Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) persistence in COVID-19 patients could play a key role in the emergence of variants of concern. The rapid intra-host evolution of SARS-CoV-2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID-19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID-19 patients with persistent SARS-CoV-2 infection, from January 2022 to March 2023, was conducted. To characterize the intra- and inter-host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS-CoV-2 intra-host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host-based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro-active genomic surveillance of persistent SARS-CoV-2 infected patients is recommended to identify genetically divergent lineages before their diffusion.

Gut Microbiota Profile Changes in Patients with Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease: A Metagenomic Study.

Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. ß-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation.

A systematic review on antibiotic therapy of cutaneous bacillary angiomatosis not related to major immunocompromising conditions: from pathogenesis to treatment.

BACKGROUND: Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella spp. that mostly affects people living with HIV (PLWH), transplanted patients and those taking immunosuppressive drugs. Since cBA is mostly related to these major immunocompromising conditions (i.e., T-cell count impairment), it is considered rare in relatively immunocompetent patients and could be underdiagnosed in them. Moreover, antimicrobial treatment in this population has not been previously investigated. METHODS: We searched the databases PubMed, Google Scholar, Scopus, OpenAIRE and ScienceDirect by screening articles whose title included the keywords "bacillary" AND "angiomatosis" and included case reports about patients not suffering from major immunocompromising conditions to provide insights about antibiotic treatments and their duration. RESULTS: Twenty-two cases of cBA not related to major immunocompromising conditions were retrieved. Antibiotic treatment duration was shorter in patients with single cBA lesion than in patients with multiple lesions, including in most cases macrolides and tetracyclines. CONCLUSIONS: cBA is an emerging manifestation of Bartonella spp. infection in people not suffering from major immunocompromising conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Changing and evolution of influenza virus: is it a trivial flu?

BACKGROUND: Influenza viruses are etiological agents which cause contagious respiratory, seasonal epidemics and, for Influenza A subtypes, pandemics. The clinical picture of Influenza has undergone continuous change over the years, due to intrinsic viral evolution as well as "reassortment" of its genomic segments. The history of Influenza highlights its ability to adapt and to rapidly evolve, without specific circumstances. This reflects the complexity of this pathology and poses the fundamental question about its assumption as a "common illness" and its impact on public health. SUMMARY: The global influenza epidemics and pandemics claimed millions of deaths, leaving an indelible mark on public health, and showing the need for a better comprehension of the influenza virus. The clear understanding of genetic variations during the Influenza seasonal epidemics is a crucial point for developing effective strategies for prevention, treatment, and vaccine design. The recent advance in Next Generation Sequencing approaches, model systems to virus culture and bioinformatics pipeline played a key role in the rapid characterization of circulating Influenza strains. In particular, the increase of computational power allowed to perform complex tasks in healthcare setting through Machine Learning (ML) algorithms, which analyze different variables, such as medical and laboratory outputs, to optimize medical research and to improve public health systems. The early detection of emerging and re-emerging pathogens is of matter importance to prevent next pandemics. KEY MESSAGES: The perception of influenza as a "trivial flu" or a more serious public health concern is a subject of ongoing debate, reflecting the multifaceted nature of this infectious disease. The variability in the severity of influenza shed the light on the unpredictability of the viral characteristics, coupled with the challenges in accurately predicting circulating strains. This adds complexity to the public health burden of Influenza and highlights the need of targeted interventions.

Characterization of SARS-CoV-2 Variants in Military and Civilian Personnel of an Air Force Airport during Three Pandemic Waves in Italy.

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy in order to classify viral isolates in a potential hotspot for virus spread. Positive samples were subjected to Next-Generation Sequencing (NGS) of the whole viral genome and Sanger sequencing of the spike coding region. Phylogenetic analysis classified viral isolates and traced their evolutionary relationships. Clusters were identified using 70% cut-off. Sequencing methods yielded comparable results in terms of variant classification. In 2020 and 2021, we identified several variants, including B.1.258 (4/67), B.1.177 (9/67), Alpha (B.1.1.7, 9/67), Gamma (P.1.1, 4/67), and Delta (4/67). In 2022, only Omicron and its sub-lineage variants were observed (37/67). SARS-CoV-2 isolates were screened to detect naturally occurring resistance in genomic regions, the target of new therapies, comparing them to the Wuhan Hu-1 reference strain. Interestingly, 2/30 non-Omicron isolates carried the G15S 3CLpro substitution responsible for reduced susceptibility to protease inhibitors. On the other hand, Omicron isolates carried unusual substitutions A1803V, D1809N, and A949T on PLpro, and the D216N on 3CLpro. Finally, the P323L substitution on RdRp coding regions was not associated with the mutational pattern related to polymerase inhibitor resistance. This study highlights the importance of continuous genomic surveillance to monitor SARS-CoV-2 evolution in the general population, as well as in restricted communities.

