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Relationship between blood clots and COVID-19 vaccines: A literature review

  • Seyed Mohammad Hassan Atyabi , Foad Rommasi , Mohammad Hossein Ramezani EMAIL logo , Mohammad Fazel Ghane Ezabadi , Mehdi AghaAmooi Arani , Mohammad Hossein Sadeghi , Mohammad Mehdi Ahmed , Amir Rajabi , Nima Dehghan , Ali Sohrabi , Mojtaba Seifi and Mohammad Javad Nasiri EMAIL logo
Published/Copyright: April 26, 2022
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Open Life Sciences
From the journal Open Life Sciences Volume 17 Issue 1

Abstract

SARS-CoV-2 pandemic is one of the most critical pandemics during human civilization. Several therapeutic strategies for COVID-19 management have been offered; nonetheless, none of them seems to be sufficiently beneficial. In effect, vaccines have been proffered as a viable option. The critical issue now is to concentrate on protecting individuals against illness through immunization. One of the causes for concern among the researchers, physicians, and generally the whole community from the onset of vaccination has been the adverse effects (specifically blood clots) that may be observed after the injection of the COVID-19 vaccine. In some countries, such concerns have even resulted in the temporary or permanent discontinuation or abandonment of the application of some vaccines (especially AstraZeneca and Janssen). By evaluating rigorous studies published on this subject, the present article is aimed at identifying the association between blood clot incidence and COVID-19 vaccination. Various methods for producing the COVID-19 vaccines are analyzed, along with their possible pros and cons as well as common and rare side effects, especially VITT and blood clots. Finally, the differences of various vaccines on thrombotic events, WHO recommendations for VITT treatment, and blood clots statics are discussed.

Keywords: COVID-19 vaccines; thrombotic thrombocytopenia syndrome; blood clots; anti-PF4 antibody; immune system overactivation

1 Introduction

Coronaviruses are numerous enveloped viruses, and their genetic material is made up of ss-RNA [1]. In December 2019, SARS-CoV-2 was discovered following the identification of strange pneumonia in a group of patients in Wuhan, China, Mainland. 2019-novel Coronavirus (nowadays known as SARS-CoV-2) is a human beta-coronavirus responsible for COVID-19, the most sustainable pandemic catastrophe in the last century [2,3]. Apart from the commonly known respiratory symptoms, COVID-19 could cause cardiovascular, neurological, gastrointestinal, and renal complications and involvements, among others. The majority of individuals infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Almost 20% of COVID-19 patients require hospitalization, and nearly 5% could get into critical condition [2]. In the first 6 months of the pandemic, the novel Coronavirus brought about the demise of about one million people and wreaked havoc on the global economy and social order [4]. Since then, several mutations have occurred in the SARS-CoV-2 genome causing the incidence of other variants. Other types of COVID-19 – which originated in the United Kingdom, South Africa, and Brazil, respectively – are more transmissible and virulent, inclusive of B.1.1.7, B.1.351, and P.1. The existence of Spike (S) protein is a defining feature of all coronaviruses, which are linked to severe acute respiratory syndrome (SARS) [5]. The Coronaviruses’ Spike protein assists virus entry through host cells [6,7]. With the development of the pandemic, new variants of SARS-CoV-2 have emerged with mutations in the Spike protein, posing many challenges to the disease management [7,8].

2 COVID-19 treatment and management

In the early days of the COVID-19 pandemic, some antibacterial drugs (e.g., teicoplanin and azithromycin) as well as some systemic corticosteroids (e.g., methylprednisolone) were used to control the disease, but were later limited due to the ineffectiveness or widespread side effects [9,10]. Currently, the most common treatments to impede the disease include antiplatelet agents such as aspirin and antiviral drugs such as remdesivir, ribavirin, lopinavir/ritonavir, and umifenovir [11]. Early administration of nitazoxanide has been reported to reduce the viral load in individuals with COVID-19 [12,13]. Nevertheless, there is some controversy over chloroquine and hydroxychloroquine; it has not been particularly effective in recent clinical trials [14,15,16]. Remdesivir is a drug that is now used in many countries. Remarkable recovery from pneumonia and the decreased mortality rate have been observed in the clinical trials following the administration of remdesivir [17,18]. Initially, it was held that ribavirin and lopinavir/ritonavir are able to accelerate the COVID-19 recovery process and reduce the viral load. However, recent clinical studies have detected no effective performance, nor any significant improvement for ribavirin and lopinavir/ritonavir [18,19,20]. Umifenovir has been demonstrated to significantly contribute to clinical improvements such as chest imaging and oxygen saturation [21]. Convalescent plasma (CP) therapy has also been reported to diminish the mortality rate and improve clinical scales. It should be mentioned, however, that further studies have unveiled that the reliability of the evidence on the effect of convalescent plasma in COVID-19 is drastically low and indeterminate [22,23].

Overall, no conclusive and definitive cure has yet been discovered for SARS-COV-2. Therefore, the development of practical medicine and vaccines for the treatment and control of SARS-COV-2 is a priority.

3 Vaccination pros

Based on the information obtained from the Centers for Disease Control and Prevention (CDC), approved COVID-19 vaccines will have several benefits for preventing COVID-19. Vaccination aims to suppress the prevalence of COVID-19. In general, it may also protect uninfected individuals against infected ones by interrupting the chain of transmission; therefore, it will be quintessential for hampering the pandemic [8]. Vaccination is a more secure method of boosting immunity and is able to protect people by triggering an antibody (immune system) response without causing illness [24].

4 Efficacies of COVID-19 vaccines

The efficacy and impact of the vaccine on the SARS-CoV-2 pandemic are complex, and numerous possibilities could occur following the deployment. Since hospitalization and critical-care admissions put a tremendous burden on the healthcare organizations, the protection capability of a vaccine upon severe disease and mortality is the most substantial endpoint. The promising effect of vaccines on the population can be observed if the vaccination is sufficiently effective in older adults (e.g., >60 years). Vaccination now is widely distributed, including for people who are most susceptible to COVID-19. Admittedly, vaccines do not improve the clinical course but relieve the SARS-CoV-2 transmissibility [4].

5 Various types of COVID-19 vaccine

A very brief overview of the potential primary vaccines will be provided with a focus on the vaccines’ safety and influence records in the following sections.

5.1 mRNA-based vaccines

The mechanism behind the mRNA vaccination is that mRNA is an intermediary messenger that must be converted into an antigen after being delivered into host cells via multiple pathways. Pfizer and Moderna, as potential candidates for COVID-19 mRNA vaccines, exert their effect via injecting SARS-CoV-2 spike protein-encoding mRNA directly into the host cell. Although pure mRNA has been swiftly degraded over the last decade, various technical progressions in transfer systems and RNA carriers have enabled fast and secure uptake of mRNA into the cytosol, where ribosomes transform mRNA into a protein that could trigger an immunological reaction [25]. Theoretically, this method has a variety of advantages over the more traditional vaccination types. First, its ease and high speed with which it can trigger protein synthesis in the host cell can be counted. Second, immediately after the transfection, the target protein is expressed through translation from mRNA. Finally, protein-based vaccinations are frequently made by bacteria. In contrast, mRNA vaccines are typically translated by the host translation machinery, leading to an antigen that closely resembles the protein structure generated from the viral genome (e.g., posttranslational modifications) [26,27].

5.2 Modified Adenovirus vector-based vaccines

The global requirement for mass immunization against the COVID-19 pandemic is the main impetus for developing adenovirus vector vaccines [28]. Phase III of clinical trial studies has been completed for several vaccines based on the full-length S protein and nonreplicating adenovirus vectors. These vaccines include sputnik V, AstraZeneca (ChAdOx1-S/AZD1222), CanSino, and Janssen (Ad26.COV2) [29].

