Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Enhancer deregulation inTET2-mutant clonal hematopoiesis is associated with increased COVID-19 severity and mortality

Background: COVID-19 causes significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. It remains unclear which host factors determine disease severity and survival. Given the propensity of clonal hematopoiesis (CH) to promote inflammation in healthy individuals, we investigated its effect on COVID-19 outcomes. Method(s): We performed a multi-omics interrogation of the genome, epigenome, transcriptome, and proteome of peripheral blood mononuclear cells from COVID-19 patients (n=227). We obtained clinical data, laboratory studies, and survival outcomes. We determined CH status and TET2-related DNA methylation. We performed single-cell proteogenomics to understand clonal composition in relation to cell phenotype. We interrogated single-cell gene expression in isolation and in conjunction with DNA accessibility. We integrated these multi-omics data to understand the effect of CH on clonal composition, gene expression, methylation of cis-regulatory elements, and lineage commitment in COVID-19 patients. We performed shRNA knockdowns to validate the effect of one candidate transcription factor in myeloid cell lines. Result(s): The presence of CH was strongly associated with COVID-19 severity and all-cause mortality, independent of age (HR 3.48, 95% CI 1.45-8.36, p=0.005). Differential methylation of promoters and enhancers was prevalent in TET2-mutant, but not DNMT3A-mutant CH. TET2- mutant CH was associated with enhanced classical/intermediate monocytosis and single-cell proteogenomics confirmed an enrichment of TET2 mutations in these cell types. We identified celltype specific gene expression changes associated with TET2 mutations in 102,072 single cells (n=34). Single-cell RNA-seq confirmed the skewing of hematopoiesis towards classical and intermediate monocytes and demonstrated the downregulation of EGR1 (a transcription factor important for monocyte differentiation) along with up-regulation of the lncRNA MALAT1 in monocytes. Combined scRNA-/scATAC-seq in 43,160 single cells (n=18) confirmed the skewing of hematopoiesis and up-regulation of MALAT1 in monocytes along with decreased accessibility of EGR1 motifs in known cis-regulatory elements. Using myeloid cell lines for functional validation, shRNA knockdowns of EGR1 confirmed the up-regulation of MALAT1 (in comparison to wildtype controls). Conclusion(s): CH is an independent prognostic factor in COVID-19 and skews hematopoiesis towards monocytosis. TET2-mutant CH is characterized by differential methylation and accessibility of enhancers binding myeloid transcriptions factors including EGR1. The ensuing loss of EGR1 expression in monocytes causes MALAT1 overexpression, a factor known to promote monocyte differentiation and inflammation. These data provide a mechanistic insight to the adverse prognostic impact of CH in COVID-19.

Clinical and laboratory features of patients with post-COVID- 19 condition and reactivation of herpesvirus infections

Background: After infection with SARS-CoV- 2 is observed short-term and long-term post-acute sequelae of COVID-19 (PASC). A systematic review of 57 studies comprising more than 250 000 survivors of COVID-19 indicates that more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders [Groff D et al]. It has been suggested that co-infection of SARS-CoV- 2 with EBV or other herpes viruses (HSV1 / 2, HHV6, CMV) contributes to both severe COVID-19 and post-COVID symptoms. Method(s): 88 patients with the post-COVID- 19 condition were examined, including 52.3 % female, 47.7 % male, mean age 41.4 +/- 6.7 years. Patients underwent the following studies: anamnestic, clinical, general laboratory, biochemical and immunological analysis. PCR DNA of EBV, HHV6, CMV in blood, saliva, and the posterior pharyngeal mucosa was performed by Rotor-Gene 6000 (Corbett Research, Australia) and EBNA-IgG, VCAEBV-IgG, HHV6-IgG was performed by ELISA. Result(s): There were 2 groups of patients: the first included 68 patients with the post-COVID- 19 condition and active phase of herpesviruses. They were found positive EBV DNA -in 29 (42.6%) patients, positive HHV6 DNA -17 (25.0%) patients, positive EBV DNA, and HHV6 -in 22 (32, 4%) patients;the second group included 20 patients with the post-COVID- 19 condition and latent phase of herpesviruses and negative DNA EBV and/or HHV6 were found. In patients of the first group compared with the second group, patients were found COVID-19 had a severe course, pneumonia was diagnosed more often (77.9% vs. 40.0%), patients needed oxygen support and inpatient treatment lasted longer (16 +/- 7 vs. 10 +/- 4 days). In the first group patients compared with the second group patients were subfebrile temperature, headache, irritability, depression, myalgia, arthralgia, shortness of breath (p < 0.05). In patients of the first group compared with the second group in serum blood, we found elevated ESR, lymphopenia, monocytosis, increased activity of liver enzymes ALT and AST, CRP, D-dimer (p < 0.05) Conclusion(s): 1. Reactivation of herpesvirus infections is common in 72.3% of patients with the post-COVID- 19 condition: the EBV DNA positive were found in 42,6% of patients, the HHV6 DNA positive in 25,0% of patients, and EBV+HHV6 DNA positive in 32,4% of patients. 2. Patients with the post-COVID- 19 condition and reactivation of herpesviruses were characterized by severe COVID-19, manifestations of subfebrile, impaired mobility, mental disorders, and pulmonary abnormalities, as well as changes in laboratory parameters. 3. Our studies confirm the possible participation of reactivated herpesvirus infections (EBV, HHV6) in the formation of post-COVID- 19 conditions, which suggests the need for diagnosis of these infections and specific treatment. (Figure Presented).

