Revised May 10th, 2020
It is now abundantly clear that COVID-19 affects more than just the respiratory system. While oxygen deprivation from damaged lungs is still a leading cause of death, other manifestations include strokes and pulmonary emboli from blood clots, loss of smell and taste caused by nerve cell infection, vomiting and diarrhea in certain people, dangerous arrhythmias and heart attacks due to the formation of small clots, damage to kidneys resulting in the need for dialysis, purple toes or fingers from an attack on blood vessels, intense headaches, prolonged fever and chills, body aches, intense coughing, pink eye, Kawasaki disease-like inflammatory syndrome in some previously exposed children, and finally, death brought about by an overactive immune response known as a cytokine storm.
Dr. Mandeep Mehra, a professor of medicine at Harvard Medical School, has described COVID-19 thusly “What this virus does is it starts as a viral infection and becomes a more global disturbance to the immune system and blood vessels — and what kills is exactly that…Our hypothesis is that COVID-19 begins as a respiratory virus and kills as a cardiovascular virus.” (1)
Because this virus first begins in the respiratory system, I want to link to several papers about the gut-lung axis and the importance of our microbiome in preventing secondary pneumonia infections. All of these papers are open access and can be downloaded in full at the links provided.
The first is an opinion paper published in 2016 titled Emerging pathogenic links between microbiota and the gut–lung axis. It’s fairly easy to read so I encourage all of you to download and share a copy.
As this paper makes clear,
“The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut–lung axis. Although the gut–lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.”
“The gut microbiota is broadly protective against respiratory infection, as its depletion or absence in mice leads to impaired immune responses and worsens outcomes following bacterial or viral respiratory infection. Administration of SFB [segmented filamentous bacteria] improved resistance to Staphylococcus aureus pneumonia and Bifidobacterium spp. protected against both bacterial and viral pulmonary infection in mice. Lactobacillus spp. and Bifidobacterium spp.-based probiotics also improved the incidence and outcomes of respiratory infections in humans.”
One hypothesis for how this is done involves granulocyte–macrophage colony-stimulating factor or GM-CSF. This is how a 2017 paper described the mechanism:
“The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte–macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling. Increased pulmonary GM-CSF production in response to infection is primed by the microbiota through interleukin-17A. By combining models of commensal colonization in antibiotic-treated and germ-free mice, using cultured commensals from the Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla, we found that potent Nod-like receptor-stimulating bacteria in the upper airway (Staphylococcus aureus and Staphylococcus epidermidis) and intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens) promote resistance to lung infection through Nod2 and GM-CSF. Our data reveal the identity, location, and properties of bacteria within the microbiota that regulate lung immunity, and delineate the host signaling axis they activate to protect against respiratory infection.”
Further confirmation of the importance of gut flora to lung immunity was recently published in a paper titled Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production:
“Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.”
Please note that while the last two papers dealt with a bacterial pneumonia model, there is nothing to suggest that the same would not be true for viral pneumonia.
So now, more than ever, healthy gut flora may make the difference between being in the 80% of cases that are mild to moderate should you be unlucky enough to be infected with COVID-19 as opposed to the 20% of cases who go on to require hospitalization. The fact that the elderly, those suffering from high blood pressure, type-2 diabetics, the obese, and those with cardiovascular issues are most at risk for serious complications suggests to me that gut dysbiosis (and resulting endotoxemia and chronic immune activation) may be an unrecognized risk factor.
Therefore, I strongly advise my readers to begin taking prebiotics and probiotics to build up your colonies of healthy gut flora. I currently recommend Jarrow Formulas Inulin FOS and Balance One Probiotic. This probiotic is made by the same manufacturer (Probi) that used to make my probiotic formula. The reason I recommend it is because of the BIO-Tract™ patent that ensures that these probiotic bacteria survive transit through the stomach. No other probiotic manufacturer on the market offers this technology.
Other recommendations include ceasing all smoking and vaping, and yes that includes marijuana. Smoking, and to a lesser extent vaping, alter oral flora which in turn alters gut flora for the worse and both irritate lung tissue. I would also refrain from binge drinking as that will only lower your immunity and contribute to gut dysbiosis as detailed here. And it should go without saying that you must eat a healthy diet and get plenty of rest to keep your immune system in good shape.
Recent research also points to the importance of adequate serum vitamin D levels in preventing cytokine storms. (2) This may explain some of the higher mortality rates seen in African-Americans as dark-skinned people are more prone to vitamin D deficiency. Be aware that should you choose to supplement with vitamin D, it needs to be taken with vitamin K2 to avoid calcification of the arteries.
Obviously none of this will prevent you from being infected if you come in prolonged contact with someone shedding coronavirus. Only social distancing can do that at this time. For the best information on how to avoid contracting COVID-19, I highly recommend reading this post written by an Associate Professor of Biology at the University of Massachusetts Dartmouth. But should you become infected, current research strongly suggests that having a healthy gut flora is far more advantageous than not.
Stay safe everyone!