This letter exposes some of the many reasons why microbiota modulation in patients with COVID-19 disease and more in general, in all people at greatest risk of contracting SARS-CoV2 virus infections, should be taken into consideration

Pantanella, Fabrizio

Schippa, Serena

English

Serena Schippa

Fabrizio Pantanella

Archivio della ricerca- Università di Roma La Sapienza

SARS-CoV-2 and MicrobiotaSerena Schippa*, Fabrizio PantanellaDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Section of Microbiology, P.le A. Moro 5, 00185,Rome, ItalyLETTER TO EDITORThis letter exposes some of the many reasons why microbiotamodulation in patients with COVID-19 disease and more ingeneral, in all people at greatest risk of contracting SARS-CoV2virus infections, should be taken into consideration.Corona Virus (CoV) is a single-stranded positive-sense RNAvirus familythat is able to infect a wide range of vertebrates, birdsand mammals, including humans. In December 2019, a newbeta-coronavirus has been isolated in Wuhan, Hubei province,China, which was found responsible of a potentially fatalatypical pneumonia. Beta-coronaviruses belong to a subfamily ofcoronaviruses that primarily cause respiratory and intestinaldiseases. To date, seven beta-coronaviruses capable of attackinghumans have been identified: Human Coronavirus 229E;Human Coronavirus OC43; Human Coronavirus NL63;Human Coronavirus HKU1; SARS-CoV; MERS-CoV; SARS-CoV-2. Of these, particularly dangerous are the Severe AcuteRespiratory Syndrome (SARS) caused by Sars-CoV, and theMiddle East respiratory syndrome caused by Mers-CoV. The newcoronavirus isolated in Wuhan has been named Sars-CoV-2.SARS-CoV-2 is found to be similar to the SARS-CoVresponsible for the epidemic SARS that occurred in 2002. Anaccurate comparative analysis of the available genomic datashowed that, this virus most likely shouldn't be a laboratoryconstruct, and what could be likely scenarios from which SARS-CoV-2 evolved. Researchers proposed two possibilities: i) naturalselection in an animal host before the zoonotic transfer; ii)natural selection in humans following zoonotic transfer [1].Today the atypical pneumonia caused by SARS-CoV-2 hasturned into a pandemic, it changed the way we live, and willhave strong economic repercussions worldwide. To date, there isunfortunately no known specific therapy, a vaccine is notavailable, and the only chance we have to stop the spread ofinfection is quarantine. Several strategies for symptomsalleviation, already in use for other infectious and non-infectiousdiseases, are continuously proposed, but at the moment thereare no indications for a medical therapy of choice forCOVID-19. Master data on mortality rates clearly listed thehighest mortality rates in people over 70, in young individualswith comorbidities, but also in younger healthcare workers. Forexample, in Italy, the data updated to 16 April 2020 by thenational college of health IIS, (Istituto Superiore di Sanità),displays 16,991 cases diagnosed among health-workers (medianage 48 years, 32% male). The high risk for health-workers istherefore evident even at a young age for this typology of people(Table 1).Many studies indicate that gut microbiota has a great influenceon the status of human health and on the correct functioning ofour immune system [2-4]. On the other hand, microbiotacomposition may play itself a role in triggering infections, as wellas on infections sequel [4].In a preliminary veterinary study on the fecal microbiotacomposition in healthy cats compared to Feline Coronaviruses(FCoV)-infected cats, Meazzi S, et al. showed that in the FCoV-positive cats, firmicutes and bacteroidetes were respectively over-and under-represented, compared to the healthy cats microbiota,demonstrating a possible correlation between microbiota andcoronavirus infections in animals [5].Even if respiratory symptoms such as cough and dyspnoea andinflammatory symptoms such as fever are the most frequentclinical manifestation in patients infected with SARS-CoV-2,also intestinal involvement has emerged from data collected onpatients' symptoms. A recent document by the Italian Federationof Digestive System Diseases Society (FISMAD) reports that anon-negligible number of SARS-CoV-2 infected patients havediarrhoea, nausea, vomiting and/or abdominal discomfort, atthe beginning or even before respiratory symptoms. The samedocument also indicates that the virus SARS-CoV-2 uses theACE2 protein as a receptor, which is expressed in the lung,kidney, and gastrointestinal tract [6,7]; Viral RNA isdemonstrable in 29-53% of the faeces samples collected inCOVID-19 patients; possible oro-faecal transmission maycontinue after respiratory tract viral clearance [8]. Recently somestudies have examined the possible variations of the intestinalmicrobiota in relation to COVID-19 [9-11]. We have not enoughdata to say with certainty that modulation of the gut microbiotacould play a therapeutic role in the treatment of COVID-19, butmaybe targeting microbiota composition could represent anJournal of Probiotics & HealthISSN: 2329-8901 Journal of Probiotics & Health Letter to EditorCorrespondence to: Serena Schippa, Department of Public Health and Infectious Diseases, Sapienza University of Rome, Section of Microbiology,P.le A. Moro 5, 00185, Rome, Italy; Tel: + 390649914638, E-mail: serena.schippa@uniroma1.itCitation: Schippa S, Pantanella F (2020) SARS-CoV-2 and Microbiota. J Prob Health. 