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The COVID-19 pandemic offered a unique opportunity to study shifts in environmental antibiotic resistance that could be associated with the changes in disinfectant and/or antibiotic usage patterns, coinfections, or other behaviors. The aim of this study was to document temporal changes (pre-, early-, versus later-pandemic) in antibiotic resistance genes (ARGs), ARG hosts, biomarkers of potential coinfections, and the total microbiome in municipal wastewater influent from one separate sanitary and one combined sewer system. The 16S rRNA gene copy normalized concentration of qacE was higher in early- than prepandemic samples, and sul1 and tet(G) were higher in early- than later-pandemic samples. Metagenomics revealed significant changes in the abundance of the macrolide and sulfonamide ARG classes. COVID-19 cases positively correlated with the disinfectants/antiseptics group of ARGs and negatively correlated with the sulfonamide and aminoglycoside resistance classes. Discussion is provided regarding the correspondence of these observations with antibiotic prescription pattern changes during the study period. Putative waterborne pathogens were identified, which is of potential interest for understanding the prevalence of community coinfections. No changes in host-ARG associations were observed. Overall, the results of this study may help in understanding the impact of the pandemic and/or lack thereof on another public health crisis: antibiotic resistance.