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2.
QJM ; 114(11): 810-811, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-2190228
4.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.19.23284803

ABSTRACT

Background Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevations in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluations of the potential associations. Methods We conducted self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged 65 years and older. Adjusted incidence rate ratio (IRRs) and 95% confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following booster doses for AMI, PE, ITP, Bells Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). Results Among 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The IRR for inpatient PE cases following BNT162b2 primary series and booster was 1.19 (95% CI: 1.03 to 1.38) and 0.86 (95% CI: 0.78 to 0.95), respectively; and for mRNA-1273 primary series and booster, 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79 to 0.96), respectively. The IRR for BP following BNT162b2 and mRNA-1273 booster was 1.17 (95% CI: 1.06 to 1.29) and 1.16 (95% CI: 1.05 to 1.29), respectively. Conclusion In these two studies of the U.S. elderly we did not find an increased risk for AMI, ITP, DIC, and Myo/Peri; the results were not consistent for PE; and there was a small elevated risk of BP after exposure to COVID-19 mRNA vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the elderly.


Subject(s)
34170 , 12092 , 59585 , 14306 , 9395 , 9397 , 4272
5.
Turkiye Parazitol Derg ; 46(4): 339-341, 2022 11 28.
Article in English | MEDLINE | ID: covidwho-2155564

ABSTRACT

Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic infectious disease transmitted by ticks, accompanied by fever, bleeding, myalgia, weakness and similar non-specific symptoms, and can have an acute and serious course. In this article, two CCHF cases seen during the Coronavirus disease-2019 (COVID-19) pandemic in a non-endemic province are described. The common feature of both cases; contact with animals in the endemic region during the feast of sacrifice, non-specific symptoms, liver function test, lactate dehydrogenase and creatine phosphokinase elevation, leukopenia and thrombocytopenia. Especially during the COVID-19 pandemic, tick and livestock contact of patients with non-specific symptoms should be questioned.


Subject(s)
COVID-19 , Hemorrhagic Fever Virus, Crimean-Congo , Hemorrhagic Fever, Crimean , Leukopenia , Thrombocytopenia , Animals , Humans , Hemorrhagic Fever, Crimean/diagnosis , Pandemics
6.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2402533.v1

ABSTRACT

Introduction: COVID - 19 viruses are responsible for endemic respiratory tract infection in the wide world. Following vaccination with the nCoV-19 vaccine, however, cases of thrombosis and thrombocytopenia, to detect these cases D-dimer test should be done. Aims: this study aims to detect the relation between D- dimer and vaccination of COVID19 Methods: This study that done by vaccinated patients from the special labs in Amman the capital of Jordan between January 2022 to October 2022 using PCR tests for detecting the virus. XL-FDP level estimated by using Atlas D-Dimer Latex Kit (Atlas Medical, Cowley Rd, Cambridge) Following manufacturing instruction. Discussion/Conclusion. We conclude that the vaccinated COVID-19 patients suffer from elevated baseline D-dimer. thrombosis can occur in different organs, leading to organ failure in serious COVID-19 cases.


Subject(s)
12561 , 59585 , 14306 , 14312
7.
Front Immunol ; 13: 872683, 2022.
Article in English | MEDLINE | ID: covidwho-2141852

ABSTRACT

Despite their proven efficacy and huge contribution to the health of humankind, vaccines continue to be a source of concern for some individuals around the world. Vaccinations against COVID-19 increased the number of distressed people and intensified their distrust, particularly as the pandemic was still emerging and the populations were encouraged to be vaccinated under various slogans like "back to normal life" and "stop coronavirus", goals which are still to be achieved. As fear of vaccination-related adverse events following immunization (AEFIs) is the main reason for vaccine hesitancy, we reviewed immune and autoimmune AEFIs in particular, though very rare, as the most worrisome aspect of the vaccines. Among others, autoimmune AEFIs of the most commonly administered COVID-19 vaccines include neurological ones such as Guillain-Barre syndrome, transverse myelitis, and Bell's palsy, as well as myocarditis. In addition, the newly introduced notion related to COVID-19 vaccines, "vaccine-induced immune thrombotic thrombocytopenia/vaccine-induced prothrombotic immune thrombotic thrombocytopenia" (VITT/VIPITT)", is of importance as well. Overviewing recent medical literature while focusing on the major immune and autoimmune AEFIs, demonstrating their rate of occurrence, presenting the cases reported, and their link to the specific type of COVID-19 vaccines represented the main aim of our work. In this narrative review, we illustrate the different vaccine types in current use, their associated immune and autoimmune AEFIs, with a focus on the 3 main COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx1). While the rate of AEFIs is extremely low, addressing the issue in this manner, in our opinion, is the best strategy for coping with vaccine hesitancy.


