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1.
BMJ Open Ophthalmol ; 7(1)2022 06.
Article in English | MEDLINE | ID: covidwho-2053227

ABSTRACT

OBJECTIVE: To analyse corneal tissues from asymptomatic donors with a postmortem nasopharyngeal swab tested positive for the presence of SARS-CoV-2 RNA, and therefore, understand the role that corneal transplantation may have in viral transmission. METHODS AND ANALYSIS: Between March 2020 and October 2021, 101 corneas (out of 8154 collected in Italy) from 51 donors (out of a total of 4155 Italian donors) positive for SARS-CoV-2 after postmortem nasopharyngeal swab tests were analysed for the presence of SARS-CoV-2 RNA through real-time RT-PCR. When available, the corneal tissue storage media were also assessed. Corneas and/or storage media with confirmed presence of SARS-CoV-2 RNA were further investigated by isolating SARS-CoV-2 virions, which were used to infect VeroE6 target cells. RESULTS: Only N=4 corneas and/or storage media out of 101 showed presence of SARS-CoV-2 RNA. No VeroE6 cell infection was detected with viral isolates, thus suggesting no presence of SARS-CoV-2 virions in corneal specimens and storage media. CONCLUSIONS: The presence of SARS-CoV-2 in cornea specimens would seem to be more likely due to prolonged detection of RNA rather than to active viral replication, with very low risk of infectivity and transmission through keratoplasty.


Subject(s)
COVID-19 , COVID-19/epidemiology , Cornea/chemistry , Humans , Pandemics , RNA, Viral/genetics , SARS-CoV-2/genetics
2.
Nat Commun ; 13(1): 5870, 2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-2050380

ABSTRACT

Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Italy/epidemiology , SARS-CoV-2/genetics
3.
Genome Med ; 14(1): 61, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1951320

ABSTRACT

BACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). RESULTS: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2 , Vaccination
4.
PLoS One ; 17(6): e0270024, 2022.
Article in English | MEDLINE | ID: covidwho-1910667

ABSTRACT

During the first wave of infections, neurological symptoms in Coronavirus Disease 2019 (COVID-19) patients raised particular concern, suggesting that, in a subset of patients, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could invade and damage cells of the central nervous system (CNS). Indeed, up to date several in vitro and in vivo studies have shown the ability of SARS-CoV-2 to reach the CNS. Both viral and/or host related features could explain why this occurs only in certain individuals and not in all the infected population. The aim of the present study was to evaluate if onset of neurological manifestations in COVID-19 patients was related to specific viral genomic signatures. To this end, viral genome was extracted directly from nasopharyngeal swabs of selected SARS-CoV-2 positive patients presenting a spectrum of neurological symptoms related to COVID-19, ranging from anosmia/ageusia to more severe symptoms. By adopting a whole genome sequences approach, here we describe a panel of known as well as unknown mutations detected in the analyzed SARS-CoV-2 genomes. While some of the found mutations were already associated with an improved viral fitness, no common signatures were detected when comparing viral sequences belonging to specific groups of patients. In conclusion, our data support the notion that COVID-19 neurological manifestations are mainly linked to patient-specific features more than to virus genomic peculiarities.


Subject(s)
Ageusia , COVID-19 , Central Nervous System , Genomics , Humans , SARS-CoV-2/genetics
5.
JCI Insight ; 7(10)2022 05 23.
Article in English | MEDLINE | ID: covidwho-1794307

