Covid-19: Is the placenta a safe space

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.

Blood derivative therapy

There are three main components manufactured from whole blood: red blood cells (RBCs), plasma, and platelets. Plasma contains a multitude of different proteins, peptides, and biologic substances. Approximately 53 million liters of plasma was collected in the United States in 2019. Following collection, plasma is frozen and manufactured into plasma-derived medicinal products (PDMPs). During the manufacture process, several thousand plasma units are pooled for Cohn fractionation, which is based upon cold ethanol precipitation of proteins. The PDMPs are further prepared using ion exchange or affinity chromatography and additional steps to inactivate and remove infectious diseases such as viruses. Almost 20 different therapeutic plasma proteins are purified from plasma via these multi-step manufacturing processes. Interestingly, the demand for pharmaceutical plasma products, particularly intravenous immunoglobulin (IVIG) products, has been increasing. The manufacture and therapeutic role of blood derivatives particularly immunoglobulin therapy, Rh immunoglobulin (RhIG), COVID-19 convalescent plasma (CCP) and hyperimmune globulins, albumin, clotting factors, fibrin sealants, and platelet rich plasma will be described.Copyright © 2022 AME Publishing Company. All Rights Reserved.

Maxillary osteomyelitis secondary to mucormycosis, a sequel of COVID-19: a clinical case report

Introduction: One of the consequences of COVID-19 is the incidence of mucormycosis in the jaws and subsequent osteomyelitis in patients with undiagnosed or uncontrolled comorbidities, such as diabetes mellitus and associated immunosuppression. Case Report: A 52-year-old male patient with a history of COVID-19 two months ago presented a painful ulcerative lesion of insidious onset in the palatal raphe measuring approximately 2 mm. He referred to numbness of the palatal region of one month of evolution. During the physical examination, purulent content, multiple pustules in the anterior maxillary buccal mucosa, and mobility of upper anterior teeth were observed. The CT revealed isodense bilateral images in maxillary and ethmoidal sinuses, bone sequestrations, and partial loss of anterior vestibular cortical bone. Laboratory tests revealed no abnormality, except for HbH1c: 10.2gr/dl. The patient was hospitalized for control of newly diagnosed diabetes mellitus. Maxillary incisional biopsy was performed, and microscopic analysis showed a mixed inflammatory infiltrate, fibrin deposits with eosinophilic and birefringent ribbon-like hyphae, branched at right angles, compatible with maxillary osteomyelitis secondary to mucormycosis. The treatment started with antifungal and intravenous antibiotics, followed by surgical cleaning under general anesthesia. The patient progressed favorably. Conclusion(s): Immunosuppression resulting from COVID-19 and/or uncontrolled systemic diseases can condition the appearance of rare opportunistic microorganisms causing infections such as mucormycosis. Early diagnosis and treatment make a difference in the morbidity and mortality of patients.

Management of Acquired von Willebrand Syndrome During Prolonged VV-ECMO

Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.

Factors affecting admission to intensive care unit of COVID-19 patients in the Kingdom of Bahrain

Objective: Coronavirus disease-2019 (COVID-19) is a newly emerging infectious disease that has become a global pandemic. This study aimed to identify the risk factors at presentation to predict intensive care unit (ICU) admissions. Materials & Methods: This retrospective observational study recruited 188 confirmed laboratory COVID-19 patients who were hospitalized in Jidhafs Maternity Hospital (JMH) from 1st June to 5th July 2020. Univariate and multivariate analyses were used to Explore risk factors associated with the increased risk of ICU admission. Results: The study revealed that older age (>60 years old) (16[38.1%], P=0.044), male gender (30 [40.0%], P=0.000) were significantly associated with the increased risk of ICU admissions. The most prevalent symptoms in admission were myalgia (13[40.6%], P=0.035), fever (39[34.2%], P=0.002) and cough (37[31.4%], P=0.032). In addition, raised serum level of alanine amino-transferase (ALAT) (34.7% vs. 20.7%, P=0.033), D-dimers (30.7% vs 12.2%, P=0.012), lactate dehydrogenase (LDH) (31.6% vs 0.0%, P=0.025) and ferritin (37.7% vs 16.7%, P=0.011) found to be important predictor of ICU admission. Conclusion: The finding indicates that older age, male gender, with increased alanine transferase (ALT), increased lactate dehydrogenase (LDH), high D-dimer and high ferritin was associated with an increased risk of ICU admissions. Identification of such factors will help to detect people who are more likely to develop severe COVID-19 disease and will help physicians to determine if patients need regular health care or ICU admission.

