A Retrospective Study on Coinfections, Antimicrobial Resistance, and Mortality Risk Among COVID-19 Patients (2020–2021) with Consideration of Long-COVID Outcomes

Coinfections in COVID-19 patients can worsen disease severity by enhancing SARS-CoV-2 replication and proinflammatory cytokine levels. This study analyzes the characteristics of coinfected COVID-19 patients across the pandemic and their association with in-hospital mortality. We retrospectively examined data from 351 COVID-19 patients hospitalized in a Spanish secondary hospital between March 2020 and February-March 2021. Nasopharyngeal swabs from 340 patients were analyzed using multiplex RT-PCR to identify 26 respiratory pathogens. A total of 136 patients were coinfected with 191 bacteria (100 Gram-negative and 91 Gram-positive), 20 viruses, 18 fungi, and 1 protist. In 2021, empirical cephalosporin use increased (<i>p</i> = 0.009). The incidence of enterococcal coinfections tripled from 2020 to 2021 (<i>p</i> < 0.001). In 2021, a greater proportion of patients experienced urine (<i>p</i> = 0.001) and bloodstream (<i>p</i> = 0.010) coinfections. In 2020, there was one bloodstream infection, while in 2021, there were seven, with half of them being fatal. Coinfected patients experienced longer hospital stays and higher odds of long COVID (<i>p</i> < 0.001; <i>p</i> = 0.014; <i>p</i> = 0.045). Non-respiratory coinfections in 2021 correlated with increased mortality (<i>p</i> = 0.002). Antimicrobial resistance remained stable (<i>p</i> = 0.149). The rise in cephalosporin use correlated with increased <i>Enterococcus</i> infections, notably bloodstream infections, which were linked to mortality (<i>p</i> = 0.016). In 2021, coinfections were linked to prolonged hospital stays and an increased risk of mortality in our patient cohort.