Different adenoviruses are utilized as vectors in modern COVID-19 vaccines for the mentioned vaccines; nonetheless, the primary manufacturing platforms and mechanism of action are the same in all of them. For example, Janssen is based on a human adenovirus, whereas Oxford vaccination is based on a chimpanzee (ChAdOx1) adenovirus. The Oxford approach used a chimpanzee virus to decrease the impact of human adenovirus antibodies over time. The SARS-CoV2 Spike protein gene is produced as DNA; then, the synthesized DNA is inserted into the DNA genome of adenoviruses, substituting a crucial adenovirus gene (E1) for virus replication; adenovirus cannot multiply. After this change, it cannot initiate a complete infection cycle as a result of this alteration. However, it may penetrate cells and show the inserted unfamiliar gene to make the S protein of Coronavirus [29]. High dosages of vector particles are required for effective adenovirus vector vaccinations. When these particles penetrate host cells, they are identified by innate immunity receptors, causing the production of cytokines and chemokines responsible for the adverse effects of vaccination [28,30].

5.3 Subunit vaccines

The organism’s purified protein extracts – usually administered together with an adjuvant to elevate the immune response – are a more traditional method of advancing in vaccines. So far, only NVX-CoV2373 has passed the third phase of the clinical trials [31]. Novavax vaccine has a recombinant full-length S protein as an antigen generated in Sf9 insect cells with stabilizing mutations. Adenovirus vector and inactivated vaccines preserve the vaccine at 4°C for extended cycles due to its durability. It has huge advantages over similar approved mRNA vaccines that need low freezing temperatures for storage [32].

5.4 Live-attenuated and inactivated virus vaccines

The available inactivated vaccines made by China, the Indian vaccine named Bharat Biotech (Bharat, Hyderabad, Telangana, India), and Valneva vaccine in development by the European Union all are created using very comparable and well-established technology. Generated in Vero cells, the virus is chemically inactive and is purified to varying degrees, with adjuvants added. In all situations, beta-propiolactone (BPL) is used to attenuate the virus [33]. New research has demonstrated that the BPL-inactivated molecular configuration of SARS-CoV2 could be cause for concern since it is found that almost all spikes had acquired a post-fusion shape [34]. Different methods that are adopted to produce COVID-19 vaccines are shown in Figure 1.

Figure 1 COVID-19 vaccines can be synthesized by employing various methods. All SARS-CoV-2 vaccines aim to present a viral antigen to the immune system, resulting in cellular and humoral immune responses. The process of cellular and humoral immune responses activation is illustrated in detail.
Figure 1

COVID-19 vaccines can be synthesized by employing various methods. All SARS-CoV-2 vaccines aim to present a viral antigen to the immune system, resulting in cellular and humoral immune responses. The process of cellular and humoral immune responses activation is illustrated in detail.

6 Side effects of COVID-19 vaccines

Some side effects have been reported after receiving COVID-19 vaccines, most of which are short term and resolve after a few days without any medical intervention. However, some more severe side effects have also been reported.

The findings by the Brighton Collaboration as well as other previous studies on vaccines’ side effects are briefly mentioned here: various types of strokes like nonhemorrhagic and hemorrhagic, encephalomyelitis, appendicitis, immune thrombocytopenia, Bell’s palsy, acute myocardial infarction, anaphylaxis, deep vein thrombosis, pulmonary, myocarditis or pericarditis, disseminated intravascular coagulation, and narcolepsy [35].

7 Short-term and common side effects

Common side effects after receiving the first dosage of COVID-19 vaccine include about 63.7% injection site tenderness, 54.2% injection site pain, 53.1% fatigue, nearly 52.6% headache, 44.2% malaise, 44.0% myalgia, about 33.6% pyrexia and feverishness, and 7.9% fever >38 °C [36].

Flu-like symptoms such as joint and muscle pain or headache are common side effects and could last for 1–2 days after vaccination [37]. In South Africa, a possibly vaccine-related severe adverse effect was confirmed 2 days after vaccination of a person who had a fever of more than 40°C but recovered quickly without needing to be hospitalized [38]. According to preliminary evidence from clinical trials in Russia, the most common side effects of the adenovirus-based Sputnik V vaccine are flu-like symptoms and injection-site reactions [39]. Reactions were identified more often after receiving the second dose of the Pfizer-BioNTech vaccine than after receiving the first one [8].

Vaccination has several side effects such as sudden pain in the chest, abdomen, headache, and dizziness. If side effects continue or recur after 3 days, further medical diagnostics should be performed to rule out thrombosis [37].

8 Rare severe and long-term side effects

In a clinical trial study in the United Kingdom and Brazil, only 168 participants (among 11,636) experienced severe adverse effects. Seventy-nine participants who had serious side effects had received ChAdOx1 of-19, and 89 of them had received MenACWY [38].

8.1 Some of the serious and long-term side effects that have been identified

8.1.1 Anaphylactic shock

There have been reports of allergic reactions including anaphylaxis. The most common adverse reactions to vaccination are local reactions and mild symptoms. Recently, 4.5 per million reports of anaphylaxis have been identified after the administration of both doses [8].

8.1.2 Neurological complications

Neurological symptoms that emerge after the vaccine administration include headache, myalgia, dizziness, muscle spasm, and paresthesia. Sporadic symptoms such as tremors, diplopia, tinnitus, dysphonia, epilepsy, and reactivation of herpes zoster appear after vaccination [8].

A case of transverse myelitis was identified 14 days after receiving the ChAdOx1 nCoV-19 booster vaccine, which is thought to have occurred potentially due to vaccination [38]. Two additional cases of transverse myelitis were initially identified to have been possibly resulted due to vaccination; however, this possibility was later questioned by an independent group of neurological researchers [38]. Researchers have stated that some slight risk of severe neurological disorders (e.g., Bell’s palsy, Guillain‐Barré syndrome (GBS), transverse myelitis, and acute disseminated encephalomyelitis) is caused by vaccination. However, no conclusive clue has been found to link the latter disorders to the vaccine [8].

8.1.3 Problems with blood clotting disorders

Due to the incidence of some instances of DIC and CVT, on March 15, 2021, the European Union put out a motion to temporarily cease the vaccination by AstraZeneca as a precaution, pending the EMA verdict [25]. According to a report, on March 16, about 20 million people in the United Kingdom and European Economic Area had received ChAdOx1 nCoV-19. On the basis of EMA reports, only seven patients had blood clots in multiple vessels (diffuse intravascular coagulation, or DIC), and 18 patients had CVST (cerebral venous sinus thrombosis). While a causal connection to the vaccine has not been established, it is plausible and warrants further investigation [40]. AstraZeneca creates thrombocytopenia and thrombosis in rare cases, such as the cerebral venous sinus or thrombosis in the portal, splanchnic, or hepatic veins. In healthy people, these symptoms appear 5–24 days after the first injection. Most of the patients in that report were women younger than 50 years, and some were prescribed estrogen replacement therapy or oral contraceptives [41].

The specialists on the Committee examined the reports of nine deaths with DIC and CVST recorded by the Member States, most of them being younger than 55 years and women [40]. Recently, the frequency of VITT has been estimated to be about 1 case per 100,000 exposures. However, it is very improbable that several cases of thrombosis will result directly after vaccination, but it should be discovered in a general population year [41].

8.1.4 Prevention and general management of vaccines complications

Factually, the number of confirmed deaths after vaccination is very limited. The majority of them are caused by other reasons (such as underlying illness, accidents, and so on) rather than the vaccine [8,38]. Patients with severe allergies or immediate reaction during 4 hours to polyethylene glycol (PEG) and its derivatives (e.g., poly-sorbates) should not be vaccinated with Pfizer-BioNTech or Moderna mRNA vaccines according to the CDC [8].

