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1.
Intensive Care Medicine ; 14:14, 2022.
Article in English | MEDLINE | ID: covidwho-2027451

ABSTRACT

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%;with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%;with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2;1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

2.
Modern Pathology ; 35(SUPPL 2):1276-1278, 2022.
Article in English | EMBASE | ID: covidwho-1857284

ABSTRACT

Background: SARS-CoV-2 placentitis is defined by the triad of histiocytic or mixed inflammatory intervillositis, increased perivillous fibrin deposition, and villous trophoblastic necrosis. We have observed multiple cases of intrauterine fetal demise (IUFD) or perinatal morbidity with intraparenchymal thrombohematomas, a feature not previously linked to poor outcomes associated with SARS-CoV-2-placentitis. Here we present 17 cases with such findings and provide a possible point of intervention as these lesions can be identified by ultrasonography. Design: A retrospective study, approved by the Institutional Review Board, was performed by searching the terms SARS-CoV-2 placentitis or SARS-CoV-2 infection or COVID in our pathology database for all in-house deliveries and cases from the consult practice of the authors between 1/1/21 and 9/24/21. Clinical data was obtained via the electronic medical records or through contacting the consulting pathologists. Results: Twenty-three cases were retrieved and reviewed for the presence of thrombohematomas in the maternal space. Seventeen cases had thrombohematomas, intervillous thrombi, or intervillous hemorrhage in addition to classic SARS-CoV-2 placentitis, and 12 of those cases (71%) were associated with IUFD. The period between a positive maternal COVID test and loss was less than 14 days in all but three cases of IUFD (75%). The non-IUFD cases were all associated with other perinatal morbidity. In 8 of 17 cases (47%), thrombohematomas were noted grossly. The presence of multiple placental lakes were identified in three cases where placental imaging was available. Representative gross and histologic findings and an ultrasound displaying placental lakes are presented in Figures 1 and 2, respectively. Clinical data associated with each case is in Table 1. Conclusions: We identify a novel feature present in placentas with SARS-CoV-2 placentitis associated with poor outcomes. The often grossly identifiable thrombohematomas were present in 17 cases of SARS-CoV-2 placentitis, the majority of which were associated with IUFD, suggesting that their presence is a marker for increased perinatal morbidity and mortality. We also show that these thrombohematomas can be identified by ultrasound, demonstrating that imaging the placenta is critical in pregnancies affected by COVID-19 independent of maternal symptoms as it may identify markers of severe placental damage that can be associated with IUFD or significant perinatal morbidity.

4.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-330191

ABSTRACT

SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and DELTA H69/ DELTA V70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing DELTA H69/ DELTA V70 and D796H conferred decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility, but incurred an infectivity defect. The DELTA H69/ DELTA V70 single mutant had two-fold higher infectivity compared to wild type and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, monoclonal antibodies targeting the RBD were not impacted by either or both mutations, but a non RBD binding monoclonal antibody was less potent against DELTA H69/ DELTA V70 and the double mutant. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies.

5.
International Journal of Travel Medicine and Global Health ; 9(3):124-131, 2021.
Article in English | CAB Abstracts | ID: covidwho-1559171

ABSTRACT

Introduction: The COVID-19 pandemic has caused a lot of changes on an individual and societal level. The current study was designed to investigate the impact of the isolation/social distancing period on people's sense of Being, Belonging, and Becoming at the early stages of the COVID-19 measures.

6.
Cochrane Database of Systematic Reviews ; 2021(10), 2021.
Article in English | EMBASE | ID: covidwho-1473793

ABSTRACT

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. Using a living systematic review approach, to assess whether hyperimmune immunoglobulin therapy is effective and safe in the treatment of people with COVID-19; and to maintain the currency of the evidence.

