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1.
Int J Infect Dis ; 121: 157-160, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1821282

ABSTRACT

OBJECTIVES: The effectiveness of a 3-day course of remdesivir to prevent severe disease in patients with COVID-19 who received solid organ transplant (SOT) is unknown. We wanted to study the efficacy of this therapeutic option in patients with COVID-19 who received SOT in preventing both hospitalizations for outpatients and clinical worsening due to COVID-19 for those already hospitalized for other reasons. METHODS: This is a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of patients with COVID-19 receiving SOT who received and did not receive pre-emptive remdesivir between December 23, 2021, and February 26, 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalization. RESULTS: A total of 24 patients who received SOT were identified. Among these, seven patients (29, 1%) received pre-emptive remdesivir, whereas 17 (70, 9%) patients did not. Receiving remdesivir significantly reduced the hospitalization rate in outpatients who received SOT and the clinical worsening of the condition of already hospitalized patients who received SOT (hazard ratio 0.05; confidence interval [0.00-0.65], P-value = 0.01). CONCLUSION: In our cohort of patients infected with SARS-CoV-2 who received SOT, pre-emptive remdesivir was effective in reducing the hospitalization rate due to COVID-19 and in preventing the clinical worsening of the condition of patients who received SOT who were hospitalized for reasons other than COVID-19.


Subject(s)
COVID-19 , Organ Transplantation , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , COVID-19/prevention & control , Humans , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334280

ABSTRACT

Background: the hyperinflammation phase of severe SARS-CoV-2 is characterized by complete blood count alterations. In this context, the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) can be used as prognostic factors. We study NLR and PLR trends at different timepoints and compute optimal cutoffs to predict four outcomes: use of Continuous Positive Airways Pressure (CPAP), ICU admission, invasive ventilation and death. Methods: : we retrospectively included all adult patients with SARS-CoV-2 pneumonia admitted from 23 rd January 2020 to 18 th May 2021. Data were extracted using ICD9 codes and our Covid-19 registry. Analyses included descriptive statistics and non parametric tests to study the ability of NLR and PLR to distinguish the patients’ outcomes at each timepoint. ROC curves were built for NLR and PLR at each timepoint (minus discharge) in order to identify cutoffs to distinguish severe and non severe disease and their statistical significance was assessed with the Chi-square test. NLR and PLR were compared with DeLong’s test. Results: : we included 2169 patients. NLR and PLR were higher in severe Covid-19 at all the timepoints, with a difference that gets bigger and a trend that is steeper in more severe disease. Both ratios were able to distinguish the outcomes at each timepoint. For NLR, the areas under the curve (AUROC) ranged between 0.59 and 0.81, for PLR, between 0.53 and 0.67. From each ROC curve we computed an optimal cutoff value (e.g. NLR 7 for CPAP for males at admission). NLR performed better than PLR. Conclusion: our results are in line with other studies that computed NLR and PLR trends and values in disease, especially with those that distinguished between different grades of severity. Our study is retrospective and single centre, and is limited by selection bias, but includes more than 2000 patients, thus limiting the confounding factors and outliers. Our cutoffs do not only deal with severity and mortality but allow for a more tailored approach. Future prospect include validating our cutoffs in a prospective cohort and comparing their performance against other Covid19 scores.

3.
Heliyon ; 8(2): e08895, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1778151

ABSTRACT

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328806

ABSTRACT

Background: the hyperinflammation phase of severe SARS-CoV-2 is characterized by complete blood count alterations. In this context, the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) can be used as prognostic factors. We study NLR and PLR trends at different timepoints and compute optimal cutoffs to predict four outcomes: use of Continuous Positive Airways Pressure (CPAP), ICU admission, invasive ventilation and death. Methods: we retrospectively included all adult patients with SARS-CoV-2 pneumonia admitted from 23 rd January 2020 to 18 th May 2021. Data were extracted using ICD9 codes and our Covid-19 registry. Analyses included descriptive statistics and non parametric tests to study the ability of NLR and PLR to distinguish the patients’ outcomes at each timepoint. ROC curves were built for NLR and PLR at each timepoint (minus discharge) in order to identify cutoffs to distinguish severe and non severe disease and their statistical significance was assessed with the Chi-square test. NLR and PLR were compared with DeLong’s test. Results: we included 2169 patients. NLR and PLR were higher in severe Covid-19 at all the timepoints, with a difference that gets bigger and a trend that is steeper in more severe disease. Both ratios were able to distinguish the outcomes at each timepoint. For NLR, the areas under the curve (AUROC) ranged between 0.59 and 0.81, for PLR, between 0.53 and 0.67. From each ROC curve we computed an optimal cutoff value (e.g. NLR 7 for CPAP for males at admission). NLR performed better than PLR. Conclusion: our results are in line with other studies that computed NLR and PLR trends and values in disease, especially with those that distinguished between different grades of severity. Our study is retrospective and single centre, and is limited by selection bias, but includes more than 2000 patients, thus limiting the confounding factors and outliers. Our cutoffs do not only deal with severity and mortality but allow for a more tailored approach. Future prospect include validating our cutoffs in a prospective cohort and comparing their performance against other Covid19 scores.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325523

