akshith thimmaiah - Academia.edu (original) (raw)
Papers by akshith thimmaiah
Scientific Reports, Jan 18, 2024
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Res... more Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers-iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory sequelae of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection in children 1-3. Several children present with severe multi-organ dysfunction and an exaggerated inflammatory response as a late manifestation of SARS-CoV-2 infection (within 4-6 weeks) 1. Previous studies have described exaggerated inflammatory responses that are present in MIS-C including elevated levels of pro-inflammatory cytokines, chemokines, growth factors, complement activation, acute phase proteins, activated neutrophils and monocytes, thrombocytopenia, and lymphopenia 4. It is widely known that biological sex could have an impact on the probability and susceptibility to disease and its sequelae 5 and between-sex differences have been recognized in medical research. In this context, in previous epidemics of COVID (Acute Respiratory Syndrome-CoronaVirus (SARS-CoV), the Middle East Respiratory Syndrome-CoronaVirus (MERS-CoV)), studies determined that sex differences have a different impact on disease severity and clinical outcomes 6,7. Various epidemiologic reports have demonstrated the presence of sex disparities in COVID-19 outcomes 8. Several studies have shown that men were more frequently affected by COVID-19 than women 6,9 and sex has also been recognized as a determinant of the progression and health outcomes of COVID-19 10. Various studies reported that males may be highly represented in MIS-C, however, only a minor male dominance is observed in six studies 3,9,11-17. As of November 27, 2023, there have been 9,604 reported cases of MIS-C in the United States, with 79 reported deaths. The median age of affected cases is 9 years, and notably, 60% of the reported MIS-C
Frontiers in Pediatrics, Dec 4, 2023
PLOS Pathogens, Nov 2, 2022
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as... more The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8 + T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4 + and CD8 + T cells, classical, activated memory B and plasma cells and monocyte (intermediate and nonclassical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.
Frontiers in Medicine, Dec 5, 2022
Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory seq... more Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. Methods: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). Results: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84-100% and specificity 80-100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with Frontiers in Medicine 01 frontiersin.org Pavan Kumar et al. 10.3389/fmed.2022.1050804 mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. Discussion: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.
The Journal of Infectious Diseases, Aug 6, 2022
Background. Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and ... more Background. Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods. We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. Results. MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis based on these cytokines and chemokines could clearly distinguish MIS-C from both COVID-19 and other infections. In addition, these responses were significantly diminished and normalized 6-9 months after recovery. Conclusions. Our data suggest that MIS-C is characterized by an enhanced production of cytokines and chemokines that may be associated with disease pathogenesis. Keywords. MIS-C; SARS-CoV-2; COVID-19; cytokines; chemokines; pediatric population; in vitro cell culture. Coronavirus disease 2019 (COVID-19) is milder in children than adults and accounts for <0.1% of total deaths (Centers for Disease Control and Prevention [CDC] COVID-19 Response Team; American Academy of Pediatrics and Children's Hospital Association, Children and COVID-19: State Data Report 2020; Pediatric Mortality Investigation Team; https://www.aap.org/en/pages/2019-novel-coronaviruscovid-19-infections/children-and-covid-19-state-level-data-re port/). The reasons for differences in pediatric and adult severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still unclear [1, 2]. Following the early wave of COVID-19, children presented with multisystem inflammatory
Frontiers in Medicine
IntroductionMultisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory seque... more IntroductionMultisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases.MethodsTo elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations).ResultsChildren with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical dis...
PLOS Pathogens
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as... more The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentati...
American Journal of Infection Control
Indian Journal of Medical Microbiology
The Journal of Infectious Diseases
Background Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and p... more Background Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We characterized the SARS-CoV-2 antigen–specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. Results MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2–specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis...
Indian Journal of Nephrology, 2020
Melioidosis is a tropical infection that is increasingly being reported from South India. It is f... more Melioidosis is a tropical infection that is increasingly being reported from South India. It is frequently observed in patients with diabetes mellitus, chronic ethanol consumption and chronic kidney disease (CKD). It presents commonly with pneumonia, deep seated abscesses or osteoarticular infections. Cardiac complications are very rare with endocarditis being reported in very few patients. We report the first case of endocarditis in melioidosis in India. Although infections are common in patients with CKD, melioidosis at the time of diagnosis of CKD has never been reported in the past. Our patient had multiple liver abscesses and endocarditis, and responded well to a 6 week course of ceftazidime and doxycycline, with the latter being continued for 20 weeks.
