Health

How do host factors like the lung microbiome aid in SARS‐CoV‐2 infection?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that belongs to the Coronaviridae genus and the betacoronavirus subgenus. It is the novel and highly infectious pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19). Since it was first detected in December 2019, the virus has claimed over 4 million lives worldwide.

Even though this virus predominantly infects the lungs, it systematically affects other organs as well. The severity of the disease varies from one individual to another; where some are asymptomatically infected, others show mild to severe symptoms.

How severely an individual may be affected by the virus has also been linked to host-specific factors and co-morbidities, for example, age, immunodeficiencies, hypertension, chronic lung diseases, or metabolic disorders. Additionally, changes in the microbiome in COVID-19 infected patients are also linked with the severity of the symptoms.

A new article by researchers in Germany has been published in Cellular and Molecular Lifesciences, which focuses on the connection between host factors and the worsening of the COVID-19. Further, the impact of the virus on the host’s microbiome and secondary infection has also been studied.

Comorbidities and COVID‑19

Although SARS-CoV-2 infects people of all ages, older age groups or those with pre-existing medical conditions were more susceptible than the younger age groups with no pre-existing health issues.

In older adults, the overexpression of angiotensin-converting enzyme 2 (ACE2) – a major host cell receptor that facilitates viral entry into cells – or the existence of many age-related co-morbidities makes them a particularly vulnerable group.

Some comorbidities which are strongly associated with severe COVID-19 infections are obesity, hypertension, diabetes, lung, liver, and kidney disease, immune-compromised patients, patients undergoing steroids treatments, and smokers.

Mechanistically, severe COVID-19 and hypertension could be linked by the fact that hypertension patients are treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These treatments could potentially enhance the levels of ACE2 in several tissues thereby, increasing the chance of SARS-CoV-2 infection.

Individuals with underlying cardiovascular disease (CVD) are often severely affected by COVID-19. The reason for this may be similar to that in the case of hypertension (i.e., the use of ACE inhibitors and ARB). Many antiviral drugs have an impact on cardiac arrhythmia or other cardiovascular disorders.

Further, metabolic disorders (MDs), e.g., diabetes and obesity, are associated with a pro-inflammatory and prothrombotic state. These conditions can induce atherosclerosis that restricts blood flow which results in organ dysfunction owing to insufficient oxygen supply. Diabetes increases type-1 membrane-bound protease furin, which aids the entry of coronaviruses into the cell.

Host genetic factors and COVID 19

Several genome-wide association studies (GWAS) have been conducted to analyze the effect of genetic variations with COVID-19 clinical phenotypes. The researchers found that two types of genes are associated with COVID-19 infection: a) genes that enable SARS-CoV-2 entry into the host’s epithelial cells; and b) genes that regulate innate and adaptive immune responses.

Further, the researchers also established a connection between the ABO blood group and COVID-19 symptoms. Their findings suggest that individuals with the O blood group less frequently test positive while people with the A blood group are more susceptible to COVID-19 infection and are more inclined towards severe disease. The expression of certain proteins, such as L cathepsin, TMPRSS2, TMPRSS4, and high-mobility group protein B1 (HMGB1), is associated with enhanced viral entry and replication.

Host microbiome and viral infection

The microbiome can be described as a collection of genomes of all the microorganisms, such as bacteria, fungi, archaea, and viruses, in a specific niche. The human microbiome (holobiont) plays a vital role in the health and functioning of the body.

The researchers hypothesized that the lung microbiome takes part in the initiation and progression of the disease. The lung microbiome plays a protective role due to its high diversity, which is involved with the competition within the microbiome and immune priming. Very few studies are available which deals with lung microbiota. Some of the microbes present in the lungs of COVID-19 patients are Proteobacteria, Acinetobacter Cryptococcus, etc.

Researchers who have studied the association between the gut microbiome and COVID-19 disease reported that ACE2, the receptor for SARS-CoV-2 spike protein, is highly expressed in intestinal enterocytes.

Further, many of the COVID-19 symptoms of digestive symptoms, vomiting, and diarrhea are directly connected to gut function. Researchers have reported that certain microbes that are present in the gut, such as Coprobacillus, Clostridium ramosum, and Clostridium hathewayi are positively correlated with severe COVID-19 disease.

Risks of co‑infection on the course of disease

The researchers stated that in the event that the human microbiome is dominated by pathogens, there an increased risk of co-infection. Two main factors that lead to microbial infection are dysbiosis and immune imbalance.

A recent study has reported that in Barcelona, Spain, 3% of the patients admitted to the hospital because of severe COVID-19 symptoms presented with community-acquired bacterial infections. Some of the bacterial pathogens that were found are Streptococcus pneumoniae, Enterobacterales, Haemophilus infuenzae and S. aureus.

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