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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1695423

ABSTRACT

We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.

2.
Eur Radiol Exp ; 4(1): 55, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1388845

ABSTRACT

We investigated whether the internal gantry components of our computed tomography (CT) scanner contain severe acute respiratory syndrome 2 (SARS-CoV-2) ribonucleic acid (RNA), bacterial or fungal agents. From 1 to 27 March 2020, we performed 180 examinations of patients with confirmed SARS-CoV-2 infection using a dedicated CT scanner. On 27 March 2020, this CT gantry was opened and sampled in each of the following components: (a) gantry case; (b) inward airflow filter; (c) gantry motor; (d) x-ray tube; (e) outflow fan; (f) fan grid; (g) detectors; and (h) x-ray tube filter. To detect SARS-CoV-2 RNA, samples were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). To detect bacterial or fungal agents, samples have been collected using "replicate organism detection and counting" contact plates of 24 cm2, containing tryptic soy agar, and subsequently cultured. RT-PCR detected SARS-CoV-2 RNA in the inward airflow filter sample. RT-PCR of remaining gantry samples did not reveal the presence of SARS-CoV-2 RNA. Neither bacterial nor fungal agents grew in the agar-based growth medium after the incubation period. Our data showed that SARS-Cov-2 RNA can be found inside the CT gantry only in the inward airflow filter. All remaining CT gantry components were devoid of SARS-CoV-2 RNA.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Equipment Contamination , Pneumonia, Viral/virology , Tomography Scanners, X-Ray Computed/virology , Tomography, X-Ray Computed/instrumentation , COVID-19 , Humans , Pandemics , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , SARS-CoV-2
3.
J Allergy Clin Immunol ; 147(4): 1217-1225, 2021 04.
Article in English | MEDLINE | ID: covidwho-1111670

ABSTRACT

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , COVID-19 Drug Treatment , Glucocorticoids/administration & dosage , Interleukin 1 Receptor Antagonist Protein/administration & dosage , SARS-CoV-2 , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/mortality , COVID-19/physiopathology , Cohort Studies , Disease Progression , Drug Administration Schedule , Female , Humans , Injections, Intravenous , Italy/epidemiology , Kaplan-Meier Estimate , Male , Methylprednisolone/administration & dosage , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , Treatment Outcome
4.
Eur Radiol Exp ; 4(1): 39, 2020 06 26.
Article in English | MEDLINE | ID: covidwho-615378

ABSTRACT

BACKGROUND: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. METHODS: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. RESULTS: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26-95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1-30) and 4.94 mg/L (range 0.1-28.3), respectively. Median VoD was 249.5 cm3 (range 9.9-1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. CONCLUSIONS: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/diagnostic imaging , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged , Pandemics , Patient Outcome Assessment , Pneumonia, Viral/diagnostic imaging , Predictive Value of Tests , Prognosis , Reproducibility of Results , SARS-CoV-2
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