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1.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-332507

ABSTRACT

Background: Reinfection by SARS-CoV-2 is a rare but possible event. We evaluated the prevalence of reinfections in the Province of Modena and performed an overview of systematic reviews to summarize the current knowledge. Methods: We applied big data analysis and retrospectively analysed the results of oro- or naso-pharyngeal swab results tested for molecular research of viral RNA of SARS-CoV-2 between 1 January 2021 to 30 June 2021 at a single center. We selected individuals with a samples sequence of positive, negative and then positive results. Between first and second positive result we considered a time interval of 90 days to be sure of a reinfection.We also performed a search for and evaluation of systematic reviews reporting SARS-CoV-2 reinfection rates. Main information was collected and the methodological quality of each review was assessed, according to A MeaSurement Tool to Assess systematic Reviews (AMSTAR). Results: Initial positive results were revealed in more than 35,000 (20%) subjects;most (28%) were aged 30-49 years old. Reinfection was reported in 1,258 (3.5%);most (33%) were aged 30-49 years old. Reinfection rates according to vaccinated or non-vaccinated subjects were 0.6% vs 1.1% (p<0.0001).Nine systematic reviews were identified and confirmed that SARS-CoV-2 reinfection rate is a rare event. AMSTAR revealed very low-moderate levels of quality among selected systematic reviews. Conclusions: There is a real, albeit rare risk of SARS-CoV-2 reinfection. Big data analysis enabled accurate estimates of the reinfection rates. Nevertheless, a standardized approach to identify and report reinfection cases should be developed.

2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328786

ABSTRACT

Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4 + T cells, specific antibodies are reported along with features of lung macrophages. Elderly subjects have higher levels of pro-inflammatory cytokines, more circulating plasmablasts, reduced plasmatic level of anti-S and anti-RBD IgG3 antibodies, lower proportions of central memory CD4 + T cells, more immature monocytes and CD56 + pro-inflammatory monocytes, lower percentages of circulating follicular helper T cells (cTfh), antigen-specific cTfh cells with a less activated transcriptomic profile, lung resident activated macrophages that promote collagen deposition and fibrosis. Our study underlines the importance of inflammation in the response to SARS-CoV-2 and suggests that inflammaging, coupled with the inability to mount a proper anti-viral response, could exacerbate disease severity and the worst clinical outcome in old patients.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320080

ABSTRACT

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p<0.001), fibrinogen (p<0.001) and ferritin (p<0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC=0.76, 95% CI: 0.66-0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4;RR=4.91, 95% CI: 1.73-13.96;OR=7.14, 95% CI: 2.06-24.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (i) easy to obtain, (ii) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (iii) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (iv) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318865

ABSTRACT

Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensibility, generating false negative results with important implications for the correct identification of infected patients and subsequent repercussions on the entire community. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false-negatives at initial testing for COVID-19. We systematically searched Pubmed, Embase, and CENTRAL as well as a list of reference literature. We included observational studies enrolling subject collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021. We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false negative rate was of 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence;a range between 2 –58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%,increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%. This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false negative results and decreasing the disease burden among the population.Funding: None to declare. Declaration of Interest: None to declare.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306885

ABSTRACT

In 14 pregnant women who had asymptomatic or paucisymptomatic SARS-CoV-2 infection, we performed a detailed 38-parameter analysis of peripheral blood mononuclear cells by mass cytometry, studied the expression of T-cell master regular genes, investigated cell proliferation and cytokine production, and measured plasma levels of 62 cytokines. No patient showed lymphopenia or gross alterations of white blood cells. Unsupervised analyses revealed that most immune parameters were similar in patients and uninfected controls, apart from an increase in low density neutrophils in SARS-CoV-2 positive women. Also, patients did not show altered plasma levels of interleukin-6 or other main inflammatory molecules, but displayed significant increases of anti-inflammatory cytokines such as IL-1RA, IL-10 and IL-19, and decreased levels of IL-17, PD-L1 and D-dimer. The endogenous control of inflammation, as evidenced by plasma levels of soluble molecules, could be a strategy used during pregnancy to avoid virus-induced damages and maintain a normal immune response.

7.
Eur J Clin Invest ; 52(2): e13706, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1501402

ABSTRACT

BACKGROUND: Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false-negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false negatives at initial testing for COVID-19. METHODS: We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false-negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021. RESULTS: We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false-negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%. CONCLUSIONS: This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false-negative results and decreasing the disease burden among the population.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , SARS-CoV-2/genetics , Diagnostic Errors , False Negative Reactions , Humans , RNA, Viral
10.
Nat Commun ; 12(1): 4677, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1387356

ABSTRACT

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.


Subject(s)
COVID-19/immunology , Cytokines/blood , Inflammation/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Adolescent , Adult , Asymptomatic Infections , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Case-Control Studies , Cross-Sectional Studies , Cytokines/immunology , Female , Humans , Inflammation/blood , Inflammation/prevention & control , Inflammation/virology , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , SARS-CoV-2/isolation & purification , Young Adult
11.
Sci Rep ; 11(1): 12716, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1275959

ABSTRACT

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p < 0.001), fibrinogen (p < 0.001) and ferritin (p < 0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66-0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73-13.96; OR = 7.14, 95% CI: 2.06-24.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.


