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1.
Minerva Endocrinol (Torino) ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1737520

ABSTRACT

BACKGROUND: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. METHODS: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. RESULTS: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac Troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. CONCLUSIONS: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19.

2.
Viruses ; 14(3)2022 03 05.
Article in English | MEDLINE | ID: covidwho-1732241

ABSTRACT

Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave (n = 35) and second wave (n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.


Subject(s)
COVID-19 , Humans , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317113

ABSTRACT

Background: The easy access to a quick diagnosis of coronavirus disease 2019 (COVID-19) is a key point to improve the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to contain its spread. Up to now, laboratory real-time PCR is the standard of care, but requires a fully equipped laboratory and significant infrastructure. Consequently, new diagnostic tools are required. Methods: : In the present work, the diagnostic accuracy of the point-of-care rapid test "bKIT Virus Finder COVID-19" (Hyris Ltd ) is evaluated by a retrospective and a prospective analysis on SARS CoV-2 samples previously assessed with an FDA “authorized for the emergency use - EUA” reference method. Descriptive statistics were used for the present study. Results: : Results obtained with the Hyris Kit are the same as that of standard laboratory-based real time PCR methods for all the analyzed samples. In addition, the Hyris Kit provides the test results in less than 2 hours, a significantly shorter time compared to the reference methods, without the need of a fully equipped laboratory. Conclusions: : To conclude, the Hyris kit represents a promising tool to improve the health surveillance and to increase the capacity of SARS-CoV-2 testing.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316430

ABSTRACT

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing two days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. Since these patients should not be denied or delayed effective treatments, we suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of currently available SARS-CoV-2 vaccines.

5.
Sci Rep ; 12(1): 1212, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1649849

ABSTRACT

The molecular basis of the wide clinical heterogeneity of Coronavirus disease 2019 (COVID-19) is still unknown. Matrix metalloproteinases (MMPs) may have a role in the lung damage and regeneration that occur in severe patients. We studied serum MMP3 and MMP9 as potential biomarkers of COVID-19 severity, in 108 hospitalized patients with different World Health Organization (WHO) severity stage and in 48 controls. At hospital admission, serum MMP3 was increased in COVID-19 patients with a significant trend along the progression of the WHO stage, while serum levels of MMP9 were significantly increased in COVID-19 patients with no correlation with disease severity. At 1 week from hospitalization, MMP3 was reduced, suggesting an early pathogenic role of the protein in lung inflammation, while MMP9 levels were further increased, indicating a late role of the protein in the inflammatory process, specifically during the repairing phase. Furthermore, serum MMP9 was positively correlated with serum interleukin-6, myeloperoxidase, and circulating neutrophils and monocytes number. In conclusion, serum MMP3 may help to early predict the severity of COVID-19 and both proteins, MMP3 and MMP9, may contribute to define severe COVID-19 patients that may benefit from a targeted therapy on MMPs.


Subject(s)
COVID-19/blood , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 9/blood , Patient Acuity , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged
6.
Monaldi Arch Chest Dis ; 92(3)2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1593755

ABSTRACT

Pulmonary hamartomas represent the most frequent family of benign lung tumors that typically involve the lung parenchyma and only rarely grow as endobronchial tumors. The elective treatment of endobronchial hamartoma is the bronchoscopic resection, and in those cases in which tumor extension and localization makes it not possible, surgical treatment must be evaluated. Patients with symptomatic COVID-19, hospitalized, frequently undergo a chest CT scan and in some cases, occasional findings may emerge, requiring diagnostic investigations such as bronchoscopy and interventional pulmonology procedures. Therefore, in such a delicate pathological condition, such as COVID-19, the need to perform bronchoscopy and interventional pulmonology procedures, minimizing the risk of viral transmission and ensuring necessary assistance, represents a great challenge for pulmonologists. In this article authors describe, for the first time in literature, a rare case of endobronchial hamartoma, radically resected using a single use bronchoscope, in a young female patient hospitalized for symptomatic COVID-19.


Subject(s)
Bronchial Diseases , COVID-19 , Hamartoma , Lung Neoplasms , Bronchial Diseases/pathology , Bronchoscopes , Bronchoscopy/methods , Female , Hamartoma/diagnosis , Hamartoma/pathology , Hamartoma/surgery , Humans
10.
Monaldi Arch Chest Dis ; 91(4)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1478189

ABSTRACT

Identification of risk factors for severe outcome of SARS-CoV-2 infection is an important issue in COVID-19 management. Much attention has been focused on comorbidities as well as drugs taken by patients. Usage of proton pump inhibitors (PPIs) appears to potentially influence disease course. These drugs are known to reduce stomach acid and also modulate the immune system. Their use, prior to and during COVID-19 infection, seems to predispose to the development of more severe pneumonia and therefore to a greater risk of mortality. Instead, the use of histamine receptor 2 antagonists (H2RAs) seems to be associated with a better outcome in patients with COVID-19, in terms of symptoms, risk of intubation and death. As PPIs are essential for treatment of many disorders, usage of these drugs should be balanced considering the benefits and risk ratio, in order to guarantee their correct use for the necessary time. It remains to be clarified whether the detrimental effects, in terms of COVID-19 severe outcome, are due to PPIs or to the underlying disease for which they are administered. New controlled-randomized trials are required to better understand their impact in SARS-CoV-2 infections. *Vanvitelli/Monaldi COVID Group: Adriano Cristinziano, Carolina Delle Donne, Cecilia Calabrese, Fabio Perrotta, Filippo Scialò, Francesco Lassandro, Gennaro Mazzarella, Giorgio Paoli, Leonardo De Luca, Maria Galdo, Miriam Buonincontro, Roberta Cianci, Rosalba Donizzetti, Stefano Sanduzzi Zamparelli, Tullio Valente, Vito D'Agnano, Vittorio Bisogni.