ABSTRACT

T cells play a prominent role in orchestrating the immune response to viral diseases, but their role in the clinical presentation and subsequent immunity to SARS-CoV-2 infection remains poorly understood. As part of a population-based survey of the municipality of Vo', Italy, conducted after the initial SARS-CoV-2 outbreak, we sampled the T cell receptor (TCR) repertoires of the population 2 months after the initial PCR survey and followed up positive cases 9 and 15 months later. At 2 months, we found that 97.0% (98 of 101) of cases had elevated levels of TCRs associated with SARS-CoV-2. T cell frequency (depth) was increased in individuals with more severe disease. Both depth and diversity (breadth) of the TCR repertoire were positively associated with neutralizing antibody titers, driven mostly by CD4+ T cells directed against spike protein. At the later time points, detection of these TCRs remained high, with 90.7% (78 of 96) and 86.2% (25 of 29) of individuals having detectable signal at 9 and 15 months, respectively. Forty-three individuals were vaccinated by month 15 and showed a significant increase in TCRs directed against spike protein. Taken together, these results demonstrate the central role of T cells in mounting an immune defense against SARS-CoV-2 that persists out to 15 months.


Subject(s)
COVID-19 , CD4-Positive T-Lymphocytes , Humans , Receptors, Antigen, T-Cell/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
6.
Cell Tissue Bank ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1718789

ABSTRACT

Covid pandemic affected donation activities worldwide, especially for living donation due to the lack of elective surgery. Moreover, the number of heart-beating and non-heart beating donors has recorded a decrease. Fondazione Banca dei Tessuti di Treviso (FBTV) is a non-profit healthcare organisation, located in Veneto Region, tasked with procurement, processing, preserving, validating and distributing human tissue for clinical use. During Covid-19 outbreak, operations in FBTV have never stopped and a great effort was required to maintain a standard trend of activity. The aim of this study was to describe the impact of Sars-CoV-2 on the activity of a multitissue bank in Italy. Moreover, we investigated the presence of the virus in tissues retrieved from two Sars-CoV-2 positive cadaver donors. Our survey demonstrated that the transplantation network of Veneto Region has positively reacted to the pandemic scenario, thanks to the effort of all personnel involved. Statistical analyses underlined that most of the activities of the tissue bank were unaffected during the Sars-CoV-2 pandemic.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322936

ABSTRACT

We report on the design, characterization and validation of a spherical irradiation system for inactivating SARS-CoV-2, based on UV-C 275 nm LEDs. The system is designed to maximize ir-radiation intensity and uniformity, and can be used for irradiating a volume of 18 liters. To this aim: (i) several commercially available LEDs have been acquired and analyzed;(ii) a complete optical study has been carried out in order to optimize the efficacy of the system. (iii) The re-sulting prototype has been characterized optically, and tested for the inactivation of SARS-CoV-2 for different exposure times, doses and surface types. Results indicate that a 99.9% inactivation can be reached after 1 minute of treatment with a dose of 83.1 J/m2.

8.
Exp Eye Res ; 217: 108975, 2022 04.
Article in English | MEDLINE | ID: covidwho-1664931

ABSTRACT

COVID-19's impact on the ocular surface has already been recognized, however the molecular mechanisms induced by the infection on the ocular surface are still unclear. The aim of this paper is to provide a first overview of the transcriptional perturbations caused by SARS-CoV-2 on the ocular surface by analyzing gene expression profile of corneoscleral ring samples from post-mortem SARS-CoV-2 positive donors (PD). The presence of SARS-CoV-2 on the ocular surface, in tears and corneal tissues has rarely been detected in infected individuals in both the presence and the absence of ocular manifestations. In this preliminary study, 6 human corneoscleral tissues of 3 PD and two tissues from a negative donor (CTRL) were obtained at the local eye bank. The presence of genomic and sub-genomic SARS-CoV-2 RNAs was assessed by qRT-PCR, while transcriptome analysis (RNA-sequencing) was performed by Illumina. Principal Component Analysis (PCA), search for differentially expressed genes (DEGs) and Gene Ontology (GO)-enrichment analysis were performed. Three samples from PD were found positive for SARS-CoV-2 genomic RNA, although the absence of sub-genomic RNAs indicated an inactive virus. PCA analysis grouped 3 different clusters, one including CTRL, and the other two including, respectively, PD with undetected SARS-CoV-2 (PD-SARS-neg) and PD with detected SARS-CoV-2 (PD-SARS-pos). The DEGs in common with the 2 PD clusters included several genes associable to the interferon pathway, such as ADAMTS4, RSAD2, MMP1, IL6, ISG15 and proinflammatory cytokines. Among the down-regulated genes we found AQP5. GO analysis revealed 77 GO terms over-represented in PD-SARS-neg vs. CTRL, and 17 GO terms in PD-SARS-pos vs. CTRL. The presence of SARS-CoV-2 RNA and RNA-sequencing reads in ocular surface tissues supports the possibility that the eye acts as an entry route. The modulation of early responsive genes, together with several ISGs suggests a potential protective responsiveness of the ocular tissues to SARS-CoV-2.