Subject(s)
COVID-19/blood , Cell Size , Monocytes/pathology , SARS-CoV-2 , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/virology , Female , Ferritins/blood , Fibrinogen/analysis , Humans , Inflammation/blood , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Patient Admission , Pilot Projects , Prognosis , Retrospective Studies , Sensitivity and Specificity , Young Adult
13.
Eur J Clin Microbiol Infect Dis ; 40(9): 1891-1898, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1173921

ABSTRACT

In response to the rapidly evolving of SARS-CoV-2 infection, numerous serological tests have been developed but their sensitivity and specificity are unclear. We collected serum samples of patients and health-care professionals to assess the accuracy of chemiluminescent (CLIA) and two lateral flow immunochromatographic assays (LFIA) to determine IgG and IgM antibodies to SARS-CoV-2 virus. We calculated the φ correlation for qualitative results and test accuracy, adopting the following case definition: either real-time-PCR positivity or serological positivity with at least two different tests. We analyzed 259 samples, obtaining strong correlation between CLIA and both LFIA for IgG (φ=0.9), and moderate correlation for IgM (φ=0.6). For patients, the sensitivity was suboptimal for all methods (CLIA 81%, LFIA A 85%, LFIA B 78%), while it was poor in asymptomatic health-care workers (CLIA 50%, LFIA A 50%, LFIA B 33%). Overall, CLIA is more sensitive and specific for the determination of both IgG and IgM, whilst both LFIA methods reported good sensitivity and specificity for IgG, but scarce sensitivity for the IgM determination. The determination of SARS-CoV-2-specific IgG is useful to detect infection 6 days from symptom onset.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/standards , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Young Adult
15.
Blood Adv ; 5(3): 662-673, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1063181

ABSTRACT

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.


Subject(s)
Angiopoietin-2/blood , COVID-19/pathology , Antiviral Agents/therapeutic use , Area Under Curve , Biomarkers/blood , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Hospital Mortality , Hospitalization , Humans , Interleukin-6/blood , Proportional Hazards Models , ROC Curve , Risk Factors , SARS-CoV-2/isolation & purification , Survival Rate
18.
Artif Organs ; 45(5): E130-E135, 2021 May.
Article in English | MEDLINE | ID: covidwho-883243

ABSTRACT

The cytokine storm has been frequently reported to occur in patients with severe coronavirus disease 2019 (COVID-19). Data from the literature suggest that elevated levels of inflammatory mediators, such as interleukin (IL)-6, IL-8, and tumor necrosis factor, indicate a severe course or the fatality of the disease. Several therapeutic options have been employed to treat critically ill patients, including hemoadsorption of inflammatory mediators. We here present a case of severe acute respiratory syndrome caused by COVID-19 and acute renal failure. The patient was admitted to our intensive care unit and treated with mechanical ventilation, renal replacement therapy, and hemoadsorption to reduce the cytokine release syndrome, which plays a fundamental role in the clinical presentation of COVID-19 patients. We also discuss the potential advantages of reducing cytokine plasma levels using a hemoadsorption cartridge.


Subject(s)
Acute Kidney Injury/therapy , COVID-19/therapy , Continuous Renal Replacement Therapy/instrumentation , Cytokine Release Syndrome/therapy , Pneumonia, Viral/therapy , Acute Kidney Injury/etiology , Aged , Antiviral Agents/therapeutic use , Biomarkers/blood , COVID-19/diagnosis , Critical Illness , Cytokine Release Syndrome/virology , Cytokines/blood , Drug Therapy, Combination , Humans , Intensive Care Units , Male , Organ Dysfunction Scores , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2
20.
Platelets ; 31(8): 1085-1089, 2020 Nov 16.
Article in English | MEDLINE | ID: covidwho-733448

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.


Subject(s)
Betacoronavirus/pathogenicity , Bone Marrow/pathology , Coronavirus Infections/pathology , Cytokine Release Syndrome/pathology , Disseminated Intravascular Coagulation/pathology , Lung/pathology , Pneumonia, Viral/pathology , Thrombosis/pathology , Adult , Aged , Autopsy , Betacoronavirus/immunology , Bone Marrow/immunology , Bone Marrow/virology , COVID-19 , Cell Nucleus/immunology , Cell Nucleus/pathology , Cell Nucleus/virology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/virology , Critical Illness , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Fatal Outcome , Host-Pathogen Interactions/immunology , Humans , Interleukin-6/biosynthesis , Interleukin-6/immunology , Lung/immunology , Lung/virology , Male , Megakaryocytes/immunology , Megakaryocytes/pathology , Megakaryocytes/virology , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Thrombopoiesis/immunology , Thrombosis/complications , Thrombosis/immunology , Thrombosis/virology
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