Subject(s)
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Humans , Thrombocytopenia/etiology , Vaccination/adverse effects
8.
Nat Commun ; 13(1): 7169, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2133431

ABSTRACT

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Here we compare rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 with the background (expected) rates in the general population. In addition, we compare the rates of the same adverse events among persons infected with SARS-CoV-2 with background rates. Primary care and linked hospital data from Catalonia, Spain informed the study, with participants vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-23/06/2021), COVID-19 cases (01/09/2020-23/06/2021) or present in the database as of 01/01/2017. We included 2,021,366 BNT162b2 (1,327,031 with 2 doses), 592,408 ChAdOx1, 174,556 COVID-19 cases, and 4,573,494 background participants. Standardised incidence ratios for venous thromboembolism were 1.18 (95% CI 1.06-1.32) and 0.92 (0.81-1.05) after first- and second dose BNT162b2, and 0.92 (0.71-1.18) after first dose ChAdOx1. The standardised incidence ratio for venous thromboembolism in COVID-19 was 10.19 (9.43-11.02). Standardised incidence ratios for arterial thromboembolism were 1.02 (0.95-1.09) and 1.04 (0.97-1.12) after first- and second dose BNT162b2, 1.06 (0.91-1.23) after first-dose ChAdOx1 and 4.13 (3.83-4.45) for COVID-19. Standardised incidence ratios for thrombocytopenia were 1.49 (1.43-1.54) and 1.40 (1.35-1.45) after first- and second dose BNT162b2, 1.28 (1.19-1.38) after first-dose ChAdOx1 and 4.59 (4.41- 4.77) for COVID-19. While rates of thrombosis with thrombocytopenia were generally similar to background rates, the standardised incidence ratio for pulmonary embolism with thrombocytopenia after first-dose BNT162b2 was 1.70 (1.11-2.61). These findings suggest that the safety profiles of BNT162b2 and ChAdOx1 are similar, with rates of adverse events seen after vaccination typically similar to background rates. Meanwhile, rates of adverse events are much increased for COVID-19 cases further underlining the importance of vaccination.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Humans , SARS-CoV-2 , Spain/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , BNT162 Vaccine , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Vaccination/adverse effects
9.
Nat Commun ; 13(1): 7167, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2133430

ABSTRACT

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).


Subject(s)
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Humans , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Vaccination/adverse effects , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , United Kingdom
10.
Niger J Clin Pract ; 25(11): 1889-1895, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2144249

ABSTRACT

Background: Although COVID-19 has a milder course in pediatric patients than in adults, it can have a severe and fatal course in children with an underlying disease (UD). Aims: In this study, we aimed to evaluate the demographic, clinical, laboratory, and radiological characteristics, treatment methods, and prognosis of pediatric patients diagnosed with COVID-19. Patients and Methods: The files of patients aged 0-18 years diagnosed with COVID-19 were retrospectively evaluated. Clinically and radiologically suspicious cases were accepted as confirmed cases if SARS-CoV-2 PCR positivity was found in nasopharyngeal swab samples. The severity of the disease was defined as asymptomatic, mild, moderate, and severe according to clinical, laboratory, and radiological features. Results: A total of 322 pediatric patients, 51.2% male and 48.8% female, were included in the study. The median age of the patients was 12.08 years (1 month-18 years). Of the 322 patients, 81 (25.1%) were asymptomatic. Disease severity was as follows: 218 were (67.7%) mild, 14 were (4.3%) moderate, and 9 (2.7%) were severe. 35.7% of the patients were hospitalized. Six percent were admitted to the intensive care unit, and three (0.93%) patients died. The mortality rate in patients with the UD was 3.3%. Conclusion: In our study, we determined that the disease had a more severe course in patients with initial procalcitonin, D-dimer, troponin increase, and thrombocytopenia. Although COVID-19 has a mild course in children, this is unfortunately not true for children with an UD.


