Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally and poses a major challenge to healthcare systems worldwide. A high incidence of hospitalisation and death due to COVID-19 has been reported among older patients and those with certain coexisting conditions, such as obesity, diabetes mellitus, cardiovascular disease, chronic obstructive pulmonary disease, and chronic kidney disease (Petrilli et al., 2020; Huang et al., 2020). The implementation of mass vaccination campaigns has markedly reduced the healthcare burden related to COVID-19. Nevertheless, SARS-CoV-2 vaccination rates differ considerably across countries, and growing evidence suggests a reduced efficacy of vaccines against new viral variants of concern (VOC) (Cao et al., 2022; Planas et al., 2022; Dejnirattisai et al., 2022; Andrews et al., 2022).

Therapeutic agents directed against SARS-CoV-2 have been developed to prevent the COVID-19 progression, especially addressing high-risk groups of patients. Neutralising monoclonal antibodies (mAbs) target the spike protein of SARS-CoV-2 that mediates viral entry into host cells (Benton et al., 2020). Based on the results of randomised placebo-controlled trials showing the efficacy in preventing COVID-19 progression, drug regulatory authorities, such as the US Food and Drug Administration (FDA), the European Medicines Agency, and the Italian Medicines Agency (AIFA), had granted the emergency use authorisation status for bamlanivimab 700 mg combined with etesevimab 1400 mg, casirivimab 600 mg combined with imdevimab 600 mg, and sotrovimab 500 mg to treat early COVID-19 in patients at high risk of progression (Dougan et al., 2021; Weinreich et al., 2021; Gupta et al., 2021).

To date, two randomised trials have compared the clinical outcomes of these mAbs in preventing severe COVID-19, showing similar effectiveness of bamlanivimab/etesevimab vs casirivimab/imdevimab in patients infected with the alpha VOC (McCreary et al., 2022) and casirivimab/imdevimab vs sotrovimab in patients infected with the Delta VOC, respectively (Huang et al., 2022).

This paper reports the results of the MANTICO trial, a non-inferiority randomised controlled trial comparing the clinical efficacy of routinely-used mAbs in a real-life setting of outpatients aged 50 or older with early mild-to-moderate COVID-19. The patient enrolment started in December 2021 and was interrupted after the publication of in-vitro evidence that two treatments under investigation (bamlanivimab/etesevimab and casirivimab/imdevimab) were not effective against the new emerging viral Omicron VOC (Cao et al., 2022; Planas et al., 2022; Dejnirattisai et al., 2022). The analysis is therefore restricted to 319 randomised patients, who were enrolled up to the interruption for possible futility, and was performed according to the SARS-CoV-2 VOC (Delta and Omicron).

The first patient was enrolled on 9 December 2021. Overall, 319 patients underwent randomisation by 20 January 2022 and were assigned to receive bamlanivimab/etesevimab (106 patients), sotrovimab (107 patients), or casirivimab/imdevimab (106 patients). No patients reported previous SARS-CoV-2 infections. No patients were lost to follow-up. VOC data were available for 311 patients: 170 (53.3%) were infected with Omicron and 141 (44.2%) with Delta. Eight (2.5%) patients were excluded from this analysis due to the lack of SARS-CoV-2 VOC identification. Figure 1 shows the flow diagram of the progress through the trial phases. Baseline characteristics of the population by type of SARS-CoV-2 VOC are reported in Table 1.

Figure 1

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Comparing symptoms at enrolment by VOC, anosmia/ageusia (p<0.001), nausea/vomiting (p<0.001), and feeling feverish or hot (p<0.01) were significantly more frequent among patients infected with Delta, while sore throat (p<0.001) was significantly more frequent among patients infected with Omicron. Serological positivity to anti-SARS-CoV-2 antibodies (p<0.001) and complete primary COVID-19 vaccination series within 120 days of the enrolment or booster vaccination (p<0.001) were significantly more frequent among patients infected with Omicron. Table 2 shows the bivariate Cox regression of symptom resolution predictors by type of SARS-CoV-2 VOC. No predictors were associated with the time to symptom resolution in both SARS-CoV-2 VOC.

