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1.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.10.06.23296657

ABSTRACT

'Coronavirus Disease 2019' (C19) is a respiratory illness caused by 'new Coronavirus' SARS-CoV-2. The C19 pandemic, which engulfed the world in 2021, also caused a national C19 epidemic in Pakistan, who responded with initial forced lockdowns (15-30 March 2020) and a subsequent switch to a smart lockdown strategy, and, by 31 December 2020, Pakistan had managed to limit confirmed cases and case fatalities to 482,506 (456 per 100,000) and 10,176 (4.8 per 100,000). The early switch to a smart lockdown strategy, and successful follow-up move to central coordination and effective communication and enforcement of Standard Operating Procedures, was motivated by a concern over how broad-based forced lockdowns would affect poor households and day-labour. The current study aims to investigate how the national Pakistan C19 epidemic would have unfolded under an uncontrolled baseline scenario and an alternative set of controlled non-pharmaceutical intervention (NPI) policy lockdown scenarios, including health and macroeconomic outcomes. We employ a dynamically-recursive version of the IFPRI Standard Computable General Equilibrium model framework (Lofgren, Lee Harris and Robinson 2002), and a, by now, well-established epidemiological transmission-dynamic model framework (Davies, Klepac et al 2020) using Pakistan-specific 5-year age-group contact matrices on four types of contact rates, including at home, at work, at school, and at other locations (Prem, Cook & Jit 2017), to characterize an uncontrolled spread of disease. Our simulation results indicate that an uncontrolled C19 epidemic, by itself, would have led to a 0.12% reduction in Pakistani GDP (-721mn USD), and a total of 0.65mn critically ill and 1.52mn severely ill C19 patients during 2020-21, while 405,000 Pakistani citizens would have lost their lives. Since the majority of case fatalities and symptomatic cases, respectively 345,000 and 35.9mn, would have occurred in 2020, the case fatality and confirmed case numbers, observed by 31. December 2020 represents an outcome which is far better than the alternative. Case fatalities by 31. December 2020 could possibly have been somewhat improved either via a more prolonged one-off 10 week forced lockdown (66% reduction) or a 1-month forced lockdown/2-months opening intermittent lockdown strategy (33% reduction), but both sets of strategies would have carried significant GDP costs in the order of 2.2%-6.2% of real GDP.


Subject(s)
COVID-19 , Coronavirus Infections , Respiratory Insufficiency , Ataxia
2.
Contemp Clin Trials Commun ; 33: 101106, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2299814

ABSTRACT

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.), Operation Warp Speed (OWS) was the program designated to coordinate such efforts. OWS was a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector, that aimed to help accelerate control of the COVID-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. The U.S. Department of Veterans Affairs' (VA) was identified as a potential collaborator in several large-scale OWS Phase III clinical trial efforts designed to evaluate the safety and efficacy of various vaccines that were in development. Given the global importance of these trials, it was recognized that there would be a need for a coordinated, centralized effort within VA to ensure that its medical centers (sites) would be ready and able to efficiently initiate, recruit, and enroll into these trials. The manuscript outlines the partnership and start-up activities led by two key divisions of the VA's Office of Research and Development's clinical research enterprise. These efforts focused on site and enterprise-level requirements for multiple trials, with one trial serving as the most prominently featured of these studies within the VA. As a result, several best practices arose that included designating clinical trial facilitators to study sites to support study initiation activities and successful study enrollment at these locations in an efficient and timely fashion.

3.
Curr Opin Organ Transplant ; 26(4): 412-418, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-2267967

ABSTRACT

PURPOSE OF REVIEW: The COVID-19 pandemic is a major challenge to global health, particularly among vulnerable populations. Here, we describe the emerging epidemiology and relevant data on treatment options for COVID-19. We discuss the implications of current knowledge for solid organ transplant (SOT) recipients. RECENT FINDINGS: Risk factors and outcomes of COVID-19 among SOT recipients remain uncertain, but recent data suggest similar outcomes to the general population. Case reports of donor-derived SARS-CoV-2 infection are emerging. Few studies on treatment of COVID-19 among SOT recipients are available, and therefore, general recommendations are similar to the general population. Vaccine efficacy in the SOT population is uncertain. SUMMARY: COVID-19 remains a significant threat to SOT recipients and studies on treatment and prevention specific to this population are urgently needed. Although vaccines represent the greatest hope to control this pandemic, their efficacy in this immunocompromised population is uncertain.


Subject(s)
COVID-19/epidemiology , Organ Transplantation/statistics & numerical data , SARS-CoV-2 , Transplant Recipients/statistics & numerical data , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/administration & dosage , Humans , Immunocompromised Host , Risk Factors , Tissue Donors
4.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.03.519511

ABSTRACT

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of common cold. In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from alpha and beta hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the omicron variant was reduced by approximately 50%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between alpha and beta hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV2 antigens, whereas a distinct anti-SARS-CoV2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.


