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Background: The COVID-19 pandemic has brought about widespread effects on communities on a global scale, with impacts varying among different demographics. This study focuses on a unique cohort of COVID-19-positive patients from Arunachal Pradesh, a region in northeast India with a substantial indigenous population. This study aims to delve into the features and consequences of COVID-19 in this indigenous population within this distinct demographic region, with a special focus on assessing the effects on tribal communities. Out of a total of 1627 COVID-19 positive cases, 1392 belonged to various tribes of Arunachal Pradesh, categorized as the indigenous population of the region. Our research primarily focuses on examining the biochemical and inflammatory indicators that forecast the clinical results of COVID-19 patients, specifically within both indigenous and non-indigenous groups. Methods: Biochemical markers, including hematological parameters, liver and kidney function biomarkers, D-DIMER, and inflammatory markers, were assessed along with immune-inflammatory ratios: neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Differences in biomarker levels and ratios across disease severities were analyzed, and significant data were observed using descriptive statistics. Results: Elevated levels of Ferritin (CRP, IL-6, D-DIMER, Creatinine, Urea, AST/SGOT, and ALT/SGPT) were associated with increasing disease severity in COVID-19 cases, reflecting increased inflammation, multi-organ dysfunction, and coagulopathy in the severe COVID-19 category amongst the indigenous population. The data showed an aligned report with the non-indigenous population of India when compared with various other studies (using a Spearman rank correlation test). Similarly, an increase in the neutrophil-to-lymphocyte ratio (NLR) and a declining shift in the lymphocyte-to-monocyte ratio (LMR) indicated deregulated immune responses and systemic inflammation in the severe category of COVID-19. Conclusion: This population-based study from northeast India offers important perspectives into the pathophysiology of COVID-19 and its link with disease severity among indigenous and non-indigenous populations.