Elevated platelet large cell-ratio levels as a demonstrative biomarker associated with severe COVID-19

Objective: To represent the effects of the severity of COVID-19 infection on platelet large cell ratio (PLC-R). Materials and Methods: A hundred eleven patients diagnosed with COVID-19 were included in this study. Positive results for SARS-CoV-2 based on a typical RT-PCR test performed on nasopharyngeal swabs were included in the study Groups. Patients with COVID-19 were divided into three Groups according to their chest CT features. Group 1 (45 patients) was defined as mild, Group 2 (34 patients) as moderate and Group 3 (32 patients) as severe. Complete blood count parameters including platelet volume indices (PVI) values, CRP, D-dimer and lipid profiles were analyzed in all study participants. The correlation between COVID-19 patient Groups and PLC-R values were demonstrated using SPSS and ANFC methods. Results: The significant impact of our study is that PLC-R was significantly higher in the severe COVID-19 patients than the moderate and mild patients. Spearman's rho correlation analysis showed that PLC-R and WBC levels increased, and Htc and Hb levels decreased with the severity of the disease. ROC analysis showed that PLC-R > 38.3% had 59.4% sensitivity and 68.4% specificity in predicting severe COVID-19 disease (AUC 0.672, %95 CI 0.560, 0.784;p=0.005, cut off=38.3). CRP, ferritin and D-dimer values of the patients in Group 3 were significantly higher than the patients in Group 1, and the iron values of the patients in Group 3 were significantly lower than the patients in Group 1. Conclusion: PLC-R values are useful for anticipating acute thrombotic events. Based on the results of our study, PLC-R values can be used as appropriate biomarkers to describe the severity of COVID-19 infection.

CASE REPORT: FETAL DEATH in UTERO COMPLICATED by DISSEMINATED INTRAVASCULAR COAGULATION in MATERNAL COVID-19 INFECTION

Background: COVID-19 infection during pregnancy is associated with an increased risk of stillbirth, likely due to placental insufficiency through the associated inflammatory response and hypoperfusion. A spectrum of associated placental changes has been reported. Whilst pregnancy alone is a hypercoagulable state, concurrent COVID-19 further increases the risk of coagulopathy. Disseminated intravascular coagulation (DIC) is uncommon in pregnancy but is increased in both COVID-19 infection and fetal death in utero (FDIU). Method(s): Case report. Informed written consent was obtained from the patient. Result(s): A 31-year-old G5P2 presented with a FDIU at 23 + 3 weeks gestation, in the setting of maternal COVID-19 infection without respiratory symptoms or oxygen requirements. The pregnancy had been uncomplicated, and her presenting issue was two days of reduced fetal movements, when FDIU was confirmed on ultrasound. On admission, the case was further complicated by disseminated intravascular coagulopathy (DIC). This DIC could have resulted from COVID-19 infection, FDIU or a combination of both. Placental histopathology showed evidence of inflammation, with chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The inflammatory response, evidenced by histopathological findings of CHI and MPFD, likely contributed to placental insufficiency and FDIU. Conclusion(s): COVID-19 infection is associated with increased risk of hematological abnormalities, placental inflammation and pregnancy loss. This case is the first to report both DIC and CHI in the context of FDIU in COVID-19 infection. We present this case to highlight the impact of COVID-19 infection on placental function, coagulation disturbances and subsequently adverse pregnancy outcomes.