Scientific Reports, Jan 18, 2024
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Res... more Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers-iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory sequelae of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection in children 1-3. Several children present with severe multi-organ dysfunction and an exaggerated inflammatory response as a late manifestation of SARS-CoV-2 infection (within 4-6 weeks) 1. Previous studies have described exaggerated inflammatory responses that are present in MIS-C including elevated levels of pro-inflammatory cytokines, chemokines, growth factors, complement activation, acute phase proteins, activated neutrophils and monocytes, thrombocytopenia, and lymphopenia 4. It is widely known that biological sex could have an impact on the probability and susceptibility to disease and its sequelae 5 and between-sex differences have been recognized in medical research. In this context, in previous epidemics of COVID (Acute Respiratory Syndrome-CoronaVirus (SARS-CoV), the Middle East Respiratory Syndrome-CoronaVirus (MERS-CoV)), studies determined that sex differences have a different impact on disease severity and clinical outcomes 6,7. Various epidemiologic reports have demonstrated the presence of sex disparities in COVID-19 outcomes 8. Several studies have shown that men were more frequently affected by COVID-19 than women 6,9 and sex has also been recognized as a determinant of the progression and health outcomes of COVID-19 10. Various studies reported that males may be highly represented in MIS-C, however, only a minor male dominance is observed in six studies 3,9,11-17. As of November 27, 2023, there have been 9,604 reported cases of MIS-C in the United States, with 79 reported deaths. The median age of affected cases is 9 years, and notably, 60% of the reported MIS-C
Frontiers in Pediatrics, Dec 4, 2023
PLOS Pathogens, Nov 2, 2022
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as... more The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8 + T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4 + and CD8 + T cells, classical, activated memory B and plasma cells and monocyte (intermediate and nonclassical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.
Frontiers in Medicine, Dec 5, 2022
Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory seq... more Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. Methods: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). Results: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84-100% and specificity 80-100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with Frontiers in Medicine 01 frontiersin.org Pavan Kumar et al. 10.3389/fmed.2022.1050804 mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. Discussion: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.
The Journal of Infectious Diseases, Aug 6, 2022
Background. Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and ... more Background. Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods. We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. Results. MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis based on these cytokines and chemokines could clearly distinguish MIS-C from both COVID-19 and other infections. In addition, these responses were significantly diminished and normalized 6-9 months after recovery. Conclusions. Our data suggest that MIS-C is characterized by an enhanced production of cytokines and chemokines that may be associated with disease pathogenesis. Keywords. MIS-C; SARS-CoV-2; COVID-19; cytokines; chemokines; pediatric population; in vitro cell culture. Coronavirus disease 2019 (COVID-19) is milder in children than adults and accounts for <0.1% of total deaths (Centers for Disease Control and Prevention [CDC] COVID-19 Response Team; American Academy of Pediatrics and Children's Hospital Association, Children and COVID-19: State Data Report 2020; Pediatric Mortality Investigation Team; https://www.aap.org/en/pages/2019-novel-coronaviruscovid-19-infections/children-and-covid-19-state-level-data-re port/). The reasons for differences in pediatric and adult severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still unclear [1, 2]. Following the early wave of COVID-19, children presented with multisystem inflammatory
Frontiers in Medicine
IntroductionMultisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory seque... more IntroductionMultisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases.MethodsTo elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations).ResultsChildren with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical dis...
PLOS Pathogens
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as... more The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentati...
American Journal of Infection Control
Indian Journal of Medical Microbiology
The Journal of Infectious Diseases
Background Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and p... more Background Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We characterized the SARS-CoV-2 antigen–specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. Results MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2–specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis...
Indian Journal of Nephrology, 2020
Melioidosis is a tropical infection that is increasingly being reported from South India. It is f... more Melioidosis is a tropical infection that is increasingly being reported from South India. It is frequently observed in patients with diabetes mellitus, chronic ethanol consumption and chronic kidney disease (CKD). It presents commonly with pneumonia, deep seated abscesses or osteoarticular infections. Cardiac complications are very rare with endocarditis being reported in very few patients. We report the first case of endocarditis in melioidosis in India. Although infections are common in patients with CKD, melioidosis at the time of diagnosis of CKD has never been reported in the past. Our patient had multiple liver abscesses and endocarditis, and responded well to a 6 week course of ceftazidime and doxycycline, with the latter being continued for 20 weeks.