Does the Human Gut Virome Contribute to Host Health or Disease?

The human gastrointestinal (GI) tract harbors eukaryotic and prokaryotic viruses and their genomes, metabolites, and proteins, collectively known as the "gut virome". This complex community of viruses colonizing the enteric mucosa is pivotal in regulating host immunity. The mechanisms involved in cross communication between mucosal immunity and the gut virome, as well as their relationship in health and disease, remain largely unknown. Herein, we review the literature on the human gut virome's composition and evolution and the interplay between the gut virome and enteric mucosal immunity and their molecular mechanisms. Our review suggests that future research efforts should focus on unraveling the mechanisms of gut viruses in human homeostasis and pathophysiology and on developing virus-prompted precision therapies.

Prevalence of Colonization with Multidrug-Resistant Bacteria: Results of a 5-Year Active Surveillance in Patients Attending a Teaching Hospital.

Combating antimicrobial resistance (AMR) requires comprehensive efforts, such as screening to identify patients colonized by multidrug-resistant microorganisms (MDROs). The primary purpose of this study was to estimate the AMR pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolated from nasal surveillance swabs and MDROs isolated from pharyngeal and rectal surveillance swabs in patients attending a teaching hospital. Data were sought retrospectively, from 1 January 2017 to 31 December 2021, from the records produced by the hospital microbiology laboratory. Duplicate isolates, defined as additional isolates of the same microorganism with identical antibiograms, were excluded. Among Staphylococcus aureus isolates from nasal swabs, 18.2% were oxacillin-resistant. Among Gram-negative bacteria, 39.8% of Klebsiella pneumoniae and 83.5% of Acinetobacter baumannii isolates were carbapenem-resistant. Resistance to three antibiotic categories was high among Acinetobacter baumannii (85.8%) and Klebsiella pneumoniae (42.4%). The present data highlight a high prevalence of MDRO colonization among patients admitted to the hospital and suggest that screening for MDROs could be an important tool for infection control purposes, especially in geographical areas where limiting the spread of MDROs is crucial. The results also underline the importance of active surveillance, especially for carbapenem-resistant, Gram-negative bacteria in reducing their transmission, especially in high-risk units.

The Role of Gut Microbiota in the Clinical Outcome of Septic Patients: State of the Art and Future Perspectives.

Sepsis is a life-threatening multiple-organ dysfunction caused by a dysregulated host response to infection, with high mortality worldwide; 11 million deaths per year are attributable to sepsis in high-income countries. Several research groups have reported that septic patients display a dysbiotic gut microbiota, often related to high mortality. Based on current knowledge, in this narrative review, we revised original articles, clinical trials, and pilot studies to evaluate the beneficial effect of gut microbiota manipulation in clinical practice, starting from an early diagnosis of sepsis and an in-depth analysis of gut microbiota.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Evaluation of IL-35, as a Possible Biomarker for Follow-Up after Therapy, in Chronic Human Schistosoma Infection.

The host response to helminth infections is characterized by systemic and tissue-related immune responses that play a crucial role in pathological diseases. Recently, experimental studies have highlighted the role of regulatory T (Tregs) and B (Bregs) cells with secreted cytokines as important markers in anti-schistosomiasis immunity. We investigated the serical levels of five cytokines (TNFα, IFN-γ, IL-4, IL-10 and IL-35) in pre- and post-treatment samples from chronic Schistosoma infected patients to identify potential serological markers during follow-up therapy. Interestingly, we highlighted an increased serum level of IL-35 in the pre-therapy samples (median 439 pg/mL for Schistosoma haematobium and 100.5 pg/mL for Schistsoma mansoni infected patients) compared to a control group (median 62 pg/mL and 58 pg/mL, respectively, p ≤ 0.05), and a significantly lower concentration in post-therapy samples (181 pg/mL for S. haematobium and 49.5 pg/mL for S. mansoni infected patients, p ≤ 0.05). The present study suggests the possible role of IL-35 as a novel serological biomarker in the evaluation of Schistosoma therapy follow-up.

