of cases was 37.3 ± 16.3. Statistically significant association was observed between age, gender and COVID-19 RT-PCR positive status. B+ blood group was most frequent both among cases (35.4%) and controls (36.2%), followed by O+ and A+. However, no significant association was observed between blood groups and COVID-19 RT-PCR positivity. Odds ratios calculated for blood group O and non-O (OR=0.95), A antigen (OR=0.97) and Rh factor (OR 0.93) among cases and controls showed week negative association. Whereas a weak positive association of B antigen + and B antigen-with PCR positivity (1.07) was observed between cases and controls. Conclusion: Susceptibility to acquire COVID-19 infection is not associated with ABO and Rh blood groups according to this study. © 2021, Army Medical College. All rights reserved.
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Background: SARS-CoV-2 infection (COVID-19) is clinical threat to healthy individuals around the world. Risk of disease and related complications are high among immunocompromised individuals and those with pre-existing chronic diseases. Aim: To assess the fear of Covid-19 among patients having chronic diseases and to determine its relationship with preventive practices among them. Study Design: Cross-sectional study Place and Duration of Study: Department of Community Medicine, HITEC Hospital Taxila from 1st September2020 to 31st March 2021. Methodology: Three hundred and seventeen patients having chronic diseases were included. Fear of Covid-19 scale used to assess the fear level and questions related to preventive practices. Results: Fear of Covid-19 was high among females, hypertensive, diabetics and those having cardiovascular disease. Fear was found among 133 (42%) participants. Regarding Covid-19 preventive practices, 8(2.5%) had unsatisfactory, 115 (36.3%) had satisfactory and 194(61.2%) had good preventive practices. Covid precautions were significantly practiced among those having fear. Statistically significant positive correlation was found between mean Covid fear and practices scores (r=.30, p=.001) Conclusion: Fear of Covid is a recognized risk factor for anxiety and depression among people. However, fear is found to promote risk perception and health related preventive behaviors among chronic patients that can positively ensure safety, decrease the risk of infection and serious complications among chronic patients.
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Background : Covid-19 appeared quaint with evolving hyperinflammation phase, vasculoendothelial dysfunction, and a distinct coagulopathy. Aims : We present our experience regarding coagulopathy predictive factors in hospitalized Covid-19 patients just after pandemic declaration. Methods : The data were obtained retrospectively by screening the institution's electronic data system between March and May 2020. The treatment protocol based on Health Ministry guidelines, includes hydroxychloroquine, azithromycin, favipiravir, low-molecular-weight heparin, dipyridamole, and anti-cytokine agents on the hyperinflammation phase. We stratified 3 groups, patients with proven coagulopathy, highly suspected coagulopathy, and patients without coagulopathy. Highly suspected coagulopathy encompasses clinical deterioration with sudden and inconsistent D-dimer elevation. Results : A total of 511 patients were screened. Forty-nine of them were excluded due to accompanying conditions resulting in high D-dimer levels. The median age of the remaining patients was 56 years with a male/female ratio of 284/178. Proven coagulopathy as documented thrombosis developed in 3.2% with a male predominance (60%). Highly suspected coagulopathy was decided in 10.1% of patients. Among predictive factors for coagulopathy, the risk factors at admission were being over 65-year-old, having coronary artery disease, dyspnea, severe lymphopenia (<500/μl), monocytopenia (<300/ μl), and elevated LDH. For highly suspected coagulopathy, in addition to these having more than 3 comorbidities, high initial ferritin (>1000 ng/ml) and d-dimer levels as greater than 3600 U/ml were also predictive. The clinical pictures in the proven coagulopathy group included 5 myocardial infarctions, 4 disseminated intravascular coagulation (DIC), 2 deep vein thrombosis, 1 catheter-related venous thrombosis, 1 catheter-related venous thrombosis, and pulmonary embolism, 1 lower extremity arterial thrombosis, 1 stroke. All DIC cases had gram-negative bacterial sepsis. Conclusions : Our data suggest coagulopathy is not directly correlated with inflammation severity but patients in hyperinflamation phase should be pursued for possible proven coagulopathy.
