Individuals with comorbidities, particularly type 2 diabetes (T2D), were considered the most vulnerable subgroups during the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
A recentScientific Reportsstudy determined the role of anti-SARS-CoV-2 antibody levels on COVID-19 outcomes in patients with T2D.
Study:COVID-19 patients with type 2 diabetes: a prospective cohort study. Image Credit:Ink Drop/Shutterstock.com
Patients with T2D account for9.5% of severe SARS-CoV-2 infected patients and 16.8% of COVID-19-related deaths. This group of patients was more prone to require hospitalization and intensive care due to COVID-19. Several factors have been identified that increase the risk of severe infection and mortality rates.
Some of these factors are endothelial dysfunction, hypercoagulation due to overexpression of prothrombotic factors, reduced respiratory function, upregulation of inflammatory cytokines, pre-existing insulin resistance, and chronic diseases.
Even though there has been a high COVID-19 vaccine coverage globally, very few studies have determineda correlate of protection to indicate the efficacy of immunization in high-risk subgroups.
Since patients with T2D are at a high risk of severe SARS-CoV-2 infection, it is imperative to understand the link between anti-SARS-CoV-2 antibody levels and COVID-19 outcomes.
If this association is established, effective strategies based on booster vaccination could be formulated to protect individuals belonging to this high-risk group.
The current multicentre, prospective cohort study investigated whether anti-SARS-CoV-2 spike antibodies could be used as a correlate of protection against hospitalization of T2D patients. The effect of pre-existing organ damage on anti-SARS-CoV-2 antibodies was also assessed.
For this study, participants were enrolled from five Austrian hospitals and admitted between August 1, 2021, and April 10, 2022. All participants tested positive for COVID-19 in a polymerase chain reaction (PCR)-based assay.
Blood samples were collected upon hospital admission. Participants hospitalized during the study period and continued beyond the timeframe were excluded.
Patients were classified as diabetic, and COVID-19 vaccinated. The vaccinated individuals received either single or two doses of approved COVID-19 vaccine.
Besides diabetes, other factors that enhance the risk of severe infection are age and obesity. An elevated mortality risk was associated with the prevalence of hypercoagulation, inflammation, and mechanical obstruction. The mortality rate also varied based on the virulence of the SARS-CoV-2 strains.
This study assessed serum creatinine, anti-SARS-CoV-2 spike antibodies, and NT-proBNP levels.
Creatinine levels were defined to be elevated when it was above 1.2 mg/dl in men and over 0.9 mg/dl in women. Similarly, NTproBNP levels were deemed to be elevated over 125 pg/ml.
1,254 hospitalized patients were screened for this study, among which 1,152 were recruited. It must be noted that anti-SARS-CoV-2-spike antibody levels were estimated for all the participants, whereas NT-proBNP and creatinine were measured for only 1,046 patients due to inadequate residual samples.
In this study cohort, 118 patients died, 165 patients required an intensive care unit admission, 587 patients supplementation of oxygen, and 47 patients were subjected to endotracheal intubation. A total of 275 participants in the study cohort had a history of diabetes or were diagnosed during their hospital stay.
Low anti-SARS-CoV-2 spike antibody levels during hospital stay were strongly associated with elevated endotracheal intubation, admission to intensive care units, high rates of in-hospital mortality, and oxygen administration in T2D patients. The higher mortality rates were attributed to increased rates of hyperglycemia.
Previous studies have shown that increased glucose concentration in monocytes of T2D patients enhances the expression of the pro-inflammatory cytokines, which is strongly associated with the COVID-19 cytokine storm.
Consistent with the findings of this study, previous studies have also indicated high mortality rates in diabetic patients compared to non-diabetic patients. It must also be noted that the majority of patients with T2D also possess other serious comorbidities, including renal and cardiovascular diseases.
The T2D patients recruited in the present study were significantly older and with higher BMIs. Furthermore, this study cohort exhibited significant rates of coronary artery disease, hypertension, heart failure, renal disease, and cerebrovascular disease.
When patients were stratified based on elevated creatinine or NTproBNP levels, no significant changes in mortality rates between diabetic and matched, non-diabetic patients were observed.
This finding indicated that diabetic patients might not be at a higher mortality risk linked to COVID-19 due to diabetes alone but due to the cumulative effect of multiple factors, including older age, prevalence of serious comorbidities, and obesity.
A higher anti-SARS-CoV-2 spike in antibody levels could reduce the mortality rates in high-risk mortality groups due to severe SARS-CoV-2 infection. Compared to non-vaccinated patients, vaccinated T2D patients exhibited better COVID-19 outcomes.
The current study demonstrated that anti-SARS-CoV-2 spike antibody levels during hospital admission were inversely correlated with endotracheal intubation, intensive care admission, oxygen administration, and in-hospital mortality in hospitalized T2D patients with COVID-19.
It also showed that patients with T2D can be protected from adverse COVID-19 outcomes by providing booster vaccinations based on antibody tiers.
Specialty
Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional. Infectious Disease Integrative/Complementary Medicine Internal Medicine Internal Medicine-Pediatrics Medical Education and Simulation Medical Physics Medical Student Nephrology Neurological Surgery Neurology Nuclear Medicine Nutrition Obstetrics and Gynecology Occupational Health Oncology Ophthalmology Optometry Oral Medicine Orthopaedics Osteopathic Medicine Otolaryngology Pain Management Palliative Care Pathology Pediatrics Pediatric Surgery Physical Medicine and Rehabilitation Plastic Surgery Podiatry Preventive Medicine Psychiatry Psychology Pulmonology Radiation Oncology Radiology Rheumatology Substance Use and Addiction Surgery Therapeutics Trauma Urology Miscellaneous
The U.S. Food and Drug Administration recently authorized an updated vaccine made by the company Novavax, which differs from the better-known vaccines by Pfizer and Moderna. Novavax is a protein-based vaccine made using a traditional vaccine technology, while the shots made by Pfizer and Moderna are both made with messenger RNA technology. The science has been around for decades, but the COVID vaccines became the first mRNA vaccines to be approved for use.
But while public health experts see an opening for a vaccine that uses an older technology for fighting viruses, demand for Novavax appears low and it remains a serious underdog among more popular options.
The mRNA in the vaccines is created in a laboratory and causes a recipients cells to make a protein that triggers an immune response. Novavax uses a protein in this case, a harmless piece of the coronavirus spike protein to train a persons immune system to recognize and fight back against the real coronavirus. Novavaxs protein-based method has been used for decades in routine vaccinations such as the hepatitis B vaccine.
Novavax first gained approval for its vaccine earlier in the pandemic, but only after Pfizer and Moderna had gained approval and begun distributing shots. Novavax has always trailed well behind the larger makers and even now its updated booster is a distant third.