Differences in Prevalence of Haematological Abnormalities on Presentation to Hospital in COVID 19 Infected adult and Paediatric Patients: A Retrospective Multicenter Descriptive Study

Background: It is well known that COVID 19 infection affects multiple systems in the body. Reports have documented many changes in the hematopoietic system in the pathophysiology of the disease. Aim: The aim of the study was to find out the prevalence and any significant difference in routine haematological parameters on presentation in Paediatric and adult patients with COVID 19 infection. Methodology: We conducted a multicenter retrospective descriptive observational study and investigated the prevalence of haematological abnormalities at presentation of 1000 PCR swab confirmed COVID 19 infected randomly selected adult and Paediatric patients admitted to 3 tertiary hospital in Dubai. Data was gathered through their electronic medical records and all analysis was done using the Statistical Package for the Social Sciences software (SPSS). Results: The prevalence of at least one abnormal haematological parameter was 95.1% (794/835) on first presentation to the hospital. After adjusting of age and gender the prevalence of any white cell abnormality was 34.7% (290/835) (5.7% leukopenia, 9.6% leucocytosis, 25.4% lymphopenia, 5.5% neutropenia, 16.4% had neutrophilia, 7.3% monocytosis, and 1.2% eosinopenia). A prevalence of 15.3% (128/835) anaemia, 9.5% (79/835) thrombocytopenia and 4.3% (36/ 835) thrombocytosis was also observed. The prevalence of other abnormal blood parameters: C reactive protein 69.5%(573/835), D dimer 57.5% (280/835), high LDH 52%(383/835), high ferritin 72.1%(452/835), high INR 5.1%(38/835), prolonged PT 32.2% (240/835), and prolonged APTT 35.6%(264/835). A significant difference in prevalence of these abnormalities was evident between adult and Paediatric population, these abnormalities were much more prevalent in adults but interestingly paediatric population tended to have higher incidence of neutropenia, eosinophilia and monocytosis (p<0.001). Conclusion: The effects of COVID 19 infection are different in adult and paediatric patients. Many mechanisms have been hypothesized for this observation. This study revealed another less studied and interesting variation in the manifestation among the two populations.

Monocytosis in patients with Coronavirus pneumonia on the background of treatment with glucocorticoids

Features of variation of peripheral blood leukocyte formula parameters in 86 patients with coronavirus pneumonia with leukocytosis with a background of glucocorticoid treatment were investigated. All patients were divided into 2 groups. Group 1 was 22 individuals who showed clinical signs of the bacterial infection (purulent sputum cough in combination with neutrophilic leukocytosis at hospital the admission). The 2nd group was made up of 64 patients with the glucocorticoids developed against the background of treatment with glucocorticoids (dexamethasone 20 mg/day or prednisolone 150 mg/day, intravenously for 3 days) leukocytosis >10 x109/l without signs of a bacterial infection. It was found that in patients of the 1st group compared to the 2nd group, levels of the white blood cells and neutrophils were significantly (p < 0.001) exceeded the reference values in the absence of a significant change in the number of monocytes. In patients of the 2nd group after a three-day intravenous application of the glucocorticoids on the 4th day of hospitalization, a statistically significant (p < 0.001) increase in the number of neutrophils and monocytes was established. When comparing the quantitative parameters of the leukocyte formula between the 2nd group on the 4th day of the hospitalization and the 1st group at admission, there were no differences in the level of leukocytes and neutrophils. Number of monocytes in group 2 (1.11 (0.90;1.34) x 109/l), on the contrary, statistically significantly (p < 0.001) exceeded their level in the 1st group (0.59 (0.50;0.77) x 109/l). Thus, an indicator of the number of monocytes in the peripheral blood could be a promising differential diagnostic criterion for the genesis of the leukocytosis in patients with the COVID-19. This parameter may be one of the factors influencing the decision to prescribe the antibacterial therapy.

A REVIEW OF MORPHOLOGICAL ABNORMALITIES ON PERIPHERAL BLOOD FILM: BEYOND ROUTINE ANALYSIS IN THE COVID-19 POPULATION IN THE FIRST WAVE OF THE DISEASE

Background: Vaccination is considered the most promising approach for ending or containing the coronavirus disease 2019 (COVID-19) pandemic. Available vaccines have proven highly safe and effective. The morphology appearance of the blood film is an excellent tool to analyse the disease severity. In late February of 2021, a prothrombotic syndrome was observed in a small number of individuals who received the ChAdOx1 CoV-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), an adenoviral vector-based vaccine. This syndrome has been designated vaccine-induced immune thrombotic thrombocytopenia (VITT) with a particular and intriguing characteristic. Aims: An examination of peripheral blood smear findings in COVID-19 patients was performed in 50 consecutive patients at the first wave of the disease and prior to the full vaccination program instituted with current-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (PCR)-Pneumonia Methods: A morphology analysis was aimed at identifying the principal abnormalities in patients diagnosed with COVID-19. Interestingly (but not surprisingly) the most severe forms were associated with a more prominent abnormalities, including leukoerythorblastic features and secondary hemophagocytic lymphohistiocytosis, leading to an often fatal outcomes. In this study, absolute lymphopenia (despite non constant) were the predominant feature despite its not specific to COVID-19. A spectrum of variant lymphocytes is seen in COVID-19 cases, albeit constituting less than 1% prolymphocytes in most cases. Plasmacytoid lymphocytes were more common as well as acquired Pelger-Huët were significantly observed (but not representative). Results: A laboratory findings reported in association with COVID-19 included leukopenia, lymphopenia, monocytosis, neutrophilia, eosinopenia, These abnormalities mainly highlight the severe, transitory and reversible perturbation of myelopoiesis, especially in the form of accelerated and disordered granulopoiesis, in patients with COVID19 in severe symptomatic phase. The hypothesis of quantitative and qualitative abnormalities can be related to the cytokine storm and hyperinflammation, which is a pathogenic factor in the evolution of COVID19 pneumonia. Summary/Conclusion: An early identification of severe lymphoid abnormality could represent a high risk factor for poor outcomes with COVID-19. A decreased number of mature lymphocytes, and eosinophils in peripheral blood smear were observed in the severe stage patients (p <0.05). The limitation of the study is in the small numbers of the analysed population and the absent of the control comparative group. The subsequent analysis after patient received at least two dose of the vaccination shows a less severe lymphopenia (P< 0.05) and disease severity.

High Monocyte Count Associated with Human Cytomegalovirus Replication In Vivo and Glucocorticoid Therapy May Be a Hallmark of Disease.

Cytomegalovirus (CMV) syndrome and infectious disease are defined as pathogen detection with appropriate clinical symptoms, but there are not pathognomonic signs of CMV disease. Although the prodrome of acute minor viral infections leukopenia (lymphopenia and neutropenia) is noted with onset of fever, followed by monocytosis, the role of monocytosis in CMV disease has not been described. Furthermore, under influence of corticosteroid therapy, CMV reactivation and monocytosis are described, but without a strict relationship with steroids dose. In the study, the monocyte level was investigated during the CMV infectious process. Regrettably, a non-selected group of 160 patients with high CMV viremia showed high dispersion of monocyte level and comparable with the median value for healthy subjects. Therefore, we investigated monocyte level in CMV-infected patients in relation to the logarithmic phase of the infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. Significant monocytosis (above 1200/µL) during the logarithmic phase of CMV infection (with exponent between 3.23 and 5.77) was observed. Increased count and percentage of monocytes correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, glucocorticoids equivalent to 10 and 20 mg of dexamethasone during a 2-3-week period caused monocytosis-significant increase (to 1604 and 2214/µL, respectively). Conclusion: In light of the logarithmic increase of viral load, high monocytosis is a hallmark of CMV replication. In the COVID-19 era, presence of high virus level, especially part of virome (CMV) in the molecular technique, is not sufficient for the definition of either proven or probable CMV replication at any site. These preliminary observations merit additional studies to establish whether this clinical response is mediated by monocyte production or by decrease of differentiation to macrophages.

