Introduktion COVID-19 orsakas av viruset SARS-CoV-2. 3-chymotrypsin-liknande cysteinproteaset (3CLpro) är ett enzym som styr coronavirus replikation och är viktigt för viruset livscykel. Därför 3CL pro är en viktig måltavla för att hämma SARS-CoV-2. Syfte Syftet med detta projekt är att undersöka om proteashämmare kan vara en framkomlig väg för att ta fram antivirala läkemedel mot COVID-19. Metod Arbetet är en litteraturstudie och databasen PubMed har använts för att hitta vetenskapliga artiklar med hjälp av olika sökord, såsom SARS-CoV 2 and protease inhibitors, SARS-CoV-2 and 3CL-pro, MERS-CoV and 3CLpro inhibitors och SARS-CoV and 3CLpro. Totalt valdes 10 vetenskapliga artiklar ut som grund för att undersöka om några proteashämmare finns rapporterade och hur de utvärderats, dvs i prekliniska studier eller kliniska studier. Resultat  Peptidomimetiska alfa-ketoamider är effektiva bredspektrum hämmare för att hämma 3CL pro i SARS-CoV-2 och enterovirus, t.ex. alfa-ketoamiderna (13a och 13b) som även visade goda farmakokinetiska egenskaper i prekliniska studier. Även läkemedelskandidater (11a och 11b) har utvärderats i prekliniska studier och både visade hög SARS-CoV-2 3CL-pro hämmande aktivitet. Två nya studier visade att genomsekvensen för SARS-CoV-2 3CLpro är mycket lik den för SARS-CoV-1 än MERS-CoV. Herbacetin, rhoifolin pectolinarin och Biflavonoid amentoflavon 9 visade en effektiv hämning av SARS-CoV-1 3CL pro. Herbacetin, isobavachalcone, quercetin 3 ‐ β ‐ d ‐ glukosid, helikrysetin och enterovirushämmare (6b, 6c och 6d) visat sig ha hämmande aktivitet och kunde hämma den enzymatiska aktiviteten hos MERS-CoV 3CL pro. De redan framtagna HIV-proteashämmarna lopinavir och ritonavir har utvärderats i kliniska prövningar och både visade ingen skillnad mot standardbehandling samt minskade inte dödlighet. Slutsats Slutsatsen som kan dras av studien är att det finns flera proteashämmare i preklinisk fas mot SARS-COV-2 3CL-pro samt finns flera proteashämmare mot SARS-CoV-1 och MERS-CoV. Proteashämmare kan vara ett möjligt läkemedel mot COVID-19 i framtiden, men det tar lång tid för att utveckla ett nytt läkemedel.

Following the detection of SARS-CoV-2 RNA fragments in wastewater in March 2020, the use of wastewater-based epidemiology is rapidly emerging as a non-invasive approach to assessing community wide COVID-19 prevalence. Wastewater-based epidemiology is promoted as a complement to clinical testing in terms of improving public health authorities’ preparedness and supporting them in taking required interventions to protect the public health.  To utilize the occurrence of SARS-CoV-2 in wastewater in a public health context and evaluate trends in viral prevalence on a community level, robust data interpretation is required. This master's thesis work examines what is currently known about the factors that influence the concentrations of SARS-CoV-2 in wastewater, as well as the impact of alternative normalization approaches on the relationship between viral wastewater data and clinical case numbers. The work is divided into two parts where this report provides a state-of-the-art review as well as an overview of key findings in the accompanied scientific paper.  The study involved collection of wastewater samples from two different sized wastewater treatment plants (WWTPs) in Luleå municipality, between January and March 2021.  Concentrations of SARS-CoV-2 RNA were quantified in each sample as well as concentrations of total nitrogen (TN), total phosphorus (TP) and pepper mild mottle virus (PMMoV). Average daily WWTP flow and environmental data (precipitation and temperature) were continuously measured over the sampling period. The population size was estimated based on mass loads of TN and TP and literature values of the domestic contribution of these parameters to the sewer system. The viral wastewater data was normalized using the estimations of population size, census data, WWTP flow and PMMoV. The impact of the alternative normalization approaches was evaluated using statistical analyses to explore the relationship to clinical case numbers.  The result showed that the strength of the correlation between the different normalization approaches and clinical case data differed between the WWTPs. However, within each WWTP the differences in correlation between the different normalization approaches and clinical cases were not significant. Moreover, normalization using WWTP flow (i.e., viral loads) showed a stronger correlation to clinical cases compared to population and PMMoV normalized viral loads. However, when comparing wastewater data between the two catchment areas, the normalization approaches utilizing population (either census or TN and TP estimated population) or PMMoV better reflect the number of clinical cases. Additionally, according to time-shifted analysis, wastewater data of SARS-CoV-2 RNA predated an increase in clinical cases by 0-2 and 5-8 days, respectively, for the larger and smaller WWTPs.