In Georgia, out of the 17.7 million COVID vaccine doses administered since early in the pandemic, only 3,906 were a Novavax vaccine. Its a minuscule share of well under 1%, according to data obtained by the Georgia Department of Public Health.
I think its always great to have additional options, said Jodie Guest, senior vice chair of the Department of Epidemiology at Emorys Rollins School of Public Health about Novavax, But I think theres a familiarity with Pfizer and Moderna, and for people who are most excited and most interested in getting this newest vaccine, those vaccines got there first.
Even so, public health experts see the potential for the Novavax vaccine and say it deserves consideration. Dr. Jayne Morgan, executive director of health and community education at Piedmont Hospital, said this vaccine can appeal to people who dont trust the mRNA vaccines or have a medical reason to not take them.
Novavax can work for people who had an allergic reaction or strong side effects with an mRNA vaccine, Morgan said. For those who took an original vaccine or booster from the other manufacturers, its fine to switch to Novavax.
Novavax went through the same intense safety testing process as any other vaccine, and it was found to be safe by the FDA.
Novavax appears to have about the same efficacy as other COVID vaccines. A study published in JAMA this month found that the Novavax booster was about 50% effective at preventing COVID symptoms and 31% effective at preventing infection, which is similar to the mRNA vaccines. While they may not prevent infection, all of the updated fall vaccines are doing a good job at preventing severe illness, hospitalization, and death, according to Guest and Morgan.
All three vaccines were reformulated earlier this year to fight the XBB.1.5 variant of the virus. While thats no longer the dominant variant, preliminary research has shown that the vaccines still offer protection.
Dr. Eric Topol, a physician and scientist who directs the Scripps Research Translational Institute and is a prolific blogger on COVID research, wrote that was interested in getting an updated Novavax COVID vaccine. But with upcoming travel and questions about Novavaxs availability, he told Science, the peer-reviewed academic journal of the American Association for the Advancement of Science, that he decided to make an easier choice, getting a Pfizer booster at a grocery store. He said he still wonders how a dose of Novavax might have been different.
Three years since coronavirus arrived, it has become more complicated to measure the effectiveness of vaccines. The majority of people have been exposed, but in different ways and many have had various combinations of vaccinations. Trials to verify a vaccines effectiveness can take all of these things into account. But they would be based on circulating variants at the time, and by the time the study is completed, new variants are circulating. There are also no head-to-head studies comparing different vaccines.
Its still early in the rollout of the updated vaccines, and issues with distribution and insurance coverage continue to arise.
Uptake of the new vaccines is well below what it was when the vaccines were tweaked last year and 17% of the U.S. population got it. In Georgia, it was only about 11%.
Since the newly updated vaccines were released in September, 293,247 doses of the updated COVID vaccine have been administered in Georgia, which covers about 3% of the population. Only 302 of the vaccine doses were Novavax, according to recent data from the Georgia Department of Public Health.
While Novavax said millions of doses of the updated COVID vaccine have been distributed in the U.S., finding one remains a challenge. Locations and availability listed on vaccines.gov isnt always up to date. A Georgia Department of Public Health spokeswoman said the department has not yet ordered any doses of the updated Novavax vaccine for local health departments because there have been no requests for it.
Public health experts say its not that important which vaccine you get but that you get an updated shot.
Right now, is the perfect time to be doing it, said Guest. It does appear COVID infections are on their way down. We can hope they will stay this way, but this is a similar trend weve seen year after year: they do come down and then go back up later in the fall and beginning of winter.
The FDA approved the updated Novavax vaccine in October 2023 for ages 12 and older.
The Novavax vaccine is a traditional one compared to the other vaccines. Its technology has been used before in vaccines to prevent such conditions as shingles, human papillomavirus (HPV) and DTaP (diphtheria, tetanus and pertussis), among others.
Anyone 12 or older can get the updated Novavax vaccine. Anyone who has previously been vaccinated (with any COVID vaccine) may get one dose at least two months after the first dose. Those who have never been vaccinated should get two doses administered three weeks apart.
People who are immunocompromised may get an additional dose at least two months after their last dose of the updated vaccine.
Source: Yale Medicine
WASHINGTON Select Subcommittee on the Coronavirus Pandemic Chairman Brad Wenstrup (R-Ohio) and Ranking Member Raul Ruiz (D-Ca.) have requested that the Government Accountability Office (GAO) conduct an analysis of the international biosafety and biosecurity standards implemented by G20 countries. In a letter to the GAO today, the Chairman and Ranking Member asked Comptroller General Gene Dodaro to provide a comprehensive report comparing the current biosafety and biosecurity standards employed by G20 countries with existing United States policies.
In an October hearing, Select Subcommittee members underscored the need for improved oversight of high-risk laboratories in the United States and abroad. Members also heard concerning testimony from expert witnesses who detailed gaps in current biosafety and biosecurity standards. As the Select Subcommittee continues to evaluate the long-term effects of the coronavirus pandemic, ensuring judicious, modernized biosafety and biosecurity practices are implemented across the world may help prevent a future health crisis.
As we saw during the COVID-19 pandemic, biosafety and biosecurity issues have the potential to affect the international community. While the United States evaluates its own biosafety and biosecurity standards, precautions taken by other nations remain highly relevant to the Select Subcommittees work. To that end, the Select Subcommittee requests a comprehensive report of the G20 member nations biosafety and biosecurity standards, wrote Chairman Wenstrup and Ranking Member Ruiz.
Read the full letter to GAO Comptroller General Gene Dodaro here.
###
1Department of Pulmonary and Critical Care Medicine, Zhengzhou University Peoples Hospital, Henan Provincial Peoples Hospital, Zhengzhou, Henan, 450003, Peoples Republic of China; 2Department of Pulmonary and Critical Care Medicine, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, 451464, Peoples Republic of China; 3Department of Health Management, Henan Provincial Peoples Hospital, Zhengzhou University Peoples Hospital, Zhengzhou, Henan, 450003, Peoples Republic of China; 4Department of Pulmonary and Critical Care Medicine, Zhengzhou University Peoples Hospital, Henan Provincial Peoples Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450003, Peoples Republic of China; 5Department of Pulmonary and Critical Care Medicine, Henan University Peoples Hospital, Henan Provincial Peoples Hospital, Zhengzhou, Henan, 450003, Peoples Republic of China; 6Department of Pulmonary and Critical Care Medicine, Zhengzhou University Peoples Hospital, Henan Provincial Peoples Hospital, Henan University Peoples Hospital, Zhengzhou, Henan, 450003, Peoples Republic of China
Correspondence: Yong Qi, Department of Pulmonary and Critical Care Medicine, Zhengzhou University Peoples Hospital, Henan Provincial Peoples Hospital, Henan University Peoples Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, Peoples Republic of China, Tel +8615890110258, Email [emailprotected]
Background: Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients. Methods: COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases. We overlapped the genes of COVID-19 and PE to obtain common genes for additional analysis, including functional enrichment, proteinprotein interaction, and immune infiltration analysis. Hub genes were identified using cytoHubba, a plugin of Cytoscape, and validated using the independent datasets GSE167000 and GSE13535. The genes validated by the above datasets were further validated in clinical samples. Results: We obtained 36 genes shared by PE and COVID-19. Functional enrichment and immune infiltration analyses revealed the involvement of cytokines and immune activation. Five genes (CCL2, CXCL10, ALB, EGF, and MKI67) were identified as hub genes common to COVID-19 and PE. CXCL10 was validated in both independent datasets (GSE167000 and GSE13535). Serum levels of CXCL10 in the COVID-19 group and the COVID-19 combined with PE group were significantly higher than those in the healthy control group (P< 0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (P< 0.01). Conclusion: Our study reveals common genes shared by PE and COVID-19 and identifies CXCL10 as a possible cause of susceptibility to PE in COVID-19 patients.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, remains an acute infectious disease of global pandemic proportions and is a public health disease that critically endangers human health.1,2 COVID-19 patients have multiple complications, including pulmonary embolism (PE).3 PE refers to the clinical and pathophysiological syndrome in which a thrombus occurs in the main trunk of the pulmonary artery or its branches, causing blockage and pulmonary circulation disorders.4,5 PE, with high incidence, missed diagnosis and mortality rates, is the third most common cause of cardiovascular death worldwide after stroke and heart attack.6
Accumulating evidence suggests that inpatients with COVID-19 more frequently develop PE events than inpatients without COVID-19.79 A meta-analysis including 3342 COVID-19 patients showed that the incidence of PE events in COVID-19 patients was 16.5%, considerably higher than that in patients without COVID-19.10 After a meta-analysis of 13 postmortem studies of COVID-19 patients, Zuin et al concluded that the possibility of acute PE events in COVID-19 patients has been underestimated in clinical practice.11 Recently, a large Swedish cohort study revealed that compared with the control period, the risk ratio for a first PE during days 130 after COVID-19 was 33.05, and the increased risk lasted for six months after COVID-19.12 Early in the COVID-19 epidemic, German researchers performed autopsies on 12 patients who died from the disease and found PE to be the direct cause of death in four of them (1/3).13 Furthermore, compared with the PE patients without COVID-19 infection, PE patients with COVID-19 had an increased risk of in-hospital mortality, septic shock, respiratory failure, and a longer hospital stay.14
PE is widely believed to be one of the forms of venous thrombosis. However, the idea that PE is the result of the migration of blood clots from the venous system is questioned because no initial thrombus is found in many patients.1517 Histologic analysis of pulmonary vessels in patients with COVID-19 shows widespread thrombosis with microangiopathy,18 and in situ immunothrombosis plays a role in the pathophysiology of COVID-19-associated PE.19,20 This perspective is supported by Katsoularis study in which risk ratios during days 130 after COVID-19 were 33.05, significantly exceeding that for deep-vein thrombosis (4.98).12 In one study, traditional risk factors for venous thromboembolic disease were not associated with the occurrence of PE in COVID-19 patients.21 In addition, prophylactic anticoagulation did not prevent the occurrence of PE in hospitalized patients.22 Therefore, it is necessary to specifically study COVID-19-associated PE rather than treat it as a form of venous thrombosis.
Currently, research on COVID-19-associated PE is dominated by observational studies of incidence, prognosis, and imaging characteristics, whereas few studies have been conducted to investigate the mechanisms of COVID-19-associated PE. Bioinformatics analysis provides a means to explore the genetic relationship between two diseases. Previous studies have indicated that SARS-CoV-2 infection can cause a myriad of complications because there are common genes between COVID-19 and these complications.2326 Therefore, this study aimed to explore the possible genetic relationship between COVID-19 and PE through bioinformatics to reveal the underlying pathogenesis of susceptibility to PE events in COVID-19 patients.
In this study, we used COVID-19 transcriptome data from the GEO (https://www.ncbi.nlm.nih.gov/geo/) database and COVID-19-related genes and PE-related genes from disease-related databases to perform bioinformatics analyses and then validated common key genes between COVID-19 and PE. This is the first genomics study of COVID-19 and PE.
By searching the OMIM (http://omim.org/), CTD (http://ctdbase.org/), GeneCards (https://www.genecards.org/), and DisGeNET (https://www.disgenet.org/) databases, we collected genes related to COVID-19 and PE. In addition, microarray expression data of COVID-19 patients were obtained from the GEO database. GSE157103 was selected, which consisted of 126 samples, including 100 patients with COVID-19 and 26 patients without COVID-19, consisting of both ICU and non-ICU patients. Unfortunately, as no human data are available in the GEO database, we only obtained PE genes through the four disease-related databases mentioned above.
We collected the top 500 genes in each database according to each database scoring rule. If there were fewer than 500 genes in the database, all of them were included. The GSE157103 dataset was analyzed using the DESeq2 package, and an adjusted p-value (false discovery rate) <0.05 andlog2FoldChange>1 were used as the screening criteria for important differentially expressed genes (DEGs).
Subsequently, we obtained COVID-19 genes by taking the intersection of the COVID-19-related genes in the disease-related database and the DEGs of GSE157103. We then overlapped the genes of COVID-19 and PE to obtain common genes for further analysis. We accessed these websites on 4 March 2022.
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to investigate biological activities and pathways. To understand the functional characteristics of the common genes of COVID-19 and PE, we executed GO and KEGG enrichment analyses using Rs cluster profile package, with a p-value <0.05 as the cutoff.
We constructed a PPI network based on the STRING database (https://string-db.org/), with a medium confidence score of >0.4, and the PPI network was visualized via Cytoscape (Version 3.9.1).27 Furthermore, we identified hub genes through five algorithms (BottleNeck, Closeness, Radiality, Betweenness, Stress) of the cytoHubba plugin of Cytoscape. Common hub genes of COVID-19 and PE were obtained by taking the intersection of the top 10 genes in each of the five algorithms.
Immune infiltration analysis was performed via the CIBERSORTx tool,28 a deconvolution algorithm that evaluates the expression of related genes based on gene expression, to calculate the ratio of COVID-19 samples. Correlations between each immune cell and hub genes were calculated using the Sangerbox online tool.29
To reduce the possibility of false positives, we validated hub genes separately using other COVID-19 and PE datasets from the GEO database. For COVID-19, we selected GSE167000 for validation, which includes 65 SARS-CoV-2-positive patients and 30 SARS-CoV-2-negative patients. Additionally, we used the rat PE model dataset GSE13535 for PE. GSE13535 includes 6 control rats and 16 PE model rats. Models with mild PE were established at 2 hours after modeling and models with severe PE were established at 18 hours later. Expression data for the hub genes were obtained using the GEOquery package.
To further verify the genes validated above, we collected 6 blood samples from COVID-19 combined with PE inpatients. COVID-19 was determined by a positive polymerase chain reaction test for SARS-CoV-2 and PE was diagnosed by computed tomography pulmonary angiography. In addition, we collected 6 blood samples from COVID-19-alone inpatients and 4 healthy individuals who were negative for anti-SARS-CoV-2 IgM/IgG. The COVID-19-alone patients and the healthy controls were matched with the COVID-19 combined with PE patients for age and sex. Blood samples were obtained from Henan Provincial Peoples Hospital (Henan, China) and centrifuged at 1000g for 10 min. Levels of CXCL10 in serum were measured using a human ELISA kit (Elabscience, Wuhan, China). This study was approved by the ethics committee of Henan Provincial Peoples Hospital (Ethical Review 2023(97)), and written informed consent from all participants was provided for the use of their blood samples.
GraphPad Prism version 8.0.2 was used to analyze the data. The results are displayed as the mean SD. Differences between the two groups were compared by an unpaired Students t-test. A two-tailed p-value < 0.05 was considered statistically significant.
We obtained 880 DEGs from GSE157103 and 500, 500, 500 and 3 COVID-19-related genes from the GeneCards, DisGeNET, CTD and OMIM databases, respectively. Seventy-two COVID-19 genes were obtained by merging and deduplicating the results collected from four databases and taking the intersection with DEGs from GSE157103. Similarly, after merging and deduplicating 500, 93, 500, and 207 PE-related genes from the GeneCards, DisGeNET, CTD, and OMIM databases, respectively, we obtained 1069 PE genes. By taking the intersection of 72 COVID-19 genes with 1069 PE genes, we obtained 36 genes common to both COVID-19 and PE. The screening procedure and results are shown in Table 1 and Figure 1.
Table 1 Collection of COVID-19 and PE Genes
Figure 1 Common gene representation through a Venn diagram. Thirty-six genes from among 72 COVID-19 genes and 1069 PE genes were found to be common genes.
Abbreviation: PE, pulmonary embolism.
The top 10 GO terms and KEGG pathways are summarized in Figure 2. GO annotation includes three terms: biological process, cell component, and molecular function. For biological processes, the common genes were enriched in response to chemical and cytokine-mediated signaling pathways (Figure 2A). Cell component items were mainly enriched in the endomembrane system and protein-containing complex (Figure 2B). The molecular function category was mainly enriched in anion binding and carbohydrate derivative binding (Figure 2C). KEGG pathway enrichment analysis included focal adhesion, the cell cycle, and the p53 signaling pathway (Figure 2D).
Figure 2 GO and KEGG pathway enrichment analyses of 36 common genes between COVID-19 and PE. (A) Biological process of GO. (B) Molecular function of GO. (C) Cellular component of GO. (D) KEGG pathway.
Abbreviations: PE, pulmonary embolism; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
To explore protein interactions, we constructed a PPI network of 36 common genes using the STRING database. There were a total of 36 nodes and 152 edges in the network, which was visualized by Cytoscape (Figure 3A). We screened the top 10 hub genes with five algorithms from the cytoHubba plugin. Five hub genes (CCL2, CXCL10, ALB, EGF, and MKI67) were obtained by taking the intersection of the top 10 genes in the five algorithms (Figure 3B). CCL2, CXCL10, EGF, and MKI67 were upregulated in GSE157103; ALB, encoding the most abundant protein in human blood, was downregulated (Table 2).
Table 2 Hub Genes
Figure 3 Proteinprotein interaction (PPI) network analysis. (A) The PPI network of 36 common genes. (B) Five common hub genes were identified by five algorithms (BottleNeck, Closeness, Radiality, Betweenness, Stress) of the cytoHubba plugin.
There is evidence that immune cell infiltration is involved in the development of COVID-19.30 The CIBERSORTx algorithm has been applied to investigate the landscape of immune infiltration in COVID-19. The proportions of 22 immune cell types in COVID-19 are shown in Figure 4A. Specifically, the types of immune cells in COVID-19 were B cells, plasma cells, naive CD4+ T cells, activated memory CD4+ T cells, regulatory T cells, monocytes, and resting mast cells. In addition, we analyzed the correlation between each immune cell and the 5 hub genes. As shown in Figure 4B, CCL2 expression was associated with resting memory CD4+ T cells, gamma delta T cells, and neutrophils; CXCL10 correlated with activated memory CD4+ T cells and activated dendritic cells; ALB correlated with naive CD4+ T cells; EGF correlated with activated memory CD4+ T cells and Tregs; and MKI67 correlated with plasma cells and activated memory CD4+ T cells. In summary, these results suggest that CCL2, CXCL10, ALB, EGF, and MKI67 may contribute to the immune microenvironment of COVID-19.
Figure 4 Immune infiltration analysis. (A) The ratio of 22 immune cells in COVID-19 samples. (B) Correlation between each of the immune cells and five hub genes. *p < 0.05; **p < 0.01; ***p < 0.005; ****p < 0.001; - p>0.05.
To validate the reliability of the five hub genes, we first verified the expression of these genes in the GSE167000 dataset. As shown in Figure 5A, CXCL10, EGF, and MKI67 in this dataset were significantly upregulated in the SARS-CoV-2-positive group compared with the SARS-CoV-2- negative group. In the GSE13535 dataset, the expression levels of CCL2 and CXCL10 were significantly increased in the PE model group compared with the control group, both at 2 and 18 hours after modeling. The results are shown in Figure 5B and C. In summary, only CXCL10 was discrepant in both external datasets. Therefore, we consider CXCL10 to be the most likely key gene involved in COVID-19 and PE.
Figure 5 Validation of the hub genes in the external datasets. (A) The expression of CCL2, CXCL10, ALB, EGF, and MKI67 in the COVID-19 dataset (GSE16700). (B) The expression of CCL2, CXCL10, ALB, EGF and MKI67 in the PE dataset (GSE13535) at 2 hours after modeling. (C) The expression of CCL2, CXCL10, ALB, EGF and MKI67 in the PE dataset (GSE13535) at 18 hours after modeling.
To verify whether CXCL10 is a key gene involved in COVID-19 associated with PE, we validated CXCL10 with blood samples. The protein encoded by CXCL10 is a secreted protein, also known as interferon-inducible protein 10 (IP-10), which belongs to the CXC chemokine family of chemokines and is present in serum and plasma. We measured serum levels of CXCL10 in 4 healthy controls, 6 COVID-19 patients, and 6 COVID-19 patients with PE. Levels of CXCL10 in the COVID-19 and the COVID-19 combined with PE groups were significantly higher than those in the healthy control group (p <0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (p <0.01), as shown in Figure 6.
Figure 6 Verification of serum CXCL10 levels in human samples (4 healthy controls, 6 COVID-19 patients, and 6 COVID-19 patients with PE). **p < 0.01, ****p < 0.001.
During the COVID-19 pandemic, several studies have described an increased risk of developing PE, which contributes to a significant increase in mortality among COVID-19 patients. However, the underlying pathogenesis of susceptibility to PE in COVID-19 is not yet fully understood. In this study, we first performed a genomics analysis of COVID-19 and PE to reveal genetic interrelations between the two diseases.
We identified 36 common genes shared in COVID-19 and PE. In a sense, these common genes suggest that there are relationships between COVID-19 and PE. Enrichment analysis showed that these genes were involved in cytokine-mediated signaling pathways, and immune infiltration analysis indicated that immune activation was involved in COVID-19. SARS-CoV-2 can continuously activate the bodys natural immune system and, as a result, cause the release of inflammatory cytokines.30,31 Cytokines play critical roles in the pathogenesis of COVID-19.3234 In particular, uncontrolled cytokines could lead to a systemic inflammatory response syndrome and release messenger substances, which cause thrombosis and blood vessel blockage.13 This is consistent with clinical studies in which histologic analysis of the lung in patients with COVID-19 showed infiltration of multiple immune cells and widespread microthrombosis.18,35,36 Inflammation may be a major contributor to PE in the context of COVID-19.
We then performed a comprehensive analysis to construct the PPI network, and a strong genetic, protein-based relationship was found among common genes shared in COVID-19 and PE. CCL2, CXCL10, ALB, EGF, and MKI67 were identified as hub genes, with CXCL10 validated by external datasets and human samples. These results suggest that CXCL10 is a key gene common to both COVID-19 and PE and that it may be responsible for susceptibility to PE in COVID-19 patients.
CXCL10, also termed IP-10, is secreted after interferon-gamma production by a wide variety of cell types, such as endothelial cells, fibroblasts, monocytes, and T lymphocytes.37 CXCL10 is a key regulator of the cytokine storms caused by SARS-CoV-2 infection38 and tends to be elevated earlier in COVID-19 patients than other inflammatory cytokines.39 There is sufficient evidence that in COVID-19 patients, CXCL10 levels are significantly elevated and associated with adverse clinical outcomes.4042 Consistent with these findings, our study showed elevated levels of CXCL10 in the COVID-19 group with or without PE compared with healthy controls.
The role of CXCL10 in atherosclerosis and myocardial infarction has been extensively described.43,44 However, it is not clear whether CXCL10 plays a role in the development of PE. Studies have shown that CXCL10 induces not only chemoattraction of inflammatory cells but also migration and proliferation of endothelial cells and vascular smooth muscle cells.45,46 CXCR3, the receptor for CXCL10, has been reported to be expressed in pulmonary artery endothelial cells (PAECs), and CXCL10 can lead to PAEC dysfunction.47 Improved endothelial healing prevents arterial thrombosis, but CXCL10 can inhibit endothelial healing.48 Therefore, CXCL10 may be involved in the formation of arterial thrombosis. In our study, the CXCL10 levels in the COVID-19 combined with PE group were significantly higher than those in the COVID-19 group.
In summary, we hypothesize that CXCL10, as an early upregulated inflammatory factor in COVID-19, plays a dual role by recruiting diverse inflammatory cells to infiltrate and release messenger substances, promoting thrombosis, while also potentially causing dysfunction of PAECs and contributing to pulmonary thrombosis in COVID-19 patients. In the future, we will focus on elucidating the underlying mechanisms by which CXCL10 may contribute to the development of pulmonary artery thrombosis in COVID-19 patients.
The study has several limitations, which must be acknowledged. Given the paucity of available human datasets for PE, we used the dataset from rats to validate hub genes. However, CXCL10 has also been validated in clinical samples. In addition, limited clinical samples were available for this study, and we only compared CXCL10 levels in 4 healthy controls, 6 COVID-19 patients, and 6 COVID-19 patients with PE. We will further validate our conclusions by expanding the sample size.
In this study, we obtained 36 common genes, established a coexpression network between COVID-19 and PE, and identified and validated CXCL10 as a common key gene in both diseases that may be responsible for susceptibility to PE events in COVID-19 patients. Consequently, our research first describes the possible genetic relationship between COVID-19 and PE to further reveal the mechanisms of COVID-19-associated PE.
COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; PE, pulmonary embolism; DEGs, differentially expressed genes; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; PPI, proteinprotein interaction; PAECs, pulmonary artery endothelial cells.
We provide details of the materials and methods in our manuscript.
This study was performed in accordance with the Helsinki declaration and was approved by the ethics committee of Henan Provincial Peoples Hospital (Ethical Review 2023(97)), and written informed consent from all participants was provided for the use of their blood samples.
We sincerely thank the public databases GEO, OMIM, CTD, GeneCards, DisGeNET, and STRING for providing data for our research and Cytoscape, CIBERSORTx, and Sangerbox for analyzing data.
This study is supported by the Natural Science Foundation of Henan Province (Yong Qi, No. 232300421122).
The authors declare that they have no conflicts of interest.