Morphologic Features of Peripheral Blood Smears in COVID-19 Infection

Background: At the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel coronavirus responsible for causing the global coronavirus disease 19 (COVID-19) pandemic. Symptoms range from asymptomatic to severe respiratory symptoms. SARS-CoV-2 infection is well known to be associated with immune dysregulation and hematologic aberrancies. Few studies have reviewed peripheral blood smears abnormalities from COVID-19 patients. In this study, we aimed to characterize the morphologic features of peripheral blood smears from COVID-19 patients. Design: Hospitalized patients with PCR-confirmed COVID-19 infection were identified. Complete Blood Count (CBC) data, clinical findings, and peripheral blood morphology were compared to control patients with confirmed negative COVID-19 PCR. Results: Twelve PCR confirmed covid 19 positive patients (male- 9, female- 3) with an age range 38 to 95 were compared to 11 control patients PCR-negative for COVID-19. Most patients presented with fever or respiratory symptoms. Among the COVID-19 positive patients absolute lymphopenia was seen in 9/12 patients. Absolute monocytosis was seen in 2/12 and monocytopenia was seen in 3/12 cases. Interestingly, large, activated monocytes with abundant gray-blue cytoplasm with prominent cytoplasmic vacuoles were seen in all the COVID-19 positive patents (see fig. 1 D-F) as compared to normal controls. These activated monocytes consist of 1-11% of leukocytes, with absolute counts ranging from 0.12-0.69 x 10∧3/microliter. Other morphologic findings found in peripheral blood smears include plasmacytoid and atypical lymphocytes (Fig 1A-C), as well as neutrophils with pseudo-Pelger-Huet nuclei (Fig 1G-I). 10/12 patients with COVID-19 infection were unvaccinated;differences between peripheral blood smears from vaccinated and unvaccinated patients were not seen. All patients recovered upon follow up. Conclusions: In conclusion, activated monocytes with distinct morphology are present in varying numbers in the peripheral blood from hospitalized COVID-19 patients. These activated monocytes are not present in non-COVID-19 patients. These findings are consistent with those found in previous studies. Some of these studies have shown the presence of activated monocytes may indicate favorable outcomes. (Figure Presented).

A DIFFERENTIAL AND DIAGNOSTIC SIGNIFICANCE OF MONOCYTOSIS IN TREATMENT OF MODERATE COVID-19 FORMS

Despite the relatively rare comorbidity with bacterial infections, in most cases treatment of COVID-19-associated pneumonia is accompanied by empirical antibiotic therapy. In addition, the occurrence of leukocytosis in response to glucocorticosteroid (GCS) therapy is often perceived as comorbid bacterial flora and is a reason for initiating antibiotic therapy. Therefore, an urgent task is to properly interpret leukocytosis in response to GCS therapy in COVID-19. The aim of the study was to examine dynamic changes in count of venous blood leukocytes, neutrophils and monocytes in patients with moderate COVID-19 after systemic GCS. We analyzed parameters of complete blood count in 154 patients with verified moderate COVID-19, at the Temporary Infectious Diseases Hospital, the “Patriot” Park of the Moscow Region. The comparison group (I) consisted of 128 patients without clinical signs of bacterial infection and leukocytosis observed on admission, who were prescribed GCS therapy. The control group (II) consisted of 26 subjects showing on admission signs of bacterial infection — a cough with purulent sputum combined with neutrophilic leukocytosis. The dynamics in venous blood cell count was assessed in group I of patients before the onset, 3 and 6 days after beginning GCS therapy. We also compared count of leukocytes, neutrophils and monocytes between patients with developed leukocytosis in group I vs. group II. As a result, an increased count of leukocytes, neutrophils and monocytes was revealed according to assessing complete blood count test in patients from group I on days 3 and 6 of ongoing GCS therapy. All patients with developed leukocytosis after GCS admission (103 subjects) had no clinical signs of bacterial infection. Patients with developed leukocytosis from group I had increased count of monocytes (0.90 (0.84;1.02) on day 3 after GCS onset and 0.94 (0.87;1.26) on day 6 of GCS) compared with group II (0.61 [0.50;0.71]), p < 0.001. The inter-group count of leukocytes and neutrophils did not differ. Monocytosis after GCS therapy may serve as a differential diagnostic criterion to distinguish between glucocorticoid-induced leukocytosis and comorbid bacterial infection. This may be one of the factors influencing a decision to prescribe antibiotic therapy.