Subject(s)
COVID-19 , Thrombocytopenia , Adult , Child , Humans , Male , Female , COVID-19/epidemiology , Retrospective Studies , SARS-CoV-2 , Hospitals, University
11.
Blood Coagul Fibrinolysis ; 33(1): 67-70, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-2135719

ABSTRACT

We reported three cases of immune thrombocytopenia (ITP) that developed within 6 weeks after ChAdOx1 nCoV-19 vaccination. Antiplatelet factor 4 antibodies were undetectable in all three cases. Therefore, vaccine-induced immune thrombotic thrombocytopenia was very unlikely. Other potential causes of thrombocytopenia were excluded. Their clinical presentations, severity of thrombocytopenia and outcomes were varied. Only one ITP case, an 80-year-old man, received ITP treatments and achieved complete response after 2 weeks of eltrombopag. An 84-year-old man had spontaneous complete remission, and a 55-year-old woman had partial platelet recovery without ITP treatments. Among 107 720 Thais administered the ChAdOx1 vaccine between 16 March and 10 May 2021, these three ITP cases resulted in an estimated risk of ITP of at least one per 36 000 doses, which was approximately similar to the risk of ITP after measles-mumps-rubella immunization. This raises the concern of an increased risk of ITP after ChAdOx1 vaccination.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Vaccines , Aged, 80 and over , COVID-19 Vaccines , Female , Humans , Male , Middle Aged , Thailand , Vaccination
13.
Medicine (Baltimore) ; 101(45): e31385, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2115791

ABSTRACT

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.


Subject(s)
COVID-19 , Hepatitis B , Thrombocytopenia , Humans , Male , Adult , Middle Aged , Female , Hepatitis B virus , Retrospective Studies , Prevalence , COVID-19/diagnosis , COVID-19/epidemiology , Pandemics , Acute Disease , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B Antibodies , Thrombocytopenia/epidemiology
14.
Eur J Haematol ; 109(6): 619-632, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2112972

ABSTRACT

In late February 2021, a prothrombotic syndrome was encountered for the first time in some of the recipients of ChAdOx1 CoV-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India). Since the hallmark of this syndrome is the development of thrombocytopenia and/or thrombosis between 4 and 42 days after receiving a COVID-19 vaccine, it was named vaccine-induced immune thrombotic thrombocytopenia (VITT). Other names include "vaccine-induced prothrombotic immune thrombocytopenia" and "thrombosis with thrombocytopenia syndrome" by the Centers for Disease Control and the Food and Drug Administration (FDA). VITT appears similar to heparin-induced thrombocytopenia in that "platelet activating" autoantibodies are produced in both these conditions due to prior exposure of COVID-19 vaccine and heparin respectively, in turn causing thrombotic complications and consumptive thrombocytopenia. In this article, recent advances in the understanding of pathobiology, clinical features, investigative work-up, and management of VITT are reviewed.


Subject(s)
COVID-19 Vaccines , COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Humans , COVID-19/complications , COVID-19 Vaccines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/therapy , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology , Vaccines/adverse effects
15.
Rinsho Ketsueki ; 63(10): 1430-1439, 2022.
Article in Japanese | MEDLINE | ID: covidwho-2110947

ABSTRACT

The COVID-19 pandemic has cast a shadow over transfusion medicine based on the blood donation system. However, managing alloimmune platelet transfusion refractoriness (allo-PTR) has already been difficult. As a first step toward resolving this issue using induced pluripotent stem cell-derived platelet products (iPSC-PLTs), a clinical trial of autologous products (iPLAT1) was conducted in a patient with allo-PTR caused by anti-HPA-1a antibodies who had no compatible donor, and safety was confirmed. To produce iPSC-PLTs, a master cell bank (MCB) of expandable megakaryocyte lines (imMKCLs) is established from iPSCs. From this MCB, iPSC-PLTs are manufactured using a newly developed turbulent-type bioreactor and various compounds. Their quality, safety, and efficacy are confirmed by extensive preclinical studies. Based on the findings of the iPLAT1 study, a clinical trial of allo-transfusion of HLA homozygous iPSC-PLTs is currently ongoing and HLA class I-deficient O-type universal iPSC-PLTs are also being developed. iPSC-PLTs are expected to solve various problems, including allo-PTR in platelet transfusion, and greatly contribute to the advancement of transfusion medicine.


