Challenge | Association with disease and microbiome | Mitigation |
---|---|---|
Antibiotic usage | More severe patients are more likely to receive antibiotics, making it difficult to differentiate between association w/disease severity and association w/antibiotic use. | Studies profiling patients prior to treatment avoid this effect (i.e., Bradley et al. [49]). Other studies with both COVID and non-COVID-19 patients receiving antibiotics can identify the effect of specific antibiotics, which can then be separated from the effects of COVID (i.e., Lloréns-Rico [48]) |
Mechanical ventilation | More severe patients require mechanical ventilation, which is known to impact the respiratory microbiome. | Similar mitigation techniques as used for high antibiotic use can apply to mechanical ventilation. |
SARS CoV-2 variant | Some SARS CoV-2 variants may cause more or less severe disease, though the impact of variants on the respiratory microbiome is unknown. | The vast majority of studies here predate the emergence of any variants of concern, but in future studies, it will be important to sequence SARS CoV-2 genomes and report the variants included in microbiome studies to determine if there is an impact on the respiratory microbiome. |
Sample storage in viral transport media | Swabs initially collected for SARS CoV-2 testing are often stored in VTM, which contains antibiotics and also nutrients that allow some bacteria to grow out. | Several studies sample the upper respiratory tract microbiome without storing in VTM (e.g., Braun et al., Mostafa et al. Hurst et al. [50,51,52]). |
Prior immunity to SARS Cov-2 | Patients with prior immunity via vaccination or prior infection are less likely to have severe COVID, but the impact of prior immunity on the microbiome are unknown. | No studies have yet reported the microbiome of COVID-19 patients with prior immunity. The impact can be mitigated by ensuring balanced enrollment of immunized and naïve patients at each level of disease severity in future microbiome studies. |
Inconsistent analytical techniques | Each study uses different analysis methods to identify differential taxa in the microbiome. This is known to significantly impact which associations are identified. | Making data publicly available for reanalysis and meta-analysis would allow for standardization across studies. A minority of studies make sufficient data available (e.g., Gupta et al., Kullberg et al. [53, 54]). |