Chest or back pain, breathlessness, shoulder swelling or coldness, blurred vision, extreme and deteriorating headache following vaccination, intermittent bleeding, several minor bruising, red or purple stains, and under skin blood blisters are all signs that may signify a clot caused by the COVID-19 vaccine, according to EMA [25]. Anaphylaxis is a fatal side effect, and the vaccinated individuals must be closely monitored and attended to as soon as possible [8].

9 Mechanism of thrombotic thrombocytopenia after COVID-19 vaccination

In this section, we first look at a syndrome that clinically resembles postvaccination thrombotic thrombocytopenia. Then, we will review the WHO guideline for the treatment of VITT, and in the end, we will discuss the blood clots statics.

9.1 Autoimmune heparin-induced thrombocytopenia

HIT is characterized by unusually severe thrombotic events accompanied by thrombocytopenia. Thrombocytopenia is caused by rogue antibodies directed against platelet factor 4 (PF4), which causes massive platelet aggregation and thrombosis and a reduction in the platelet count resulting in bleeding. As a consequence, patients may experience both severe thrombosis and severe bleeding [42].

In a molecular view, platelet-activating antibodies’ transitory generation of the IgG class – which detects the multimolecular set of the cationic platelet factor 9 (PF4) coupled with poly-anionic heparin – causes heparin-induced thrombocytopenia (HIT), a pro-thrombotic adverse medication event [43].

Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic adverse medication event caused by the transient formation of platelet-activating antibodies from the IgG class, which recognizes multimolecular complexes of (cationic) platelet factor 9 (PF4) coupled with (poly-anionic) heparin. Heparin administration can result in the formation of HIT antibodies since heparin can act as a hapten, and hence, it is recognized by the immune system [44,45]. Platelet factor 4 is heparin bound to a protein, and the immune system produces antibodies against it, causing HIT. These antibodies are mainly of IgG type, and they take around 5 days to form. However, in the last few months, those exposed to heparin may have IgG circulating, as IgG-type antibodies are still generated even after removing their precipitant. In the circulation, IgG antibodies combine with heparin and PF4 to create a complex. The molecular tail of the antibody subsequently attaches to the FcIIA receptor on the platelet’s area of protein. This results in platelet activation, and the formation of platelet micro-particles imports the establishment of blood clots. As a result, the platelet number decreases dramatically, leading to thrombocytopenia. Furthermore, the reticuloendothelial system (mainly the spleen) eliminates antibody-coated platelets and then conducts thrombocytopenia [44,45].

Apart from heparin, other poly-anions (e.g., DNA and RNA, chondroitin sulfate, hyper sulfated, polyphosphates, and bacterial cell wall components) can cause adaptive changes in PF4 required to reveal the HIT antigen. Furthermore, in the absence of additional poly-anions, significant PF4 binding to platelets may result in HIT antigen(s) exposure. In the latter case, poly-anions on the platelet area are likely to increase the proximity of PF4. This issue demonstrates that antigens could be impacted by factors other than heparin administration called autoimmune HIT (A-HIT). These factors could be bacterial wall ingredients or trauma-induced nucleic acid unleash (i.e., a potential cause of spontaneous HIT syndrome), platelet-derived poly-anions, or the AstraZeneca COVID-19 vaccination [43].

9.2 Vaccine-induced thrombotic thrombocytopenia

Occasional cases of thrombotic thrombocytopenia caused by the resistance of platelet-activating antibodies against PF4 may happen after inoculation with ChAdOx1 n-Cov-19. The clinical sight of moderate-to-severe thrombocytopenia and thrombotic consequences at uncommon locations happening 1–2 weeks after immunization with ChAdOx1 n-Cov-19 against SARS-CoV-2 indicates a syndrome that clinically mimics severe heparin-induced thrombocytopenia. According to one study, five patients infected by venous thrombosis and thrombocytopenia 7–10 days after injecting the first AstraZeneca dose of adenoviral vector vaccine showed significant levels of antibodies to platelet factor 4-poly-anion complexes, without any prior heparin exposure. Antibodies to SARS-CoV-2 nucleocapsid protein were negative in all five individuals. Thus, the previous infection with SARS-CoV-2 could be deemed to have been highly unlikely. In a population of about 130,000 vaccinated individuals, only five cases of VITT were observed. The clinical parameters compared to those of immune system heparin-induced thrombocytopenia were distinguished within the vaccine-induced resistant thrombotic thrombocytopenia patients. Scientists conjecture that these complications are vaccine-induced thrombotic thrombocytopenia (VITT), an infrequent vaccine-related form of spontaneous heparin-induced thrombocytopenia [46].

10 Mechanism of VITT

The pathogenic mechanism of VITT, which the German Greifswald Company recently explained by Andreas Greinacher, is similar to heparin-induced thrombocytopenia (HIT). In this complication, IgG-type antibodies cause a pro-thrombotic condition that detects multimolecular complexes between the cationic platelet factor 4 and the anionic heparin and trigger platelet activation via the FcRIIA receptor. However, this syndrome is unusual since it occurs in immunized people with COVID-19 who have not received any heparin therapy during their lives. For the formation of this prothrombotic condition, known as “spontaneous” or autoimmune HIT, some explanations can be provided. It has recently been discovered that factors except heparin can produce a progressive syndrome with clinical and laboratory characteristics that closely mimic HIT. The mentioned factors include certain highly sulfated and highly negatively charged oligosaccharides (e.g., Pentosan poly-sulfate, hyper-sulfated chondroitin sulfate, and other similar compounds) [46]. A HIT-like phenomenon has been documented after knee substitution surgery and bacterial or viral infections in addition to poly-anionic drug exposure. These results are consistent with PF4’s antibacterial and anticoagulant potential. Indeed, active platelets unleash PF4 in response to pathogens, which aids neutrophil recruitment and enables neutrophil exocytosis to unleash myeloperoxidase and lysozyme.

Furthermore, PF4 binds directly to bacteria, forming a neo-antigen recognized by anti-PF4/heparin or anti-PF4/poly-anion antibodies. This will result in immune complexes that are important in antibacterial host defense. Many scientists have been researching COVID-19, and they have found nonplatelet-activating and platelet-activating anti-PF4/heparin antibodies. The aforementioned mechanisms of two antibodies could also be implicated in the antiviral response to SARS-CoV-2 infection [47].

11 Anti-PF4 antibody inducers

The inflammatory stimulation of the immunization or vaccination activates anti-PF4 antibodies, which cross-reacts with PF4 and platelets in the cases of VITT syndrome. It has been discovered that AstraZeneca COVID-19 vaccination increased the reactivity of VITT patients’ serum with platelets, implying the interactions between the vaccine and platelets or the vaccine and PF4 [43].

A theory could be buttressed by adenovirus utilized as a vector in AstraZeneca vaccine: the affinity of adenovirus for PF4 is high and can activate platelets. Free DNA in the vaccination might be a cause of these PF4-reactive antibodies. Previously, it has been demonstrated that DNA and RNA create multimolecular PF4 complexities that fasten antibodies against heparin-induced thrombocytopenia and induce antibodies. Based on what is mentioned, other adenovector vaccines such as Janssen (J&J) and Sputnik V may be potent for causing VITT. Other reports have indicated a similar mechanism; the records state that there may be a link between adenovector vaccines and blood clots [7].