Correlation of morphological abnormality in Peripheral blood smears with disease severity and mortality in Covid 19

Introduction: COVID 19 pandemic, caused by SARS –CoV-2 virus causes flu like mild symptoms to severe acute respiratory syndrome. Pathogenesis is Immune system deregulationand is haracterized by the presence of lymphopenia in the peripheral blood smears. The clinical laboratory plays an important role in the diagnosis, treatment and prognosis of coronavirus patients. Aims &Objectives: • To describe the morphological changes in white blood cells, red blood cells, and platelets in the peripheral blood smears of COVID 19 positive patients. • To perform a blinded study on morphological parameters by two pathologists and study the inter-observer variability. •To correlate morphological changes with the haematological parameters obtained on complete blood counts. • To study the association of morphological changes with disease severity and survivor status of the patients Material &Methods: A total of 100 adults,aged more than 18 years who tested positive on RT PCR were enrolled for the study. Based on the symptoms, the patients were divided into two groups: mild to moderate and severe. Venous blood sample was collected and peripheral blood smearswere examined by pathologists. Results: The most characteristic haematological findings noted in peripheral blood smears inCOVID 19 patients were leucocytosis, neutrophilia, lymphopenia, monocytosis and thrombocytopenia.In neutrophils both nuclear as well as cytoplasmic abnormalities were noted. Nuclear abnormalities ranged from ring shaped nucleus tohypolobular neutrophils termed as pseudo pelgerhuet anomaly to presence of band forms. Cytoplasmic abnormality included presence of dark blue granulation which is similar to toxic granules. Apoptotic bodies were also noted. In platelets, we observed strikingly a unique feature showing presence of large platelets and increased frequency of platelet clumps along with normal to low platelet counts. Conclusions: These routinely used, non-invasive, quick and cost-effective tests for morphological details along with routine CBC parameters can play an important role which will have great clinical relevance helping to predict the disease progression and severity at an early stage aiding in patient triage and management.

A DIFFERENTIAL AND DIAGNOSTIC SIGNIFICANCE OF MONOCYTOSIS IN TREATMENT OF MODERATE COVID-19 FORMS

Despite the relatively rare comorbidity with bacterial infections, in most cases treatment of COVID-19-associated pneumonia is accompanied by empirical antibiotic therapy. In addition, the occurrence of leukocytosis in response to glucocorticosteroid (GCS) therapy is often perceived as comorbid bacterial flora and is a reason for initiating antibiotic therapy. Therefore, an urgent task is to properly interpret leukocytosis in response to GCS therapy in COVID-19. The aim of the study was to examine dynamic changes in count of venous blood leukocytes, neutrophils and monocytes in patients with moderate COVID-19 after systemic GCS. We analyzed parameters of complete blood count in 154 patients with verified moderate COVID-19, at the Temporary Infectious Diseases Hospital, the "Patriot" Park of the Moscow Region. The comparison group (I) consisted of 128 patients without clinical signs of bacterial infection and leukocytosis observed on admission, who were prescribed GCS therapy. The control group (II) consisted of 26 subjects showing on admission signs of bacterial infection - a cough with purulent sputum combined with neutrophilic leukocytosis. The dynamics in venous blood cell count was assessed in group I of patients before the onset, 3 and 6 days after beginning GCS therapy. We also compared count of leukocytes, neutrophils and monocytes between patients with developed leukocytosis in group I vs. group II. As a result, an increased count of leukocytes, neutrophils and monocytes was revealed according to assessing complete blood count test in patients from group I on days 3 and 6 of ongoing GCS therapy. All patients with developed leukocytosis after GCS admission (103 subjects) had no clinical signs of bacterial infection. Patients with developed leukocytosis from group I had increased count of monocytes (0.90 (0.84;1.02) on day 3 after GCS onset and 0.94 (0.87;1.26) on day 6 of GCS) compared with group II (0.61 [0.50;0.71]), p < 0.001. The inter-group count of leukocytes and neutrophils did not differ. Monocytosis after GCS therapy may serve as a differential diagnostic criterion to distinguish between glucocorticoid-induced leukocytosis and comorbid bacterial infection. This may be one of the factors influencing a decision to prescribe antibiotic therapy.