8:217. DOI: 10.4172/2329-8901.1000217Received: May 05, 2020; Accepted: May 07, 2020, 2020; Published: May 14, 2020Copyright: © 2020 Schippa S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.J Prob Health, Vol.8 Iss.3 No:217 1adjuvant therapeutic option, that will supports patients recovery,or it can also be considered an index of potential risk-factor tobe taken into account in prevention, especially in people at risk,such as old people and the most exposed health personnel. As amatter of fact, during the epidemic critical phases, as in the caseof the recent SARS-CoV-2 pandemic, hospitals andconsequently doctors and nurses are under strong pressure, bothpsychological (they must face a much higher than normalmortality rate) and physiological (greater work performance). Infact, tight shift work and sleep loss and circadian misalignmentinevitably lead to changes in the gut microbiota [12]. TheNational Commission for Chinese Health and the NationalAdministration of Traditional Chinese Medicine include theuse of probiotics to maintain the gut microbiota balance in theirrecommendations for the treatment of patients with severeCOVID-19. This indicates that the Chinese government andfirst-line medical personnel take in serious consideration therole that the gut microbiota plays in the COVID-19 infection.Furthermore, the extensive use of antibiotics, which is especiallydiffused in the most virus-affected countries such as Italy, Spainand France, corroborate the idea of a gut microbiota’s role inCOVID-19, as antibiotics are indeed well known to induce anintestinal dysbiosis status, leading to immune systemmalfunctioning. Regarding the choice of probiotics, it must beremembered that not all probiotics act in the same way.Gabryszewski SJ, et al. identified and characterized an effectiveLactobacillus-mediated innate immune shield, which mayultimately serve as critical and long-term protection against viralrespiratory infection in the absence of specific antiviral vaccines[13].The comorbidities reported among SARS-CoV-2 positive deaths,such as diabetes, hypertension, atrial fibrillation, dementia andstroke, are pathologies cured by metformin, statins, PPIs (ProtonPump Inhibitors), psychiatric drugs, all drugs with the ability tomodify the gut microbiota’s composition. Also the advanced ageof the majority of patients with severe COVID-19, especially theones who do not overcome viral pneumonia, could also belinked to gut microbiota, as it is well known that in elderlypeople gut microbiota is depleted, especially in terms ofbiodiversity. Considering that the main way of entry of theSARS-CoV-2 is the nasal mucosa, it is worthy of interest thatseveral studies indicate that patients affected by virus airwayinfections are often associated to having a specific nasalmicrobiota and, vice versa, specific nasal microbiota seems to beassociated to a more severe outcome of the airway infection[14-16]. It is very likely that the presence of SARS-CoV-2 exerts astrong selective pressure able to have an effect on the microbiotastructure of the upper airways and intestine districts, as well asfor the microbiota structure to exert an influence on SARS-CoV-2 infection outcome. Modifications in respiratory tract andgut districts have recently been linked to alterations in immuneresponses and to disease development in the lung [17,18]. Theexistence of a "gut-lung axis" has been recently strengthened byseveral studies [19]. Brown and collaborators showed that lungmicrobiota protect versus Streptococcus pneumoniae and Klebsiellapneumoniae respiratory infections, by priming pulmonaryproduction of granulocyte-macrophage colony-stimulating factor(GM-CSF), by IL-17 and Nod2 stimulus [20]. An increasedmorbidity and mortality, during K. pneumoniae, S. pneumoniae orP. aeruginosa acute lung infection, was observed in germ-freemice [20,21]. Recent studies conducted in mice with a gutdysbiosis induced by antibiotic treatment, revealed that alveolarmacrophages were less reactive to stimulus and showed areduced phagocytic capacity [22]. It is possible that themicrobiota acts on macrophages by the release of short-chainfatty acids (SCFAs), known to have wide ranging effects onimmune cell function [23]. It has been reported that the SCFAbutyrate can repress the expression IL6, IL12b, and Nos2 bycolonic macrophages [24,25], while propionate can decreasemacrophage stimulation in vitro [26]. The control of infectiousdiseases by macrophage activation plays an important role.Numerous environmental features seem to control macrophagedifferentiation and function [27,28] and, among those, gut andlung microbiota seem both to play an equally important role incontrolling infectious diseases. From this brief discussion it isevident that not only the intestinal, but also the nasalmicrobiota could be involved in COVID-19 and its course. In arecent study [29] it was highlighted as an efficient immunesystem, capable of early adaptive immune responses, mightcorrelate with a better clinical outcome in the case of a SARS-CoV-2 patient.As up to date we have no certainty, studies aimed at recognizingintestinal/nasal microbial ecosystem changes in patients withCOVID-19 are urgent and highly necessary. Results will greatlyimprove our knowledge and help us prescribe more appropriatepro/prebiotic supporting therapies. Nevertheless, the urgency ofthe present situation, together with the numerous evidencessupporting the nasal and gut microbiota role in COVID-19,should suggest the immediate use of pro/prebiotic therapies, asa therapeutic support in these patients.Table 1: Distribution of cases and deaths in health-workers. (Datasource: https://www.epicentro.iss.it/coronavirus/bollettino/Bollettino-sorveglianza-integrata-COVID-19_16-aprile-2020.pdf) Epidemiology forpublic health-Istituto Superiore di Sanità-National Update April 16,2020).Age class Cases Deceasedyears N % N %18-29 1.622 9,6 0 0,030-39 2.857 16,9 2 3,340-49 4.782 28,2 4 6,750-59 5.757 34,0 16 26,760-69 1.84 10,9 26 43,370-79 95 0,6 12 20,0Total 16.953  60  In critical emergency cases, such as those that are occurringaround the world these days, where it is not possible to reducestress levels, a properly designed diet (ad personam), the use ofSchippa and PantanellaJ Prob Health, Vol.8 Iss.3 No:217 2specific probiotics and prebiotics, and a microbiological analysison the health status of the intestinal microbiota of health-personnel, doctors and nurses, could help reduce the level ofrisk for these types of professionals.The data in this table, from a recent ISS report, show that, incertain critical situations, also young healthcare workers can beexposed to the risk of contracting SARS-CoV-2 infection, muchmore than their coetaneous in the rest of the population.REFERENCES1. 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SARS-CoV-2 and microbiota

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SARS-CoV-2 and microbiota

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