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Pakistan is among the countries affected during the period of Covid-19 pandemic. A high prevalence of psychological distress was observed among the general population as well as doctors in this outbreak. Aims & Objectives: This research was conducted to study the relationship of psychological resilience, burnout and secondary traumatic stress among doctors in COVID-19 pandemic. It also identified the mediating effect of burnout between the relationship of psychological resilience and secondary traumatic stress. Patients and Method: It is a descriptive study with purposive sampling strategy and correlational research design. The sample comprised of 100 doctors from two hospitals of Lahore between September 2020 to February 2021. Participants age range was between 25-40 years. Data was collected by using the following tools, The Brief Resilience Scale (Smith et al., 2008), Secondary Traumatic Stress Scale (Bride et al., 2004), and Oldenburg Burnout Inventory (Halbesleben & Demerouti, 2005). Results: Results have signified a negative relationship of psychological resilience with secondary traumatic stress and burnout. Burnout has a significant positive relationship with secondary traumatic stress. Moreover, both subscales of burnout (i.e. disengagement and exhaustion) emerged as mediators in the relationship between one subscale of secondary traumatic stress (i.e. intrusion) and psychological resilience. Conclusion: It is concluded that psychological resilience has a significant negative relationship with burnout and secondary traumatic stress. Future researches can design emotional coping strategies and should try to promote programs that can help doctors to enhance resilience so it helps them combat their stress and burnout.
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Background: COVID-19 runs a variable course resulting in acute respiratory distress syndrome and death in a subset of patients. The entry of SARS-CoV-2 into the cell stimulates innate immunity including NLRP3 inflammasome and lead to development of adaptive immunity later. Hyperinflammatory response with the release of proinflammatory cytokines including IL-1β and IL-6 results in cytokine storm in some patients with a worse outcome. Colchicine acts on NLRP3 inflammasome and inhibits and IL-1 mediated inflammatory attacks in gout and familial Mediterranean fever (FMF) patients. Patients with inadequate response to colchicine may benefit from anti-IL-1 biologic agents such as anakinra and canakinumab. Recently, favourable effects of anakinra have been observed in COVID-19 patients with findings of cytokine storm. Objectives: We aimed to evaluate the impact of COVID-19 among refractory FMF patients followed-up in tertiary referral with the treatment of biologic agents and also document the course of COVID-19 in these patients. Methods: We searched out database of FMF patients to identify those using biologic agents (anti-IL-1, anti-IL-6 or anti-TNF) for colchicine-refractory FMF. We interviewed the patients using a standard questionnaire by phone call for symptomatic COVID-19 and evaluated those patients who described findings of COVID-19 further by their hospital records or inviting them to the hospital for additional investigations. Results: We identified 183 patients and contacted 106 of them by phone in May-October 2020. A history of symptomatic COVID-19 was documented in 7 FMF patients who were on a biologic agent. Six were on anti-IL-1 and one was on anti-TNF, and one of the patients was not taking his biologic agents for 1 year. All of 7 patients had a favourable outcome. All but 1 patient followed at home and none of them developed findings of cytokine storm, thromboembolism and secondary bacterial infection. Hospitalized patient did not require intensive care unit (ICU) support or mechanical ventilation, and he was not given additional anti-inflammatory medications. Conclusion: This series of refractory FMF patients with potentially higher inflammatory characteristics showed COVID-19 did not result in a worse outcome in those patients during the first phase of the pandemic, and none developed findings of cytokine storm. Observations in these patients supports further that biologic agents blocking IL-1 and possibly TNF may contribute to the uneventful course of COVID-19 by preventing the development of hyperinflammatory response. Data collection from a larger group of patients, especially those with amyloidosis, will clarify the protective effects of colchicine and contribution of anti-IL-1 treatments on the favourable disease course during the second phase of the pandemic.