7.
Transfusion Medicine ; 31(SUPPL 1):10, 2021.
Article in English | EMBASE | ID: covidwho-1458117

ABSTRACT

Safety and efficacy of COVID-19 Convalescent Plasma (CCP) was tested as part of two large randomised controlled trials in UK (REMAP-CAP and RECOVERY). CCP collections by apheresis were started across NHSBT from early in the pandemic to support the trials. Data from CCP donors who had donated at least once in the period between April 2020 and March 2021 (inclusive) was reviewed. Of the 57 213 attendances during this period, 6908 (12.1%) resulted in at least one adverse event, reported within seven days of attendance. Donors experiencing an adverse event were more likely to be first-time donors than donors with no adverse event were. The risk of having any adverse event reduced from 14% for first-time donors to 7% for repeat donors. Bruising was seen in58%and vasovagal events were the second most commondonor adverse events accounting for 37% (2570/6908). Most (2373/2570, 92%) were mild with no loss of consciousness. CCP donors experienced lower rates of mild vasovagal events to new/returning whole blood donors overall but appear to be at higher risk after stratifying by sex and age. They are significantlymore likely to feel faint than new/returning apheresis donors. Differences between new/returning whole blood and CCP donors are statistically significant (p < 0.05) in both men and women in all age groups from 35 years upwards. In all cases where there is a significant difference, the rate was higher for CCP donors. When compared with new/returning apheresis donors, the rate in CCP donors was higher overall. One serious adverse event of donation was recorded in a new male CCP donor in his mid-40s who had severe immediate vasovagal reaction with hypotensive seizure requiring hospitalisation following his first CCP donation. He recovered subsequently and was withdrawn from donation. Donating CCP was largely safe but complications were seen following donation in 12% with vasovagal events, bruising and arm pain being the most reported donor adverse events. Vasovagal events could be multifactorial with increased anxiety, new/first time donors, vascular dysregulation or subclinical cardiac dysfunction secondary to recent COVID-19 infection possibly contributory. It is encouraging to see that the risk of having any adverse event halved with repeat donations.

9.
Stroke ; 52(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1234410

ABSTRACT

Introduction: The impact of the COVID-19 pandemic response on medical care for stroke is unknown. Methods: We used local “Get With The Guidelines” stroke data for patients with ischemic stroke (IS), transient ischemic attack (TIA), and intracerebral hemorrhage/subarachnoid hemorrhage (ICH/SAH) from March 20-April 14, 2020 (study period) and January 1-March 19, 2020 (control period #1) and March 20-April 14, 2019 (control period #2). We examined daily admission rates, transfers, tPA administration, thrombectomy, and time from last well to hospital arrival. Results: There were 349 patients (n=40 study period, n=225 control period #1, n=84 control period #2);263 with IS, 37 with TIA, and 49 with ICH/SAH. Overall, 46% were female, 82% white, with median age 70 years (IQR 58-82 years). Daily admission rates were 1.4 IS/day for the study period compared to 2.1 IS/day (Incident rate ratio [IRR] 1.49 95% CI 1.05-2.13, p=0.027) and 2.2 IS/day (IRR 1.57 1.04-2.37, p=0.033) for control periods #1 and #2 (Table), respectively. There was only one admission for TIA in the study period compared to approximately one every 4 days in control period #1 (IRR 7.2 95% CI 1.0-53.7, p=0.053) and one every 2 days in control period #2 (IRR 14.0 95% CI 1.8-106.5, p=0.011). ICH/SAH admissions were fewer in the study period. Transfers were less common with approximately one transfer every four days in the study period compared to one each day of the control periods. Rates of tPA, thrombectomy, and time from last well to first hospital contact did not differ across the epochs. Conclusions: Our data suggest the COVID-19 pandemic response has led to reduced admissionvolumes for all stroke types in the University of Rochester Medical Center catchment area, partlydue to decreases in hospital transfers. These data raise the question whether fewer patients soughtcare for stroke symptoms at the height of the COVID-19 pandemic.

10.
Open Forum Infectious Diseases ; 7(SUPPL 1):S161, 2020.
Article in English | EMBASE | ID: covidwho-1185691

ABSTRACT

Background: While hospitalized COVID-19 patients are well described in the literature, studies of the natural history and ambulatory cases are limited. We aim to describe the symptoms and clinical course of COVID-19 among ambulatory patients seen at the Emory University multidisciplinary Acute Respiratory Clinic (ARC) developed to care for patients with confirmed or suspected COVID-19. Methods: PCR-confirmed COVID-19 cases seen at ARC from 4/3-5/16/2020 were included in a retrospective chart review. Encounters were classified as acute, subacute, or convalescent depending on the duration since illness onset (< 1, 1-4, or >4 weeks, respectively). Demographic, clinical, physical exam, diagnostic test, and disposition data were abstracted and analyzed with standard descriptive statistics. Results: Among 404 visits at ARC, 127 (31.4%) were for confirmed COVID-19 illness (107 unique patients with 1-4 visits). The majority (75.7%) of patients were female, and the median age was 55 years (range 24-89). Patients presented during acute, subacute, and convalescent phases of illness (15.7%, 58.3%, and 26.0%, respectively;Table). Prevalent co-morbidities included hypertension (39.3%), obesity (27.1%), diabetes (20.6%), and asthma (21.5%). While measured or subjective fever was reported in the majority of acute visits (60.0%), it was less common in subacute and convalescent encounters (27.0% and 30.3%). Cough was commonly reported in acute, subacute, and convalescent visits (70.0%, 79.7%, 66.7%), as were dyspnea on exertion (45.0%, 70.3%, 66.7%) and chest tightness (40.0%, 40.5%, 60.6%). Although smell or taste alteration was present in almost half of acute and subacute patients, it was only reported in a quarter of convalescent patients. Among the three stages of illness, transfers from ARC to the ED or direct hospitalizations occurred in 15.0%, 23.0%, and 12.1% of acute, subacute and convalescent visits, respectively. Conclusion: Following acute illness, COVID-19 patients can experience persistent symptoms, primarily respiratory symptoms, which can be severe enough to warrant hospitalization. Clinics evaluating recovering patients should prepare to manage these symptoms. Further study of the pathophysiology and treatment of persistent pulmonary symptoms in COVID-19 is needed. (Table Presented).