Subject(s)
COVID-19 , Cornea/metabolism , Humans , RNA, Viral , SARS-CoV-2 , Transcriptome
9.
Microorganisms ; 9(8)2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1630764

ABSTRACT

Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against the emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development of host-targeting antivirals could be an alternative strategy for the control of emerging CoVs infections, as they could be quickly repositioned from one pandemic event to another. To contribute to these pandemic preparedness efforts, here we report on the broad-spectrum CoVs antiviral activity of MEDS433, a new inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 inhibited the in vitro replication of hCoV-OC43 and hCoV-229E, as well as of SARS-CoV-2, at low nanomolar range. Notably, the anti-SARS-CoV-2 activity of MEDS433 against SARS-CoV-2 was also observed in kidney organoids generated from human embryonic stem cells. Then, the antiviral activity of MEDS433 was reversed by the addition of exogenous uridine or the product of hDHODH, the orotate, thus confirming hDHODH as the specific target of MEDS433 in hCoVs-infected cells. Taken together, these findings suggest MEDS433 as a potential candidate to develop novel drugs for COVID-19, as well as broad-spectrum antiviral agents exploitable for future CoVs threats.

10.
Int J Environ Res Public Health ; 18(20)2021 10 19.
Article in English | MEDLINE | ID: covidwho-1477947

ABSTRACT

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.


Subject(s)
COVID-19 , Lactoferrin , Animals , Antiviral Agents/therapeutic use , Cattle , Humans , RNA, Viral , SARS-CoV-2
12.
Materials (Basel) ; 14(9)2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1389429

ABSTRACT

We report on the design, characterization and validation of a spherical irradiation system for inactivating SARS-CoV-2, based on UV-C 275 nm LEDs. The system is designed to maximize irradiation intensity and uniformity and can be used for irradiating a volume of 18 L. To this aim: (i) several commercially available LEDs have been acquired and analyzed; (ii) a complete optical study has been carried out in order to optimize the efficacy of the system; (iii) the resulting prototype has been characterized optically and tested for the inactivation of SARS-CoV-2 for different exposure times, doses and surface types; (iv) the result achieved and the efficacy of the prototype have been compared with similar devices based on different technologies. Results indicate that a 99.9% inactivation can be reached after 1 min of treatment with a dose of 83.1 J/m2.

14.
Nat Commun ; 12(1): 4383, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1317806

ABSTRACT

In February and March 2020, two mass swab testing campaigns were conducted in Vo', Italy. In May 2020, we tested 86% of the Vo' population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8-4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7-100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0-28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2-36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Testing/methods , COVID-19/immunology , COVID-19/transmission , SARS-CoV-2/immunology , Serologic Tests/methods , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Contact Tracing , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy/epidemiology , Male , Nucleocapsid , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology
15.
Biomolecules ; 11(6)2021 05 26.
Article in English | MEDLINE | ID: covidwho-1310053