Delta VOC

Baseline characteristics of 141 patients infected with Delta VOC by type of treatment are reported in Table 3. The main detected lineages were 34 AY.4 (24.1%), 33 AY.43 (23.4%), and 26 AY.122 (18.4%). 69 (48.9%) were male, median age was 65.7 years (IQR ±15.4), 115 (78.8%) had at least one comorbidity, 70 (49.6%) were serum antibody-positive at the enrolment, and 23 (16.3%) received complete primary COVID-19 vaccination series within 120 days of the enrolment or booster vaccination.

Table 3

Characteristic	TotalN=141	SotrovimabN=43	Bamlanivimab/etesevimabN=48	Casirivimab/imdevimabN=50
Sex (male) – n (%)	69 (48.94)	22 (51.16)	21 (43.75)	26 (52.00)
Age – median (IQR) (range)	65.7 (15.4) (50–92)	65.8 (16.4) (50–90)	68.6 (11.8) (50–92)	63.2 (12) (50–89)
Smoking status – n (%)
Smoker	8 (5.67)	2 (4.65)	4 (8.33)	2 (4.00)
Former smoker	32 (22.70)	8 (18.60)	11 (22.92)	13 (26.00)
Non-smoker	101 (71.63)	33 (76.74)	33 (68.75)	35 (70.00)
BMI – n (%)
≤29	101 (71.63)	29 (67.44)	36 (75.00)	36 (72.00)
≥30	40 (28.37)	14 (32.56)	12 (25.00)	14 (28.00)
SARS-CoV-2 serological status – n (%)
Antibody-positive	70 (49.65)	20 (46.51)	29 (61.70)	21 (43.75)
Antibody-negative	68 (48.23)	23 (53.49)	18 (38.30)	27 (56.25)
Other	3 (2.13)	0	1 (2.08)	2 (4.00)
Anti-SARS-CoV-2 vaccination status – n (%)
3 doses	16 (11.35)	6 (13.95)	3 (6.25)	7 (14.00)
2 doses ≤120 days	7 (4.96)	2 (4.65)	2 (4.17)	3 (6.00)
1 or 2 doses ≥120 days	54 (38.30)	14 (32.56)	26 (54.17)	14 (28.00)
Not vaccinated	59 (41.84)	19 (44.19)	15 (31.25)	25 (50.00)
Other	5 (3.55)	2 (4.65)	2 (4.17)	1 (2.00)
Comorbidities – n (%)
Diabetes	3 (2.13)	0	2 (4.17)	1 (2.00)
Cardiovascular disease	56 (39.72)	18 (41.86)	20 (41.67)	18 (36.00)
Chronic kidney disease	7 (4.96)	1 (2.33)	2 (4.17)	4 (8.00)
Chronic liver disease	3 (2.13)	0	1 (2.08)	2 (4.00)
Chronic pulmonary disease	16 (11.35)	6 (13.95)	4 (8.33)	6 (12.00)
Immunocompromising conditions	17 (12.06)	6 (13.95)	6 (12.50)	5 (10.00)
Symptoms at enrolment – n (%)
Cough	96 (68.09)	28 (65.12)	36 (75.00)	32 (64.00)
Nasal congestion	69 (48.94)	20 (46.51)	22 (45.83)	27 (54.00)
Sore throat	32 (22.70)	10 (23.26)	8 (16.67)	14 (28.00)
Feeling hot or feverish	103 (73.05)	31 (72.09)	36 (75.00)	36 (72.00)
Myalgia	46 (32.62)	11 (25.58)	16 (33.33)	19 (38.00)
Fatigue	47 (33.33)	13 (30.23)	15 (31.25)	19 (38.00)
Headache	59 (41.84)	15 (34.88)	15 (31.25)	29 (58.00)
Anosmia/ageusia	39 (27.66)	12 (27.91)	15 (31.25)	12 (24.00)
Nausea/vomiting	28 (19.86)	6 (13.95)	9 (18.75)	13 (26.00)
Diarrhoea	15 (10.64)	1 (2.33)	5 (10.42)	9 (18.00)
Serum C-reactive protein level – n	136	41	46	49
Mean (SD), mg/L	20.58 (29.00)	22.84 (33.70)	25.27 (34.20)	14.29 (15.99)

Primary and secondary outcomes of the study population infected with Delta VOC by type of treatment are reported in Table 4 with the exclusion of time to sustained patient-reported symptom resolution. No COVID-19 progression was recorded in Delta infections. All-cause mortality through day 28 was the same as that through day 14. An emergency department visit without hospitalisation was observed once in one patient in the casirivimab/imdevimab group. This visit was deemed to be unrelated to COVID-19.