Introduction: The coronavirus is an RNA virus with a lipid envelope. The initially known coronaviruses are (MERS-CoV and SARS-CoV) which caused fatal endemics in 2002 and 2012. At the end of 2019, a new variant of coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) was discovered in Wuhan in China. SARS-CoV-2 has caused serious diseases especially in the older groups with millions of infections and deaths. The World Health Organization (WHO) identified Covid-19 as a global health emergency on 30 January 2020 and classified it as a pandemic on March 11, 2020. Several companies started developing a vaccine to stop the spread of SARS-CoV-2. Several vaccination programs have been approved and are currently used against Covid-19. Objectives: The work aimed to investigate the safety and efficacy of the approved mRNA-based vaccines against SARS-CoV-2. Method: The work was based on reviewing published, scientific articles that examined safety and efficacy of mRNA-based vaccines (Pfizer BionTech BNT162b and mRNA-1273 Modern). In total there were five clinical trials selected from Pubmed. Two studies examined the safety and efficacy of mRNA-1273 Moderna and three other studies examined the safety and effectiveness of the Pfizer BionTech BNT162b. Results: Both vaccines have shown good safety and efficacy and were well tolerated in patients in different ages. mRNA-based vaccines have shown mild to moderate symptoms that were higher after dose 2 and disappeared after a few days. Both Pfizer BionTech and Modern mRNA-1273 have shown efficiencies over 90%.

Les composés organiques volatils (COV) jouent un rôle majeur au sein du système atmosphérique puisqu’ils interviennent en tant que précurseurs d’ozone troposphérique et d’aérosols organiques secondaires (composés aux divers impacts sanitaires et climatiques) ; d’où le réel besoin de mieux les caractériser. A ce jour, de fortes incertitudes demeurent quant à leur nature, leur quantification et la contribution de leurs sources d’émissions respectives.Cette thèse propose, au travers d’expérimentations de laboratoire et de terrain, une caractérisation exhaustive des COV et de leurs principales sources d’émissions en région Île-de-France. Les méthodes mises en place dans ce travail de thèse reposent sur la détermination de profils de spéciation caractéristiques du trafic routier, du chauffage au bois et du gaz naturel à partir d’investigations en champ proche (en tunnel, en cheminée et à partir d’un conduit de gaz domestique). Ces différents profils de source ont été utilisés comme empreinte chimique de référence pour l’identification des principales sources d’émissions de COV, dont les contributions respectives ont été estimées à l’aide du modèle source-récepteur Positive Matrix Factorization (PMF), appliqué sur une année d’acquisition de mesures COV (HCNM+COVO) à Paris. Ce travail de thèse a ainsi permis, pour la première fois, d’étudier la variabilité saisonnière des COV et de leurs sources majeures. Les émissions liées au trafic routier ont été révélées comme la principale source de COV d’origine locale/régionale à Paris (contribuant à ¼ des émissions totales à l’échelle annuelle). L’impact prépondérant du chauffage au bois en hiver (50 % de la masse totale COV mesurée) a également été mis en évidence. Les résultats de cette étude de répartition de sources ont été confrontés à l’inventaire des émissions d’Airparif. Nous avons souligné un bon accord entre nos observations et l’inventaire pour les sources liées au trafic automobile et au chauffage au bois.Cette évaluation indépendante des inventaires est essentielle puisque ces derniers sont aujourd’hui utilisés comme données d’entrée au sein des modèles de prévision de qualité de l’air. / Volatile organic compounds (VOCs) play a key role within the atmospheric system acting as precursors of ground-level ozone and secondary organic aerosols (causing health and climatic impacts); hence the growing interest of better characterizing them. Significant uncertainties are still associated with compounds speciation, quantification and respective contributions from the different emission sources.This thesis proposes, through several laboratory and intensive field campaigns, a detailed characterization of VOCs and their main emissions sources within the Île-de-France region. We used methods based on the determination of speciation profiles indicative of road traffic, wood burning and natural gas sources obtained from near-field investigations (inside a tunnel, at a fireplace and from a domestic gas flue). These different source profiles were used as chemical fingerprints for the identification of the main VOC emission sources, which respective contributions were estimated using the Positive Matrix Factorization (PMF) source-receptor model applied to one-year VOCs (including NMHC+OVOC) measurements in Paris. This thesis allowed, for the first time, to evaluate the seasonal variability of VOCs and their main emission sources. Road traffic-related emissions are major VOC local/regional sources in Paris (contributing to a quarter of total annual emissions). The important impact of wood burning in winter (50 % of the VOC total mass) was observed. Results obtained from this approach were compared with the regional emissions inventory provided by the air quality monitoring network Airparif. Finally, a good agreement was found between our observations and the inventory for road traffic and wood burning-related sources.This independent assessment of inventories is of great interest because they are currently used as input data within air quality prediction models.

