Role of the Microbiome in the Pathogenesis of COVID-19

Abstract

The ongoing pandemic coronavirus disease COVID-19 is caused by the highly contagious single-stranded RNA virus, SARS-coronavirus 2 (SARS-CoV-2), which has a high rate of evolution like other RNA viruses. The first genome sequences of SARS-CoV-2 were available in early 2020. Subsequent whole-genome sequencing revealed that the virus had accumulated several mutations in genes associated with viral replication and pathogenesis. These variants showed enhanced transmissibility and infectivity. Soon after the first outbreak due to the wild-type strain in December 2019, a genetic variant D614G emerged in late January to early February 2020 and became the dominant genotype worldwide. Thereafter, several variants emerged, which were found to harbor mutations in essential viral genes encoding proteins that could act as drug and vaccine targets. Numerous vaccines have been successfully developed to assuage the burden of COVID-19. These have different rates of efficacy, including, although rarely, a number of vaccinated individuals exhibiting side effects like thrombosis. However, the recent emergence of the Britain strain with 70% more transmissibility and South African variants with higher resistance to vaccines at a time when several countries have approved these for mass immunization has raised tremendous concern regarding the long-lasting impact of currently available prophylaxis. Apart from studies addressing the pathophysiology, pathogenesis, and therapeutic targets of SARS-CoV-2, analysis of the gut, oral, nasopharyngeal, and lung microbiome dysbiosis has also been undertaken to find a link between the microbiome and the pathogenesis of COVID-19. Therefore, in the current scenario of skepticism regarding vaccine efficacy and challenges over the direct effects of currently available drugs looming large, investigation of alternative therapeutic avenues based on the microbiome can be a rewarding finding. This review presents the currently available understanding of microbiome dysbiosis and its association with cause and consequence of COVID-19. Taking cues from other inflammatory diseases, we propose a hypothesis of how the microbiome may be influencing homeostasis, pro-inflammatory condition, and the onset of inflammation. This accentuates the importance of a healthy microbiome as a protective element to prevent the onset of COVID-19. Finally, the review attempts to identify areas where the application of microbiome research can help in reducing the burden of the disease.

Altered infective competence of the human gut microbiome in COVID-19

“…Our findings suggest that it is imperative to elucidate all the implications of SARS-CoV-2 infection, especially its effect on the gut microbiome community and functions. Although other studies have involved the severe cases of COVID-19 [7,65,66], none of these studies include both metagenomic and metatranscriptomic sequencing data. We found that the virulence factors and antimicrobial resistance genes were indeed expressed in higher levels in the COVID-19 group compared to the controls.…”

“…PathoFact was run on the contigs assembled by IMP together with their predicted protein sequences (ORFs) for each sample separately. PathoFact uses DeepARG [63] and RGI [61] for the prediction of ARGs, DeepVirFinder [64] and VirSorter [65] for the prediction of phages and PlasFlow [66] for the prediction of plasmids. Additionally, PathoFact uses its own developed tool, a combination of a HMM database (built on the VFDB [67]) and a random forest model, for the prediction of virulence factors.…”

Gut microbiota composition in COVID-19 hospitalized patients with mild or severe symptoms

“…However, few studies evaluated the gut microbiota as a prognostic factor for disease progression in hospitalized patients. The existence of a correlation between the COVID-19 severity and fecal microbiota dysbiosis (including depletion of commensal bacteria) has been reported ( De and Dutta, 2022 ). As shown by Zuo et al (2020) , twenty-three bacterial taxa were significantly correlated with disease severity, with the main bacteria belonging to the phylum Firmicutes and the genus Coprobacillus , as well as the Clostridium ramosum and Clostridium hathewayi species.…”

Appropriate Human Serum Albumin Fluid Therapy and the Alleviation COVID-19 Vulnerabilities; An Explanation of the HSA Lymphatic Nutrient Pump

“…HSA is known to act as a receptacle in protecting bacterial microbiomes [9]. A microbiome formation is possible between COVID-19 virions [10]. Due to the long halflife of HSA both in the interstitial spaces and the body any bound COVID-19 virions therefore may be trapped for weeks or months.…”