There might be an essential connection between the SARS-COV2 Spike protein itself or similar molecules, with side effects in the body (e.g., thrombosis). Soluble Spike protein has been shown to negatively affect endothelial cells, such as a severe inflammatory response. Furthermore, there are numerous viruses with Spike surface protein in the bloodstream. In practice, all cases of critical SARS-CoV-2 infections (COVID-19) may be exposed to the death danger after thromboembolic events. Even pseudoviruses with Spike protein on their face produce severe inflammatory responses in the tissues and endothelial cells, showing the risk of this protein when it is present systemically. Therefore, different formulations and posttranscription modifications (e.g., capping, splicing, and poly-adenylation) may cause similar heparin–PF4 complex and trigger immune response [7]. The possible mechanism in which COVID-19 vaccines, especially the AstraZeneca vaccine, may cause VITT and blood clots is displayed in Figure 2.

Figure 2 COVID-19 vaccines may cause blood clots: Although VITT is one of the most uncommon side effects of COVID-19 vaccines, it is essential to know the possible mechanisms in which they cause blood clots.
Figure 2

COVID-19 vaccines may cause blood clots: Although VITT is one of the most uncommon side effects of COVID-19 vaccines, it is essential to know the possible mechanisms in which they cause blood clots.

12 VITT risk factors

According to several cases, young women who use hormonal contraceptives are more likely to experience harm and adverse reactions to the vaccines [47]. It can be conjectured that the relatively more robust immune systems in women make their bodies more irritable and sensitive; as a result of being more sensitive, the immune stimulant (vaccine) can cause clots at a higher rate vis-à-vis men. As we know, women’s estrogen strengthens their immunity; hence, the use of hormonal contraceptive pills can increase their immune response and make them more sensitive. It is also undeniable that a person’s physical health status can be deemed to be causing VITT.

13 VITT diagnosis

At first glance, the VITT recognition seems comparatively straightforward. However, numerous immune thrombocytopenia cases have been reported following the injection of Moderna and Pfizer vaccines. It is worth noting that other clinical conditions also can raise anti-PF4 antibodies in the blood (e.g., after cardiovascular surgery, and even in healthy people although VITT is not ruled out) [48].

The evidence indicates that venous or arterial thrombosis might occur in uncommon sites such as the brain or stomach in specific individuals, with clinical signs appearing 5–20 days after immunization. If followed by thrombocytopenia, this event can lead to an adverse impact of the preceding COVID-19 vaccination [46]. Because the mortality rate for individuals with cerebral venous thrombosis is more significant than predicted, early treatment actions are considered crucial [49].

14 Differences and causes of the effects of various vaccines on blood clots

In the following section, the vaccines whose injection has been officially reported to be accompanied by VITT and blood clots in the receivers will be discussed.

14.1 AstraZeneca COVID-19 vaccine

ChAdOx1 nCoV-19 (also named Vaxzevria) is a low-cost and easy-to-store vaccine manufactured by the Oxford University and AstraZeneca. It also has been the most controversial COVID-19 vaccine due to the diverse reports of thrombosis following its administration [50]. The thrombotic events after Vaxzevria vaccination was reported in many countries including Germany, Austria, and Norway [46,51]. It has been stated that patients diagnosed with TTS have developed one or more thrombotic events such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis, pulmonary embolism, or deep vein thrombosis (DVT). However, CVST was the most prevalent one, which mainly occurred before secondary cerebral hemorrhage [50]. The laboratory tests in VITT patients indicated low fibrinogen and platelet counts but dramatically high D-dimer concentration [52]. As mentioned earlier, the thrombotic events in such patients were caused by the synthesis of antibodies against platelet factor 4 (PF4) and incommensurate activation of the immune system.

14.2 Pfizer/Biontech COVID-19 vaccine

BNT162b1 (known as Comirnaty) produced by BioNTech and Pfizer is the first authorized COVID-19 vaccine and the first vaccine utilizing mRNA technology in the vaccine history [53]. This vaccine is reported to have the highest efficacy in preventing symptomatic COVID-19, but it is also the most expensive and hard-to-restore vaccine. In fact, it needs to be stored at −60°C [50,54]. Thrombotic events have been officially reported after the Pfizer COVID-19 vaccine. DVT was confirmed in one case in February 2021 [55]. Moreover, the first case on immune thrombocytopenia was also reported in a 22-year-old patient suffering from gum bleeding and petechiae after vaccination with Comirnaty in January 2021 [56]. Although these events are closely related to blood, they cannot accurately be counted as VITT or TTS; therefore, such cases can be purely coincidental despite the incidence rate (reported to be 3.3 per 100,000) [57]. However, it could be obviously concluded that VITT is presumably caused by the production of antibodies against PF-4 in patients who demonstrate TTS symptoms after vaccination [50].

14.3 Moderna COVID-19 vaccine

mRNA-1273 or Moderna COVID-19 vaccine is one of the other mRNA-based vaccines, which is produced by Moderna company [58]. A study conducted by Gee et al. reported that almost all (i.e., 90.8%) of the side effects after vaccination with mRNA-1273 could be categorized as nonserious adverse effects [59]. The first related event to clotting was reported in a 60-year-old man who experienced thrombocytopenia (but not a VITT/TTS) and purpuric after being vaccinated by Moderna COVID-19 vaccine [60]. However, the incidence of acute deep vein thrombosis (ADVT) was also reported as a blood clotting-related event after Moderna vaccination [61]. Thrombosis after Moderna vaccination is probably related to anti-PF4 antibodies such as previously mentioned vaccines.

14.4 Janssen’s COVID-19 vaccine

Ad26.COV2 (also branded as J&J COVID-19 vaccine), which was approved by the United States Food and Drug Administration (US-FDA) in February 2021, is one of the most controversial COVID-19 vaccines. According to various reports, rare and unknown types of thrombosis have been witnessed [62,63]. Similar to VITT in patients vaccinated by the AstraZeneca COVID-19 vaccine, CSVT and splanchnic veins thrombosis were also reported in individuals immunized by the J&J vaccine [50], corroborating the role of anti-PF4 synthesis in VITT. The causes and effects of VITT in the aforementioned vaccines were primarily similar, but it is worthy of noting prescribing anti-Xa inhibitors first-line anticoagulants. Avoiding the use of heparin is strongly advised for VITT patients who had received viral vector-based COVID-19 vaccine [64].

14.5 Other COVID-19 vaccines

A study by Liu et al. [65] targeted 406 healthcare employees who had received BBIBP-CorV Sinopharm vaccine (as a most common inactivated-virus-based vaccine) to evaluate the occurrence of VITT or other thrombotic-related events by measuring ten autoantibodies before and after vaccination [65]. The elicited results testify that although the concentration of anti-PF4-heparin antibodies has elevated in seven cases, none of the 406 cases showed VITT or thrombotic-related disorders [65], which evidently indicates more safety in the inactivated virus-based vaccines at VITT. It can also be mentioned that no official VITT cases were reported for Sputnik V as a viral vector-based vaccine. Argentina and Serbia – as two widely consumers of Sputnik V vaccine where a large number of this vaccine was inoculated – reported no blood clotting or thrombotic-related events [66,67]. However, it is clear that the causes and effects of different vaccines, which cause VITT on blood clots, are almost the same and no significant difference can be perceived among them.

15 Clinicians should consider these recommendations when facing patients with VITT

Anti-PF4-heparin and PF4-polyanion antibodies can be tested alone or together using a commercially approved method. However, false-negative results are possible in some rapid immunoassays and chemo-luminescence tests. ISTH guidelines recommend affirmation employing a functional test such as carbon 14-labeled serotonin discharge measure. The preliminary assessment of suspected VITT ought to incorporate a total blood cell tally, D-dimer and fibrinogen levels, PF4-polyanion ELISA, and imaging [48]. Overall, laboratory assessment of all important blood factors is helpful for VITT diagnosis and treatment. However, D-dimer concentration and detection of thrombus incidence by imaging methods play a more essential and critical role in proposed algorithms for VITT management [68].