La sensibilisation du grand public à la pollution intérieure, les exigences croissantes des réglementations/recommandations le tout combiné à une nécessité de se démarquer de la concurrence, font de la limitation de la concentration des COV (COV : Composés Organiques Volatiles) dans l’air habitacle un enjeu crucial pour l’industrie automobile. En effet, à l’intérieur des véhicules, les COV sont principalement issus de l’air extérieur par combustion et évaporation du carburant mais, contrairement aux autres polluants, peuvent également avoir une origine intérieure à l’habitacle de par la désorption de substances chimiques utilisées lors de la fabrication des matériaux présents dans le véhicule. La capture des COV par adsorption sur charbons actifs ou zéolithes est à ce jour l’une des techniques d’abattement des COVs les plus efficaces et les moins coûteuses mais souffre de certaines limitations (sélectivité, régénération). L’objectif de cette thèse a consisté à étudier une alternative avec l’emploi d’une autre classe d’adsorbants ‘hybrides’ : les Metal-Organic Frameworks (MOFs). Formés de briques inorganiques connectées par des ligands organiques, ces matériaux poreux cristallisés présentent une grande diversité structurale ainsi qu’une composition chimique (métal, ligand) et une porosité (taille des pores, surface spécifique et volume poreux) extrêmement modulables. Cela vient de la possibilité quasi-infinie de faire varier à la fois le centre métallique et le ligand organique, ce que l’on ne retrouve pas à cette échelle chez les zéolithes et les charbons actifs. Le travail a consisté à évaluer les performances d’une série d’une dizaine de MOFs, possédant des propriétés chimiques (acidité, redox, hydrophiles/hydrophobes, …) et structurales (taille et forme des pores, réseaux rigides ou flexibles…) différenciées mais aussi de leur stabilité avérée (eau, température) et mise à l’échelle déjà établie. En plus des caractérisations usuelles (diffraction des rayons X, analyse thermogravimétrique, spectroscopie Infra-Rouge, porosimétrie N2 à 77K), la spectroscopie Infra-Rouge operando a été utilisée pour simuler le comportement de ces MOFs en présence de COV dans des conditions aussi proches que possible de la réalité. Les adsorbants les plus prometteurs ont ensuite été mis à l’échelle (50-100 g) et mis en forme (pastilles) puis testés en chambre de simulation environnementale. / The indoor air pollution awareness of general public and the increasing demands of regulations / recommendations, combined with a need to stand out from the competition, make limiting the concentration of VOCs (VOCs : volatile organic compounds ) in the air cockpit crucial for the automotive industry. For example, inside a vehicle, the VOCs are originated from the outside air by combustion and evaporation of fuel. However, unlike other pollutants, it may also have an inner origin from the desorption of existing chemical substances used in the manufacture of the vehicle. Thus, the capture of VOCs by adsorption is one of the challenging techniques today. In this context, activated carbon and zeolite based VOC abatement are effective and least expensive but suffers some limitations in stability, selectivity and regeneration. The aim of this thesis was to study an alternative class of 'hybrid' adsorbents i.e. Metal-Organic Frameworks (MOFs). These porous crystalline materials are built by the association of inorganic bricks connected by organic ligands. They have highly tunable structural diversity,chemical composition (metal:ligand) and porosity (pore size, surface area and pore volume). Moreover, they possess almost infinite ability to vary both the metal center and the organic ligand that is not found at this level in zeolites and activated carbons. The work was to evaluate the performance of a series of ten MOFs, having diverse architecture (size and shape of the pores, rigid or flexible networks ...), chemical properties (acidity, redox, hydrophilic / hydrophobic, ...) and stability (water temperature). In addition to the usual characterization (X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, porosimetry N2 at 77K), Infra-Red spectroscopy operando was performed to simulate the behavior of these MOFs in the presence of VOCs in conditions as close as possible to the reality. Furthermore, the most promising adsorbents were scaled up (50-100 g) and formatted/fabricated as pellets and tested for environmental simulation chamber.

