Severe arterial thromboembolism in patients with Covid-19

IntroductionThe novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged early December 2019 and was recently confirmed by the World Health Organization (WHO) to be a public health emergency of international concern. Earlier reports have shown coagulopathy in patients with severe coronavirus disease 2019 (Covid-19).Main symptoms and important clinical findingsWe present four critically ill Covid-19 patients, who were admitted to our hospital. They were treated with supportive care, oral chloroquine, and standard 2500 or 5000 International Units (IU) of dalteparine subcutaneously once daily. Two patients died during the course of their stay as a consequence of severe large vessel arterial thromboembolism. The other two patients survived but symptoms of paralysis and aphasia persisted after cerebral ischemia due to large vessel arterial thromboembolism. Patients showed no signs of overt disseminated intravascular coagulation (DIC) in their laboratory analysis.ConclusionThis case series suggest that even in absence of overt DIC, arterial thromboembolic complications occur in critically ill patients with Covid-19. Further studies are needed to determine which parameters are useful in monitoring coagulopathy and which dose of anti-thrombotic therapy in Covid-19 patients is adequate, even when overt DIC is not present.     

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies

BackgroundData on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce.ObjectiveTo study 14-day mortality in patients who received CPT.Patients & methodsRetrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed.ResultsThe median age of the study cohort was 62 years (18–80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2–25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy.ConclusionsWe provide a large series of patients with hematological malignancies and role of CPT in this group.     

Association between Covid-19 surge and emergency department patient flow and experience

BackgroundPreparations for Covid-19 in the Netherlands included hospital reconfigurations to increase capacity for the expected surge at the emergency department (ED). We describe patients’ ED length of stay (LOS), crowding and experiences of patients with respiratory complaints during the first Covid-19 peak.MethodsRetrospective analysis of demand, ED LOS, crowding, and a patient experience survey during a 12-week period in 2020 and similar periods in 2018 and 2019. Crowding levels were calculated using the National ED OverCrowding Scale.ResultsThe number of patients with respiratory complaints increased significantly, while total ED numbers were unchanged. Although presentation during the Covid-19 peak and needing hospital admission were associated with a longer ED LOS in patients with respiratory complaints, significantly less crowding occurred compared with the 2018 and 2019 periods. Increased ED LOS was associated with lower patient experience scores.ConclusionAdvanced warning and its associated preparation within the hospital and the community prevented significant delays in ED throughput during the first Covid-19 peak.     

Covid-19 associated Guillain-Barre Syndrome: Contrasting tale of four patients from a tertiary care centre in India

BackgroundGlobally, more than 12 million people have been infected with COVID −19 infection till date with more than 500,000 fatalities. Although, Covid-19 commonly presents with marked respiratory symptoms in the form of cough and dyspnoea, a neurotropic presentation has been described of late as well.ObjectiveIn this brief communication we report four cases of Covid-19 who presented to our hospital with features suggestive of Guillain-Barre Syndrome (GBS).DiscussionThe mechanisms by which SARS-CoV-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokine-related injury, secondary hypoxia, and retrograde travel along nerve fibres. The pathogenesis of GBS secondary to Covid-19 is not well understood. It is hypothesised that viral illnesses related GBS could be due to autoantibodies or direct neurotoxic effects of viruses.ConclusionNervous system involvement in Covid-19 may have been grossly underestimated. In this era of pandemic, it is very important for the physicians to be aware of association of GBS with Covid-19, as early diagnosis and treatment of this complication could have gratifying results. To the best of our knowledge, this is the first such case series of Guillain-Barre Syndrome associated with Covid-19 to be reported from India.     

Early predictors of mortality for moderate to severely ill patients with Covid-19

BackgroundDetermining the factors affecting the mortality and clinical conditions of the patients with Covid-19 are indispensable needs in developing patient treatment algorithms. We aimed to determine the parameters that can predict the mortality of moderate to severely ill patients with laboratory confirmed Covid-19.MethodsModerate to severely ill, Covid-19 patients older than 18 years were included. Mild Covid-19 patients and the ones with negative polymerase chain reaction test results were excluded from the study. The primary outcome of the study was 30-day mortality rate and we aimed to determine the factors affecting mortality in moderate to severely ill Covid-19 patients.Results168 patient results were analyzed. Median age of the patients was 59.5 (48.3 to 76) and 90 (53.6%) were male. According to multivariate regression analysis results, the presence of any comorbid disease (p = 0.027, HR = 26.11 (95%CI: 1.45 to 471.31)), elevated C-reactive protein levels (CRP) (p < 0.001, HR = 1.24 (95%CI: 1.11 to 1.38)) and presence of dyspnea (p = 0.026, HR = 4.26 ((95%CI: 1.19 to 15.28)) were found to significantly increase the mortality, while high pulse O 2 saturation level (p < 0.001, HR = 0.90 (95%CI: 0.82 to 0.99) was found to decrease. When receiver operating characteristic curve was created for laboratory tests, it was determined that white blood cell counts, neutrophil counts, CRP levels and neutrophil/lymphocyte ratio predicted mortality while Lymphocyte levels did not.ConclusionDyspnea, the presence of any comorbid disease, elevated CRP levels, and low pulse O 2 saturation levels predict mortality in moderate to severely ill Covid-19 patients.     

A consideration of convalescent plasma and plasma derivatives in the care of Severely-ill patients with COVID-19

The pathogenesis and immunopathological damage of severe forms of COVID-19 resemble acute autoimmune disease sparked by SARS-CoV-2, including an early systemic overproduction of proinflammatory cytokines. Such immunopathological features provide a rationale for the use of passive immunotherapy with convalescent plasma as a source of neutralizing anti-viral antibodies and of anti-inflammatory plasma components. While convalescent plasma therapy is now being evaluated in prospective clinical trials, we further consider the therapeutic potential of human hyper immune globulins, and of heterologous, engineered and monoclonal neutralizing antibodies as anti-viral agents to treat COVID-19. Good medical practice procedures are still needed and is why we also discuss the potential use of polyclonal polyspecific immunoglobulins (IVIG), a therapeutic plasma derivative, with potent anti-inflammatory activity, in severe forms of Covid-19.     

Screening for antibodies to HLA class I in apheresis donors following Covid‐19 or SARS-CoV-2 vaccination

Transfusion of HLA-specific antibodies may play a role in induction of TRALI, the transfusion complication responsible for most transfusion-related deaths. In Oslo, we screen our apheresis donors and defer HLA-immunized donors from donation of plasma-rich blood components. During the second year of the Covid-19 pandemic and following the first months of SARS-CoV-2 vaccination, both the virus itself and the vaccines were suspected of inducing de novo production of antibodies to HLA class I in patients. For the blood center, the possibility of finding HLA-antibodies in an increased number of blood donors has serious implications. We therefore conducted a study to map the extent of de novo HLA-specific antibodies in representative donor groups. 106 apheresis donors were screened for antibodies to HLA class I/II following Covid-19 or vaccination with either mRNA or adenovirus-vector vaccines, and the findings were compared to pre-Covid blood samples from the same donors. In addition, we analyzed pre-Covid samples from 11 HLA-antibody-positive donors of Covid convalescence plasma. Only three established thrombapheresis donors were deferred due to vaccine-induced HLA-antibodies. In short, our findings did not support the hypothesis that SARS-CoV-2 virus or vaccination cause de novo HLA immunization in healthy blood donors. However, some donors with pre-existing antibodies showed increased antibody expression, confirming a general boost of the immune response following infection or vaccination.     

Convalescent plasma therapy in patients with COVID-19

IntroductionPassive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19.MethodThe data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively.ResultsDuration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6?10 days, 11?15 days) (p=0.001).ConclusionCP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.     

Diabetes or endocrinopathy admitted in the COVID-19 ward

The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.     

Asymptomatic SARS-CoV-2 infection: Incidental findings on FDG PET/CT

Rationale and ObjectivesIdentify the incidental findings of Covid-19 pneumonitis on ¹⁸F-FDG PET/CT scan in asymptomatic oncologic patients. The goal was to detect clinically unsuspected Covid-19 infections to prevent community spread.Materials and MethodsRetrospective analysis was conducted to recognize the pattern of metabolic and radiographic alterations on ¹⁸F-FDG PET/CT scans in Covid-19 patients. 492 ¹⁸F-FDG PET/CT scans were reviewed for pulmonary and systemic abnormalities.Results¹⁸F-FDG PET/CT demonstrated new lung infiltrates in 29 asymptomatic patients. 13/29 patients had Covid-19 infection confirmed by nasopharyngeal nucleic acid PCR test. The most common lung abnormality was pure ground-glass opacity (GGO) (90%) in peripheral distribution (100%), involving 1 lobe in four patients (30.8%), 2–3 lobes in four patients, and 4-5 lobes in five patients (38.4%). Mean SUVmax was 4.7 (range 1.3–13.1). Ten patients developed symptoms, mainly fever, fatigue, and dry cough, within 6.4 ± 7.8 days (range 1–24). Of the available laboratory data of 12 patients, eight developed lymphopenia, and five patients had neutrophilia. Five patients required hospitalization, and two died of complications.ConclusionFor a given geographic region in the later stage of a pandemic, such as Covid-19, community spread of the disease is common. Therefore, it is not surprising to find it in asymptomatic being imaged for other indications. Recognition of its manifestation and effectively mounting mitigation protocols is essential to further reduce SARS-CoV-2 spread, especially to susceptible groups, predominantly the elderly and people with comorbidities.     

Fatal gastrointestinal bleeding associated with acute pancreatitis as a complication of Covid-19: a case report

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus–host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death.     

PDAtt-Unet: Pyramid Dual-Decoder Attention Unet for Covid-19 infection segmentation from CT-scans

Since the emergence of the Covid-19 pandemic in late 2019, medical imaging has been widely used to analyze this disease. Indeed, CT-scans of the lungs can help diagnose, detect, and quantify Covid-19 infection. In this paper, we address the segmentation of Covid-19 infection from CT-scans. To improve the performance of the Att-Unet architecture and maximize the use of the Attention Gate, we propose the PAtt-Unet and DAtt-Unet architectures. PAtt-Unet aims to exploit the input pyramids to preserve the spatial awareness in all of the encoder layers. On the other hand, DAtt-Unet is designed to guide the segmentation of Covid-19 infection inside the lung lobes. We also propose to combine these two architectures into a single one, which we refer to as PDAtt-Unet. To overcome the blurry boundary pixels segmentation of Covid-19 infection, we propose a hybrid loss function. The proposed architectures were tested on four datasets with two evaluation scenarios (intra and cross datasets). Experimental results showed that both PAtt-Unet and DAtt-Unet improve the performance of Att-Unet in segmenting Covid-19 infections. Moreover, the combination architecture PDAtt-Unet led to further improvement. To Compare with other methods, three baseline segmentation architectures (Unet, Unet++, and Att-Unet) and three state-of-the-art architectures (InfNet, SCOATNet, and nCoVSegNet) were tested. The comparison showed the superiority of the proposed PDAtt-Unet trained with the proposed hybrid loss (PDEAtt-Unet) over all other methods. Moreover, PDEAtt-Unet is able to overcome various challenges in segmenting Covid-19 infections in four datasets and two evaluation scenarios.     

Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records–based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare–affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59–0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47–0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997–0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare–affiliated entity, including Sarah Cannon and Genospace.     

