Introduction The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. Patients and methods We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. Results Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82–5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). Conclusions Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.

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Introduction: The recovery of other respiratory viruses in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology and outcomes of co-infection and super infection are limited. The purpose of this study was to examine occurrence of respiratory co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. Patients and Methods: We searched literature databases for studies published from October 1, 2019, through June 11, 2020. We included studies that reported clinical features and outcomes of co-infection or super-infection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines and we registered the protocol with PROSPERO as: CRD42020189763. Results: Of 1310 articles screened, 48 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 12% (95% confidence interval (CI): 6%-18%, n=29, I2=98%) and that of super-infection was 14% (95% CI: 9%-21%, n=18, I2=97%). Pooled prevalence of pathogen type stratified by co- or super-infection: viral co-infections, 4% (95% CI: 2%-7%); viral super-infections, 2% (95% CI: 0%-7%); bacterial co-infections, 4% (95% CI: 1%-8%); bacterial super-infections, 6% (95% CI: 2%-11%); fungal co-infections, 4% (95% CI: 1%-8%); and fungal super-infections, 4% (95% CI: 0%-11%). Compared to those with co-infections, patients with super-infections had a higher prevalence of mechanical ventilation [21% (95% CI: 13%-31%) vs. 7% (95% CI: 2%-15%)] and greater average length of hospital stay [mean=12.5 days, standard deviation (SD) =5.3 vs. mean=10.2 days, SD= 6.7]. Conclusions: Our study showed that as many as 14% of patients with COVID-19 have super-infections and 12% have co-infections. Poor outcomes were associated with super-infections. Our findings have implications for diagnostic testing and therapeutics, particularly in the upcoming respiratory virus season in the Northern Hemisphere.