Alternative causes of thrombocytopenia and thrombosis must be considered and examined regardless of (autoimmune) HIT and VIPIT test results. Several thrombotic microangiopathy syndromes such as antiphospholipid syndrome, immunological thrombotic-thrombocytopenic purpura or atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, and underlying malignant (hematological) illnesses are only a few examples that can be counted [37].

16 VITT treatment

VITT treatment must be based on clinical and laboratory analyses. That said, this can be modulated depending on the case condition. Intravenous immunoglobulin, glucocorticoids, and anticoagulation are significant parts of VITT therapy. Platelet-mediated activation of the Fcγ receptor is inhibited by high-dose intravenous immunoglobulin [48]. The research guideline is in line with previous findings in the management of severe A-HIT. A high dose of intravenous immune globulin has led to quickly rising platelet and hypercoagulability de-escalation. The addition of immunoglobulin was beneficial in suppressing platelet activation by patients’ antibodies [46]. It should be noted that HIT/VIPIT diagnostics should be requested before IVIG is given since high-dose immunoglobulins might cause false-negative test results [37].

Anticoagulant alternatives must include nonheparin anticoagulants that are utilized for heparin-induced thrombocytopenia therapy. A compelling experiment has ruled out the heparin-dependent increase of platelet activation [46]. Although heparin does not present worse results with certainty, it is better not to use it for VITT patients. Heparin should not be prescribed to VITT patients although it has not been conclusively proven to have harmful consequences. Anticoagulants except for heparin are preferable (e.g., Argatroban and direct oral anticoagulants). In several countries, the USA’s Danaparoid has been prescribed. Platelets should not be transfused since they increase platelets to activate and provide antibody-mediated blood clotting [49]. Platelet transfusions may aggravate the thrombotic signs of VITT and should be avoided unless life-threatening bleeding is occurring [48].

17 World Health Organization’s latest recommendations for VITT and TTS treatment following vaccination

World Health Organization has constantly observed the TTS occurrence after COVID-19 vaccination and provides some recommendations, advises, and caution for VITT patients in its published guideline named “Guidance for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following vaccination to prevent coronavirus disease (COVID-19)” [69] based on the official reports. The most significant WHO recommendations for VITT patients advise against the use of heparin, infusion of platelet, and steroid treatment in TTS patients [69]. WHO also stipulates that a platelet infusion strategy should be adopted for TTS patients who suffer from severe thrombocytopenia (platelets < 50,000/µL) or who are in an emergency situation. It should also be noted that WHO explicitly advises the injection of intravenous immunoglobulins (IVIG) and/or nonheparin-based anticoagulants for the vaccine receivers who have been diagnosed with TTS/VITT [69].

WHO also recommends that for preventing exposure to the antigen, patients who have reported VITT should not receive the same vaccine as the booster dose. It also strongly advises against the use of heparin-based drugs and vaccination with adenovirus vector-based vaccines in individuals with a history of HIT [69]. Recently, different successful treatments of definite VITT were reported [68], in which nonheparin anticoagulation, along with IVIG, and prednisone were prescribed as the primary therapeutic agents [70].

18 Blood clots statistics

Although there is a connection between some COVID-19 vaccines and blood clots, it is not suggested to break on vaccination. Researchers at a new pre-print study from Oxford University have demonstrated that the rate of CVST AstraZeneca vaccination compared with the rate of CVST associated with COVID-19 is 8–10. This research was based on a U.S. health database and provided cogent evidence demonstrating the benefits of vaccines over and above its risks. All crucial information on COVID-19 vaccines is summarized in Table 1.

Table 1

The most crucial information on mentioned COVID-19 vaccines in this article

Vaccine’s scientific name Used technology Made by Common side effects Rare side effects Thrombosis reported after injection EfficacyA Refs.
BNT162b2 mRNA-based Pfizer–BioNTech companies Allergy Myocarditis Yes 94% [71–76]
CX-024414 mRNA-based Moderna company Pain, fatigue, headache, myalgia, and arthralgia Myocarditis and pericarditis Yes 66–98% [36,76–79]
ChAdOx1 nCoV-19 Modified adenovirus vector based Oxford University and AstraZeneca company Vomiting, diarrhea, fever, and swelling Thrombosis with thrombocytopenia syndrome, and anaphylaxis Yes 92% [52,80–83]
Sputnik V Modified adenovirus vector based Gamaleya Research Institute of Epidemiology and Microbiology Mild adverse effects — Not reported 68–88% [66,84–87]
Ad26.COV2.S Modified adenovirus vector based Johnson & Johnson company Pain, headache, tiredness, muscle pain, and nausea Thrombosis with thrombocytopenia syndrome and anaphylaxis Yes 71% [63,88–91]
NVX-CoV2373 Protein subunit Novavax and the Coalition for Epidemic Preparedness Innovations Headache, nausea (feeling sick) or vomiting, muscle and joint pain, and tenderness Anaphylaxis Not reported 100% (alpha variant) [92–94]
Sinopharm BIBP COVID-19 vaccine Inactivated virus Sinopharm Institute of Biological Products Injection site pain and fatigue — Not reported 67–70% [95–98]
Covaxin BBV152 Inactivated virus Bharat Biotech with the Indian Council of Medical Research - National Institute of Virology Injection site pain, Head ache, fatigue, myalgia, malaise, and pyrexia — Not reported 33–62% [99–101]

AThe effectiveness of all mentioned vaccine means their efficiency for preventing hospitalization and is measured against Delta variant.

19 Conclusion

Adenovirus vector vaccines (AstraZeneca, Janssen, Sputnik V [no official case reported]) seem to be responsible for developing vaccine-induced immune thrombotic thrombocytopenia. However, it is not entirely understood what exactly triggers the immune system to cause VITT. That said, there are some speculations about DNA/RNA-PF4 complex, Spike protein itself, and transcription complexities that describe the occurrence of thrombotic thrombocytopenia syndrome reasonably. In addition, some factors like the patient’s underlying disease or age/sex and hormonal situation of the patient are effective in the management and treatment of VITT. All in all, it appears that first and foremost, physicians should review the testes’ results of anti-PF4-heparin and PF4-polyanion antibodies. Assessment of D-dimer and fibrinogen levels, as well as imaging methods, may also be helpful for medical doctors in evaluating suspected VITT patients. WHO has recommended the use of IVIG and/or nonheparin-based anticoagulants in individuals who are suffering from TTS after the COVID-19 vaccination. It has also generally (not in exceptional cases) advised against the use of heparin, platelet infusion, and steroid treatment in such patients. It should also be noted that although there is a connection between blood clots and COVID-19 vaccination, statistics and data have provided cogent proof that the occurrence of blood clots in COVID-19 is up to 10 times more common than the vaccines’ injection.

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  1. Funding information: The authors state no funding involved.