En réponse aux changements climatiques avérés et à une qualité de l'air qui se dégrade, la quantification des émissions de gaz à effet de serre et des polluants atmosphériques des régions urbanisées suscite un intérêt croissant. La meilleure description des émissions anthropiques actuellement disponible est proposée par les inventaires d'émission. Mais leurs estimations, fournies par secteur, reposent sur la combinaison de données d'activité et de facteurs d'émission déterminés sur bancs d'essai et qui ne représentent pas forcément bien les conditions réelles d'émission. Paris, en tant que 3e mégapole européenne, se place dans ce contexte et nous avons choisi d'utiliser des méthodes reposant sur l'acquisition de mesures in situ en région parisienne pour caractériser le signal urbain et vérifier les estimations de l'inventaire régional haute résolution d'Airparif. Les méthodes mises en place dans ce travail de thèse reposent sur l'utilisation conjointe de différents traceurs atmosphériques (CO, NOx, COV). En effet, ils sont co-émis au CO2 lors des processus de combustions incomplètes dans des proportions supposées caractéristiques du secteur d'émission. Les rapports de concentration entre les différentes espèces co-émises sont donc un outil de choix pour cette étude. Nous avons alors développé différentes méthodes d'évaluation de ces rapports pour caractériser les émissions pour l'une des sources prédominantes de CO2 à Paris (le trafic routier) ou dans le panache parisien. Les variabilités spatiale et saisonnière des rapports ont notamment pu être étudiées et les conclusions obtenues n'étaient pas forcément référencées dans les estimations des inventaires ou d'études antérieures. Nous avons comparé nos résultats aux estimations fournies par l'inventaire le plus récent d'Airparif qui apparait généralement surestimer ces rapports. Enfin, nous avons combiné les résultats de l'approche multi-espèces à ceux fournis par l'analyse des isotopes du carbone dans le CO2 (souvent utilisés comme référence pour l'étude des émissions anthropiques). D'après leur analyse, les émissions de CO2 à Paris sont majoritairement d'origine fossile (81 %) et l'utilisation des combustibles fossiles est répartie quasi équitablement. Finalement, l'accord satisfaisant trouvé entre les deux démarches (multi-espèces et isotopique) a permis d'affirmer leur pertinence pour l'étude des signaux urbains moyens. / In response to changing air quality and climate, there is a growing interest in quantifying emissions ofatmospheric pollutants and greenhouse gases from urban areas. Currently emission inventories provide the most detailed description of anthropogenic emissions. However, their estimates rely on the combination of activity proxies and emission factors for individual source sectors calibrated for benchmarck situations that may significantly differ from real conditions. Paris, the third largest megacity in Europe, can be considered in this context. We used methods based on in situ measurements in this region to characterise the urban signal and independently assess the latest estimates from the regional inventory. The methods we developed rely on the joint analysis of atmospheric tracers (CO, NOx, VOCs) which are co-emitted with CO2 during incomplete combustion processes in ratios that are characteristic of each emission sector. These ratios between co-emitted species are thus an appropriate tool to study the urban signal. During this PhD, we developed several methods to evaluate the ratios using measurements for a major CO2 emission source in Paris (road traffic) or for measurements acquired in the urban atmosphere. We revealed spatial and seasonal variabilities in these ratios and the main conclusions were not necessarily in complete accordance with the ones from inventories or previous studies. We also compared our results to the estimates provided by the latest regional inventory, which appears to overestimate them in most cases. Finally, we combined the results obtained with the multi-species analysis to the ones provided by isotopic analyses (which are often used as a reference to study anthropogenic emissions). According to the analyses of these measurements, CO2 emissions in Paris came mostly from combustion of fossil fuels (81 %) and the use of each fossil fuel is almost equally distributed. Finally, the satisfactory agreement found between the two approaches (multi-species and isotopic one) confirmed their relevancefor the analysis of mean urban signals.

La maladie à coronavirus (COVID-19) est une infection virale hautement contagieuse causée par le virus SRAS-CoV-2. La maladie s’est rapidement propagée entrainant une épidémie mondiale, causant la mort des personnes à risque. De nombreuses mesures sanitaires ont été prises durant ces deux dernières années, cependant la maladie n’est pas encore éradiquée. Considérant l’importance du système immunitaire dans le contrôle des maladies infectieuses et dans l’induction d’une mémoire immunitaire de longue durée, le SRAS-CoV-2 pourrait être une cible du système immunitaire, en particulier du système adaptatif représenté par les lymphocytes B et T. La réponse humorale induite chez les personnes convalescentes est largement perçue comme étant efficace pour combattre le virus. Par conséquent, toutes les plateformes de vaccination actuelles se sont basées sur la réponse humorale induite, particulièrement par la protéine SPIKE du virus. Compte tenu de la variabilité des réponses humorales ainsi que leur déclin rapide observé chez certains patients, et l’émergence de variants, il est nécessaire d’inclure d’autres stratégies permettant de renforcer la réponse immunitaire. Nous avons émis l’hypothèse qu’une réponse cellulaire pouvait être induite par les lymphocytes T contre les différentes protéines virales du SRAS-CoV-2. Dans cette étude nous avons détecté la réactivité des lymphocytes T contre les protéines virales (SPIKE, membrane, nucléocapside) par ELISPOT chez les patients convalescents. Nous avons ensuite identifié plus précisément les séquences riches en épitopes au niveau de la protéine membranaire et de la nucléocapside en préparant des délétants successifs (approche « mRNA PCR-based epitope chase technique” ou mPec). La validation de ces séquences a été confirmée par l’utilisation de banques de peptides dans des zones définies, se chevauchant de 12 acides aminés. En vue d’inclure ces régions dans une stratégie vaccinale future, une protéine de fusion MN contenant les séquences riches en épitopes a été créée et la réactivité des lymphocytes T contre la protéine MN a été évaluée de nouveau par ELISPOT. Nos données démontrent une réponse T dirigée principalement contre la nucléocapside et la protéine membranaire. Trois zones immunogènes sont identifiées au niveau de la nucléocapside et une zone au niveau de la membrane. La réactivité observée contre la protéine de fusion MN souligne le potentiel pouvoir immunogène des protéines (membrane et nucléocapside) et l’importance d’inclure ces protéines dans une stratégie vaccinale future afin de solliciter une réponse immunitaire cellulaire protectrice. / Coronavirus disease (COVID-19) is a highly contagious viral infection caused by the SARS-CoV-2 virus. The disease has spread rapidly resulting in a worldwide epidemic, causing death in those at risk. Numerous health measures have been taken over the past two years, but the disease has not yet been eradicated. Considering the importance of the immune system in the control of infectious diseases and in the induction of a long-lasting immune memory, SARS-CoV-2 could be a target of the immune system, in particular of the adaptive system represented by B and T lymphocytes. The humoral response induced in convalescent individuals is widely used as an effective therapy to combat the virus. Therefore, all current vaccination platforms have relied on the humoral response induced particularly by the virus' SPIKE protein. Given the variability of humoral responses and their rapid decline in some patients, and the emergence of variants, it is necessary to include other strategies to enhance the immune response. We hypothesized that a cellular response could be induced by T cells against the different viral proteins of SARS-CoV-2. In this study, we detected the reactivity of T cells against viral proteins (SPIKE, membrane, nucleocapsid) by ELISPOT in convalescent patients. We then identified more precisely the immunogenic sequences at the level of the membrane protein and the nucleocapsid by successive deletants using the mRNA PCR-based epitope chase technique (mPec). The validation of these sequences was confirmed by the use of small peptide libraries (overlapping by 12 amino acids), covering defined sequences rich in epitopes. In order to include these regions in a future vaccine strategy, a MN fusion protein containing the selected sequences was created and T cell reactivity against the MN protein was further confirmed by ELISPOT. Our data show a T-cell response primarily against the nucleocapsid and membrane protein. Three immunogenic zones were identified at the nucleocapsid level and one zone at the membrane level. The reactivity observed against the MN fusion protein cassette rich in epitopes, highlights the potential immunogenicity of the proteins (membrane and nucleocapsid) and the importance of including these proteins in a future vaccine strategy.

Background: Vaccination against SARS-CoV-2 significantly reduces the transmissibility of the virus and the likelihood of a severe course of COVID-19, and is thus a critical component in overcoming the current pandemic. The factors associated with adverse reactions after vaccination against SARS-CoV-2 have not yet been sufficiently evaluated. Methods: We used the Disease Analyzer database (IQVIA) to identify 531,468 individuals who received a total of 908,869 SARS-CoV-2 vaccinations in 827 general practices in Germany between April and September 2021. Cox regression models were used to analyze the frequency of vaccination-related side effects reported within 14 days after SARS-CoV-2 vaccination, as well as subjects’ demographic characteristics and comorbidities. Results: The total number of side effects documented was 28,287 (3.1% of all vaccinations). Pain in the limb (24.3%), fatigue (21.0%), dizziness (17.9%), joint pain (15.7%), fever (9.5%), nausea (7.5%), and myalgia (6.4%) were the most common side effects documented among the 12,575 vaccinations with definite side effects. In the multivariate regression analysis, young age was associated with much higher odds of reported side effects (OR18–30 years: 4.45, OR31–40 years: 3.50, OR41–50 years: 2.89). In addition, pre-existing comorbidities such as dementia (OR: 1.54), somatoform disorder (OR: 1.53), anxiety disorder (OR: 1.43), depression (OR: 1.37), chronic respiratory tract disease (OR: 1.27), hypertension (OR: 1.20), and obesity (1.14) significantly increased the odds of side effects. Finally, the male sex was associated with increased odds of reported side effects (OR: 1.17). Conclusion: Our study, based on a large outpatient database from Germany, identified young age, male sex, and pre-existing comorbidities such as dementia, somatoform disorders, anxiety disorders, and depression as factors associated with vaccine-related adverse events diagnosed in GP practices. These data could help to identify subgroups needing particular advice and care in the context of SARS-CoV-2 vaccinations.

Introduction: Community mitigation strategies (CMS) have demonstrated to be effective in the reduction of transmission and incidence of COVID-19, especially in the population with symptoms associated with the disease. The aim of this study was to evaluate the association between the presence of COVID-19 symptoms and adherence to CMS in Latin American adults. Methods: We carried out a secondary analysis of a database developed by the University of Maryland and Facebook social network during the COVID-19 pandemic. We included Latin American adults that used the Facebook platform and participated in a survey conducted from April 23 to May 23, 2020. The principal outcome variable was reported compliance with the three main CMS (physical distancing, use of face masks, and hand washing). The exposure variable included symptoms suspicious for COVID-19 defined as the presence of three or more symptoms of an acute clinical case of COVID-19. We performed generalized linear models of the Poisson family with a logarithmic link function to evaluate the association between the presence of COVID-19 symptoms and reported compliance with CMS. We calculated crude and adjusted prevalence ratios (PR) with their 95% confidence intervals (95%CI). Results: We analyzed 1,310,690 adults from Latin America; 48.1% were male and 42.9% were under 35 years of age. The prevalence of suspicious symptoms of COVID-19 was 18.5% and reported compliance with the three CMS was 45.3%. The countries with the highest proportion of reported compliance with the three CMS were Peru, Bolivia and Panama, while those with the lowest reported compliance were Costa Rica, Nicaragua and Honduras. In the adjusted model, people with suspicious symptoms for COVID-19 had a 14% lower compliance with the three CMS (aPR = 0.86; 95%CI: 0.85–0.87; p < 0.001). Conclusions: Less than half of the participants complied with the CMS, and those presenting suspicious symptoms for COVID-19 had lower reported compliance with the three CMS. / University of Maryland / Revisión por pares

PURPOSE OF REVIEW: This review article aims to explore the GI changes induced by SARS-CoV-2 and how gut microbial homeostasis can influence these changes and affect the lung-gut axis and its relationship with the induction of the cytokine release syndrome in severe COVID-19 patients. RECENT FINDINGS: Coronavirus disease 2019 (COVID-19) affects not only the respiratory system but can produce multi-systemic damage. The expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the gastrointestinal (GI) tract, the high prevalence of GI symptoms in severely ill COVID-19 patients, and the abnormalities described in the gut microbiome in these patients have raised concerns about the influence of GI tract as a risk factor or as a potential modulator to reduce the severity of COVID-19. Understanding the mechanisms by which gut dysbiosis may influence viral transmission and disease progression in COVID-19 may help in shaping how accessible therapies, like diet modulation, can potentially help beat the devastating consequences of COVID-19.