A study on the side effects caused by the Pfizer/BioNTech COVID-19 vaccine: Focus on IgG antibodies and serological biomarkers.

Introduction: The SARS-CoV-2 pandemic that spread swiftly is now a major global public health issue. Vaccines are currently being distributed in an effort to limit the viral transmission and mortality. The aim of the study was monitoring of both safety and efficacy in determining the overall effectiveness of the vaccine and identifying any potential safety concerns. Material and methods: A retrospective, cross-sectional study employing a validated 13-item structured questionnaire divided into two sections was performed between March 2022 and September 2022. Different post-vaccination side effects (SE) according to symptoms severity in terms of age and sex for participants were reported. Additionally, some pertinent serological assays for participants' post-vaccinations were investigated. Results: A total of 502 participants (male: 262, female: 240) with comorbidity (healthy: 258, morbid: 244) who received two Pfizer/BioNTech mRNA vaccine doses were included. Importantly, second dose (D2) vaccination was associated with significantly more SE than single dose (D1) vaccination (p < 0.0001). In D1 vaccination injection site pain (ISP) (45%), followed by equal proportions of headache and fever (40%) were the most common vaccine SE, while in D2 vaccination, ISP (66%) and nausea (57%) were reported. In all, 97% (p < 0.0001) of participants were IgG antibody positive at D2 vaccination. Similarly, serum CR protein level was elevated significantly (p < 0.0001) corresponding to the severity of SE between D1 and D2. Significant differences in IgG concentration were found between D1 and D2 vaccination in different gender and age groups (p < 0.0001). Conclusions: In light of the extensive data from this study, it is evident that mRNA vaccines, particularly the Pfizer/BioNTech vaccine, have proven to be highly safe and effective in mitigating the impact of the SARS-CoV-2 pandemic.

The influence of SARS-CoV-2 on male reproduction and men's health.

BACKGROUND: SARS-CoV-2, the virus responsible for COVID-19, primarily affects the respiratory system by targeting the Angiotensin-converting enzyme 2 (ACE2) receptor and TMPRSS2. However, these receptors are also present in other organs, including the testes, where a higher concentration of ACE2 receptors has been observed. This raises concerns about the potential impact of the virus on male fertility. AIMS: In this study, we aimed to assess the effects of SARS-CoV-2 on semen parameters by comparing samples during and after infection in the same patients. MATERIALS & METHOD: The study enrolled 51 individuals who had contracted COVID-19 and analysed various parameters related to sperm quality and quantity, including C-reactive protein, testosterone levels, total sperm concentration, motility and morphology. A comparison was made between these parameters during the initial infection with SARS-CoV-2 and after a 2- and 5-month recovery period. RESULTS: The results indicated that all of the mentioned parameters were significantly affected during COVID-19 infection (PCR-ct, CRP, WBCs LH, FSH and testosterone levels, p-value = .0001). Furthermore, the study assessed TC, TM and sperm morphology in patients infected with SARS-CoV-2 and found that these parameters were also significantly influenced during the infection, (p-value = .0001; Morphology, p-value = .0004). We observed significant alterations in sperm count and morphology during infection, suggesting a potential negative impact on sperm quality. Additionally, lower hormone levels were observed during COVID-19 infection, possibly due to increased inflammatory cytokines. However, both hormones and inflammation markers returned to normal following recovery. Our findings indicate a statistically significant change in total sperm count, motility and morphology post-infection, which aligns with previous studies. Discussion, COVID-19 have a transient impact on sperm parameters and fertility, emphasizing the importance of further investigation into the long-term implications.

Clinical outcomes and phylogenetic analysis in reflection with three predominant clades of SARS-CoV-2 variants.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoes continuous evolution, resulting in the emergence of several variants. Each variant has a different severity and mortality rate. MATERIALS AND METHODS: In this study, 1174 COVID-19 patients were studied for mortality and severity over three SARS-CoV-2 predominating variant periods in 2021 and 2022 in Sulaimani Province, Iraq. In each period, a representative, variant virus was subjected to phylogenetic and molecular and clinical analysis. RESULTS: Phylogenetic analysis revealed three SARS-CoV-2 variants, belonging to: Delta B.1.617.2, Omicron BA.1.17.2, and Omicron BA.5.6. The Delta variants showed more severe symptoms and a lower PCR-Ct value than Omicron variants regardless of gender, and only 4.3% of the cases were asymptomatic. The mortality rate was lower with Omicron (.5% for BA.5.2 and 1.3% for BA.1.17.2) compared with Delta variants (2.5%). The higher mortality rate with Delta variants was in males (2.84%), while that with Omicron BA1.17.2 and BA.5.2 was in females, 1.05% and .0%, respectively. Age group (≥70) years had the highest mortality rate; however, it was (.0%) in the age group (30-49) years with Omicron variants, compared with (.96%) in Delta variants. CONCLUSIONS: There has been a surge in COVID-19 infection in the city due to the predominant lineages of SARS-CoV-2, B.1.617, Omicron BA.1.17.2 and Omicron BA.5.6, respectively. A higher PCR-Ct value and severity of the Delta variant over Omicron BA.1.17.2 and/or BA.5.2 variants were significantly correlated with a higher death rate in the same order.