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Background: The negative impact of COVID-19 in patients with ANCA associated vasculitis (AAV) and patients on rituximab (RTX) treatment have been reported (1). Risk factors for severe course of COVID-19 and increased mortality in these patients are unclear. Objectives: To evaluate the course of COVID-19 in our AAV cohort and identifying risk factors for mortality. Methods: Patients with AAV who were classified according to CHCC and whose scheduled last visit were after December 2019 were screened and evaluated for COVID-19 either by phone call or in the clinic. Records of patients with a history of hospital admission due to COVID-19 were evaluated. Cumulative clinical findings and treatment history were noted. Hypogammaglobulinemia (hIgG) was defined as IgG level below 700 mg/dl. All inpatients with a diagnosis of COVID-19 were screened for hIgG and IVIG was administered if necessary. Results: Eighty-nine patients (47.2% female, mean age 56 + 12.5 (28-81)) were included into the study. The diagnosis was GPA in 56 (62.9%) and MPA in 33 (37.1%) patients. Mean follow up time was 91 + 53.4 (26-272) months. Anti-PR3 and anti-MPO were positive in 46 (51.7%) and 32 (35.9%) patients, respectively. Lower respiratory tract (LRT) involvement was present in 72 (80.9%) and 10 patients had a history of diffuse alveolar haemorrhage (DAH). Sixty-one patients (68.2%) had a history of rapidly progressive glomerulonephritis (RPGN) and 21 (23.6%) had peripheral nervous system (PNS) involvement. Fifteen (16.9%) patients had COVID-19;14 of them were PCR positive, one patient had symptoms and thorax CT findings compatible with COVID-19. Pulmonary infiltrates were observed in 13 patients (86.7%);9 (60%) had severe pneumonia. Twelve patients (85.7%) were hospitalized, 6 patients (42.9%) needed ICU admission and 5 patients (35.7%) died. Tocilizumab and anakinra for hyperinflammation during COVID-19 were used in 1 (6.7%) and 4 (26.7%) patients, respectively. Four out of five deceased patients (3 on RTX treatment, 1 with renal transplant) were in remission at the time of COVID-19. COVID-19 was detected in a patient with disease flare and DAH, during treatment with high dose steroids and plasmapheresis. hIgG was detected in all deceased patients from COVID-19 during hospital admission (mean IgG: 495±113.2 mg/dL). Symptomatic COVID-19 was more frequent in patients with a history of DAH, RPGN and hIgG. hIgG during the follow-up was significantly associated with COVID-19 in multivariable analysis (p=0.01, OR=20,6 %95 CI (2-210). Comparison of patients who died of COVID-19 and survived showed that female sex, PNS involvement and hIgG during the clinical course and hospital admission were risk factors for increased mortality (Table 1). Age, smoking, treatments, history of flares or serious infections, remission status and chronic renal insufficiency did not differ between groups. Conclusion: The frequency and mortality from COVID-19 is found to be high in our AAV cohort compared to previous reports (1). Patients with serious lung or renal involvement are prone to symptomatic COVID-19. Previously reported severe outcomes on RTX therapy might be related to consequent hIgG. High dose IVIG treatment may not be sufficient in improving survival in AAV patients with severe COVID-19 and hIgG.
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Background: COVID-19 runs a severe disease associated with acute respiratory distress syndrome in a subset of patients, and a hyperinflammatory response developing in the second week contributes to the worse outcome. Inflammatory features are mostly compatible with macrophage activation syndrome (MAS) observed in other viral infections despite resulting in milder changes. Early detection and treatment of MAS may be associated with a better outcome. However, available criteria for MAS associated with other causes have not been helpful. Objectives: To identify distinct features of MAS associated with COVID-19 using a large database enabling to assess of dynamic changes. Methods: PCR-confirmed hospitalized COVID-19 patients followed between March and September 2020 constituted the discovery set. Patients considered to have findings of MAS by experienced physicians and given anakinra or tocilizumab were classified as the MAS group and the remaining patients as the non-MAS group. The MAS group was then re-grouped as the cases with exact-MAS and borderline-MAS cases by the study group. Clinical and laboratory data including the Ct values of the PCR test were obtained from the database, and dynamic changes were evaluated especially for the first 14 days of the hospitalization. The second set of 162 patients followed between September-December 2020 were used as the replication group to test the preliminary criteria. In the second set, hospitalization rules were changed, and all patients required oxygen support and received dexamethasone 6mg/day or equivalent glucocorticoids. Daily changes were calculated for the laboratory items in MAS, borderline, and non-MAS groups to see the days differentiating the groups, and ROC curves and lower and upper limits (10-90%) of the selected parameters were calculated to determine the cutoff values. Results: A total of 769 PCR-confirmed hospitalized patients were analysed, and 77 of them were classified as MAS and 83 as borderline MAS patients. There was no statistically significant difference in the baseline viral loads of MAS patients compared to the non-MAS group according to the Ct values. Daily dynamic changes in the MAS group differed from the non-MAS group especially around the 6th day of hospitalization, and more than a twofold increase in ferritin and a 1.5-fold increase in D-dimer levels compared to the baseline values help to define the MAS group. Twelve items selected for the criteria are given in Table 1 below. The total score of 45 provided 79.6% sensitivity for the MAS (including borderline cases) and 81.3% specificity around days 5 and 6 in the discovery set, and a score of 60 increased the specificity to 94.9% despite a decrease in sensitivity to 40.8%. The same set provided a similar sensitivity (80.3%) in the replication, but a lower specificity (47.4-66% on days 6 to 9) due to a group of control patients with findings of MAS possibly masked by glucocorticoids. Conclusion: This study defined a set of preliminary criteria using the most relevant items of MAS according to the dynamic changes in the parameters in a group of COVID-19 patients. A score of 45 would be helpful to define a possible MAS group with reasonable sensitivity and specificity to start necessary treatments as early as possible.