Platelet Rich Fibrin for Post Covid Nasal Swab Cerebrospinal Fluid Leak

Nasopharyngeal swab collection procedure has been used as a part of COVID-19 testing. Few cases of cerebrospinal fluid (CSF) leak following nasopharyngeal swab have been reported so far. Here, we report an interesting case of CSF leak following nasopharyngeal swab for COVID testing which we repaired using platelet-rich fibrin as an outpatient department procedure.

PERSONALIZED CORRECTION OF HEMOSTASIS SYSTEM DISORDERS IN PATIENTS WITH COVID-19.

Violations of the hemostasis (blood aggregation control, BAC) system in patients with COVID-19 in the acute period and at the stage of convalescence have been studied and methods of targeted correction of the identified disorders are considered. Prevention of serious complications related to COVID-19 infection requires complex assessment of the hemostasis system and prompt correction of disorders. Methods of clinical hemostasiograms and low-frequency piezothromboelastography (LPTEG) provide comprehensive and informative assessment of functional state of the BAC system and monitoring of the effectiveness of therapy, both in hospital and on outpatient basis. It was established that hemostasis system disorders had unspecified character with hyper- or hypocoagulation in the acute period and structural or chronometric hypercoagulation in the recovery period. Under LPTEG monitoring in hospital, the identified disorders were corrected by low-molecular-weight (LMW) heparins, blood-based preparations, and fibrinolysis inhibitors;at the outpatient stage, the therapy was supplemented with sulodexide and anticoagulants. Personalized correction of the hemostatic potential was based on the following LPTEG parameters. Prescription of the anti-aggregant and vasoprotective therapy required that the response time (t1) would be reduced below 0.9 min and thrombin activity (TA) constant increased above 40 relative units. The anticoagulant therapy was prescribed when the gelation point (t3) decreased to 4.7 min and the coagulation drive intensity (CDI) index was above 50 relative units. The fibrinolytic activity was corrected when the clot polymerization intensity (CPI) index was above 20 relative units, the cross-linked fibrin formation time (t5) decreased to 27 min, and the clot retraction and lysis intensity (CRLI) index exceeded 15%. The boundary values of these LPTEG parameters were adjusted at the levels of moderate hypercoagulation or reference normal coagulation. The LPTEG monitoring and personalization of the prescribed antithrombotic therapy allowed the risk of thrombo-hemorrhagic complications to be reduced at all stages of COVID-19 treatment.Copyright © 2021 Authors. All rights reserved.

Fibrin monomers evaluation during hospitalization for COVID-19 is a predictive marker of in-hospital mortality.

Background: Coagulopathy is one of the main triggers of severity and worsening of Coronavirus disease 2019 (COVID-19) particularly in critically ill patients. D-dimer has been widely used to detect COVID-19 coagulation disorders and has been correlated with outcomes such as disease severity and in-hospital mortality. Involvement of other fibrin degradation products, particularly fibrin monomers (FM), remains an ongoing question. Methods: We performed a monocentric study of adult patients with COVID-19, who were admitted either in the medical ward (MW) or in the intensive care unit (ICU) and who had FM measurements performed on them during the first wave of COVID-19 outbreak. We analyzed the positivity of FM levels (FM > 7 µg/mL) to assess the ability of FM monitoring during the first days of hospitalization to predict COVID-19 outcomes. Results: In our cohort, 935 FM measurements were performed in 246 patients during their first 9 days of hospitalization. During patient follow-up, the FM levels were higher in patients admitted directly to the ICU than in those admitted to the MW. Moreover, we observed significantly increased levels of FM in patients when the data were stratified for in-hospital mortality. At hospital admission, only 27 (11%) patients displayed a positive value for FM; this subgroup did not differ from other patients in terms of severity (indicated by ICU referral at admission) or in-hospital mortality. When analyzing FM positivity in the first 9 days of hospitalization, we found that 37% of patients had positive FM at least once during hospitalization and these patients had increased in-hospital mortality (p = 0.001). Thus, we used non-adjusted Kaplan-Meier curves for in-hospital mortality according to FM positivity during hospitalization and we observed a statistically significant difference for in-hospital mortality (hazard ratio = 1.48, 95% CI: 1.25-1.76, p < 0.001). However, we compared the AUC of FM positivity associated with a ratio of D-dimer >70% and found that this combined receiver operating characteristic (ROC) curve was superior to the FM positivity ROC curve alone. Conclusion: Monitoring of FM positivity in hospitalized patients with COVID-19 could be a reliable and helpful tool to predict the worsening condition and mortality of COVID-19.