Table 4

Outcome	TotalN=141	SotrovimabN=44	Bamlanivimab/etesevimabN=47	Casirivimab/imdevimabN=50
Composite primary outcome – n (%)	0	0	0	0
Hospitalisation	0	0	0	0
Need of supplemental oxygen therapy	0	0	0	0
Death from any cause through day 14	0	0	0	0
Secondary outcomes
Emergency department visits through day 28 – n (%)	1 (0.71)	0	0	1 (2)
All-cause mortality through day 28 – n (%)	0	0	0	0
Duration of supplemental oxygen therapy – days	0	0	0	0
Rate of non-invasive ventilation – n (%)	0	0	0	0
Duration of non-invasive ventilation – days	0	0	0	0
Rate of mechanical ventilation – n (%)	0	0	0	0
Duration of mechanical ventilation – days	0	0	0	0

The median time to symptom resolution was 7 days (95% CI 6–13) in the bamlanivimab/etesevimab group, 10 days (95% CI 7–14) in the sotrovimab group, and 10 days (95% CI 7–15) in the casirivimab/imdevimab group, not differing significantly across the overall groups of treatment (Log-rank Chi-square 0.22, p 0.895) and for each comparison between treatment groups, namely bamlanivimab/etesevimab with casirivimab/imdevimab (Log-rank Chi-square 0.08, p 0.776), sotrovimab with casirivimab/imdevimab (Log-rank Chi-square 0.40, p 0.527), and bamlanivimab/etesevimab with sotrovimab (Log-rank Chi-square 0.01, p 0.92). Figure 2A shows the time to symptom resolution by type of treatment in the Delta study population. The Cox regression analysis confirmed the non-significantly different effects upon the time to symptom resolution between casirivimab/imdevimab (reference standard according to the original trial protocol) and both bamlanivimab/etesevimab and sotrovimab (HR 1.052 and HR 1.097, 95% CI 0.70–1.57 and 0.73–1.65, p 0.805 and 0.657, respectively).

Figure 2

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During the SARS-CoV-2 pandemic, the paradigm of discovering and implementing mAb and antiviral treatments based on randomised controlled trials has lagged significantly behind the new evidence coming from in-vitro studies, which has driven clinical recommendations causing ethical dilemmas on the continuation of ongoing trials. At the time of approving the MANTICO trial protocol (November 2021), casirivimab/imdevimab, bamlanivimab/etesevimab, and, later, sotrovimab were the only therapies recommended by the COVID-19 treatment guidelines for outpatients with mild-to-moderate COVID-19 at high risk of progressing to severe COVID-19. Delta was the SARS-CoV-2 dominant VOC worldwide, and the selection of the study mAbs was based on their in-vitro activity against the circulating variants and on the existing evidence of their clinical efficacy. Since mid-December 2021, the Omicron VOC has been spreading worldwide, rapidly becoming the dominant VOC. Preliminary in-vitro studies on Omicron demonstrated numerous mutations in the gene encoding the spike protein, predicting a markedly reduced susceptibility to bamlanivimab/etesevimab and casirivimab/imdevimab (Cao et al., 2022; Planas et al., 2022; Dejnirattisai et al., 2022). According to these findings, FDA and AIFA have revised the emergency use authorisation for bamlanivimab/etesevimab and casirivimab/imdevimab, halting their use, in line with the National Institutes of Health COVID-19 Treatment Guidelines Panel, which advised against the use of these mAbs due to reduced activity against Omicron and because real-time testing to identify rare, non-Omicron variants is not readily available (National Institutes of Health, 2022). Therefore, the study enrolment in a real-life outpatient setting was prematurely discontinued for possible futility, after the inclusion of barely one fourth of the predefined sample size (1260 patients). Nevertheless, the recruitment timeframe provided a unique opportunity to collect data on the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in patients infected with Omicron.

Overall, the three treatment groups appeared to be balanced with respect to the predictors of outcomes in both Delta and Omicron population, as expected under the randomised allocation design. As reported by previous studies, patients infected with Omicron, compared with patients infected with Delta, were more likely to present with symptoms limited to the upper respiratory tract and to have pre-existing immunity, considering that Omicron is better equipped than Delta to infect people with pre-existing immunity (Nyberg et al., 2022).