1. Yuan Y, Jiao B, Qu L, et al. The development of COVID-19 treatment. Front Immunol. 2023;14:1125246. doi:10.3389/fimmu.2023.1125246
2. Zhang JJ, Dong X, Liu GH, et al. Risk and protective factors for COVID-19 morbidity, severity, and mortality. Clin Rev Allergy Immunol. 2023;64(1):90107. doi:10.1007/s12016-022-08921-5
3. Dou Q, Wei X, Zhou K, et al. Cardiovascular manifestations and mechanisms in patients with COVID-19. Trends Endocrinol Metab. 2020;31(12):893904. doi:10.1016/j.tem.2020.10.001
4. Agnelli G, Becattini C. Anticoagulant treatment for acute pulmonary embolism: a pathophysiology-based clinical approach. Eur Respir J. 2015;45(4):11421149. doi:10.1183/09031936.00164714
5. Essien EO, Rali P, Mathai SC. Pulmonary Embolism. Med Clin North Am. 2019;103(3):549564. doi:10.1016/j.mcna.2018.12.013
6. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543603. doi:10.1093/eurheartj/ehz405
7. Poissy J, Goutay J, Caplan M, et al. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation. 2020;142(2):184186. doi:10.1161/CIRCULATIONAHA.120.047430
8. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):10891098. doi:10.1007/s00134-020-06062-x
9. Piroth L, Cottenet J, Mariet AS, et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Respir Med. 2021;9(3):251259. doi:10.1016/S2213-2600(20)30527-0
10. Suh YJ, Hong H, Ohana M, et al. Pulmonary embolism and deep vein thrombosis in COVID-19: a systematic review and meta-analysis. Radiology. 2021;298(2):E70E80. doi:10.1148/radiol.2020203557
11. Zuin M, Engelen MM, Bilato C, et al. Prevalence of acute pulmonary embolism at autopsy in patients with COVID-19. Am J Cardiol. 2022;171:159164. doi:10.1016/j.amjcard.2022.01.051
12. Katsoularis I, Fonseca-Rodriguez O, Farrington P, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ. 2022;377:e069590. doi:10.1136/bmj-2021-069590
13. Wichmann D, Sperhake JP, Lutgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a Prospective Cohort Study. Ann Intern Med. 2020;173(4):268277. doi:10.7326/M20-2003
14. Safiriyu I, Fatuyi M, Mehta A, et al. Impact of COVID-19 infection on the clinical outcomes of pulmonary embolism hospitalizations: a nationwide analysis. Curr Probl Cardiol. 2023;48(7):101669. doi:10.1016/j.cpcardiol.2023.101669
15. Tadlock MD, Chouliaras K, Kennedy M, et al. The origin of fatal pulmonary emboli: a postmortem analysis of 500 deaths from pulmonary embolism in trauma, surgical, and medical patients. Am J Surg. 2015;209(6):959968. doi:10.1016/j.amjsurg.2014.09.027
16. Ahuja J, Shroff GS, Benveniste MF, et al. In situ pulmonary artery thrombosis: unrecognized complication of radiation therapy. AJR Am J Roentgenol. 2020;215(6):13291334. doi:10.2214/AJR.19.22741
17. Cao Y, Geng C, Li Y, et al. In situ pulmonary artery thrombosis: a previously overlooked disease. Front Pharmacol. 2021;12:671589. doi:10.3389/fphar.2021.671589
18. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120128. doi:10.1056/NEJMoa2015432
19. Poor HD. Pulmonary thrombosis and thromboembolism in COVID-19. Chest. 2021;160(4):14711480. doi:10.1016/j.chest.2021.06.016
20. Quartuccio L, Sonaglia A, Casarotto L, et al. Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19. Thromb Res. 2022;219:95101. doi:10.1016/j.thromres.2022.09.012
21. Fauvel C, Weizman O, Trimaille A, et al. Pulmonary embolism in COVID-19 patients: a French multicentre cohort study. Eur Heart J. 2020;41(32):30583068. doi:10.1093/eurheartj/ehaa500
22. Bompard F, Monnier H, Saab I, et al. Pulmonary embolism in patients with COVID-19 pneumonia. Eur Respir J. 2020;56(1). doi:10.1183/13993003.01365-2020
23. Chen Z, Chen C, Chen F, et al. Bioinformatics analysis of potential pathogenesis and risk genes of immunoinflammation-promoted renal injury in severe COVID-19. Front Immunol. 2022;13:950076. doi:10.3389/fimmu.2022.950076
24. Li Y, Liu Y, Duo M, et al. Bioinformatic analysis and preliminary validation of potential therapeutic targets for COVID-19 infection in asthma patients. Cell Commun Signal. 2022;20(1):201. doi:10.1186/s12964-022-01010-2
25. Lv Y, Zhang T, Cai J, et al. Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2022;13:952987. doi:10.3389/fimmu.2022.952987
26. Zhang W, Di L, Liu Z, et al. TIMELESS is a key gene mediating thrombogenesis in COVID-19 and antiphospholipid syndrome. Sci Rep. 2022;12(1):17248. doi:10.1038/s41598-022-21694-3
27. Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):24982504. doi:10.1101/gr.1239303
28. Chen B, Khodadoust MS, Liu CL, et al. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol. 2018;1711:243259. doi:10.1007/978-1-4939-7493-1_12
29. Shen W, Song Z, Zhong X, et al. Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta. 2022;1(3):e36. doi:10.1002/imt2.36
30. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):10331034. doi:10.1016/S0140-6736(20)30628-0
31. Ramasamy S, Subbian S. Critical determinants of cytokine storm and Type I interferon response in COVID-19 pathogenesis. Clin Microbiol Rev. 2021;34(3). doi:10.1128/CMR.00299-20
32. Coperchini F, Chiovato L, Ricci G, et al. The cytokine storm in COVID-19: further advances in our understanding the role of specific chemokines involved. Cytokine Growth Factor Rev. 2021;58:8291. doi:10.1016/j.cytogfr.2020.12.005
33. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, et al. SARS-CoV-2 infection: the role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:6275. doi:10.1016/j.cytogfr.2020.06.001
34. Hsu RJ, Yu WC, Peng GR, et al. The role of cytokines and chemokines in severe acute respiratory syndrome Coronavirus 2 infections. Front Immunol. 2022;13:832394. doi:10.3389/fimmu.2022.832394
35. Wang S, Yao X, Ma S, et al. A single-cell transcriptomic landscape of the lungs of patients with COVID-19. Nat Cell Biol. 2021;23(12):13141328. doi:10.1038/s41556-021-00796-6
36. Khismatullin RR, Ponomareva AA, Nagaswami C, et al. Pathology of lung-specific thrombosis and inflammation in COVID-19. J Thromb Haemost. 2021;19(12):30623072. doi:10.1111/jth.15532
37. Luster AD, Ravetch JV. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med. 1987;166(4):10841097. doi:10.1084/jem.166.4.1084
38. Zhang N, Zhao YD, Wang XM. CXCL10 an important chemokine associated with cytokine storm in COVID-19 infected patients. Eur Rev Med Pharmacol Sci. 2020;24(13):74977505. doi:10.26355/eurrev_202007_21922
39. Lu Q, Zhu Z, Tan C, et al. Changes of serum IL-10, IL-1beta, IL-6, MCP-1, TNF-alpha, IP-10 and IL-4 in COVID-19 patients. Int J Clin Pract. 2021;75(9):e14462. doi:10.1111/ijcp.14462
40. Gudowska-Sawczuk M, Mroczko B. What is currently known about the role of CXCL10 in SARS-CoV-2 infection? Int J Mol Sci. 2022;23(7). doi:10.3390/ijms23073673
41. Chen Y, Wang J, Liu C, et al. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol Med. 2020;26(1):97. doi:10.1186/s10020-020-00230-x
42. Kalinina O, Golovkin A, Zaikova E, et al. Cytokine storm signature in patients with moderate and severe COVID-19. Int J Mol Sci. 2022;23(16). doi:10.3390/ijms23168879
43. Heller EA, Liu E, Tager AM, et al. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation. 2006;113(19):23012312. doi:10.1161/CIRCULATIONAHA.105.605121
44. Koten K, Hirohata S, Miyoshi T, et al. Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size. Clin Biochem. 2008;41(12):3037. doi:10.1016/j.clinbiochem.2007.10.001
45. Wang X, Yue TL, Ohlstein EH, Sung CP, Feuerstein GZ. Interferon-inducible protein-10 involves vascular smooth muscle cell migration, proliferation, and inflammatory response. J Biol Chem. 1996;271(39):2428624293. doi:10.1074/jbc.271.39.24286
46. Taub DD, Lloyd AR, Conlon K, et al. Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med. 1993;177(6):18091814. doi:10.1084/jem.177.6.1809
47. Zabini D, Nagaraj C, Stacher E, et al. Angiostatic factors in the pulmonary endarterectomy material from chronic thromboembolic pulmonary hypertension patients cause endothelial dysfunction. PLoS One. 2012;7(8):e43793. doi:10.1371/journal.pone.0043793
48. Lupieri A, Smirnova NF, Solinhac R, et al. Smooth muscle cells-derived CXCL10 prevents endothelial healing through PI3Kgamma-dependent T cells response. Cardiovasc Res. 2020;116(2):438449. doi:10.1093/cvr/cvz122
Out of the 144 participants analyzed in this study, 33 (22.9%) were in the employed group, whereas 111 (77.1%) were in the non-employed group. Even after adjustment for age and sex, the attention function was significantly higher in the employed group than in the non-employed group (OR: 0.96, 95% CI 0.940.99).
The attention function includes four elements: persistence, selection, transfer, and distribution. However, each element is interrelated26,27. In addition, the classification of the attention function is not standardized28. Therefore, it is challenging to examine which element of the attention function has an effect. However, the TMT-A used in this study includes visual reading ability, graphomotor speed (correct writing speed), and visual motion processing speed in addition to the four elements of the attention function29. It is proposed that since attentional functions are required for the routine execution of tasks while performing jobs, the employed group showed better attention function than the non-employed group. Similarly, there are many opportunities to process visual information and for writing while carrying out jobs. This may be attributed to improved visual reading ability and graphomotor speed depending on the type of job.
In the univariate analysis, significantly higher grip strength and SMI values in the working group could be due to the skewed malefemale ratio between the two groups. In this study, 16 out of 33 participants in the employed group were females (48.5%), whereas 87 out of 111 participants in the unemployed group (78.4%) were females. In 2018, the employment rate of the elderly by sex had been reported to be 33.2% for males and 17.4% for females, which is almost a 2:1 ratio30. According to a Cabinet Office survey, the employment rate for men over the age of 15years in Japan is 69.4% for men and 53.0% for women; this rate is slightly higher for men, but it is not as large as the difference in employment rates between men and women among the elderly31. Hence it is clear that the working scenario of males and females in Japan differs greatly between the younger and elderly generations.
In the case of other motor functions, there were no differences in walking speed, locomotive 2-step test, and frailty between the two groups. Because the type and content of employment varied, it could be speculated that the motor function was affected by the work content. In particular, of the 33 employees in the working group, 1 (3.0%) continued to work as a full-time employee, suggesting that the daily employment characteristics had little effect on motor function. In addition, a previous study reported that working individuals were associated with pre-frailty32. However, this study found no difference in the number of frail participants between the two groups. The reason for this could be the average age of the participants, which is about 3years younger than in previous studies.
The most common reason for working was found to be health (30.3%). In contrast, other surveys33 showed that the majority were working for financial reasons. The difference could be due to the participants of this study, who were interested in getting examined for motor and cognitive functions, and the recruitment was limited to those who could engage for about 1h and 30min during the daytime on weekdays. Therefore, it is difficult to generalize and examine the reasons for employment.
There are some limitations to this study. First, it was not possible to establish a causal relationship between doing paid work and the decline in attention function for a cross-sectional survey. Hence, we are conducting a follow-up survey to verify whether the attention function could be kept high by working. Second, the investigation was carried out in an emergency scenario due to the pandemic. Third, the sample size was small, and additional research is needed to generalize the results. Fourth, the lack of information on underlying diseases related to motor and cognitive function does not rule out the effects identified herein. Furthermore, although age was adjusted for in the final multivariate analysis, the effect of aging must be considered as a limitation of this study, as there is an age difference of approximately 2.6years between the two groups.
However, the impact on employment due to the emergency scenario is still unclear. Therefore, we plan to re-examine the participants and analyze the details starting from 2022.
It depends on the symptoms. Because there is currently no cure for Long COVID, doctors aim to treat the symptoms associated with the condition.
As many as 200 Long COVID symptoms were identified in an international study published in 2021 in EClinicalMedicine (a Lancet journal) that surveyed more than 3,700 people with Long COVID. Many symptoms are sorted into categories by specialty, where treatments are similar to what they would be for non-COVID patients with similar symptoms.
The specialists you may need to see for Long COVID include:
Pulmonologists: These doctors have played a central role in treating both COVID and Long COVID since the early days of the pandemic, when many patients went to the hospital with urgent symptoms, such as low oxygen levels and lung issues. They treat breathing difficulties, sometimes prescribing treatments like an inhaler (a handheld device that delivers a puff of medicine into the lungs). For some of my Long COVID patients with asthma-type symptoms, biologic treatments are making a difference, Dr. Lutchmansingh says.
Exercise may also be beneficial for some patients, she adds. It's just a different way of exercising than we're accustomed to, she says. While rehabilitation for non-COVID pulmonary patients may involve a push to build muscle and strength, that type of exercise method can worsen symptoms for some Long COVID patients. So, we have to figure out a way to get them to exercise that targets their needs but isn't detrimental to them, she says.
Neurologists: "Long COVID can cause a variety of neurological symptoms, and one patient can have multiple types," Dr. McAlpine says. There can be a constellation of symptoms. She has treated patients for headaches, including new or worsening migraine symptoms. Some have developed neuropathy, a disease of the peripheral nerves that causes numbness or weakness.
But the most common neurological symptoms Dr. McAlpine sees are cognitive difficulties, including issues with attention and memory recall, and language and executive functioning. Patients will say, I can't find my words. I lose track of my thoughts in the middle of my sentences. I have to write everything down. I can't multitask anymore, she says. With the Alpha and Delta variants, the cognitive impairment was quite severe around the acute illness. Then, it would very slowly get better.
Gastroenterologists: Some patients report bloating, constipation, diarrhea, vomiting, and other signs of stomach distress. In March 2023, a study in Nature Communications reported that people who had COVID experienced significantly more gastrointestinal symptoms a year after their infection than people who had not had the virus. The study compared almost 150,000 people who were infected in the early days of the pandemic with 5.6 million similar patients who had not had the virus. In the first group, conditions, including GERD (gastroesophageal reflux disease) and peptic ulcer disease, were among the most commonly reported symptoms.
Cardiologists: Cardiovascular symptoms are less common than some in other specialties, accounting for about 5% to 10% of Long COVID issues, explains Dr. Spatz. Acute COVID can lead to myocarditis, which causes significant inflammation of the heart muscle, she adds. It also can cause other cardiovascular problems, including thrombosis and acute stress to the heart, resulting in cardiomyopathy or arrhythmia. We are learning to look for the potential for any of those issues to have occurred and their residual effects, she says.
