COVID-19 in rheumatic diseases: A random cross-sectional telephonic survey (preprint)

Objective. To describe the incidence, clinical course, and predictive factors of coronavirus 2019 (COVID-19) infection in a cohort of rheumatological patients residing in New Delhi (National Capital Region), India. Methods. We performed a cross-sectional, random telephonic survey from 20th April to 20th July 2020 on patients with rheumatic diseases. Patients were interviewed with a predesigned questionnaire. The incidence of COVID-19 in the general population was obtained from open access government data repository. Report of reverse transcriptase polymerase chain reaction report was taken as confirmatory of COVID-19 infection. Results. Among the 900 contacted patients 840 responded (713 with rheumatoid arthritis (RA), 100 with systemic lupus erythematosus (SLE), 20 with spondylarthritis (SpA) and 7 with others; mean age 45 years, mean duration 11.3 years; 86% female). Among them 29 reported flu-like symptoms and four RA patients had confirmed COVID-19 infection. All of them were hospitalized with uneventful recovery. Rheumatological drugs were discontinued during the infectious episode. Disease modifying agents and biologics were equally received by those with or without COVID-19. The incidence of COVID-19 was similar to general Delhi population (0.476% vs 0.519% respectively, p=0.86). Two patients had relapse of rheumatic disease after recovery. After recovery from COVID-19 or Flu-like illness, eight patients (27.6%, 95% confidence interval 14.7-45.7) reported disease flare. Conclusion. Patients with rheumatic diseases in India have similar incidence of COVID-19 infection compared to the community. Relapse of underlying rheumatic disease after recovery is not uncommon and continuation of glucocorticoid through the infection should be considered.

Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19 (preprint)

Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of “size” (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infection and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested: methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway: Measles, Influenza A, West Nile virus, Japanese B virus, Yellow Fever virus, respiratory syncytial virus, Kaposi’s sarcoma virus, Hepatitis B and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho= -0.815, R 2 = 0.676, p=0.007, for vertex cover rho= -0.793, R 2 = 0.635, p=0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection.

Interaction between malarial transmission and BCG vaccination with COVID-19 incidence in the world map: A changing landscape human immune system? (preprint)

Background: COVID-19 (Corona virus Disease-2019) is a new public health emergency and is a pandemic currently. Incidence and mortality of COVID-19 vary in different geographical areas. In this study we aimed to analyse the relationship between malaria transmission and BCG vaccination with COVID-19 incidence in the world map. Materials and methods: We collected malaria cases data (World Health Organisation (WHO), 2018), worldwide COVID-19 cases and mortality data (European Centre for Disease Prevention and Control) and data on BCG vaccination. COVID-19 incidence and mortality was compared. Findings: Data on 5316978938 persons from 166 countries were analysed. Malaria incidence rate was negatively correlated with COVID-19 incidence rate (correlation coefficient = -0.513, p<0.001). Malaria free countries had significantly higher number of COVID-19 cases compared to malaria endemic countries. In Europe and Americas, countries, which have higher BCG vaccination coverage, had significantly less mortality per thousand population compared to those with low BCG coverage (median 0.0002 (0-0.0005) vs 0.0029 (0.0002-0.0177), p=0.017). The case fatality ratio of COVID-19 was related nonlinearly to the malaria incidence. Conclusions: The results suggest the changing human immune system as we progress to eliminate parasitic diseases with time. Chloroquine exposure in malaria endemic zones might have a protective effect.