Interleukin-62/lymphocyte as a proposed predictive index for COVID-19 patients treated with monoclonal antibodies.

In a convenience sample of 93 patients treated with monoclonal antibodies (moAbs) against SARS-CoV-2, the interleukin-62/lymphocyte count ratio (IL-62/LC) was able to predict clinical worsening both in early stages of COVID-19 and in oxygen-requiring patients. Moreover, we analysed 18 most at-risk patients with asymptomatic or mild disease treated with both moAbs and antiviral treatment and found that only 2 had clinical progression, while patients with a similar risk were reported to have an unfavourable outcome in most cases from recent data. In only one of our 18 patients, clinical progression was attributable to COVID-19, and in the other cases, clinical progression was observed despite IL-62/LC being above the risk cut-off. In conclusion, IL-62/LC may be a valuable method to identify patients requiring more aggressive treatments both in earlier and later stages of the disease; however, most at-risk patients can be protected from clinical worsening by combining moAbs and antivirals, even if levels of the IL-62/LC biomarker are lower than the risk cut-off.

COVID-19 Vaccine Booster Shot Preserves T Cells Immune Response Based on Interferon-Gamma Release Assay in Inflammatory Bowel Disease (IBD) Patients on Anti-TNFα Treatment.

Immune-modifying treatment in inflammatory bowel disease (IBD) impairs the humoral response. The role of T lymphocytes in this setting is still unclear. This study aims to assess if a booster shot (third dose) of BNT162b2 mRNA COVID-19 vaccine enhanced the humoral response and elicited cellular immunity in IBD patients on different immuno-therapy regimens compared to healthy controls (HCs). Five months after a booster dose, serological and T-cell responses were assessed. The measurements were described using geometric means with 95% confidence intervals. The differences between study groups were assessed by Mann-Whitney tests. Seventy-seven subjects (n = 53 IBD patients and n = 24 HCs), who were fully vaccinated and not previously SARS-CoV-2 infected, were recruited. Regarding the IBD patients, 19 were affected by Crohn's disease and 34 by ulcerative colitis. During the vaccination cycle, half of the patients (53%) were on stable treatment with aminosalicylates, and 32% were on biological therapy. No differences in antibody concentrations between IBD patients and HCs, nor T-cell responses, were found. Stratifying IBD patients based on the type of treatment (anti-TNFα agents vs. other treatment regimens), a decrease only in antibody titer (p = 0.008), but not in cellular response, was observed. Even after the COVID-19 vaccine booster dose, the TNFα inhibitors selectively decreased the humoral immune response compared to patients on other treatment regimens. The T-cell response was preserved in all study groups. These findings highlight the importance of evaluating T-cell immune responses following COVID-19 vaccination in a routine diagnostic setting, particularly for immunocompromised cohorts.

Molecular Characterization and Cluster Analysis of SARS-CoV-2 Viral Isolates in Kahramanmaras City, Turkey: The Delta VOC Wave within One Month.

The SARS-CoV-2 pandemic has seriously affected the population in Turkey. Since the beginning, phylogenetic analysis has been necessary to monitor public health measures against COVID-19 disease. In any case, the analysis of spike (S) and nucleocapsid (N) gene mutations was crucial in determining their potential impact on viral spread. We screened S and N regions to detect usual and unusual substitutions, whilst also investigating the clusters among a patient cohort resident in Kahramanmaras city, in a restricted time span. Sequences were obtained by Sanger methods and genotyped by the PANGO Lineage tool. Amino acid substitutions were annotated comparing newly generated sequences to the NC_045512.2 reference sequence. Clusters were defined using phylogenetic analysis with a 70% cut-off. All sequences were classified as Delta. Eight isolates carried unusual mutations on the S protein, some of them located in the S2 key domain. One isolate displayed the unusual L139S on the N protein, while few isolates carried the T24I and A359S N substitutions able to destabilize the protein. Phylogeny identified nine monophyletic clusters. This study provided additional information about SARS-CoV-2 epidemiology in Turkey, suggesting local transmission of infection in the city by several transmission routes, and highlighting the necessity to improve the power of sequencing worldwide.

SARS CoV-2 spike protein-guided exosome isolation facilitates detection of potential miRNA biomarkers in COVID-19 infections.

OBJECTIVES: Nearly three years into the pandemic, SARS-CoV-2 infections are occurring in vaccinated and naturally infected populations. While humoral and cellular responses in COVID-19 are being characterized, novel immune biomarkers also being identified. Recently, an increase in angiotensin-converting enzyme 2 expressing (aka, ACE2 positive) circulating exosomes (ExoACE2) were identified in the plasma of COVID-19 patients (El-Shennawy et al.). In this pilot study, we describe a method to characterize the exosome-associated microRNA (exo-miRNA) signature in ACE2-positive and ACE2-negative exosomal populations (non-ExoACE2). METHODS: We performed a sorting protocol using the recombinant biotin-conjugated SARS CoV-2 spike protein containing the receptor binding domain (RBD) on plasma samples from six patients. Following purification, exo-miRNA were characterized for ACE2-positive and ACE2-negative exosome subpopulations by RT-PCR. RESULTS: We identified differential expression of several miRNA. Specifically let-7g-5p and hsa-miR-4454+miR-7975 were upregulated, while hsa-miR-208a-3p and has-miR-323-3p were downregulated in ExoACE2 vs. non-ExoACE2. CONCLUSIONS: The SARS CoV-2 spike-protein guided exosome isolation permits isolation of ExoACE2 exosomes. Such purification facilitates detailed characterization of potential biomarkers (e.g. exo-miRNA) for COVID-19 patients. This method could be used for future studies to further the understanding mechanisms of host response against SARS CoV-2.

The Spread of SARS-CoV-2 Omicron Variant in CALABRIA: A Spatio-Temporal Report of Viral Genome Evolution.

We investigated the evolution of SARS-CoV-2 spread in Calabria, Southern Italy, in 2022. A total of 272 RNA isolates from nasopharyngeal swabs of individuals infected with SARS-CoV-2 were sequenced by whole genome sequencing (N = 172) and/or Sanger sequencing (N = 100). Analysis of diffusion of Omicron variants in Calabria revealed the prevalence of 10 different sub-lineages (recombinant BA.1/BA.2, BA.1, BA.1.1, BA.2, BA.2.9, BA.2.10, BA.2.12.1, BA.4, BA.5, BE.1). We observed that Omicron spread in Calabria presented a similar trend as in Italy, with some notable exceptions: BA.1 disappeared in April in Calabria but not in the rest of Italy; recombinant BA.1/BA.2 showed higher frequency in Calabria (13%) than in the rest of Italy (0.02%); BA.2.9, BA.4 and BA.5 emerged in Calabria later than in other Italian regions. In addition, Calabria Omicron presented 16 non-canonical mutations in the S protein and 151 non-canonical mutations in non-structural proteins. Most non-canonical mutations in the S protein occurred mainly in BA.5 whereas non-canonical mutations in non-structural or accessory proteins (ORF1ab, ORF3a, ORF8 and N) were identified in BA.2 and BA.5 sub-lineages. In conclusion, the data reported here underscore the importance of monitoring the entire SARS-CoV-2 genome.

Role of Treg, Breg and other cytokine sets in host protection and immunopathology during human leishmaniasis: Are they potential valuable markers in clinical settings and vaccine evaluation?

Leishmaniasis is a vector-borne disease caused by obligate intracellular protozoan parasites that can infect humans and other mammals. Pro- and anti-inflammatory cytokines are important regulators of innate and specific responses in Leishmania infection. Resistance to leishmaniasis is related to T helper 1 (Th1) response with the production of pro-inflammatory cytokines: IL-12, IL-1ß, IFN-γ, TNF-α, IL-2 leading to activation of macrophages and parasite killing. Instead, a more intense Th2 (IL-4, IL-5, IL-13), Treg (IL-10 and TGF-ß) and Breg response (IL-10 and IL-35) are related to parasite persistence through the inhibition of macrophage activation, which promotes the escape from host immune system. Interestingly, a cytokine involved in the parasite killing in one form of leishmaniasis may be "pathogen friendly" in another form of the disease. To date, few studies are focusing on the role of Treg and Breg cytokines in human models of leishmaniasis; therefore, further investigations are needed to clarify their potential role in the diagnosis and prognosis of such protozoan infections, as well as in the development of vaccines against leishmaniasis. This review summarizes the current knowledge about the role of cytokines produced by Th1, Th2, Treg, and Breg cells involved in Leishmania disease progression and host protection. Some cytokines might play a role as diagnostic and prognostic clinical markers, or they could represent a novel approach leading to new anti-leishmaniasis therapies. Overall, advances in knowledge of the complex network of cytokines secreted by immune cells could help to better understand signaling pathways and host immune responses during Leishmania infection. This approach would allow these mediators to be used as therapeutic strategies against leishmaniasis.