Subject(s)
COVID-19 , Induced Pluripotent Stem Cells , Thrombocytopenia , Humans , Blood Platelets/metabolism , Pandemics , Platelet Transfusion
16.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.06.22283145

ABSTRACT

Introduction: Serious harms of the COVID-19 vaccines have been underreported in published trial reports. Methods: Systematic review of papers with data on serious adverse events (SAEs) associated with a COVID-19 vaccine. Results: We included 18 systematic reviews, 14 randomised trials, and 34 other studies with a control group. Most studies were of poor quality. The most reliable one was a systematic review of regulatory data on the two pivotal randomised trials of the mRNA vaccines. It found significantly more SAEs of special interest with the vaccines than with placebo, and the excess risk was considerably larger than the benefit, measured as the risk of hospitalisation. The adenovirus vector vaccines increased the risk of venous thrombosis and thrombocytopenia, and the mRNA-based vaccines increased the risk of myocarditis, with a mortality of about 1-2 per 200 cases. We also found evidence of serious neurological harms, including Bel's palsy, Guillain-Barre syndrome, myasthenic disorder and stroke, which are likely due to an autoimmune reaction, as has been suggested also for the HPV vaccines. Severe harms, i.e. those that prevent daily activities, were hugely underreported in the randomised trials. These harms were very common in studies of booster doses after a full vaccination and in a study of vaccination of previously infected people. Discussion: Serious and severe harms of the COVID-19 vaccines have been ignored or downplayed, and sometimes been deliberately excluded by the study sponsors in high impact medical journals. This area needs further study. Authorities have recommended virtually everyone get vaccinated and receive booster doses. They fail to consider that the balance between benefits and harms becomes negative in low-risk groups such as children and people who have already acquired natural immunity.


Subject(s)
4421 , 33768 , 59585 , 34336 , 4404 , 14306 , 34211 , 6365 , 9397 , 34247
17.
Blood ; 139(17): 2581-2583, 2022 04 28.
Article in English | MEDLINE | ID: covidwho-1813283
18.
In Vivo ; 36(6): 2813-2822, 2022.
Article in English | MEDLINE | ID: covidwho-2100682

ABSTRACT

BACKGROUND/AIM: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for generating a global pandemic with deadly consequences and life changes worldwide. With the appearance of the new variants of the virus, clinical manifestations have been reported in the pediatric population, some with severe evolution. The aim of this study was to identify the laboratory parameters necessary to establish an effective therapy. PATIENTS AND METHODS: In the period from August 2020 to September 2021, 234 pediatric patients met the inclusion criteria and were selected for the study. After confirming the COVID-19 diagnosis, laboratory parameters were analyzed and compared to the severity of the illness. RESULTS: Thrombocytopenia (p<0.001), leukocytosis (p<0.001), and lymphopenia (p<0.001) correlated with the severity of the disease. Also, D-dimer values were closely monitored due to the high association of this parameter with an unsatisfactory prognosis and a severe form of the disease. CONCLUSION: The D-dimer values and complete blood count are useful parameters in COVID-19 evaluation in children.


Subject(s)
COVID-19 , Thrombocytopenia , Humans , Child , SARS-CoV-2 , Retrospective Studies , COVID-19 Testing , Biomarkers
20.
Proc Natl Acad Sci U S A ; 119(47): e2213361119, 2022 11 22.
Article in English | MEDLINE | ID: covidwho-2096949

ABSTRACT

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.


Subject(s)
COVID-19 , Thrombocytopenia , Humans , Male , Female , Platelet Factor 4 , Heparin , Antibodies , Immunologic Factors , Severity of Illness Index
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