Currently, the world is witnessing the pandemic of COVID-19, a disease caused by the novel coronavirus SARS-CoV-2. Reported differences in clinical manifestations and outcomes in SARS-CoV-2 infection could be attributed to factors such as virus replication, infiltration of inflammatory cells, and altered cytokine production. Virus-induced aberrant and excessive cytokine production has been linked to the morbidity and mortality of several viral infections. Using a Luminex platform, we investigated plasma cytokine and chemokine levels of 27 analytes from hospitalized asymptomatic ( n = 39) and mildly symptomatic ( n = 35) SARS-CoV-2-infected patients (in the early phase of infection), recovered individuals (45-60 days postinfection) ( n = 40), and uninfected controls ( n = 36) from the city of Pune located in the state of Maharashtra in India. Levels of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and the chemokine CXCL-10 were significantly higher, while those of the antiviral cytokines IFN-γ and IL-12 p70 were significantly lower in both asymptomatic and mildly symptomatic patients than in controls. Comparison among the patient categories revealed no difference in the levels of the cytokines/chemokines except for CXCL-10 being significantly higher and IL-17, IL-4, and VEGF being significantly lower in the mildly symptomatic patients. Interestingly, levels of all key analytes were significantly lower in recovered individuals than in those in both patient categories. Nevertheless, the level of CXCL10 was significantly higher in the recovered patients than in the controls, indicating that the immune system of SARS-CoV-2 patients may take a longer time to normalize. Our data suggest that IL-6, IL-1β, TNF-α, CXCL-10, and reduced antiviral cytokines could be used as biomarkers of SARS-CoV-2 infection.

Background: Mechanisms regulating BMP and Wnt pathways and their interactions are not well studied in Hydra. Results: We report identification of BMP inhibitor gremlin, comparison of its expression with that of noggin and possible antagonism between Wnt and BMP signaling in Hydra. Gremlin is expressed in body column with high levels in budding region and in early buds. Noggin, on the other hand, is expressed in the hypostome, base of tentacles, lower body column, and basal disc. During budding, noggin is expressed at the sites of tentacle emergence. This was confirmed in ectopic tentacles in polyps treated with alsterpaullone (ALP), a GSK-3β inhibitor that leads to upregulation of Wnt pathway. RT-PCR data show that upregulation of Wnt is accompanied by downregulation of bmp 5-8b though noggin and gremlin remain unaltered till 24 hours. Conclusions: Different expression patterns of gremlin and noggin suggest their roles in budding and patterning of tentacles, respectively. Further, bmp 5-8b inhibition by activated Wnt signaling does not directly involve noggin and gremlin in Hydra. Our data suggest that Wnt/BMP antagonism may have evolved early for defining the oral-aboral axis, while the involvement of BMP antagonists during axial patterning is a recent evolutionary acquisition within the Bilateria lineage.

Background & objectives : The COVID-19 disease profile in Indian patients has been found to be different from the Western world. Changes in lymphocyte compartment have been correlated with disease course, illness severity and clinical outcome. This study was aimed to assess the peripheral lymphocyte phenotype and subset distribution in patients with COVID-19 disease from India with differential clinical manifestations. Methods : Percentages of peripheral lymphocyte subsets were measured by flow cytometry in hospitalized asymptomatic (n=53), mild symptomatic (n=36), moderate and severe (n=30) patients with SARS-CoV-2 infection, recovered individuals (n=40) and uninfected controls (n=56) from Pune, Maharashtra, India. Results : Percentages of CD4+Th cells were significantly high in asymptomatic, mild symptomatic, moderate and severe patients and recovered individuals compared to controls. Percentages of Th memory (CD3+CD4+CD45RO+), Tc memory (CD3+CD8+CD45RO+) and B memory (CD19+CD27+) cells were significantly higher in the recovered group compared to both asymptomatic, mild symptomatic patient and uninfected control groups. NK cell (CD56+CD3-) percentages were comparable among moderate +severe patient and uninfected control groups. Interpretation & conclusions : The observed lower CD4+Th cells in moderate+severe group requiring oxygen support compared to asymptomatic+mild symptomatic group not requiring oxygen support could be indicative of poor prognosis. Higher Th memory, Tc memory and B memory cells in the recovered group compared to mild symptomatic patient groups might be markers of recovery from mild infection; however, it remains to be established if the persistence of any of these cells could be considered as a correlate of protection.

13Mechanisms regulating BMP and Wnt signaling pathways have been widely studied in many 14 organisms. One of the mechanisms by which these pathways are regulated is by binding of 15 extracellular ligands. In the present study, we report studies with two BMP antagonists, gremlin 16 and noggin from Hydra vulgaris Ind-Pune and demonstrate antagonistic relationship between 17 BMP and Wnt pathways. Gremlin was ubiquitously expressed from the body column to head 18 region except in the basal disc and hypostome. During budding, gremlin was expressed 19 predominantly in the budding region suggesting a possible role in budding; this was confirmed in 20 polyps with different stages of buds. Noggin, on the other hand, was predominantly expressed in 21 the endoderm of hypostome, base of the tentacles, lower body column and at the basal disc in 22 whole polyps. During budding, noggin was expressed at the sites of emergence of tentacles 23 suggesting a role in tentacle formation. This was confirmed in alsterpaullone-treated polyps, 24 which showed noggin expression as distinct spots where ectopic organizers and ectopic tentacles 25 eventually formed. Using RT-PCR, we found that up-regulation of Wnt is accompanied with 26 down-regulation of BMP5-8b demonstrating antagonism between the two pathways. Down-27 regulation of noggin and gremlin, however, occurred only after 24 h recovery. The data suggest 28 that inhibition of BMP pathway by Wnt signaling in hydra does not directly involve noggin and 29 gremlin. Our findings indicate that the BMP/Noggin antagonism evolved early for setting up 30 2 and/or maintaining the head organizer while involvement of these BMP antagonists during 31 vertebrate axial patterning are recent evolutionary acquisitions. 32 33 Summary statement 36 We show that setting up of the Organizer by BMP/Noggin antagonism and role of BMP 37 inhibitors in tissue patterning are evolutionarily ancient, probably arising for the first time in 38 hydra 39 40 Introduction 41 Bone morphogenetic protein family, a subfamily of transforming growth factor-β (TGF-β) 42 superfamily was originally identified for role of some of its members in formation and 43 regeneration of bone in vivo. Subsequently, their roles in crucial developmental processes, such 44 as, proliferation, migration, differentiation and fate specification of embryonic cells, 45 morphogenesis and dorso-ventral patterning were discovered (Massagué, 1998; Komiya and 46 Habas, 2008). Non-optimal BMP signaling leads to a variety of developmental abnormalities and 47 disease conditions including cardiovascular diseases, symphalangism, diabetic nephropathy and 48 several types of cancers (Kattamuri et al., 2017). BMPs initiate downstream signaling by two 49 mechanisms. The first is a canonical smad-dependent pathway which involves phosphorylation 50 of Serine/Threonine kinase receptors, Type I and Type II receptor complexes (BMPRI and 51 BMPRII), and activation of smad-1/5/8. The second is a smad-independent pathway, which 52 involves TGF-β Activated Tyrosine Ki...