Subject(s)
Coronavirus Infections , COVID-19
5.
Commun Med (Lond) ; 2(1): 147, 2022 Nov 21.
Article in English | MEDLINE | ID: covidwho-2133666

ABSTRACT

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging. METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski's method with a 0.05 level of significance. RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients. CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.


Computed tomography (CT) imaging uses X-rays to obtain images of the inside of the body. It is used to look at lung damage in patients with COVID-19. However, CT imaging exposes the patient to a considerable amount of radiation. As radiation exposure can lead to the development of cancer, exposure should be minimised. Conventional plain X-ray imaging uses lower amounts of radiation but lacks sensitivity. We used dark-field chest X-ray imaging, which also uses low amounts of radiation, to assess the lungs of patients with COVID-19. Radiologists identified pneumonia in patients more easily from dark-field images than from usual plain X-ray images. We anticipate dark-field X-ray imaging will be useful to follow-up patients suspected of having lung damage.

9.
Am J Transplant ; 22(11): 2682-2688, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1927552

ABSTRACT

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.


Subject(s)
COVID-19 , Organ Transplantation , Humans , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Organ Transplantation/adverse effects , Transplant Recipients
10.
Am J Transplant ; 22(8): 2083-2088, 2022 08.
Article in English | MEDLINE | ID: covidwho-1741322

ABSTRACT

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.


Subject(s)
COVID-19 Drug Treatment , Lactams , Leucine , Nitriles , Proline , Ritonavir , Transplant Recipients , Adult , Calcineurin Inhibitors/therapeutic use , Cyclosporine/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Lactams/therapeutic use , Leucine/therapeutic use , Nitriles/therapeutic use , Organ Transplantation , Proline/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , Sirolimus/therapeutic use , Tacrolimus/therapeutic use
11.
BMJ Glob Health ; 6(12)2021 12.
Article in English | MEDLINE | ID: covidwho-1550947

ABSTRACT

OBJECTIVES: COVID-19 has altered health sector capacity in low-income and middle-income countries (LMICs). Cost data to inform evidence-based priority setting are urgently needed. Consequently, in this paper, we calculate the full economic health sector costs of COVID-19 clinical management in 79 LMICs under different epidemiological scenarios. METHODS: We used country-specific epidemiological projections from a dynamic transmission model to determine number of cases, hospitalisations and deaths over 1 year under four mitigation scenarios. We defined the health sector response for three base LMICs through guidelines and expert opinion. We calculated costs through local resource use and price data and extrapolated costs across 79 LMICs. Lastly, we compared cost estimates against gross domestic product (GDP) and total annual health expenditure in 76 LMICs. RESULTS: COVID-19 clinical management costs vary greatly by country, ranging between <0.1%-12% of GDP and 0.4%-223% of total annual health expenditure (excluding out-of-pocket payments). Without mitigation policies, COVID-19 clinical management costs per capita range from US$43.39 to US$75.57; in 22 of 76 LMICs, these costs would surpass total annual health expenditure. In a scenario of stringent social distancing, costs per capita fall to US$1.10-US$1.32. CONCLUSIONS: We present the first dataset of COVID-19 clinical management costs across LMICs. These costs can be used to inform decision-making on priority setting. Our results show that COVID-19 clinical management costs in LMICs are substantial, even in scenarios of moderate social distancing. Low-income countries are particularly vulnerable and some will struggle to cope with almost any epidemiological scenario. The choices facing LMICs are likely to remain stark and emergency financial support will be needed.


Subject(s)
COVID-19 , Developing Countries , Gross Domestic Product , Humans , Policy , SARS-CoV-2
12.
BMJ Open ; 11(11): e050656, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1533046

ABSTRACT

OBJECTIVES: To estimate occupation risk from COVID-19 among teachers and others working in schools using publicly available data on mortality in England and Wales. DESIGN: Analysis of national death registration data from the Office for National Statistics. SETTING: England and Wales, 8 March-28 December 2020, during the COVID-19 pandemic. PARTICIPANTS: The total working age population in England and Wales plus those still working aged over 65 years. PRIMARY AND SECONDARY OUTCOMES: Death with COVID-19 as a primary outcome and death from all causes as a secondary outcome. RESULTS: Across occupational groups, there was a strong correlation between COVID-19 mortality and both non-COVID-19 and all-cause mortality. The absolute mortality rates for deaths with COVID-19 were low among those working in schools (from 10 per 100 000 in female primary school teachers to 39 per 100 000 male secondary school teachers) relative to many other occupations (range: 9-50 per 100 000 in women; 10-143 per 100 000 in men). There was weak evidence that secondary school teachers had slightly higher risks of dying with COVID-19 compared with the average for all working-aged people, but stronger evidence of a higher risk compared with the average for all professionals; primary school teachers had a lower risk. All-cause mortality was also higher among all teachers compared with all professionals. Teaching and lunchtime assistants were not at higher risk of death from COVID-19 compared with all working-aged people. CONCLUSION: There was weak evidence that COVID-19 mortality risk for secondary school teachers was above expectation, but in general school staff had COVID-19 mortality risks which were proportionate to their non-COVID-19 mortality risk.