Post-immunization multisystemic inflammatory response in non-COVID patient

Case Report Moderna vaccine postvaccination symptoms include local and systemic reactions. Local side effects include pain after injection, erythema, induration, tenderness, and lymphadenopathy. Systemic reactions include fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, or chills. We describe a case of severe postvaccination symptoms that occurred after administration of Moderna vaccine in an individual with no prior history of COVID infection. Case 73-year-old male with a past medical history of diabetes, atrial fibrillation, hypertension, and hyperlipidemia presented to the Emergency Department secondary to an elevated white blood cell count (WBC). Patient started with weakness, low appetite, fever, chills, and headaches 2 days after receiving the Moderna vaccine. COVID-19 antigen and PCR test were negative. He was hemodynamically stable and afebrile. Laboratories showed WBC of 35.16 K/μL, sodium of 120 mmol/L, alanine transaminase of 84 IU/L, and aspartate transaminase of 116 IU/L. The patient denied having unintentional weight loss, fever, adenopathy, rash, pruritus, new medications, or recent infection. Chest x-ray did not show pleural effusion, consolidation or pneumothorax. Patient was started on broad spectrum antibiotics, and on hypertonic saline, fluid restriction and desmopressin for severe hyponatremia. Liver ultrasound ruled out cirrhosis;his hepatitis panel was negative. Peripheral blood smear showed normocytic anemia, neutrophilia, monocytosis, lymphopenia, and thrombocytosis. Workup for myeloproliferative process including Jak2, CALR, MPL, BCR -ABL, was negative. No bone marrow biopsy was performed as the smear results were considered a reactive process. Blood and urine cultures were negative. The patient was briefly transferred to ICU secondary to worsening hyponatremia, decreased mental status, and acute kidney injury (AKI). He developed erythematous non-pruritic rash on his arms and upper chest on day 13 which resolved after oral antihistamines. Transaminitis, hyponatremia, and AKI resolved, and patient was discharged 18 days later with WBC of 14.42 K/μL. Discussion Post-immunization side effects have been widely described after COVID vaccination. A new entity called adult multisystem inflammatory syndrome (MIS-A) which includes some of those symptoms has been described. Diagnostic criteria include severe illness requiring hospitalization in a person ≥ 21 years, positive COVID test during admission or in the previous 12 weeks, extrapulmonary organ system dysfunction, severe inflammation on laboratory test, and absence of severe respiratory illness. Our patient had characteristics consistent with MIS-A, except for negative COVID test. To our knowledge, there is only one reported case of multisystemic inflammatory syndrome associated with vaccine. Although MIS-A criteria establish that a patient must have a positive COVID test, it is worthwhile examining if there is any role of the vaccination per se on its presentation.

Correlation of Morphological Abnormalityin Peripheral Blood Smears with Disease Severityand Mortality in COVID 19

Introduction: COVID 19 pandemic, caused by SARS CoV-2 viruscauses flu like mild symptoms to severe acute respiratory syndrome.Pathogenesis is Immune system dysregulation and is characterised bythe presence of lymphopenia in the peripheral blood smears. Theclinical laboratory plays an important role in the diagnosis, treatmentand prognosis of coronavirus patients.Aims &Objectives: To describe the morphological changes in white blood cells, redblood cells, and platelets in the peripheral blood smears of COVID19 positive patients. To correlate morphological changes with the haematologicalparameters obtained on complete blood counts. To study the association of morphological changes with diseaseseverity and survivor status of the patients.Materials &Methods: A total of 100 adults, aged more than18 years who tested positive on RT PCR were enrolled for the study.Based on the symptoms, the patients were divided into two groups:mild to moderate and severe. Venous blood sample was collected andperipheral blood smears were examined by pathologists.Result: The most characteristic haematological findings noted inperipheral blood smears in COVID 19 patients were leucocytosis,neutrophilia, lymphopenia, monocytosis and thrombocytopenia. Inneutrophils both nuclear as well as cytoplasmic abnormalities werenoted. Nuclear abnormalities ranged from ring shaped nucleus tohypolobular neutrophils termed as pseudo pelgerhuet anomaly topresence of band forms. Cytoplasmic abnormality included presenceof dark blue granulation which is similar to toxic granules. Apoptoticbodies were also noted. In platelets, we observed strikingly a uniquefeature showing presence of large platelets and increased frequency ofplatelet clumps along with normal to low platelet counts. We notedsignificant positive correlation in morphology of neutrophils andplatelets among severe, mild to moderate groups and survivors or nonsurvivors groups.Conclusions: These routinely used, non-invasive, quick and costeffective tests for morphological details along with routine CBCparameters can play an important role which will have great clinicalrelevance helping to predict the disease progression and severity at anearly stage aiding in patient triage and management.