Effects on mortality of early vs late administration of convalescent plasma in the treatment of Covid-19

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first seen in the city of Wuhan, China, in December 2019 and then spread worldwide. On 24 March 2020, the U.S. Food and Drug Administration reported that the use of convalescent plasma (CP) containing antibodies against COVID-19 could be effective against infection. The aim of this study is to retrospectively investigate whether early CP transfusion treatment has an effect on recovery of clinical and laboratory parameters in patients diagnosed with severe COVID-19 who were admitted to the intensive care unit (ICU). The study included 141 consecutive patients who had laboratory confirmation of COVID-19 and were admitted to the ICU between 1 May and 30 September 2020. Of the 141 patients, 84 received CP in the first five days of hospitalization in the ICU (early group), and 57 received CP after the fifth day of hospitalization in the ICU (late group). There were no significant differences between the two groups in terms of age, gender, comorbidities and the severity of the disease (according to the evaluation of lung tomography). There was no difference between the two groups in terms of mechanical ventilator needed, inotrope support, and tracheostomy procedure during the ICU admission (p = 0.962, p = 0.680, and p = 0.927, respectively). Despite these limitations, the overriding result of our study is that it suggests that administration of CP either early or late in the treatment of COVID-19, had no effect on mortality.     

COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers

BackgroundPassive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients.Materials and MethodsWe enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use.ResultsEighty-eight donors were included (median age 35 [28–48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15–19) and 38 (33–46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13–37) and 54 (49–61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either.ConclusionThe recruitment of young patients with a mild to moderate CO­VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.     

Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients

Coronavirus disease 2019 (COVID-19) convalescent plasma (CovCP) infusions have been widely used for the treatment of hospitalized patients with COVID-19. The aims of this narrative review were to analyze the safety and efficacy of CovCP infusions in the overall population and in immunocompromised patients with COVID-19 and to identify the lessons learned concerning the use of convalescent plasma (CP) to fill treatment gaps for emerging viruses. Systematic searches (PubMed, Scopus, and COVID-19 Research) were conducted to identify peer-reviewed articles and pre-prints published between March 1, 2020 and May 1, 2021 on the use of CovCP for the treatment of patients with COVID-19. From 261 retrieved articles, 37 articles reporting robust controlled studies in the overall population of patients with COVID-19 and 9 articles in immunocompromised patients with COVID-19 were selected. While CovCP infusions are well tolerated in both populations, they do not seem to improve clinical outcomes in critically-ill patients with COVID-19 and no conclusion could be drawn concerning their potential benefits in immunocompromised patients with COVID-19. To be better prepared for future epidemics/pandemics and to evaluate potential benefits of CP treatment, only CP units with high neutralizing antibodies (NAbs) titers should be infused in patients with low NAb titers, patient eligibility criteria should be based on the disease pathophysiology, and measured clinical outcomes and methods should be comparable across studies. Even if CovCP infusions did not improve clinical outcomes in patients with COVID-19, NAb-containing CP infusions remain a safe, widely available and potentially beneficial treatment option for future epidemics/pandemics.     

Fixed dilated pupils in Covid-19 ARDS patients under rocuronium,reversed after discontinuation

Neuromuscular Blockade Agents (NMBA) are used in the management of moderate and severe Acute Respiratory Distress Syndrome (ARDS) patients. They have never been reported to present Central Nervous System adverse reactions. Shortage of cis-atracurium during the pandemic, led to the use of rocuronium. We report three patients with Covid-19 ARDS, who presented bilateral dilated, non-reactive pupils, after continuous rocuronium infusion. Brain CT findings were unremarkable and transcranial doppler tracings did not suggest brain edema or hemorrhage. NMBA's discontinuation led to reversal of the pupillary dilation. We believe that impairment of Blood-Brain-Barrier, due to Covid-19, led rocuronium access into the Central Nervous System, leading to this adverse effect. Clinicians should be aware of this adverse reaction when managing patients with Covid-19 ARDS warranting NMBA use.