  2. Author contributions: S.M.H.A. and M.H.R. participated in conceptualization, design, definition of intellectual content, literature search, and manuscript preparation. F.R. participated in manuscript preparation, writing-review and drafting the manuscript, figures preparation, edition, and revision. M.F.G.E., M.A.A., M.H.S., M.M.A., A.R., N.D., A.S., and M.S. participated in literature search and manuscript preparation. M.J.N. participated in supervision and project administration, guarantor, and manuscript review. All authors made a significant participation in manuscript preparation, read the manuscript intently, and approved all of its content.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

[1] Chandrashekharaiah P, Kodgire S, Paul V, Desai D, Kushwaha S, Sanyal D, et al. Therapeutic potential of olive’s bioactive compounds in COVID-19 disease management: a review. AIJR Prepr. 2020;203:1439–50.Search in Google Scholar

[2] Wang S, Kirillova K, Lehto X. Travelers’ food experience sharing on social network sites. J Travel Tour Mark. 2017;34(5):680–93.10.1080/10548408.2016.1224751Search in Google Scholar

[3] Chang L, Yan Y, Wang L. Coronavirus disease 2019: coronaviruses and blood safety. Transfus Med Rev. 2020;34(2):75–80.10.1016/j.tmrv.2020.02.003Search in Google Scholar

[4] Hodgson SH, Mansatta K, Mallett G, Harris V, Emary KR, Pollard AJ. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect Dis. 2020;21(2):E26–E35.10.1016/S1473-3099(20)30773-8Search in Google Scholar

[5] Rens E, Smith P, Nicaise P, Lorant V, Van den Broeck K, Rens E, Accepted manuscript–soon to be published in Frontiers in Psychiatrie. https://www. frontiersin. org/articles/10.3389/fps yt. 2021.575553/abstract Mental distress and its contributing factors.Search in Google Scholar

[6] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–80. e8.10.1016/j.cell.2020.02.052Search in Google Scholar PubMed PubMed Central

[7] Kowarz E, Krutzke L, Reis J, Bracharz S, Kochanek S, Marschalek R. “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. eLife. 2021;11:e74974. 10.7554/eLife.74974.Search in Google Scholar PubMed PubMed Central

[8] Manolis AS, Manolis TA. COVID-19 vaccines: cardiovascular perspectives: COVID-19 vaccines. Rhythmos. 2021;16(2):22–33.10.1176/appi.neuropsych.20110277Search in Google Scholar

[9] Zhangjs M. Teicoplanin potently blocks the cell entry of 2019 nCoV. bioRxiv. 2020.Search in Google Scholar

[10] Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. Cmaj. 2020;192(17):E450–3.10.1503/cmaj.200528Search in Google Scholar PubMed PubMed Central

[11] Rommasi F, Nasiri M, Mirsaiedi M. Antiviral drugs proposed for COVID-19: action mechanism and pharmacological data. Eur Rev Med Pharmacol Sci. 2021;25(11):4163–73.Search in Google Scholar

[12] Srivatsan Padmanabhan M. Potential dual therapeutic approach against SARS-CoV-2/COVID-19 with nitazoxanide and hydroxychloroquine. DO-10.13140/RG. 2.2. 28124.74882: 2020.Search in Google Scholar

[13] Raghu G, Amatto VC, Behr J, Stowasser S. Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respiratory J. 2015;46(4):1113–30.10.1183/13993003.02316-2014Search in Google Scholar PubMed

[14] World Health Organization. Informal consultation on the potential role of chloroquine in the clinical management of COVID 19 infection. 13 March 2020 (Switzerland). WHO: R&D Blue print; 2020:1–10. https://www.who.int/publications/i/item/informal-consultation-on-the-potential-role-of-chloroquine-in-the-clinical-management-of-covid-19-infection.Search in Google Scholar

[15] Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai M-C. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review. Heart Rhythm. 2020;17(9):1472–9.10.1016/j.hrthm.2020.05.008Search in Google Scholar PubMed PubMed Central

[16] Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. J Autoimmum. 2020;111(102468):16.10.1038/s41421-020-0156-0Search in Google Scholar

[17] Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 – preliminary report. N Engl J Med. 2020;383:1813–26.10.1056/NEJMoa2007764Search in Google Scholar PubMed PubMed Central

[18] Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.10.1056/NEJMoa2002032Search in Google Scholar PubMed PubMed Central

[19] Abbaspour Kasgari H, Moradi S, Shabani AM, Babamahmoodi F, Davoudi Badabi AR, Davoudi L, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. J Antimicrobial Chemotherapy. 2020;75(11):3373–8.10.1093/jac/dkaa332Search in Google Scholar

[20] Khalili JS, Zhu H, Mak NSA, Yan Y, Zhu Y. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID‐19. J Med Virol. 2020;92(7):740–6.10.1002/jmv.25798Search in Google Scholar

[21] Lopes-Pacheco M, Silva PL, Cruz FF, Battaglini D, Robba C, Pelosi P, et al. Pathogenesis of multiple organ injury in COVID-19 and potential therapeutic strategies. Front Physiol. 2021;12:29.10.3389/fphys.2021.593223Search in Google Scholar

[22] Devasenapathy N, Ye Z, Loeb M, Fang F, Najafabadi BT, Xiao Y, et al. Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis. Cmaj. 2020;192(27):E745–55.10.1503/cmaj.200642Search in Google Scholar

[23] Zhang C, Shi L, Wang F-S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428–30.10.1016/S2468-1253(20)30057-1Search in Google Scholar

[24] CDC goverment. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/vaccine-benefits.html.Search in Google Scholar

[25] Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discovery. 2018;17(4):261–79.10.1038/nrd.2017.243Search in Google Scholar PubMed PubMed Central

[26] Anderson E, Rouphael N, Widge A, Jackson L, Roberts P, Makhene M, et al. For the mRNA-1273 Study Group*(2020) Safety and immunogenicity of SARS-CoV-2 mRNA1273 vaccine in older adults. N Engl J Med. 2020;383(25):2427–38.10.1056/NEJMoa2028436Search in Google Scholar PubMed PubMed Central

[27] Jackson NA, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. npj Vaccines. 2020;5(1):1–6.10.1038/s41541-020-0159-8Search in Google Scholar PubMed PubMed Central

[28] Coughlan L. Factors which contribute to the immunogenicity of non-replicating adenoviral vectored vaccines. Front Immunol. 2020;11:909.10.3389/fimmu.2020.00909Search in Google Scholar PubMed PubMed Central

[29] Small JC, Ertl HC. Viruses – from pathogens to vaccine carriers. Curr Opvirology. 2011;1(4):241–5.10.1016/j.coviro.2011.07.009Search in Google Scholar PubMed PubMed Central

[30] Lasaro MO, Ertl HC. New insights on adenovirus as vaccine vectors. Mol Ther. 2009;17(8):1333–9.10.1038/mt.2009.130Search in Google Scholar

[31] Wadman M, Cohen J. Novavax vaccine delivers 89% efficacy against COVID-19 in UK – but is less potent in South Africa. Science. 2021. https://www.science.org/content/article/novavax-vaccine-delivers-89-efficacy-against-covid-19-uk-less-potent-south-africa.10.1126/science.abg8101Search in Google Scholar

[32] Tian J-H, Patel N, Haupt R, Zhou H, Weston S, Hammond H, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. BioRxiv. 2020.10.21203/rs.3.rs-39239/v1Search in Google Scholar

[33] Heinz FX, Stiasny K. Profiles of current COVID-19 vaccines. Wien Klinische Wochenschr. 2021;133(7):271–83.10.1007/s00508-021-01835-wSearch in Google Scholar

[34] Liu C, Mendonça L, Yang Y, Gao Y, Shen C, Liu J, et al. The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by cryo-EM and cryo-ET. Structure. 2020;28(11):1218–24. e4.10.1016/j.str.2020.10.001Search in Google Scholar

[35] Li X, Ostropolets A, Makadia R, Shaoibi A, Rao G, Sena AG, et al. Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study. medRxiv. 2021.10.1101/2021.03.25.21254315Search in Google Scholar

[36] Tobaiqy M, Elkout H, MacLure K. Analysis of thrombotic adverse reactions of COVID-19 astrazeneca vaccine reported to eudravigilance database. Vaccines. 2021;9(4):393.10.3390/vaccines9040393Search in Google Scholar

[37] Oldenburg J, Klamroth R, Langer F, Albisetti M, von Auer C, Ay C, et al. Diagnosis and management of vaccine-related thrombosis following AstraZeneca COVID-19 vaccination: guidance statement from the GTH. Hämostaseologie. 2021;41:184–9.10.1055/a-1469-7481Search in Google Scholar