Heart specialists also care for Long COVID patients who develop chest pain, palpitations, or exercise intolerance, or those who may have a cardiovascular syndrome, such as postural orthostatic tachycardia syndrome (POTS), a blood circulation disorder that causes lightheadedness or fainting when standing up from a lying down position.
Another potential concern is heart rate fluctuation, which can be caused by tachycardia (a fast heart rate) and bradycardia (a slow heart rate). Yet another issue is a chest pain syndrome that may be related to endothelial dysfunction, in which the arteries become narrow even though there is no blockage.
PETALING JAYA: There have been four cases of mpox infection reported to date with two new ones that are not linked to the first two cases, says the Health Ministry.
It said the third case was confirmed on Oct 21, involving a local found to have symptoms of fever and blisters on Oct 6.
The fourth case, also a local, was a close contact of the third case and confirmed positive on Oct 23.
"Both (patients are) undergoing isolation in their houses and their condition is stable," Health director-general Datuk Dr Muhammad Radzi Abu Hassan said in a statement on Monday (Oct 30).
"Both had been denied travelling overseas in the last 21 days before they had the symptoms," he added.
Mpox (formerly known as monkey pox) is a viral infection that spreads through physical contact.
Its symptoms include fever and blisters on the face, palms, soles and private parts.
Dr Muhammad Radzi said the incubation period before symptoms appear is between five and 21 days and the infection usually heals without any special treatment needed.
He advised medical practitioners to be on the lookout for individuals with possible mpox symptoms who seek treatment.
"District health clinics have to be notified if there are suspected carriers through the electronic notification system for investigation and (containment) measures to be taken," he added.
By Sabrina Janesick
An interdisciplinary team of Virginia Commonwealth University scientists and mathematicians has been awarded more than $660,000 by the National Science Foundation to study vaccine coverage and identify drivers of vaccine uptake in the United States.
By providing data on vaccine inequities and acceptance, particularly among minority and rural populations, the researchers hope to contribute to the global effort to predict and mitigate the impacts of current and future pandemics. The MAVEN project Multidisciplinary Analysis of Vaccination Games for Equity will gather data on multiple vaccines, including influenza, human papillomavirus, COVID-19 and monkeypox, in order to develop a comprehensive understanding of vaccine uptake.
The MAVEN project is led by Dewey Taylor, Ph.D., a professor in the Department of Mathematics and Applied Mathematics at VCUs College of Humanities and Sciences. The team includes faculty from varied departments: Sunny Jung Kim, Ph.D., an assistant professor of health behavior and policy at VCUs School of Population Health; Gabriela Len-Prez, Ph.D., an assistant professor of sociology; Oyita Udiani, Ph.D., an assistant professor of math; Jan Rychtar, Ph.D., a professor of math; Oleg Korenok, Ph.D., chair of the Department of Economics at VCUs School of Business, and Daniel Stephenson, Ph.D., an assistant professor of economics.
Taylor is an expert in mathematical modeling and conducts research on neglected tropical diseases. Her work has primarily focused on understanding how diseases affect communities with extremely limited resources that have been traditionally understudied and overlooked in public health research.
Through this project, we aim to better understand the structural, social and individual factors that influencevaccine uptake. This research will also examine how heterogeneityin our communities affect perceptions and trends around vaccination, as well as how individual behaviors related to vaccines impact disease dynamics, said Taylor. This is a large multidisciplinary project and I am excited to work with such a diverse team of researchers.
Kim, who has a background in disease prevention and vaccine uptake research, led astudyinvestigating misinformation on social media about the HPV vaccine and health communication strategies to counter the misinformation. She said understanding why people do or dont take vaccines can help policymakers and health professionals communicate about vaccines with the public.
The data can inform us on multilevel individual and structural factors that explain vaccine uptake and vaccine refusal across heterogeneous populations, and why some people have distrust for vaccines, she said.
With its interdisciplinary team of researchers, the MAVEN project will combine expertise from mathematical epidemiology and social and behavioral sciences, using multiple data sources to develop a model to estimate peoples vaccine preferences. Once the model is created, researchers will be able to conduct both retrospective and prospective calculations about vaccine acceptance and hesitance.
We will utilize multiple behavioral prediction models and game theory to understand the elements involved in decision-making, Kim said.
The outcomes of the MAVEN project will serve a twofold purpose: helping public health organizations to promote vaccines and serving as a basis for future research, particularly for developing targeted interventions to increase vaccine acceptance and build trust among vulnerable populations.
I am very excited to have this opportunity, Kim said, not only in terms of research but also the implications of the findings for policy and outreach efforts for vaccine distribution as well as patient education opportunities all of which can help reduce existing racial and ethnic disparities in vaccination uptake rates.
Subscribe to VCU News at newsletter.vcu.edu and receive a selection of stories, videos, photos, news clips and event listings in your inbox.
2023 has been a year of changing tides for Blue Water Biotech, and the last few months appear to be producing some particularly rough seas. With a freshly minted CEO, the biotech is redefining its mission to focus solely on oncology, a move that includes dropping six FDA-approved drugs and its wide-ranging vaccine portfolio.
Blue Water Biotechwhichchangedits name from Blue Water Vaccines this May after buying FDA-approved benign prostatic hyperplasia (BPH) drug Entadfi from Veruis deprioritizing all vaccine work, according to an Oct. 30 letter to shareholders from CEO Neil Campbell.
Vaccines were once the centerfold of the company, with programs in at least eight separate indications such as the flu, malaria and monkeypox. None of the programs had made it to the clinic yet, according to the companys online pipeline.
These vaccine programs were targeting a wide number of diseases and conditions that would have consumed an enormous amount of company resources, Campbell wrote, adding that evolving market dynamics and post-pandemic challenges prompted the company to conduct the strategic assessment that ultimately has resulted in the pipeline upheaval.
The biotech is also abandoning six FDA-approved assets acquired from an $8.5 million deal made with WraSer and Xspire Pharma earlier this year. The drugswhich CEO Campbell says wont meet requirements for creating greater shareholder value in 2024include thrombin receptor antagonist Zontivity; antibiotics Otovel and Cetraxal and authorized generics distributed by WraSer; calcium channel blocker Conjupri; and pain medications Trezix and Nalfon.
Blue Water has also discontinued its commercial operations related to the six drugs due to misalignment with the biotechs evolving objective in the cancer field.
Part of the strategic assessment also included overhauling the companys management team, with CEO Campbell joining earlier this month from Marizyme. Chief Financial Officer Jon Garfield also exited the company, with Bruce Harmon taking on the CFO title.
The newest changes leave Campbell with a portfolio of oneEntadfi, which won approval from the FDA in December 2021 for men with BPH. While the condition is a noncancerous enlargement of the prostate, Campbell wrote that the expected 2024 market launch will make it the inaugural therapeutic drug in our expanding portfolio of oncology therapeutics.