Plasma Soluble Fibrin Is Useful for the Diagnosis of Thrombotic Diseases.

BACKGROUND: Soluble fibrin (SF) is a form of fibrinogen that is activated by thrombin and is considered to be useful for the diagnosis of the prethrombotic state or thrombosis. METHODS: Plasma levels of fibrin-related markers (FRMs), such as SF, D-dimer, fibrinogen, and fibrin degradation prioduct (FDP) levels in critically ill patients, were examined for the diagnosis of disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), peripheral arterial thromboembolism (PATE), acute myocardial infarction (AMI), and acute cerebral infarction (ACI). RESULTS: FRMs showed the usefulness in diagnosing DIC and VTE and the cutoff values of D-dimer, FDP, and SF for DIC were 7.2-7.8 µg/mL, 10.0 µg/mL, and 9.5 µg/mL, respectively. The cutoff values of D-dimer and FDP for VTE were similar to the 97.5th percentile values of healthy volunteers, while the cutoff value of SF was 6.9 µg/mL. In AMI and ACI, the cutoff values of D-dimer and FDP were lower than the 97.5 percentile values of healthy volunteers. A receiver operating characteristic analysis for all thrombosis cases showed that an adequate cutoff value in only SF among FRMs was higher than the confidence interval of healthy volunteers. Only SF had high sensitivity for thrombosis, as the FDP/SF ratio was markedly low for ACI, AMI and VTE. CONCLUSIONS: FRMs, especially D-dimer and FDP, were useful for diagnosing thrombosis with hyperfibrinolysis (e.g., DIC). As SF showed high sensitivity for predominantly thrombotic diseases, including arterial thrombosis, such as ACI and AMI, a high SF value suggests the possibility of an association with thrombosis. Finally, SF is the most useful marker for raising suspicion of an association with thrombosis, especially arterial thrombosis.

Comparison of Activity and Safety of DSPAα1 and Its N-Glycosylation Mutants.

DSPAα1 is a potent rude thrombolytic protein with high medicative value. DSPAα1 has two natural N-glycan sites (N153Q-S154-S155, N398Q-K399-T400) that may lead to immune responses when administered in vivo. We aimed to study the effect of its N-glycosylation sites on DSPAα1 in vitro and in vivo by mutating these N-glycosylation sites. In this experiment, four single mutants and one double mutant were predicted and expressed in Pichia pastoris. When the N398Q-K399-T400 site was mutated, the fibrinolytic activity of the mutant was reduced by 75%. When the N153Q-S154-S155 sites were inactivated as described above, the plasminogen activating activity of its mutant was reduced by 40%, and fibrin selectivity was significantly reduced by 21-fold. The introduction of N-glycosylation on N184-G185-A186T and K368N-S369-S370 also considerably reduced the activity and fibrin selectivity of DSPAα1. The pH tolerance and thermotolerance of all mutants did not change significantly. In vivo experiments also confirmed that N-glycosylation mutations can reduce the safety of DSPAα1, lead to prolonged bleeding time, non-physiological reduction of coagulation factor (α2-AP, PAI) concentration, and increase the risk of irregular bleeding. This study ultimately demonstrated the effect of N-glycosylation mutations on the activity and safety of DSPAα1.

Placental pathology in sudden intrauterine death (SIUD) in SARS-CoV-2-positive oligosymptomatic women.

BACKGROUND: Pregnant women are also susceptible to SARS-CoV-2. Although an infection of the placenta may be rare, pregnancy may occasionally be affected by intrauterine failure. The knowledge of placental morphology on sudden intrauterine demise is still limited. METHODS: Fetal and placental tissue of two cases of sudden intrauterine death in the second trimester were analysed morphologically and by immunohistochemistry. One case was evaluated by RT-PCR. RESULTS: Both mothers were tested positive for the Alpha variant of SARS-CoV-2 but were oligosymptomatic for COVID-19. Unexpected sudden intrauterine death (SIUD) occurred at 15 + 2 and 27 + 3 weeks of gestation. One fetus demonstrated an intrauterine growth restriction. No malformations nor inflammatory changes were observed in either fetus on autopsy. In contrast to the placentas, the fetal tissue was negative for SARS-CoV-2 on immunohistochemical and RT-PCR analyses. Macroscopically, the placentas showed an increased consistency with a white, reticular cutting surface covering about 95% of the whole placenta. Only very focal histiocytic chronic intervillositis was noted histologically. Massive perivillous fibrin deposits with extensive necroses of the villous trophoblast were present in more than 90% of the placental tissue. Immunohistochemical staining was strong and diffusely positive for SARS-CoV-2 in the villous trophoblast and rarely within the villous stromal cells. Placental SARS-CoV-2 infection was confirmed by RT-PCR. CONCLUSION: Sudden intrauterine death may occur in mothers who are oligosymptomatic for COVID-19. Acute placental failure is responsible for SIUD, demonstrated by massive perivillous fibrin deposits and extensive necroses of the villous trophoblast with SARS-CoV-2-positivity based on immunohistochemical staining and RT-PCR. Detailed histopathological examination of placental and fetal tissue is mandatory to verify SARS-CoV-2 and to evaluate the pathogenesis and functionality of this disease.

Drain-free neck dissection: the use of Artiss fibrin sealant.

OBJECTIVE: To study the safety and efficacy of Artiss fibrin sealant in lateral neck dissection, focusing on drain retention time, length of hospital stay and post-operative complications. METHODS: A retrospective review was conducted of patients who underwent neck dissection in a UK hospital over a 12-month period. RESULTS: Twenty-three patients were identified; 13 patients had Artiss and a drain, 10 patients had Artiss only. All drains were removed by post-operative day 2. No post-operative fluid collections or complications were recorded. Patients who had Artiss only without a drain were discharged on post-operative day 1. CONCLUSION: The use of Artiss reduced the drain retention time and hospital stay, with no post-operative complications. Neck dissection can be safely undertaken with no drain, and can potentially be carried out as a day-case procedure, with the application of Artiss. These findings benefit patients and the National Health Service by improving the patient journey and reducing overall costs.

Indicators of Neurobiomarkers in Patients with Chronic Cerebral Ischemia Who Have Had a Coronavirus Infection

Annotation: The causes of the development of cerebrovascular diseases in COVID-19 may be a significant deterioration in the rheological properties of blood, activation of hemostasis, changes in the atrombogenic properties of the vascular wall endothelium. Thrombocytopenia and elevated levels of fibrinogen, D-dimer and coagulation factor VIII are most often observed in COVID-19, Changes in the indicators of neurobiomarkers, namely antibodies to gliadin- fibrillar acid protein (GFAP), S-100 protein, to serotonin and dopamine receptors in CHEM indicate the severity of this disease. The aim of the study was to study the features of neurological and biochemical parameters in patients with CHEM who had a coronavirus infection, to assess the number and prognostic value of markers of brain damage: antibodies to GFAP, serotonin, dopamine receptors and S-100 protein.

