Estimated glomerular filtration rate in identifying illness severity in newly admitted patients with COVID-19: A single-center study

Objectives: Early prediction of risk factors for serious illness and death in patients with coronavirus disease 2019 (COVID-19) appears to be a priority. This study aimed to examine whether a single estimated glomerular filtration rate (eGFR) at triage predicts the need for intensive care unit (ICU) admission of patients with COVID-19. Methods: This retrospective study included data from patients with COVID-19 at the Bursa Yuksek Ihtisas Training and Research Hospital until October 2020. Patients were assigned to two groups according to their eGFR level at admission: group 1 (eGFR >60 mL/min/1.73 m2) and group 2 (eGFR=30-60 mL/min/1.73 m2). Results: The results of 1447 consecutive patients diagnosed with COVID-19 were analyzed at hospital admissions. Of these, 1001 patients who met the study criteria were included in the study. The median age of group 2 was higher than group 1: 69 interquartile range (IQR 23) years versus 39 (IQR 23) years (p<0.01). Patients with an eGFR <60 mL/min/1.73 m2 had lower lymphocyte counts while having higher C-reactive protein, d-dimer, lactate dehydrogenase, and fibrino-gen levels. The ICU admissions were significantly higher in patients with a baseline eGFR <60 mL/min/1.73 m2 (42.85%) compared with an eGFR >60 mL/min/1.73 m2 (6.42%, p<0.001). There was a weak negative correlation between eGFR and ICU admission (rho=-0.291, p<0.001). Conclusion: The eGFR at admission was strongly correlated with the severity of the disease. Therefore, measuring eGFR in all patients at admission may warrant appropriate triage. © 2022, Kare Publishing. All rights reserved.

Impact of Smoking on Disease Severity and Mortality of Hospitalized Patients with Confirmed COVID-19

COVID-19 is a newly defined pandemic agent. Exposure to cigarette smoke causes increased mucosal inflammation, expression of inflammatory cytokines, impaired mucociliary clearance, and excessive mucus production. Changes in the lungs due to smoking can directly affect the outcome of the disease. In this study, we evaluated the relationship between smoking and the clinical severity of COVID-19. The charts of the patients with positive real-time polymerase chain reaction (RT-PCR) tests who received inpatient treatment in COVID-19 clinics between November 2020-April 2021 were reviewed retrospectively. Patients were divided into two groups smokers and non-smokers. We compared two groups' age, gender, laboratory parameters, mortality status, and disease severity. We included PCR proven 165 smokers and 351 non-smokers who needed hospitalization. The number of female patients was significantly lower in the smoker group (F/M: 33/132)( p < 0.001). The clinically severe patient rate was higher in the smoker group ( p = 0.005). Although the rate of mortality and patients who need ventilatory support were higher in the smoker group, the differences could not reach statistical significance. This study showed smokers had a more severe COVID-19 course than non-smokers, but the clinical outcome of severe/critical patients was not affected by the smoking status. Therefore, smokers should quit smoking urgently to be affected by the pandemic at a minimum level.

COVID-19 Disease in Kidney Transplant Recipients

Aim: Coronavirus infection can lead to severe acute respiratory distress syndrome. Information on COVÍD-19 infection in patients with kidney transplants (KT) is lacking yet. In our study, clinical, radiological, laboratory features and clinical course of COVÍD-19 infection in these patients were investigated. Methods: We retrospectively investigated KT recipient patients with COVID-19 diagnosed between March 15, 2020, and December 15, 2020. Clinical, radiological, laboratory features and clinical course of COVID-19 infection in these patients were recorded. Results: We identified 23 KT recipient patients with COVID-19 infection. Eighteen KT patients (78.3%) had positive reverse transcription polymerase chain reaction (RT-PCR) results for COVID-19, 5 patients (21.7%) were negative. Twelve KT patients (52.2%) were male and 11 (47.8%) were female. Fifteen of the KT patients (65.2%) had comorbidity. Thorax computed tomography showed infiltrations in 21 KT patients (91.3%). There were 14 patients (60.8%) with glomerular filtration rate (GFR) below 60 ml/ min, who were considered acute renal failure. One patient needed plasma treatment, 2 needed hemodialysis. Mortality rate was 26%. Conclusion: COVÍD-19 infection causes kidney failure in patients with kidney transplant. Mortality is high in kidney transplant patients with COVÍD-19 infection. Suggested poor prognostic factors increasing death risk are being 60 years or older, recent transplantation, low oxygen saturation level, high WBC count, high CRP level, high troponin level, high D-dimer level, high creatinine level, low GFR value, low sodium level.

POTENTIAL PREDICTORS of OUTCOME for ANAKINRA TREATMENT in COVID-19 PATIENTS with MACROPHAGE ACTIVATION SYNDROME

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.

Deep Learning-Based COVID-19 Detection Using Lung Parenchyma CT Scans

During the outbreak of the COVID-19 pandemic, it is important to improve early diagnosis using effective ways in order to lower the risks and further spread of the viruses as early as possible. This is also important when it comes to appropriate treatments and the reduction of mortality rates. In this respect, computer tomography (CT) scanning is a useful technique in detecting COVID-19. The present paper, as such, is an attempt to contribute to this process by generating an open-source, CT-based image dataset. This dataset contains the CT scans of lung parenchyma regions of 180 COVID-19 positives and 86 COVID-19 negative patients, all from Bursa Yuksek Ihtisas Training and Research Hospital. The experimental studies demonstrate that this dataset is effectively utilized deep learning-based models for diagnostic purposes. Firstly, a smart segmentation mechanism based on the k-means algorithm is applied to this dataset as a pre-processing stage. Then, the performance of the proposed method is evaluated using InceptionV3 and Xception convolutional neural networks, yielding a 96.20% and 96.55% accuracy rate and 95.00% and 95.50% F1-score, respectively. These state-of-the-art models are observed to detect COVID-19 cases faster and more accurately. In addition, the fine-tuning stage of the convolutional neural network (CNN) features sufficiently improves this accuracy rate. For these features, the support vector machine (SVM) classifier is used, resulting in remarkable 96.76% accuracy rate and 95.81% F1-score. The implications of the proposed method are immense both for present-day applications as well as future developments. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

COVID-19 pansinusitis with abducens paralysis

Increasing numbers of the papers indicate that SARS-CoV-2 also causes neurological symptoms;the underlying mechanism has not been elucidated yet. Hypothetic mechanisms to explain the CNS involvement of SARSCoV-2 include the neurotropic mechanisms and the cytokine storm developing during the disease process. A middle age female patient applied to the emergency department with complaints of eye pain, a double, foggy, and blurred vision and a severe throbbing headache. The outward gaze was found to be limited in her right eye. Nasopharyngeal swab for SARS-CoV-2 RNA was positive, radiological findings were supported the COVID pneumonia and diffuse sinonasal inflammation. Cranial imaging showed thickening and contrast involvement in the cavernous sinus in the postcontrast series. While shortness of breath improved, and the headache was completely resolved on the 10th day of treatment the right eye outward gaze restriction was continued. The control MRI reveals a significant reduction in cavernous thickening and contrast enhancement and complete resolution in dural thickening. In our case of COVID, cranial nerve involvement and pansinusitis developed without cytokine storm findings suggests that the virus has spread to the cavernous sinuses and dura by regional neighborhood. Neurological symptoms may appear as the first symptom of COVID.

Favourable short-term course of COVID-19 in patients with familial mediterranean fever using biologic agents

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.

Hypogammaglobulinemia is a significant risk factor for mortality in patients with anca associated vasculitis and COVID-19

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.

Preliminary criteria for macrophage activation syndrome associated with coronavirus disease-19

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.