ABSTRACT

Objectives: An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. Methods: All consecutive hospitalised patients from February 21 st to March 30 th , 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. Results: 426 adult patients (median age 68 (IQR, 56 to 77 years) were admitted with confirmed COVID-19 over a 5-week period;292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4 th were independent risk factors associated with in-hospital mortality. Conclusions: Olderage, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19

6.
iScience ; 25(2): 103743, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1611783

ABSTRACT

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

7.
Clin Microbiol Infect ; 27(7): 1029-1034, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1163569

ABSTRACT

OBJECTIVES: SARS-CoV-2 T-cell response characterization represents a crucial issue for defining the role of immune protection against COVID-19. The aim of the study was to assess the SARS-CoV-2 T-cell response in a cohort of COVID-19 convalescent patients and in a group of unexposed subjects. METHODS: SARS-CoV-2 T-cell response was quantified from peripheral blood mononuclear cells (PBMCs) of 87 COVID-19 convalescent subjects (range 7-239 days after symptom onset) and 33 unexposed donors by ex vivo ELISpot assay. Follow-up of SARS-CoV-2 T-cell response was performed in ten subjects up to 12 months after symptom onset. The role of SARS-CoV-2 specific CD4 and CD8 T cells was characterized in a group of COVID-19 convalescent subjects. Moreover, neutralizing antibodies were determined in serum samples. RESULTS: In 14/33 (42.4%) unexposed donors and 85/87 (97.7%) COVID-19 convalescent subjects a positive result for at least one SARS-CoV-2 antigen was observed. A positive response was observed up to 12 months after COVID-19 infection (median 246 days after symptom onset; range 118-362 days). Of note, SARS-CoV-2 T-cell response seems to be mainly mediated by CD4 T cells. A weak positive correlation was observed between Spike-specific T-cell response and neutralizing antibody titre (p 0.0028; r2 = 0.2891) and positive SARS-CoV-2 T-cell response was observed in 8/9 (88.9%) COVID-19 convalescent subjects with undetectable SARS-CoV-2 neutralizing antibodies. DISCUSSION: Cross-reactive SARS-CoV-2 T-cell response in uninfected patients may be due to previous infections with other common coronaviruses. Our data suggest that long-term SARS-CoV-2 T-cell response might accompany a waning humoral response.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antigens, Viral/immunology , Cohort Studies , Convalescence , Cross Reactions , Enzyme-Linked Immunospot Assay , Female , Follow-Up Studies , Humans , Immunity, Cellular , Male , Middle Aged , Young Adult
8.
Med (N Y) ; 2(3): 281-295.e4, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1078082

ABSTRACT

BACKGROUND: Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody (Ab) levels and specific memory B and T cell responses in convalescent coronavirus disease 2019 (COVID-19) patients. METHODS: A total of 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain Ab levels over a period of 8 months. In addition, the levels of SARS-CoV-2 neutralizing Abs and specific memory B and T cell responses were tested in a subset of samples. FINDINGS: Anti-SARS-CoV-2 Abs were present in 85% of the samples collected within 4 weeks after the onset of symptoms in COVID-19 patients. Levels of specific immunoglobulin M (IgM)/IgA Abs declined after 1 month, while levels of specific IgG Abs and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG Abs were still present, although at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B and T cell responses developed with time and were persistent in all of the patients followed up for 6-8 months. CONCLUSIONS: Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 may persist for at least 6-8 months, regardless of disease severity. Development of medium- or long-term protective immunity through vaccination may thus be possible. FUNDING: This project was supported by the European Union's Horizon 2020 research and innovation programme (ATAC, no. 101003650), the Italian Ministry of Health (Ricerca Finalizzata grant no. GR-2013-02358399), the Center for Innovative Medicine, and the Swedish Research Council. J.A. was supported by the SciLifeLab/KAW national COVID-19 research program project grant 2020.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin A , Immunoglobulin G , T-Lymphocytes
9.
Sci Rep ; 11(1): 1137, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1065934

ABSTRACT

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.


Subject(s)
COVID-19/mortality , Hospital Mortality , Registries/statistics & numerical data , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Risk Assessment
11.
Am J Transplant ; 20(7): 1882-1884, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-291819

ABSTRACT

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/therapy , Glomerulonephritis, IGA/complications , Kidney Failure, Chronic/complications , Kidney Transplantation , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Betacoronavirus , COVID-19 , Ceftriaxone/administration & dosage , Cytokines/metabolism , Glomerulonephritis, IGA/surgery , Humans , /methods , Kidney Failure, Chronic/surgery , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Pandemics , SARS-CoV-2 , Tacrolimus/administration & dosage , Treatment Outcome
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