Subject(s)
COVID-19 , Pandemics , Aged , Female , Humans , Male , Occupations , Routinely Collected Health Data , SARS-CoV-2 , Schools , Wales/epidemiology
13.
Int J Environ Res Public Health ; 18(22)2021 11 19.
Article in English | MEDLINE | ID: covidwho-1524000

ABSTRACT

Despite the widespread prevalence of cases associated with the coronavirus disease 2019 (COVID-19) pandemic, little is known about the spatial clustering of COVID-19 in the United States. Data on COVID-19 cases were used to identify U.S. counties that have both high and low COVID-19 incident proportions and clusters. Our results suggest that there are a variety of sociodemographic variables that are associated with the severity of COVID-19 county-level incident proportions. As the pandemic evolved, communities of color were disproportionately impacted. Subsequently, it shifted from communities of color and metropolitan areas to rural areas in the U.S. Our final period showed limited differences in county characteristics, suggesting that COVID-19 infections were more widespread. The findings might address the systemic barriers and health disparities that may result in high incident proportions of COVID-19 clusters.


Subject(s)
COVID-19 , Cluster Analysis , Humans , Pandemics , SARS-CoV-2 , Spatial Analysis , United States/epidemiology
14.
Thorax ; 77(1): 65-73, 2022 01.
Article in English | MEDLINE | ID: covidwho-1440837

ABSTRACT

BACKGROUND: Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity. METHODS: We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase). RESULTS: There were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1-9/day: OR 2.14, 95% CI 0.87 to 5.24; 10-19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72). INTERPRETATION: Congruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19.


Subject(s)
COVID-19 , Biological Specimen Banks , COVID-19 Testing , England , Humans , SARS-CoV-2 , Smoking/adverse effects
15.
American Journal of Transplantation ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1408328

ABSTRACT

Abstract Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence at 138 days with low polymerase chain reaction cycle threshold values and evidence of continuing viral sequence evolution indicative of ongoing virus replication. These findings have important implications for infection prevention and control recommendations in immunosuppressed patients. Immune response, including neutralizing antibody titers, T cell activity, and cytokine levels, peaked around days 44-72 after diagnosis. Anti-S trimer antibodies were low at all time points, and T cell response was attenuated by day 119. As immune response waned and viral load increased, increased genetic diversity emerged, suggesting a mechanism for the development of viral variants.

16.
HemaSphere ; 5(SUPPL 2):358-359, 2021.
Article in English | EMBASE | ID: covidwho-1393436

ABSTRACT

Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232). Zanubrutinib is a potent and highly specific next-generation BTK inhibitor designed with greater selectivity for BTK vs TEC- and EGFRfamily kinases, which are thought to be related to off-target toxicities. Therapeutic activity of zanubrutinib was established in an early-phase study (BGB-3111-AU-003) of 20 patients (pts) with R/R MZL demonstrating an ORR of 80%, with a complete response (CR) rate of 15%, and partial response (PR) rate of 65% (Tedeschi et al. EHA 2020, abstract 2804). Aims: To present initial efficacy and safety results in pts with R/R MZL enrolled in MAGNOLIA (BGB-3111-214). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary end point was ORR determined by an independent review committee in accordance with the Lugano classification. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival (PFS), and safety. Results: As of January 11, 2021, 68 pts were enrolled and treated. Median age was 70 years (range, 37-95), with 28% aged ≥75 years. Subtypes included extranodal (mucosa-associated lymphoid tissue;38%), nodal (38%), splenic (18%), and indeterminate (6%) MZL. Median number of prior therapies was 2 (range, 1-6) and 32% of pts had disease that was refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.7-84.1). Sixty-six pts were evaluable for efficacy. At a median study follow-up of 15.5 months (range, 1.6-21.7), investigator-assessed ORR (CR + PR) was 74% (CR 24%, PR 50%, stable disease 17%). Responses were observed in all subtypes, with an ORR of 68%, 84%, 75%, and 50% in extranodal, nodal, splenic, and indeterminate subtypes, respectively. CR rate was 36% for extranodal MZL, 20% for nodal, 8% for splenic, and 25% for indeterminate subtype. Median DOR and PFS were not reached;15-month PFS was 68% and 12-month DOR was 81%. IRC review is ongoing. Twenty-eight (41%) pts discontinued treatment: 20 due to disease progression, 1 withdrew consent, 3 required prohibited medications, 4 due to adverse events (AEs;2 due to COVID-19 pneumonia, 1 due to pyrexia attributed to disease transformation, and 1 due to myocardial infarction [MI]). The most common (≥10%) treatment-emergent AEs reported were diarrhea (22%), bruising (21%), constipation (15%), pyrexia (13%), abdominal pain (12%), upper respiratory tract infection (12%), back pain (10%), and nausea (10%). Most AEs were grade 1 or 2. Neutropenia was the most common grade ≥3 AE (10%). Two pts died from COVID-19 pneumonia and 1 pt with pre-existing coronary artery disease died from MI. No fatal AEs were considered related to zanubrutinib. All-grade AEs of interest included neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%). No major/serious hemorrhage was reported. No AEs led to dose reductions. Summary/Conclusion: Zanubrutinib demonstrated high response rates and durable disease control with a favorable safety profile in pts with R/R MZL.