Considering the time to symptom resolution, no differences in the effect between treatment groups were found in Delta infections, whereas sotrovimab seems to show a benefit in patients infected with Omicron BA.1 and BA.1.1. This benefit was consistent across all Omicron subgroups, regardless of the SARS-CoV-2 serology and vaccination status, confirming the preliminary in-vitro evidence on the mAbs activity against Omicron BA.1 and BA.1.1 (Cao et al., 2022; Planas et al., 2022; Dejnirattisai et al., 2022).

The COVID-19 progression was recorded in two patients infected with Omicron, who were both randomised to receive bamlanivimab/etesevimab. On the one hand, these findings seem consistent with recent in-vitro data showing that all study treatments were active against Delta, and both casirivimab/imdevimab and sotrovimab retained a residual neutralising activity against Omicron BA.1/BA.1.1, whereas bamlanivimab/etesevimab did not neutralise Omicron (Takashita et al., 2022b; Iketani et al., 2022; Takashita et al., 2022a; Arora et al., 2022). Nevertheless, the above-mentioned results are severely limited by the early discontinuation of the trial, and firm conclusions on the primary outcome parameters cannot be drawn. Furthermore, the observed rate of COVID-19 progression (2/319, 0.6%) was lower than the one used to inform the sample size calculation (5% in the casirivimab/imdevimab arm, reference standard; NCT05205759). This overestimation of the primary outcome could be influenced by the lower intrinsic-severity of Omicron, the high vaccination rate in Italy, and the prioritisation of the booster vaccination for the elderly (Bhattacharyya and Hanage, 2022). Another limitation of this study is the lack of data on the clinical efficacy of the study mAbs, as well as other commercially available early COVID-19 treatments (mAbs, such as tixagevimab/cilgavimab and bebtelovimab, and antiviral drugs, such as remdesivir, nirmatrelvir/ritonavir, and molnupiravir), against the currently circulating VOC (BA.2 subvariants, BA.4, or BA.5; CoVariants, 2022). Following an adaptive design in a real-life setting, the MANTICO trial is actively recruiting to compare the clinical efficacy of commercially available early COVID-19 treatments against the currently circulating VOC (tixagevimab/cilgavimab, nirmatrelvir/ritonavir, and sotrovimab; NCT05321394).

Additional clinical studies with an adequate sample size are required to determine whether casirivimab/imdevimab and sotrovimab are indeed effective in preventing COVID-19 progression due to Omicron infection. Should the role of casirivimab/imdevimab in preventing severe COVID-19 due to Omicron infections be confirmed, this mAb could represent a readily available and well-tolerated treatment option in case of shortages of mAbs supplies and contraindication to other early COVID-19 treatments.

The MANTICO trial provides the first data on the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab against Omicron VOC. There is an urgent need for adaptive clinical trials comparing anti-SARS-CoV-2 treatments by the currently circulating VOC to promptly inform recommendations for the management of early COVID-19.

The trial dataset has been uploaded to the Dryad repository (https://doi.org/10.5061/dryad.tdz08kq2w). As per predefined protocol, personally identifiable information (such as gender, date of birth, age, and weight) has been removed from the dataset to keep the records completely anonymous. In addition, the dataset record order was randomised so the resulting dataset is a file very similar in terms of length, fields and content to the original version, except for row order which is now completely random and the record id variable deleted.

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Author details

1. Fulvia Mazzaferri

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Conceptualization, Data curation, Software, Formal analysis, Supervision, Methodology, Writing - original draft, Writing – review and editing

   Competing interests

   No competing interests declared

2. Massimo Mirandola

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Conceptualization, Data curation, Software, Formal analysis, Supervision, Validation, Visualization, Methodology, Writing - original draft, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-2342-5867

3. Alessia Savoldi

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Resources, Data curation, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing – review and editing

   Competing interests

   No competing interests declared

4. Pasquale De Nardo

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Resources, Data curation, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing – review and editing

   Competing interests

   No competing interests declared

5. Matteo Morra

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Data curation, Software, Supervision, Validation, Investigation, Project administration, Writing – review and editing

   Competing interests

   No competing interests declared

6. Maela Tebon

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Data curation, Software, Supervision, Validation, Investigation, Project administration

   Competing interests

   No competing interests declared

7. Maddalena Armellini

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Data curation, Validation, Investigation, Project administration