[38] Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99–111.10.1016/S0140-6736(20)32661-1Search in Google Scholar

[39] Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255):887–97.10.1016/S0140-6736(20)31866-3Search in Google Scholar

[40] Pinho A. COVID-19 vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low platelets. European Medicines Agency; March 18, 2021. European Union Official Website. https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots.Search in Google Scholar

[41] Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021;397(10275):671–81.10.1016/S0140-6736(21)00234-8Search in Google Scholar

[42] Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle P, Eichinger S. A prothrombotic thrombocytopenic disorder resembling heparin-induced thrombocytopenia following coronavirus-19 vaccination. Res Sq. 2021;1–10. 10.21203/rs.3.rs-362354/v1.Search in Google Scholar

[43] Greinacher A, Selleng K, Warkentin T. Autoimmune heparin‐induced thrombocytopenia. J Thrombosis Haemost. 2017;15(11):2099–114.10.1111/jth.13813Search in Google Scholar PubMed

[44] Warkentin TE. Think of HIT. ASH Educ Program Book. 2006;2006(1):408–14.10.1182/asheducation-2006.1.408Search in Google Scholar PubMed

[45] Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007;83(983):575–82.10.1136/pgmj.2007.059188Search in Google Scholar PubMed PubMed Central

[46] Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092–101.10.1056/NEJMoa2104840Search in Google Scholar PubMed PubMed Central

[47] Franchini M, Liumbruno GM, Pezzo M. COVID‐19 vaccine‐associated immune thrombosis and thrombocytopenia (VITT): diagnostic and therapeutic recommendations for a new syndrome. Eur J Haematol. 2021;107:173–80.10.1111/ejh.13665Search in Google Scholar PubMed PubMed Central

[48] McCrae KR. Thrombotic thrombocytopenia due to SARS-CoV-2 vaccination. Clevel Clin J Med. 2021; Online ahead of print: 1–4. 10.3949/ccjm.88a.ccc078.Search in Google Scholar PubMed

[49] Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384:2202–11.10.1056/NEJMoa2105385Search in Google Scholar PubMed PubMed Central

[50] Brazete C, Aguiar A, Furtado I, Duarte R. Thrombotic events and COVID-19 vaccines. Int J Tuberculosis Lung Dis. 2021;25(9):701–7.10.5588/ijtld.21.0298Search in Google Scholar PubMed PubMed Central

[51] Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(22):2124–30.10.1056/NEJMoa2104882Search in Google Scholar PubMed PubMed Central

[52] Cines DB, Bussel JB. SARS-CoV-2 vaccine–induced immune thrombotic thrombocytopenia. Mass Med Soc. 2021;384:2254–6.10.1056/NEJMe2106315Search in Google Scholar PubMed PubMed Central

[53] Xia X. Detailed dissection and critical evaluation of the Pfizer/BioNTech and Moderna mRNA vaccines. Vaccines. 2021;9(7):734.10.3390/vaccines9070734Search in Google Scholar PubMed PubMed Central

[54] Doroftei B, Ciobica A, Ilie O-D, Maftei R, Ilea C. Mini-review discussing the reliability and efficiency of COVID-19 vaccines. Diagnostics. 2021;11(4):579.10.3390/diagnostics11040579Search in Google Scholar PubMed PubMed Central

[55] Carli G, Nichele I, Ruggeri M, Barra S, Tosetto A. Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine. Intern Emerg Med. 2021;16(3):803–4.10.1007/s11739-021-02685-0Search in Google Scholar PubMed PubMed Central

[56] Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22‐year‐old post Covid‐19 vaccine. Am J Hematol. 2021;96(5):E133–4.10.1002/ajh.26106Search in Google Scholar PubMed PubMed Central

[57] Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol. 2010;85(3):174–80.10.1002/ajh.21616Search in Google Scholar PubMed

[58] Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–16.10.1056/NEJMoa2035389Search in Google Scholar PubMed PubMed Central

[59] Gee J, Marquez P, Su J, Calvert GM, Liu R, Myers T, et al. First month of COVID-19 vaccine safety monitoring – United States, December 14, 2020–January 13, 2021. Morbidity Mortal Wkly Rep. 2021;70(8):283–8.10.15585/mmwr.mm7008e3Search in Google Scholar PubMed PubMed Central

[60] Malayala SV, Mohan G, Vasireddy D, Atluri P. Purpuric rash and thrombocytopenia after the mRNA-1273 (Moderna) COVID-19 vaccine. Cureus. 2021;13(3):e14099.10.7759/cureus.14099Search in Google Scholar PubMed PubMed Central

[61] Bhan C, Bheesham N, Shakuntulla F, Sharma M, Sun C, Weinstein M. An unusual presentation of acute deep vein thrombosis after the Moderna COVID-19 vaccine – a case report. Ann Transl Med. 2021;9(20):1605.10.21037/atm-21-2772Search in Google Scholar

[62] Schuchat A, Marks P. Joint CDC and FDA statement on Johnson & Johnson COVID-19 vaccine: the following statement is attributed to Dr. Anne Schuchat, Principal Deputy Director of the CDC and Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research: media statement: for immediate release: Tuesday, April 13, 2021; 2021.Search in Google Scholar

[63] Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM, et al. Interim results of a phase 1–2a trial of Ad26. COV2. S Covid-19 vaccine. N Engl J Med. 2021;384(19):1824–35.10.1056/NEJMoa2034201Search in Google Scholar

[64] Pai M, Grill A, Ivers N, Maltsev A, Miller K, Razak F, et al.Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) following AstraZeneca COVID-19 vaccination. Sci Briefs Ont Covid-19 Sci Advisory Table. 2021;117:10.47326.10.47326/ocsat.2021.02.17.1.0Search in Google Scholar

[65] Liu T, Dai J, Yang Z, Yu X, Xu Y, Shi X, et al. Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort. Sci Bull. 2021;66(22):2312–9.10.1016/j.scib.2021.07.033Search in Google Scholar

[66] Nogrady B. Mounting evidence suggests Sputnik COVID vaccine is safe and effective. Nature. 2021;595(7867):339–40.10.1038/d41586-021-01813-2Search in Google Scholar

[67] Cazzola M, Rogliani P, Mazzeo F, Matera MG. Controversy surrounding the Sputnik V vaccine. Respiratory Med. 2021;187:106569.10.1016/j.rmed.2021.106569Search in Google Scholar

[68] Chen P-W, Tsai Z-Y, Chao T-H, Li Y-H, Hou CJ-Y, Liu P-Y. Addressing vaccine-induced immune thrombotic thrombocytopenia (VITT) following COVID-19 vaccination: a mini-review of practical strategies. Acta Cardiol Sin. 2021;37(4):355–64.Search in Google Scholar

[69] Organization WH. Guidance for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following vaccination to prevent coronavirus disease (COVID-19). Pharmacovigilance, COVID-19: Clinical care (WHO). 2021;1–64.Search in Google Scholar

[70] Thaler J, Ay C, Gleixner KV, Hauswirth AW, Cacioppo F, Grafeneder J, et al. Successful treatment of vaccine‐induced prothrombotic immune thrombocytopenia (VIPIT). J Thrombosis Haemost. 2021;19:1819–22.10.1111/jth.15346Search in Google Scholar

[71] Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet. 2021;3:383.10.1016/S0140-6736(21)01358-1Search in Google Scholar

[72] Badiani A, Patel J, Ziolkowski K, Nielsen F. Pfizer: The miracle vaccine for COVID-19? Public Health Pract. 2020;1:100061.10.1016/j.puhip.2020.100061Search in Google Scholar PubMed PubMed Central

[73] Wadman M. Public needs to prep for vaccine side effects. American Association for the Advancement of Science. 2020;370(6520):1022. 10.1126/science.370.6520.1022.Search in Google Scholar PubMed