17.
Am J Transplant ; 21(12): 4032-4042, 2021 12.
Article in English | MEDLINE | ID: covidwho-1360447

ABSTRACT

COVID-19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy findings in the setting of COVID-19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS-CoV-2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID-19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS-CoV-2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS-CoV-2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow-up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID-19, the most common being acute rejection with arteritis.


Subject(s)
Acute Kidney Injury , COVID-19 , Allografts , Biopsy , Female , Graft Rejection/etiology , Humans , Kidney , Middle Aged , SARS-CoV-2
18.
arxiv; 2021.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2108.00860v1

ABSTRACT

During the first wave of COVID-19, hospitals were overwhelmed with the high number of admitted patients. An accurate prediction of the most likely individual disease progression can improve the planning of limited resources and finding the optimal treatment for patients. However, when dealing with a newly emerging disease such as COVID-19, the impact of patient- and disease-specific factors (e.g. body weight or known co-morbidities) on the immediate course of disease is by and large unknown. In the case of COVID-19, the need for intensive care unit (ICU) admission of pneumonia patients is often determined only by acute indicators such as vital signs (e.g. breathing rate, blood oxygen levels), whereas statistical analysis and decision support systems that integrate all of the available data could enable an earlier prognosis. To this end, we propose a holistic graph-based approach combining both imaging and non-imaging information. Specifically, we introduce a multimodal similarity metric to build a population graph for clustering patients and an image-based end-to-end Graph Attention Network to process this graph and predict the COVID-19 patient outcomes: admission to ICU, need for ventilation and mortality. Additionally, the network segments chest CT images as an auxiliary task and extracts image features and radiomics for feature fusion with the available metadata. Results on a dataset collected in Klinikum rechts der Isar in Munich, Germany show that our approach outperforms single modality and non-graph baselines. Moreover, our clustering and graph attention allow for increased understanding of the patient relationships within the population graph and provide insight into the network's decision-making process.


Subject(s)
COVID-19
19.
Liver Transpl ; 27(9): 1233-1234, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316227
20.
Transpl Infect Dis ; 23(4): e13637, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1228844

ABSTRACT

Whether solid organ transplant (SOT) recipients are at increased risk of poor outcomes due to COVID-19 in comparison to the general population remains uncertain. In this study, we compared outcomes of SOT recipients and non-SOT patients hospitalized with COVID-19 in a propensity score matched analysis based on age, race, ethnicity, BMI, diabetes, and hypertension. After propensity matching, 117 SOT recipients and 350 non-SOT patients were evaluated. The median age of SOT recipients was 61 years, with a median time from transplant of 5.68 years. The most common transplanted organs were kidney (48%), followed by lung (21%), heart (19%), and liver (10%). Overall, SOT recipients were more likely to receive COVID-19 specific therapies and to require ICU admission. However, mortality (23.08% in SOT recipients vs. 23.14% in controls, P = .21) and highest level of supplemental oxygen (P = .32) required during hospitalization did not significantly differ between groups. In this propensity matched cohort study, SOT recipients hospitalized with COVID-19 had similar overall outcomes as non-SOT recipients, suggesting that chronic immunosuppression may not be an independent risk factor for poor outcomes in COVID-19.


Subject(s)
COVID-19 , Organ Transplantation , Cohort Studies , Humans , Middle Aged , Organ Transplantation/adverse effects , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
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