Serum total bilirubin and aminotransferases in patients with COVID-19 in Nellore district of South Andhra Pradesh

BACKGROUND: Corona virus disease-19 (COVID -19) infection is an acute infectious disease caused by a newly discovered beta corona virus, severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). While the primary target organ is the lungs, involvement of many other organs is often evident in patients with COVID-19. There is emerging evidence to suggest association of SARS-CoV-2 infection with development of many liver abnormalities. The purpose of this study was to evaluate the prevalence of abnormal liver parameters in COVID-19 patients and their variation in moderate and severe cases. METHODS: This is a retrospective study. All patients with COVID -19, between the ages 20-75 years, encountered between April and May 2021, were included for the study and compared with age-matched controls. Severity of infection was defined based on the presence of symptoms, oxygen saturation, need for respiratory and intensive care support. Liver parameters such as serum total bilirubin (TBIL), serum aminotransferases, alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were analysed. Inflammatory markers such as C-reactive protein (CRP) and D-dimer were also included for assay. RESULTS: A total of 52 patients were encountered during the study period. Of these, 29% (15/52) required intensive care. Abnormal liver parameters were observed in 14 (27%) patients, and were significantly elevated compared to healthy controls. Liver dysfunction was markedly profound in severe infection than those with moderate disease. Higher levels of CRP and D-dimer were noted in severe patients of COVID-19. CONCLUSIONS: Mild liver abnormalities in the form of elevated ALT and AST are seen in COVID-19 patients suggesting mild or no liver injury. These abnormal parameters do not generally lead to significant liver function impairment/failure and no specific treatment is required.

Clinical, laboratory and radiological parameters of COVID 19 pneumonia: a single-centered retrospective observational study in Pune, India

Background: The severe acute respiratory syndrome coronavirus called the novel coronavirus caused the pandemic coronavirus disease 19 (COVID-19). All over the world, SARS-CoV-2 pneumonia is causing significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients is still unknown. Aims: To assess clinical, laboratory, and radiological parameters of COVID-19 Patients and to correlate radiological findings and disease severity among patients. Methodology: In this retrospective observational study a total of 630 patients with radiologically confirmed pneumonia and COVID-19 RT PCR positive were included from a tertiary care centre in Pune, Maharashtra, following their voluntary informed consent. Patients underwent clinical, laboratory, and radiological investigations. Results: It was observed that the majority 174 (27.6%) were in the age group of 31 to 40 years and male predominance was observed compared to female. The majority of the patients 314 (49.8%) had mild, 232 (36.8%) were moderate and 84 (13.3%) had severe illness as per CT scores (HRCT Chest score). Mean BSL levels were 181 +or- 81.44, mean pulse rate was 94.03 +or- 14.93 bpm, mean respiratory rate was 22.84 +or- 3.71cpm, systolic blood pressure was 129.09 +or- 13.18 mmHg, diastolic blood pressure was 82.80 +or- 9.67 mmHg and mean temperature was 98.56 +or- 1.67 degrees F. The mean ferritin levels were 181 +or- 81.44, the mean LDH level was 94.03 +or- 14.93, mean HbA1C was 7.45 +or- 1.68. The mean NLR was 5.51 +or- 2.41, the mean WBC count was 7238.38 +or- 4942.23 and the mean hematocrit was 39.69 +or- 4.80. The mean D dimer level was 402.29 +or- 424.70, median levels were 260 (170-450). 503 (79.8%) had CRP levels more than 5 and 127 (20.2%) had levels less than 5. The mean duration of hospital stay was 9.18 days +or- 4.34 days. Majority 570 (90.5%) had fever, 493 (78.3%) had cough, 286 (45.4%) had breathlessness, 66 (10.5%) had sore throat. Other symptoms include vomiting, and loose motion in 17 (2.7%). Among 630 subjects included in the present study, the majority 584 (92.7%) have recovered/were discharged from the hospital and 46 (7.3%) succumbed to the illness. The mean SGOT and SGPT levels were 44.86+or- 31.29 and 43.60 +or- 31.25 respectively. Mean serum creatinine and BUN levels were 0.87+or- 0.80 and 13.96 +or- 9.46 respectively. The mean values of pulse rate, systolic blood pressure, diastolic blood pressure, respiratory rate and temperature showed an increasing trend across the grades of severity. Conclusion: We concluded that age, gender, blood sugar level, blood pressure, clinical symptoms, comorbidities, inflammatory biomarkers and CT severity score were independently associated with the severity and mortality based on our findings.