   Competing interests

   No competing interests declared

8. Giulia De Luca

   Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

   Contribution

   Data curation, Validation, Investigation

   Competing interests

   No competing interests declared

9. Lucrezia Calandrino

   Infectious Disease Unit, Padova University Hospital, Padua, Italy

   Contribution

   Data curation, Supervision, Investigation

   Competing interests

   No competing interests declared

10. Lolita Sasset

    Infectious Disease Unit, Padova University Hospital, Padua, Italy

    Contribution

    Data curation, Supervision, Investigation

    Competing interests

    Lolita Sasset has served as a paid consultant to Abbvie, Janssen, MSD, Gilead Sciences, Janssen, MSD and ViiV Healthcare; she does not have any financial competing interests with this study

11. Denise D'Elia

    Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    Contribution

    Resources, Data curation, Supervision, Investigation

    Competing interests

    No competing interests declared

12. Emanuela Sozio

    Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    Contribution

    Resources, Data curation, Formal analysis, Supervision, Investigation, Writing - original draft

    Competing interests

    No competing interests declared

13. Elisa Danese

    Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy

    Contribution

    Resources, Validation, Investigation

    Competing interests

    No competing interests declared

14. Davide Gibellini

    Microbiology and Virology Unit, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

    Contribution

    Resources, Supervision, Validation, Investigation

    Competing interests

    No competing interests declared

15. Isabella Monne

    Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy

    Contribution

    Resources, Supervision, Investigation, Writing - original draft

    Competing interests

    No competing interests declared

16. Giovanna Scroccaro

    Direzione Farmaceutico, Protesica, Dispositivi Medici, Regione del Veneto, Venice, Italy

    Contribution

    Conceptualization, Resources, Supervision, Project administration

    Competing interests

    No competing interests declared

17. Nicola Magrini

    Italian Medicines Agency, Rome, Italy

    Contribution

    Conceptualization, Supervision, Writing – review and editing

    Competing interests

    No competing interests declared

18. Annamaria Cattelan

    Infectious Disease Unit, Padova University Hospital, Padua, Italy

    Contribution

    Resources, Supervision, Writing – review and editing

    Competing interests

    Annamaria Cattelan has served as a paid consultant to Abbvie, Janssen, MSD, and received research fundings from Gilead Sciences, Janssen, MSD and ViiV Healthcare; she does not have any financial competing interests with this study

19. Carlo Tascini

    Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    Contribution

    Conceptualization, Supervision, Writing – review and editing

    Competing interests

    Carlo Tascini has received grants from Correvio, Biotest, Biomerieux, Gilead, Angelini, MSD, Pfizer, Thermofisher, Zambon, Shionogi, Avir Pharma and Hikma outside the submitted work in the last two years

20. MANTICO Working Group

    Contribution

    Data curation, Investigation, Validation

    Competing interests

    No competing interests declared

    1. Francesca Simbeni, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    2. Alessandro Castelli, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    3. Ilaria Dalla Vecchia, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    4. Chiara Konishi de Toffoli, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    5. Gaia Maccarrone, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    6. Marco Meroi, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    7. Chiara Perlini, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    8. Matilde Rocchi, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    9. Giulia Rosini, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    10. Laura Rovigo, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    11. Lorenzo Tavernaro, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    12. Amina Zaffagnini, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    13. Ilaria Currò, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    14. Ruth Joanna Davis, Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    15. Elena Agostini, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    16. Carla Benfatto, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    17. Nicola Bonadiman, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    18. Marco Canova, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    19. Giuseppe Lombardo, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    20. Daniele Mengato, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    21. Danilo Puntrello, Infectious Disease Unit, Padova University Hospital, Padua, Italy
    22. Francesca Prataviera, Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
    23. Tosca Semenzin, Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
    24. Dario Carloni, Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
    25. Giuseppe Lippi, Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
    26. Davide Negrini, Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
    27. Martina Montagnana, Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
    28. Riccardo Cecchetto, Microbiology and Virology Unit, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
    29. Alice Fusaro, Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy
    30. Francesco Bonfante, Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy
    31. Elisa Palumbo, Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy
    32. Edoardo Giussani, Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy

21. Evelina Tacconelli

    Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

    Contribution

    Conceptualization, Resources, Supervision, Funding acquisition, Visualization, Methodology, Project administration, Writing – review and editing

    For correspondence

    evelina.tacconelli@univr.it

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-2010-4977

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