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , Risk Factors , SARS-CoV-2
12.
J Transl Med ; 18(1): 405, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-1477432

ABSTRACT

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Mortality , Off-Label Use , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Treatment Outcome , Validation Studies as Topic
13.
J Transl Med ; 19(1): 403, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438276

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic had a 1st wave in Europe from March to May 2020 and a 2nd wave since September 2020. We previously studied 35 hospitalized COVID-19 patients of the 1st wave demonstrating a cytokine storm and the exhaustion of most lymphocyte subpopulations. Herein, we describe the results obtained from COVID-19 patients of the 2nd wave. METHODS: We analyzed interleukin (IL)-6 by human-specific enzyme-linked immunosorbent assay and a large set of lymphocyte subpopulations by flow cytometry in 274 COVID-19 patients hospitalized from September 2020 to May 2021. RESULTS: Patients of 2nd wave compared with those of 1st wave showed lower serum IL-6 levels and a higher number of B and most T lymphocyte subpopulations in advanced stages, in relation with the age and the gender. On the other hand, we observed in 2nd wave patients: (i) a reduction of most lymphocyte subpopulations at mild and moderate stages; (ii) a reduction of natural killer cells and T regulatory cells together with a higher number of activated T helper (TH) 17 lymphocytes in all stages, which were mainly related to steroid and azithromycin therapies before hospitalization. CONCLUSIONS: COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate specific IL/lymphocyte inhibition or activation in COVID-19 patients.


Subject(s)
COVID-19 , Humans , Killer Cells, Natural , Lymphocyte Count , Pandemics , SARS-CoV-2
14.
Biomolecules ; 11(9)2021 09 16.
Article in English | MEDLINE | ID: covidwho-1408458

ABSTRACT

Systemic vascular damage with micro/macro-thrombosis is a typical feature of severe COVID-19. However, the pathogenesis of this damage and its predictive biomarkers remain poorly defined. For this reason, in this study, serum monocyte chemotactic protein (MCP)-2 and P- and E-selectin levels were analyzed in 204 patients with COVID-19. Serum MCP-2 and P-selectin were significantly higher in hospitalized patients compared with asymptomatic patients. Furthermore, MCP-2 increased with the WHO stage in hospitalized patients. After 1 week of hospitalization, MCP-2 levels were significantly reduced, while P-selectin increased in patients in WHO stage 3 and decreased in patients in WHO stages 5-7. Serum E-selectin was not significantly different between asymptomatic and hospitalized patients. The lower MCP-2 levels after 1 week suggest that endothelial damage triggered by monocytes occurs early in COVID-19 disease progression. MCP-2 may also predict COVID-19 severity. The increase in P-selectin levels, which further increased in mild patients and reduced in severe patients after 1 week of hospitalization, suggests that the inactive form of the protein produced by the cleavage of the active protein from the platelet membrane is present. This may be used to identify a subset of patients that would benefit from targeted therapies. The unchanged levels of E-selectin in these patients suggest that endothelial damage is less relevant.


Subject(s)
COVID-19 , Chemokine CCL8/blood , E-Selectin/blood , Endothelium, Vascular , P-Selectin/blood , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , COVID-19/pathology , Endothelium, Vascular/injuries , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Humans , Male , Middle Aged , Monocytes/metabolism , Monocytes/pathology
15.
PLoS One ; 16(9): e0256903, 2021.
Article in English | MEDLINE | ID: covidwho-1406751

ABSTRACT

INTRODUCTION: During COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality. METHODS: COVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020. RESULTS: 618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome. DISCUSSION: COVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Aged , COVID-19/epidemiology , Female , Hospital Mortality , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Respiratory Therapy , Retrospective Studies
16.
Int J Mol Sci ; 22(17)2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1390657

ABSTRACT

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.


Subject(s)
Biomarkers/blood , Carbon/metabolism , Liver/metabolism , Metabolome , Nitrogen/metabolism , Amino Acids/metabolism , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cytokines/blood , Discriminant Analysis , Humans , Least-Squares Analysis , Metabolic Networks and Pathways/genetics , Metabolomics/methods , SARS-CoV-2/isolation & purification , Severity of Illness Index
17.
Biology (Basel) ; 10(8)2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1376731

ABSTRACT

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

18.
Viruses ; 13(9)2021 08 29.
Article in English | MEDLINE | ID: covidwho-1374540

ABSTRACT

A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , COVID-19/blood , COVID-19/virology , SARS-CoV-2 , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/etiology , COVID-19/diagnosis , COVID-19/immunology , Disease Susceptibility , Female , Humans , Immunoassay , Male , Middle Aged , Pilot Projects , Symptom Assessment
19.
Biology (Basel) ; 10(8)2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1334990

ABSTRACT

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

20.
iScience ; 24(8): 102898, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1322153

ABSTRACT

The clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22). On the other hand, the benefit on mortality was not increased by using plasma with a high-antibody titer compared with unselected plasma. This meta-analysis might promote CP usage in patients with early-stage COVID-19 in further RCTs to maximize its benefit in decreasing mortality, especially in less affluent countries.

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