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This article focuses on examining the structure of microorganisms and their antimicrobial drug resistance during the provision of in-hospital medical care for patients with COVID-19. Among monotypic fungal infections, Candida albicans predominated at 46.82% (n = 375), followed by Candida glabrata at 21.97% (n = 176). Streptococcus pneumoniae accounted for 25.24% (n = 617), while the combined antimicrobial presence of S. pneumoniae with Candida species represented 11.17% (n = 273), ranking highest in isolation frequency among all microorganisms. In deceased patients, the dominant pathogens identified were Klebsiella pneumoniae at 36.3% (n = 159) and Candida fungi at 21.92% (n = 96). Analysis of antimicrobial resistance revealed that S. pneumoniae (n=890) exhibited low resistance rates to benzylpenicillin (4.2%, n = 37), levofloxacin (11.5%, n = 102), and linezolid (0%), but showed elevated resistance to erythromycin (27.4%, n = 244), lincomycin (25.2%, n = 224), and doxycycline (15.5%, n = 141). The vast majority of K. pneumoniae isolates (n = 326) demonstrated resistance to ampicillin (97.9%), cefuroxime (94.2%), cefotaxime (87.7%), ceftazidime (85%), and cefepime (73%), with comparatively lower resistance to amoxicillin-clavulanic acid (52.1%, n = 170) and meropenem (33.4%, n = 109). Microorganisms exhibiting pan-drug resistance accounted for 7.6% (n = 125) of isolates, with the highest proportion of PDR strains attributed to K. pneumoniae, comprising 33.4% (n = 109) of all Klebsiella isolates. C. albicans and S. pneumoniae are the most frequently isolated pathogens among COVID-19 patients receiving inpatient care. The rising detection of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Klebsiella spp. underscores the critical need for careful selection of empirical antibacterial therapies.