ABSTRACT
Background: Infection is a remarkable cause of morbidity and mortality in patients with SLE. Objectives: We aimed to determine the clinical course of COVID-19 infection in our patients with SLE and the factors affecting this course Methods: SLE patients (2012 SLICC criteria) diagnosed with COVID-19 infection by a positive PCR test and/or typical findings of lung involvement in CT (computed tomography) imaging were included. Data regarding cumulative clinical and laboratory characteristics, histopathology results, autoantibody profiles, immunsuppressives and damage (SLICC damage index/SDI)) were retrieved from the existing database and revised. SLE Disease Activity Index (SLEDAI-2K) was determined at the time of infection. Results: Sixteen SLE patients with COVID-19 infection were identified. Most (87.5%) of these patients were female. Seventy % (n=11) had lupus nephritis. Twenty-five % had thrombotic antiphospholipid syndrome. PCR was positive in 70% (n=11) of the patients. Pulmonary parenchymal findings compatible with COVID-19 were observed in 56% (n=9) of those patients. Regarding complaints upon admission, 50% (n=8) had fever, 44% (n=7) cough, 44% (n=7) dyspnea, 19% (n=3) myalgia, 12.5% (n=2) headache, 12.5% (n=2) nausea /vomiting, 6% (n=1) diarrhea, and 6 % (n=1) had anosmia. Eight patients were hospitalized. Six of these patients needed oxygen therapy via nasal cannula. None needed a follow-up in the intensive care unit. The mean hospitalization duration was 14 ± 5 (8-25) days. Regarding disease activity at the time of infection, 9 had inactive disease with a SLEDAI-2K score of 0 whilst in 5 patients SLEDA-2K score was ≥4. The mean SLEDAI-2K score at the time of infection was 1.7 ± 2.3 (0-6). System/ organwise, 1 patient with chronic thrombocytopenia presented with a worsening platelet count accompanied by serologic activity. This patient was a non-adherent to treatment who had stopped taking mycophenolic acid months before COVID19. Three patients 2 of whom had proliferative nephritis experienced nephritic flares.1 patient who had a history of cutaneous lupus and was in remission presented with oral ulcer, leukopenia and hypocomplementemia during infection. Of 16 patients, 7 had system damage at the time of infection. The mean SDI score of the patients was 1.4±1.8. Comparison of patients with and without damage revealed no significant differences in disease activity, symptoms associated with COVID, in the need for hospitalization, hospitalization duration, and the requirement for oxygen therapy. However,CT findings compatible with COVID19, were more common in patients with damage (87% vs.33%,p=0.04) and their mean CRP levels were higher at diagnosis (65 ± 47 vs.22 ± 48 mg/l;p=0.032). All patients received similar treatment for COVID-19 except active patients who required high dose steroids (2 with active renal, 1 with thrombocytopenia and 1 with oral ulcer, leukopenia and hypocomplementemia).The patient with thrombocytopenia also received intravenous immunoglobulin and 1 with cutaneous active disease received tocilizumab as she developed macrophage activation syndrome. Six patients (37.5%) had received rituximab (RTX) in the last 6 months before COVID. No significant difference, in terms of hospitalization and need for oxygen therapy due to COVID19 was found between patients who had received RTX vs who had not. No hypogammaglobulinemia was detected in patients who received RTX despite lower levels of IgG (998 ± 184 vs 1481± 51 mg/dl, p=0.02) Conclusion: Although half of the patients in our series of COVID19 infected SLE patients required hospitalization, there were no mortalities. More patients with damage (none pulmonary) displayed CT findings compatible with COVID19 and further follow up will reveal whether they will suffer from fibrotic lung disease. Patients can experience disease flares during COVID. But it is also important to consider that some manifestations such as thrombocytopenia may also be a sign of severe infection. Immunosupressive agents may not have a negative impact on the course of infection.