Changing epidemiology of hepatitis C in Italy: a population-based survey in a historically high endemic area.

BACKGROUND: General population data on hepatitis C virus (HCV) prevalence in Italy come mostly from studies conducted in small towns. The highest rates have consistently been found in southern regions, especially in Calabria. Herein, we aimed to determine HCV prevalence, awareness, and risk factors in the general population of Catanzaro, the capital city of Calabria, Italy. METHODS: A stratified probability-based random sample of adult population was drawn from the Census. Anti-HCV and HCV-RNA were assayed. Data on sociodemographycs, risk factors and awareness of infection status were also collected. Crude and age and sex directly standardized rates (DSR), using Catanzaro's general population as standard, were calculated. Log binomial regressions with sampling weights was used to identify independent predictors of infection. RESULTS: The final study population consisted of 1003 people. Of them 27 (2.69%; 95% confidence interval, [CI] 1.78-3.89) (DSR: 2.34%; 95% CI: 1.37-3.30) and 9 (0.9%; 95% CI: 0.41-1.70) (DSR: 0.79%; 95% CI: 0.21-1.37) were anti-HCV and HCV RNA positive, respectively. Most HCV-positive participants were older people. Age ≥65 and past use of illicit drugs were both positive independent predictors of anti-HCV positivity, while female sex was an independent protective predictor of infection. Only 9 (33.3%) of anti-HCV positive participants had awareness of their status. CONCLUSIONS: We detected a much lower anti-HCV prevalence than those previously found in Calabria, along with a substantial change in HCV transmission modes. Infected people were almost only elderly and mostly unaware of their infection. Improving diagnosis and linkage to care for these infected persons would be needed.

Role of IgG and IgM and proinflammatory non-specific markers in the diagnosis and prognosis of COVID-19 patients stratified by number of positive SARS-CoV-2 genes.

BACKGROUND: A prompt set of suitable biomarkers is needed in suspected COVID-19 patients. This study aims to assess patients positive for one or more gene associated with the C reactive protein (CRP) and procalcitonin (PCT) as non-specific pro-inflammatory markers and IgG and IgM kinetic as specific diagnostic and prognostic tools in SARS-CoV-2 RT-PCR positive patients. METHODS: We enrolled 101 patients within a two month time span (March 26th, 2020 to May 31st, 2020). A reverse transcription-Real-Time PCR assay on nasopharyngeal/oropharyngeal swabs was used for SARS-CoV-2 identification. Serum anti-SARS-CoV-2 IgM and IgG were measured by enzyme immunoassay, PCT levels by Enzyme linked fluorescent assay (ELFA)and CRP by nephelometry. RESULTS: We found that older patients were significantly associated with a worse prognosis. Serum IgM levels were significantly lower during the late stage of the disease, regardless of the presence of one or three genes and patients' outcome. On the contrary, IgG levels exhibited a higher concentration in the late phases of the illness, regardless of the gene found or patients' prognosis. With the exception of the very first sample tested, an increase in CRP in surviving patients (both one and three genes) and a time-dependent decrease of deceased patients CRP was found. PCT levels were always within the normal reference range. The difference between one gene and three genes patients was significant during late disease stages regarding IgG levels and also between three genes survivors versus three genes deceased, where the IgG levels were progressively increasing over time. CONCLUSIONS: The relevant finding of the present study is the significant and consistent increase of IgG and IgM in deceased patients. The associated evaluation of antibody kinetics and non specific inflammatory markers (CRP and PCT) in positive patients stratified according to the presence of one gene or three genes could help the clinician in both the diagnosis and prognosis of COVID-19 patients.