ABSTRACT

Angiotensin-converting enzyme 2 (ACE-2) is the main cell entry receptor for severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), thus playing a critical role in causing Coronavirus disease 2019 (COVID-19). The role of smoking habit in the susceptibility to infection is still controversial. In this study we correlated lung ACE-2 gene expression with several clinical/pathological data to explore susceptibility to infection. This is a retrospective observational study on 29 consecutive COVID-19 autopsies. SARS-CoV-2 genome and ACE-2 mRNA expression were evaluated by real-time polymerase chain reaction in lung tissue samples and correlated with several data with focus on smoking habit. Smoking was less frequent in high than low ACE-2 expressors (p = 0.014). A Bayesian regression also including age, gender, hypertension, and virus quantity confirmed that smoking was the most probable risk factor associated with low ACE-2 expression in the model. A direct relation was found between viral quantity and ACE-2 expression (p = 0.028). Finally, high ACE-2 expressors more frequently showed a prevalent pattern of vascular injury than low expressors (p = 0.049). In conclusion, ACE-2 levels were decreased in the lung tissue of smokers with severe COVID-19 pneumonia. These results point out complex biological interactions between SARS-CoV-2 and ACE-2 particularly concerning the aspect of smoking habit and need larger prospective case series and translational studies.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , Lung/metabolism , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Bayes Theorem , COVID-19/virology , Female , Humans , Lung/pathology , Male , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Smokers
16.
Front Pharmacol ; 12: 666600, 2021.
Article in English | MEDLINE | ID: covidwho-1295678

ABSTRACT

Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 µg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.

17.
Mycoses ; 64(10): 1223-1229, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1280362

ABSTRACT

BACKGROUND: An increasing number of reports have described the COVID-19-associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA. METHODS: We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID-19 laboratory-confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case. RESULTS: Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases. CONCLUSION: We found a high frequency of proven CAPA among patients with severe COVID-19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.


Subject(s)
COVID-19/epidemiology , Invasive Pulmonary Aspergillosis/epidemiology , Respiratory Insufficiency/mortality , Aged , Aged, 80 and over , Aspergillus , COVID-19/mortality , COVID-19/pathology , Comorbidity , Female , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/mortality , Invasive Pulmonary Aspergillosis/pathology , Male , Middle Aged , Respiratory Insufficiency/microbiology , Respiratory Insufficiency/pathology , SARS-CoV-2
18.
Front Med (Lausanne) ; 8: 637872, 2021.
Article in English | MEDLINE | ID: covidwho-1191689

ABSTRACT

Purpose: The hypothesis of the study was that a multidisciplinary approach involving experienced specialists in diffuse parenchymal lung disease might improve the diagnosis of patients with COVID-19 pneumonia. Methods: Two pulmonologists, two radiologists, and two pathologists reviewed 27 patients affected by severe COVID-19 pneumonia as the main diagnosis made by non-pulmonologists. To evaluate whether the contribution of specialists, individually and/or in combination, might modify the original diagnosis, a three-step virtual process was planned. The whole lung examination was considered the gold standard for the final diagnosis. The probability of a correct diagnosis was calculated using a model based on generalized estimating equations. The effectiveness of a multidisciplinary diagnosis was obtained by comparing diagnoses made by experienced pulmonologists with those made by non-pulmonologists. Results: In 19% of cases, the diagnosis of COVID-19-related death was mainly incorrect. The probability of a correct diagnosis increased strikingly from an undedicated clinician to an expert specialist. Every single specialist made significantly more correct diagnoses than any non-pulmonologist. The highest level of accuracy was achieved by the combination of 3 expert specialists (p = 0.0003). Conclusion: The dynamic interaction between expert specialists may significantly improve the diagnostic confidence and management of patients with COVID-19 pneumonia.

20.
J Pathol ; 254(2): 173-184, 2021 06.
Article in English | MEDLINE | ID: covidwho-1098912

ABSTRACT

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS-CoV-2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS-CoV-2, may influence their occurrence. Lungs from 26 patients who died from SARS-CoV-2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS-CoV-2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity (p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent (p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D-dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO2 ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web-app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/). In SARS-CoV-2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , Machine Learning , Respiratory Distress Syndrome/etiology , SARS-CoV-2/pathogenicity , Vascular System Injuries/etiology , Aged , Aged, 80 and over , Female , Humans , Male , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology , Vascular System Injuries/diagnosis , Vascular System Injuries/virology
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