11.
Cochrane Database of Systematic Reviews ; 2020(12), 2021.
Article in English | EMBASE | ID: covidwho-1160926

ABSTRACT

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe to prevent infection with SARS-CoV-2 and development of COVID-19; and to maintain the currency of the evidence, using a living systematic review approach.

12.
Cochrane Database of Systematic Reviews ; 2021(1), 2021.
Article in English | EMBASE | ID: covidwho-1159946

ABSTRACT

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess whether SARS-CoV-2-neutralising mAbs are effective and safe for treating patients with COVID-19 in comparison to an active comparator, placebo or no intervention, and to maintain the currency of the evidence, using a living systematic review approach. A secondary objective is to track newly developing SARS-CoV-2-targeting mAbs from first tests in humans onwards.

13.
American Journal of Obstetrics and Gynecology ; 224(2):S568-S569, 2021.
Article in English | Web of Science | ID: covidwho-1141179
14.
Pediatric and Developmental Pathology ; 23(6):550, 2020.
Article in English | EMBASE | ID: covidwho-1093937

ABSTRACT

Background: The rarity of placental infection by SARSCoV- 2 suggests the presence of protective measures. SARS-CoV-2 requires coexporession of its receptor, ACE2, and the serine proteinase TMPRSS2 for cellular infection. Both are expressed in the placenta but their protein expression pattern has not been demonstrated to date. Methods: 19 placentas from women with PCR proven SARS-CoV-2 infection were examined for SARS-CoV-2 expression by RNAish and immunohistochemistry (IHC) and for ACE2 and TMPRSS2 by IHC. Gross and histopathology were also reviewed. Two sets of controls were used: 'normal controls' - 122 placentas examined solely for GBS exposure (no other indication for examination) delivered from 2000-2004;and 'abnormal controls' - 130 placentas from neonates with a clinical diagnosis of HIE delivered from 2000-2019. The control placentas were reviewed for gross and histopathology. Results: 2 cases showed placental infection with viral RNA the villous syncytiotrophoblast (ST) and cytotrophoblast (CT) in a patchy distribution in 1 and only focally in the other. The infant with the patchy infection was SARSCoV- 2 PCR positive at 24 hours, the infant with only focal infection was PCR negative. None of the other placentas showed viral infection. All placentas showed robust expression of ACE2 in the trophoblast. The ST and CTexpression was membranous and In most cases ST expression was polarized-strongest, and in many cases only present, on the villous stromal side of the ST. TMPRSS2 was weakly expressed in the placental endothelial cells. Hofbauer cells were negative for both. We did not find a an increase in maternal or fetal vascular malperfusion (MVM or FVM) over controls. We saw MVM at 25%, FVM at 20%, acute chorioamnionitis at 30%, inflammatory pathologies (1 case each of ungradable VUE, intervillositis, Hofbauer cell hyperplasia) at 15%, all within published prevalences and similar to our controls. Conclusion:We did not find increased prevalence of MFM, FVM, infectious, or inflammatory pathology above published our our sets of controls as other have, perhaps due to small sample size. SARS-CoV-2 infection of the placenta is rare and vertical transmission, if it occurs, is even rarer. One mechanism for this is the rare occurrence of maternal SARS-CoV-2 viremia. Another mechanisms might be the unfavorable expression ACE2 and TMPRSS2. We show that their expression is uniquely distinct: ACE2 in the tropohobast and TMPRSS2 in the endothelium. Although we did not detect coexpression we cannot rule out that the vascular-syncytial membranes might coexpress ACE2 and TMPRSS2. We also show that ACE2 expression is polarized in most cases away from the maternal vascular space thereby perhaps limiting SARS-CoV-2 access to ST infection.

15.
MEDSURG Nursing ; 29(6):363, 2020.
Article in English | Scopus | ID: covidwho-1013765
16.
Cochrane Database of Systematic Reviews ; 10:10, 2020.
Article in English | GIM | ID: covidwho-995825

ABSTRACT

Background: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. Objectives: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. Search methods: We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. Selection criteria: We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. Data collection and analysis: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). Main results: This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms.

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