[74] COVID C, Team R. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine – United States, December 14–23, 2020. Morbidity Mortal Wkly Rep. 2021;70(2):46–51.10.15585/mmwr.mm7002e1Search in Google Scholar PubMed PubMed Central

[75] Tobaiqy M, MacLure K, Elkout H, Stewart D. Thrombotic adverse events reported for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines: comparison of occurrence and clinical outcomes in the EudraVigilance database. Vaccines. 2021;9(11):1326.10.3390/vaccines9111326Search in Google Scholar PubMed PubMed Central

[76] Sessa M, Kragholm K, Hviid A, Andersen M. Thromboembolic events in younger women exposed to Pfizer-BioNTech or Moderna COVID-19 vaccines. Expert Opin Drug Saf. 2021;20(11):1451–3.10.1080/14740338.2021.1955101Search in Google Scholar PubMed PubMed Central

[77] Fowlkes A, Gaglani M, Groover K, Thiese MS, Tyner H, Ellingson K. Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection among frontline workers before and during B. 1.617. 2 (Delta) variant predominance – eight US locations, December 2020–August 2021. Morbidity Mortal Wkly Rep. 2021;70(34):1167–9.10.15585/mmwr.mm7034e4Search in Google Scholar PubMed PubMed Central

[78] Organization WH. Background document on the mRNA-1273 vaccine (Moderna) against COVID-19: background document to the WHO Interim recommendations for use of the mRNA-1273 vaccine (Moderna), 3 February 2021. World Health Organization. COVID-19: Critical preparedness, readiness and response; 2021:1–41. https://www.who.int/publications/i/item/background-document-on-the-mrna-1273-vaccine-(moderna)-against-covid-19.Search in Google Scholar

[79] Control CFD. Prevention, Myocarditis and pericarditis following mRNA COVID-19 vaccination; 2021.10.9734/bpi/cimms/v5/3459CSearch in Google Scholar

[80] O’Reilly P. A phase III study to investigate a vaccine against COVID-19. ISRCTN. 2020;10. ISRCTN. 2020;10:1–3. doi: 10.1186/ISRCTN89951424.10.1186/ISRCTN89951424Search in Google Scholar

[81] Stowe J, Andrews N, Gower C, Gallagher E, Utsi L, Simmons R. Effectiveness of COVID-19 vaccines against hospital admission with the Delta (B. 1.617. 2) variant. Public Health Engl. 2021;385(7):585–94. 10.1056/NEJMoa2108891.Search in Google Scholar PubMed PubMed Central

[82] Dimitrova E, Vaxzevria (Previously COVID-19 Vaccine AstraZeneca). European Medicines Agency. https://www.ema.europa.eu/en/medicines/human…; 2021.Search in Google Scholar

[83] Shimabukuro TT. COVID-19 vaccine safety update. Advisory Committee on Immunization Practices (CDC). United States. 2021;1–40. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-02/28-03-01/05-covid-Shimabukuro.pdf.Search in Google Scholar

[84] Cohen J. Russia’s approval of a COVID-19 vaccine is less than meets the press release. Science. 2020;10. https://www.science.org/content/article/russia-s-approval-covid-19-vaccine-less-meets-press-release.10.1126/science.abe2848Search in Google Scholar

[85] Callaway E. Outrage over Russia’S fast-track coronavirus vaccine. Nature. 2020;584:334–5.10.1038/d41586-020-02386-2Search in Google Scholar PubMed

[86] Barchuk A, Cherkashin M, Bulina A, Berezina N, Rakova T, Kuplevatskaya D, et al. Vaccine effectiveness against referral to hospital and severe lung injury associated with COVID-19: a population-based case-control study in St. Petersburg, Russia. MedRxiv. 2021.10.1101/2021.08.18.21262065Search in Google Scholar

[87] Babamahmoodi F, Saeedi M, Alizadeh-Navaei R, Hedayatizadeh-Omran A, Mousavi SA, Ovaise G, et al. Side effects and immunogenicity following administration of the Sputnik V COVID-19 vaccine in health care workers in Iran. Sci Rep. 2021;11(1):1–8.10.1038/s41598-021-00963-7Search in Google Scholar PubMed PubMed Central

[88] Livingston EH, Malani PN, Creech CB. The Johnson & Johnson Vaccine for COVID-19. Jama. 2021;325(15):1575–5.10.1001/jama.2021.2927Search in Google Scholar

[89] Control CfD; Prevention; COVID, J., vaccine (Johnson & Johnson) questions.Search in Google Scholar

[90] Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B. 1.1. 7 and B. 1.351 Variants. N Engl J Med. 2021;385:187–9.10.1056/NEJMc2104974Search in Google Scholar

[91] Prevention B. A study of Ad26. COV2. S for the prevention of SARS-CoV-2-mediated COVID-19 in adult participants. World Health Organization. ClinicalTrials.gov; 2020. https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/ictrp-NCT04505722?lang=en.Search in Google Scholar

[92] Novak N, Tordesillas L, Cabanillas B. Adverse rare events to vaccines for COVID-19: from hypersensitivity reactions to thrombosis and thrombocytopenia. Int Rev Immunol. 2021;41:1–10. 10.1080/08830185.2021.1939696.Search in Google Scholar

[93] Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385(13):1172–83.10.1056/NEJMoa2107659Search in Google Scholar

[94] Chen W-H, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: an overview. Curr Tropical Med Rep. 2020;7(2):61–4.10.1007/s40475-020-00201-6Search in Google Scholar

[95] Vokó Z, Kiss Z, Surján G, Surján O, Barcza Z, Pályi B, et al. Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary – the HUN-VE study. Clin Microbiol Infect. 2021;28:398–404.10.1016/j.cmi.2021.11.011Search in Google Scholar

[96] Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2021;21(1):39–51.10.1016/S1473-3099(20)30831-8Search in Google Scholar

[97] Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side effects and perceptions following Sinopharm COVID-19 vaccination. Int J Infect Dis. 2021;111:219–26.10.1016/j.ijid.2021.08.013Search in Google Scholar

[98] Al Khames Aga QA, Alkhaffaf WH, Hatem TH, Nassir KF, Batineh Y, Dahham AT, et al. Safety of COVID‐19 vaccines. J Med Virol. 2021;93(12):6588–94.10.1002/jmv.27214Search in Google Scholar

[99] Desai D, Khan AR, Soneja M, Mittal A, Naik S, Kodan P, et al. Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study. Lancet Infect Dis. 2021;22(3):349–56. 10.1016/S1473-3099(21)00674-5.Search in Google Scholar

[100] Darbar S, Agarwal S, Saha S. COVID19 vaccine: COVAXIN®-India’s first indigenous effective weapon to fight against coronavirus (A Review). Parana J Sci Educ. 2021;7(3):1–9.Search in Google Scholar

[101] Reprter Minuscule risk of blood clots with Covishield, no clots yet with Covaxin: Expert panel. https://www.newindianexpress.com/nation/2021/may/17/minuscule-risk-of-blood-clots-with-covishield-no-clots-yet-with-covaxin-expert-panel-2303681.html (accessed 31 December 2021).Search in Google Scholar
Received: 2021-09-23
Revised: 2022-01-17
Accepted: 2022-01-17
Published Online: 2022-04-26

© 2022 Seyed Mohammad Hassan Atyabi et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

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  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
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  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
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  30. Relationship between blood clots and COVID-19 vaccines: A literature review
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  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
https://doi.org/10.1515/biol-2022-0035
Keywords for this article
COVID-19 vaccines; thrombotic thrombocytopenia syndrome; blood clots; anti-PF4 antibody; immune system overactivation
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
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