ABSTRACT
Background. TNFα and IFN-γ may synergize to induce cytokine-driven lethal hyperinflammation and immune exhaustion in COVID-19 illness. Methods. To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay), secondary infections, duration of supplemental oxygen support and hospitalization. Hospitalized patients with SARS-COV2 infection and pneumonia that were referred to the infliximab-abda study team for evaluation. Results. Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65 years age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infections. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant declines in IFN-γ, TNFα, IL-27, IL-6 (baseline above 10pg/ml), CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unaffected. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). following treatment with infliximab-abda. The status of the patient at last follow-up (discharged, alive or dead) is indicated. ECMO: extracorporeal membrane oxygenation Control of inflammatory markers and cytokines following infliximab therapy Values from individuals are connected with solid lines, with deceased individuals indicated in red. Statistics: n=18, paired ratio t-test compared to baseline;∗: P<0.05, ∗∗: P<0.01, ∗∗∗: P<0.001, ∗∗∗∗: P<0.0001, n.s.: not significant. Conclusion. Consistent with a central role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are formally evaluating infliximab therapy in this context. Funding: National Center for Advancing Translational Sciences.
ABSTRACT
Information and Communication Technology (ICT) is an important element in the education scenario to prepare citizens for the future. Since, its inception factors influencing the use have not been studied more, hence an exploratory research study has been framed for finding those factors among the students of CCS Haryana Agricultural University, Hisar, Haryana during 2018-19. The data were collected from 200 respondents using structured interview schedule and analyzed using standard methodology. The findings revealed that the institutional factors were perceived highest with composite index value (CIV) of 70.18, followed by personal (67.35), technical (59.15) and economic constraints (47.33). Although, these factors could be overcome through implementing remedies suggested by students like;teaching should be through ICTs, followed by improved internet connection, training programme related to use of ICTs, etc. but an effective national level policy related to infrastructure facilities, software licensing, availability of high quality ICT gadgets at subsidized rates, free and regular training programmes, etc. are possible ways to deal with these factors especially during COVID-19 pandemic. The correlation and regression of different variables, i.e. age, education, family education, scientism, annual expenditure, mass media exposure, information seeking behaviour and risk orientation exhibited negative and significant effect with their perceived personal factors at 0.05 level of probability. Hence, the paper recommends that effective utilization of ICT depends not only upon the available ICT resources, but also effective utilization of the same.