Disease severity and efficacy of homologous vaccination among patients infected with SARS-CoV-2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers.

From March 2021, various countries including Iraq issued prompted recommendations for increased COVID-19 vaccine protection in individuals especially those at risk of catching the virus (i.e., lifestyle, health sector workers, and chronic diseases). It is critically important to understand the impact of COVID-19 vaccinations with the most commonly used vaccines (Pfizer and AstraZeneca) among populations either on the severity of the disease or the transmissibility of SARS-CoV-2 variants of concern (VOCs) and in sequential waves. This study was conducted to establish the clinical severity of COVID-19 caused by Delta and Omicron SARS-CoV-2 variants among patients who either attended or were admitted to hospitals and to compare the effectiveness of Pfizer and AstraZeneca COVID-19 vaccines (single or double doses) at least to prevent hospitalizations if not eradicating the pandemic. A case-control study was done of 570 hospitalized patients; including 328 COVID-19 confirmed patients (166 males, 160 females) who received homologous vaccinations and 242 unvaccinated patients (128 males, 114 females) during the studied waves. The study showed that unvaccinated COVID-19 patients in both waves had expressed significantly a higher number and longer periods of symptoms than vaccinated ones. Additionally, there was no significant effect of vaccine types, Pfizer and AstraZeneca or vaccine shot numbers on the PCR-Ct in the last (Omicron) wave of the pandemic. However, in the previous (Delta) wave of the pandemic, fully vaccinated (double doses) COVID-19 patients had higher PCR-Ct values. Whether among vaccinated or unvaccinated patients, lower CRP levels recorded during the Omicron wave than that of the Delta wave, and regardless of the vaccine type or shot numbers, there were no significant differences between the two waves. Lower WBCs were observed in patients (vaccinated and unvaccinated) infected with the Delta variant in comparison to those infected with the Omicron variant and without any remarkable effect of the vaccine type or shot numbers. This is the first molecular and investigational study of the Delta variant and circulated Omicron in Iraq, regarding the severity of these two waves of SARS-CoV-2 pandemic and the efficacy of homologous vaccination, indicating the insufficiency of two doses and the demand for booster dose(s) as the most effective way of keeping on the safe-side against SARS-CoV-2.

Mineralizing Coating on 3D Printed Scaffolds for the Promotion of Osseointegration.

Design and fabrication of implants that can perform better than autologous bone grafts remain an unmet challenge for the hard tissue regeneration in craniomaxillofacial applications. Here, we report an integrated approach combining additive manufacturing with supramolecular chemistry to develop acellular mineralizing 3D printed scaffolds for hard tissue regeneration. Our approach relies on an elastin-like recombinamer (ELR) coating designed to trigger and guide the growth of ordered apatite on the surface of 3D printed nylon scaffolds. Three test samples including a) uncoated nylon scaffolds (referred to as "Uncoated"), b) ELR coated scaffolds (referred to as "ELR only"), and c) ELR coated and in vitro mineralized scaffolds (referred to as "Pre-mineralized") were prepared and tested for in vitro and in vivo performance. All test samples supported normal human immortalized mesenchymal stem cell adhesion, growth, and differentiation with enhanced cell proliferation observed in the "Pre-mineralized" samples. Using a rabbit calvarial in vivo model, 'Pre-mineralized' scaffolds also exhibited higher bone ingrowth into scaffold pores and cavities with higher tissue-implant integration. However, the coated scaffolds ("ELR only" and "Pre-mineralized") did not exhibit significantly more new bone formation compared to "Uncoated" scaffolds. Overall, the mineralizing coating offers an opportunity to enhance integration of 3D printed bone implants. However, there is a need to further decipher and tune their immunologic response to develop truly osteoinductive/conductive surfaces.

Serum troponin, D-dimer, and CRP level in severe coronavirus (COVID-19) patients.