Kidney Limited Complement-Mediated Thrombotic Microangiopathy- a Challenging Case

Introduction: Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare disease characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and organ injury. The absence of hemolysis and thrombocytopenia is rare. We present a case of kidney limited CM-TMA successfully treated with eculizumab. Method(s): A 36 year-old man with poorly controlled hypertension, obesity, CKD (baseline creatinine (sCr) 2,6mg/dL, albuminuria 150mg/g), hyperlipidemia, obstructive sleep apnea, hyperuricemia, SARS-CoV-2 infection 3 months earlier, and family history of CKD of unknown etiology (father started kidney replacement therapy (KRT) at young age) presented to the ER with high blood pressure and right hemiplegy. Head CT scan showed left thalamo-capsular hemorrhage. Oftalmologic exam was normal. Laboratory findings were: hemoglobin (Hb) 12.5g/dL, elevated white cell count (17.900/uL), platelet count 214.000/uL, sCr 4.3mg/dL, lactate dehydrogenase (LDH) 303U/L. Urine dipstick revealed protein+ and Hb++. Chest X-ray showed signs of pneumonia. The patient was admitted in ICU and mechanically ventilated. After 3 weeks, renal function recovered to its baseline (sCr 1.5mg/dL, no proteinuria) without KRT, and the patient was transferred to the medical ward. Several infectious complications prolonged hospital stay. After 3 months, a new mild SARS-CoV-2 infection was detected. At this time: Hb 9.9g/dL, platelets 220.000/uL, sCr 2.2mg/dL. Six days later the patient showed Hb 9.5 g/dL, without reticulocytosis, platelets 195.000/uL, sCr 6.3mg/dL, LDH 348U/L, normal haptoglobin, no schizocytes on blood smear. After 3 days, the patient was anuric and sCr increased to 10mg/dL, prompting KRT. Kidney ultrasound showed no abnormalities. Autoimmunity study was negative, normal C3/C4, no monoclonal gammopathy, and negative viral serologies. Kidney biopsy (KB) was performed as the etiology of AKI remained unclear. Light microscopy revealed thickned glomerular capillary walls with subendothelial expansion forming double contouring, arteriolar intimal expansion and fibrin thrombi occluding the vascular lumina. Scarse C3 deposition was observed in capillary walls. Since the morphological features were consistent with TMA, secondary causes were excluded and primary causes also investigated: ADAMTS13 activity, complement factor B and I were within normal range, slight decrease of factor H with normal anti factor H antibody. The molecular studies of complement genes were performed by NGS-based gene panel revealing a rare heterozygous missense mutation on gene CFB, c.1189G>A (p.Asp397Asn), described as a genetic risk factor of CM-TMA in the presence of a trigger. Result(s): Treatment with eculizumab was started and the patient showed signs of kidney recovery allowing KRT suspension 1 month later (sCr 5.53mg/dL). Of note, the patient never presented MAHA or thrombocytopenia. After 5 months, renal function improved to sCr 3.9mg/dL. Conclusion(s): We report a case of CM-TMA with isolated kidney injury without laboratory hallmarks of TMA. Patients usually require a secondary trigger for the disease to manifest, and in this case SARS-CoV-2 infection may have been the causative agent. A mutation in gene CFB may have predisposed the patient to the outcome. KB was crucial for diagnosis and prompted the treatment with eculizumab with partial recovery without the need for chronic KRT. No conflict of interestCopyright © 2023

Serological markers of tissue remodeling are elevated in patients with COVID-19 who develop interstitial lung disease

Background: Coronavirus disease-19 (COVID-19) is an infectious disease that can result in serious respiratory illness. It is associated with extensive systemic inflammation and changes to the lung extracellular matrix (ECM), which may result in diffuse alveolar damage and pulmonary fibrosis. In this study, the aim was to investigate whether ECM remodeling, wound healing, and neutrophil activity is altered in patients with COVID-19, with or without interstitial lung disease (ILD). Method(s): Serum was collected from 72 patients with COVID-19 infection 3 months after diagnosis, 10 of whom developed ILD, and from 16 healthy controls. A panel of neo-epitope specific ELISAs reflecting type III collagen crosslinking (PC3X), type III and VI collagen formation (PRO-C3 and PRO-C6), type I, III, and VI collagen degradation (C1M, C3M, and C6M), fibrin crosslinking (X-FIB), fibrin clot formation (PRO-FIB), elastin degradation (EL-NE and ELP-3), and calprotectin degradation (CPa9-HNE) were assessed in serum of patients. Result(s): Mean serum neo-epitopes PC3X (p<0.0001), PRO-C3 (p=0.0024), C3M (p=0.0085), PRO-FIB (p<0.0001), ELP-3 (p<0.0001), and CPa9-HNE (p<0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Additionally, PC3X (p=0.023) and PRO-C3 (p=0.0317) were significantly elevated in COVID-19 patients who developed ILD when compared to those who did not. Conclusion(s): Non-invasive serological biomarkers reflecting tissue remodeling were significantly elevated in patients infected with COVID-19. Additionally, type III collagen crosslinking and formation may differentiate patients who develop ILD consequent to COVID-19 infection.

PERICARDIAL INVOLVEMENT ASSOCIATED WITH SARS-COV-2 INFECTION. PROSPECTIVE OBSERVATION IN THE COVID- WARD.

Purpose. To identify the occurrence and structure of changes in the pericardium ultrasonography among patients who have undergone COVID-19 and have cardiological symptoms, as well as to compare these changes with the pericarditis aspects and the infection time duration in a prospective cohort observational study. Methods. Inclusion/exclusion criteria: current or transferred COVID-19, new symptoms that occurred during or after infection and forced to consult a cardiologist, the absence of other prerequisites for pericarditis and vaccination against SARS-CoV-2. Echocardiography was performed with an emphasis on the pericardium and an assessment of the echogenicity amplification, the area of the hyperechoic zone, thickness and artifacts, as well as a questionnaire. Results. From 05.2020 to On 10.2020, 335 patients from the covid ward and 284 patients from the out-patient clinic were included. 86% of patients had transient chest discomfort. The peaks of treatment accrued to 4-5 and 10-11 weeks (Me 10[2-36] (1 to 64) weeks) from SARS-CoV-2 infection occurred. Typical ECG changes were registered in 3%, pericardial friction noise - in 7% of patients. In 20% of patients discomfort in the heart area was the first, in 27% - the dominant, in 14% - the only symptom of COVID-19. According to EchoCG data, 96% of the examined patients had ultrasound signs of different changes in the pericardium: slight effusion in 65%, signs of tamponade in 2%, thickening in 12%, local hyperechogenicity in 83%, local adhesion in 8% of patients. The group without pericardial changes was distinguished by the presence of epicardial fat >7 mm. A combination of the echo-cardiography criteria with the second symptom recorded at the visit or earlier was present in 76% of the applicants. Comparison of the recorded ultrasound patterns with the time elapsed since infection allowed us to distinguish ultrasound phases: 1) the phase of damage (pattern of initial edema) occurred at 1 week, 2) the phase of edema /exudation (pattern of visible effusion) - at 3 weeks, 3) fibrosis (pattern of pericardial compaction) - at 11 weeks, 4) regression of inflammatory changes (pattern of local fibrin deposition) - on week 22, 5) residual signs of transferred inflammation may be visualized in patients with symptoms 44 weeks after COVID-19. Conclusions. Consideration of the infectious process triggered by SARS-CoV-2, as a systemic inflammation, allows us to interpret the phenomenon of pericardial involvement as a reactive serositis having ultrasound phases. It was possible to trace some patterns of echocardiography at different stages of the infectious and post-infectious period. Clinical data of 76% of patients can be interpreted as pericarditis, changes in 20% - as an increase in echogenicity of the pericardium.Copyright © 2022 Russian Electronic Journal of Radiology. All rights reserved.