BACKGROUND: Abnormal inflammation coagulation biomarker levels of troponin, C-reactive protein (CRP), and D-dimer levels in serum have been demonstrated to be associated and involved in the disease progression of coronavirus disease 2019 (COVID-19). METHODS: First: the study aimed to investigate the correlation of troponin, CRP, d-dimer, white blood cell (WBC) and polymerase chain reaction-cycle threshold (PCR-Ct) within COVID-19 survivors (143 patients; 79 males, 64 females) and in deceased (30 patients; 12 males, 18 females) group. Also, assessing any differences between both groups in studied parameters. Second: a correlation study of studied parameters' level has been conducted within families (41 patients; 23 males [seven deaths] and 18 females [eight deaths]) that lost more than one member due to the severity of the disease. Also, differences between these family and control group (132 patients; 69 males and 63 females) group in studied parameters have been assessed. RESULTS: In the first week of hospitalization, there were significant differences in D-dimer, CRP and troponin level between survived and deceased patient groups. In the second week of the admission, both groups had significant differences in the level of all studied parameters; troponin I, D-dimer, CRP, and WBCs. WBC levels positively correlated to CRP in male survivors (r = 0.75, p < 0.0001), and to troponin in deceased male patients (r = 0.74, p = 0.007). The second week of patient admission was critical in the group of families who lost more than one person, when troponin was correlated positively with D-dimer, CRP, and WBCs. CONCLUSION: Troponin, D-dimer, CRP, and WBCs level were significantly higher in COVID-19 patients who died than in COVID-19 survivors. High troponin and WBC levels, were considerably associated with families that lost more than one member, when compared with the unrelated COVID-19 patient control.

Hypoalbuminemia in patients following their recovery from severe coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is caused by a contagious virus that has spread to more than 200 countries, territories, and regions. Thousands of studies to date have examined all aspects of this disease, yet little is known about the postrecovery status of patients, especially in the long term. Here, we examined erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum albumin biomarkers in patients with a history of severe and mild-to-moderate COVID-19 following their recovery. In patients with severe COVID-19 serum albumin had a strong negative correlation with both ESR and CRP levels (R2 = - 0.861 and R2 = - 0.711), respectively. Also, there was a positive correlation between ESR and CRP level (R2 = 0.85) in the same group. However, there was no correlation between these biomarkers among mild-to-moderate COVID-19 patients. In addition, no correlation was recorded between the severe and mild-to-moderate COVID-19 groups. This finding highlights the sustained elevation of ESR and CRP level and reduced serum albumin level that may persist postrecovery in patients with a history of severe COVID-19.

Image based Machine Learning for identification of macrophage subsets.

Macrophages play a crucial rule in orchestrating immune responses against pathogens and foreign materials. Macrophages have remarkable plasticity in response to environmental cues and are able to acquire a spectrum of activation status, best exemplified by pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes at the two ends of the spectrum. Characterisation of M1 and M2 subsets is usually carried out by quantification of multiple cell surface markers, transcription factors and cytokine profiles. These approaches are time-consuming, require large numbers of cells and are resource intensive. In this study, we used machine learning algorithms to develop a simple and fast imaging-based approach that enables automated identification of different macrophage functional phenotypes using their cell size and morphology. Fluorescent microscopy was used to assess cell morphology of different cell types which were stained for nucleus and actin distribution using DAPI and phalloidin respectively. By only analysing their morphology we were able to identify M1 and M2 phenotypes effectively and could distinguish them from naïve macrophages and monocytes with an average accuracy of 90%. Thus we suggest high-content and automated image analysis can be used for fast phenotyping of functionally diverse cell populations with reasonable accuracy and without the need for using multiple markers.

Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States.

Macrophages are master regulators of immune responses toward implanted biomaterials. The activation state adopted by macrophages in response to biomaterials determines their own phenotype and function as well as those of other resident and infiltrating immune and nonimmune cells in the area. A wide spectrum of macrophage activation states exists, with M1 (pro-inflammatory) and M2 (anti-inflammatory) representing either ends of the spectrum. In biomaterials research, cell-instructive surfaces that favor or induce M2 macrophages have been considered as beneficial due to the anti-inflammatory and pro-regenerative properties of these cells. In this study, we used a gelatin methacryloyl (GelMA) hydrogel platform to determine whether micropatterned surfaces can modulate the phenotype and function of human macrophages. The effect of microgrooves/ridges and micropillars on macrophage phenotype, function, and gene expression profile were assessed using conventional methods (morphology, cytokine profile, surface marker expression, phagocytosis) and gene microarrays. Our results demonstrated that micropatterns did induce distinct gene expression profiles in human macrophages cultured on microgrooves/ridges and micropillars. Significant changes were observed in genes related to primary metabolic processes such as transcription, translation, protein trafficking, DNA repair, and cell survival. However, interestingly conventional phenotyping methods, relying on surface marker expression and cytokine profile, were not able to distinguish between the different conditions, and indicated no clear shift in cell activation towards M1 or M2 phenotypes. This highlights the limitations of studying the effect of different physicochemical conditions on macrophages by solely relying on conventional markers that are primarily developed to differentiate between cytokine polarized M1 and M2 macrophages. We therefore propose the adoption of unbiased screening methods in determining macrophage responses to biomaterials. Our data clearly show that the exclusive use of conventional markers and methods for determining macrophage activation status could lead to missed opportunities for understanding and exploiting macrophage responses to biomaterials.

The impact of surface chemistry modification on macrophage polarisation.

Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface.