by Timothy McQuiston, Vermont Business Magazine COVID-19 cases, hospitalizations and deaths have edged up in Vermont since the end of summer, continuing a trend that began in August. The Rutland Regional Medical Center and the UVM Health Network hospital in Plattsburgh, NY (CVPH), have recently tightened visitation guidelines. Meanwhile, the CDC has released a new vaccine booster.
The Vermont Department of Health reported October 11, 2023, that COVID-19 hospitalizations fell to a statewide total of 31, down from 47 last week, they were 31 before that and 22 three weeks ago. COVID-19 activity remains in the "Low" range, according to the VDH. Reported cases last week were 287, up from 283 last week, 311 before that and 197 three weeks ago.
There were 6 COVID-related deaths reported last week (after 4 the previous week) for a pandemic total of 1,032 as of October 7 (this is the most recent update). Fatalities have slowed from prior years. VDH reported 15 COVID-related deaths in March, 20 in April, 10 in May, 10 in June (these are fewest since the summer of 2021), 11 in July, 14 in August, 17 in September and 3 so far in October.
CDC states that already an estimated 97% of Americans have some level of immunity, from either vaccination or infection or both, which they said will help keep down new transmission and lessen serious outcomes.
Of the total deaths to date, 823 have been of Vermonters 70 or older. There have been 3 deaths of Vermonters under 30 since the beginning of the pandemic.
(see data below)
Report Timeframe: October 1 to October 7, 2023
Statewide hospitalization levels: Low. New COVID-19 admissions are below 10 per 100,000 Vermonters per day.
The hospitalizations dataset contains day-level data reported from all Vermont hospitals each Tuesday. Reported numbers are subject to correction by reporting hospitals, and data from several days during the previous reporting week were marked as corrected as of October 10, 2023.
The number of reportable COVID-19 cases is still available in this report, below. Laboratory-confirmed and diagnosed COVID-19 cases and COVID-19 outbreaks must still be reported to the Vermont Department of Health.
As of this report, there were 9 outbreaks last week, with 4 in long-term care facilities and 4 in schools/childcare centers. Outbreaks have fallen significantly since fall 2022.
Vermont Department of Health recommendations: Preventing COVID-19 (healthvermont.gov)
CDC recommendations: COVID-19 by County | CDC
Vermont has the second lowest fatality rate in the US (119.4 per 100K; Hawaii 99.6/100K). Mississippi (430.9/100K) and Oklahoma (428.0/100K) have the highest rates. The US average is 287.1/100K (CDC data).
There has been a total of 1,147,253 COVID-related deaths to date in the US (CDC) and 6,961,014 globally (WHO).
Following an analysis of COVID-19 data, the VDH reported in early January a cumulative 86 additional COVID-associated deaths that occurred over the course of the pandemic but had not been previously reported. Most of those deaths occurred in 2022.
COVID-19 Update for the United States
Early Indicators
Test Positivity
% Test Positivity
10.1%
(October 1 to October 7, 2023)
Trend in % Test Positivity
-0.8% in most recent week
Emergency Department Visits
% Diagnosed as COVID-19
1.4%
(October 1 to October 7, 2023)
Trend in % Emergency Department Visits
-17.7% in most recent week
These early indicators represent a portion of national COVID-19 tests and emergency department visits. Wastewater information also provides early indicators of spread.
Severity Indicators
Hospitalizations
Hospital Admissions
16,766
(October 1 to October 7, 2023)
Trend in Hospital Admissions
-8.2% in most recent week
Deaths
% of All Deaths in U.S. Due to COVID-19
2.5%
(October 1 to October 7, 2023)
Trend in % COVID-19 Deaths
-3.8% in most recent week
Total Hospitalizations
6,405,961
The Delta variant took off in August 2021, which resulted in the heaviest number of deaths before vaccines and their boosters helped alleviate serious COVID cases. Multiple Omicron variants are now circulating and appear more virulent than previous variants, but perhaps not more dangerous, according to the CDC.
AP April 5, 2023: WHO downgrades COVID pandemic, says it's no longer a global health emergency
Walk-in vaccination clinics run by the state closed on January 31, 2023. Learn more
Vermonters are reminded that all state COVID testing sites were closed as of June 25, 2022. PCR and take-home tests are available through doctors' offices, pharmacies and via mail from the federal government. The federal government officially ended its pandemic response as of May 11, 2023. See more information BELOW or here: https://www.healthvermont.gov/covid-19/testing.
Starting May 11, 2023, the CDC and Vermont Department of Health will no longer use the COVID-19 Community Level to measure COVID-19 activity in the U.S. and Vermont. Instead, Vermont's statewide COVID-19 level will be measured by the rate of COVID-19 in people being admitted to the hospital, per 100,000 residents.
Focusing on hospitalization data is a better estimate of how COVID-19 is impacting the community now that reported COVID-19 cases represent a smaller proportion of actual infections. This also allows us to compare Vermonts hospitalization levels with other parts of the country.
The Delta variant caused a surge in COVID-related fatalities last fall and into the winter.
The highest concentration of deaths was from September 2021 through February 2022. Overall, December 2020 and January 2022 were the worst months with 72 fatalities each.
The US confirmed its first case of COVID-19 on January 20, 2020.
Vermonters ages 6 months and older are eligible for COVID-19 vaccines. Getting vaccinated against COVID-19 is the safer way to build protection from serious illnesseven for those who have already had COVID-19. Learn more about COVID-19 vaccines (CDC)
COVID-19 vaccines are free and widely available. Anyone can get vaccinated in Vermont, including those who live in another state, are non-U.S. citizens, or who have no insurance. See Vermont's current vaccine rates
Know your rights when getting free vaccines.
You are considered up-to-date if you are over the age of 6 years old and have received a bivalent (updated) COVID-19 vaccine.Learn more about kid vaccines
If you are unable or choose not to get a recommended bivalent mRNA vaccine, you will be up to date if you received the Novavax COVID-19 vaccine doses approved for your age group.
Find more on recommended doses from CDC
COVID Vaccine Information for Health Care Professionals
More on COVID-19 Vaccines (CDC)
Recommended COVID Vaccine Doses (CDC)
Find a COVID-19 vaccine near you.
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Use Vaccines.gov to find a location near you, then call or visit the location's website to make an appointment.
Vaccines.gov
Everyone 6 months of age and older is eligible to get a COVID-19 vaccination.Most children are also now eligible for a bivalent dose that offers increased protection against the original strain and omicron variants.
See more on recommended vaccine doses by age group (CDC)
Resources for parents and caregivers
https://www.vermontfamilynetwork.org/ccfk/
Tips for Helping Kids Feel Ready for Any Vaccine (Vermont Family Network)
#factsheet
What Families with Children Should Know About COVID-19 Vaccines (translated)
https://www.youtube.com/watch?v=lWcqHOgQIVg&t=5s
Conversations About COVID-19 Vaccines for Children with Vermont Pediatricians (American Academy of Pediatrics)
If you cannot get vaccines through any of the options above, our local health offices
offer immunization clinics by appointment.
Need a ride? If you do not have transportation to get a free COVID-19 vaccine or booster, please contact your local public transportation provider or callVermont Public Transportation Association (VPTA)
at 833-387-7200.
English language learners, or immigrant or refugee community members, who would like to learn about more about vaccine clinics can contact theAssociation of Africans Living in Vermont
(AALV) at 802-985-3106.
If you lost your vaccine card or your information is wrong:
Recommendations for keeping your vaccination card and record up to date
Find more COVID-19 translations
COVID-19 resources for people who are deaf and hard of hearing
Report your COVID-19 test results
A vaccine being developed to combat three deadly coronaviruses has had some success in early studies in mice.
The breakthrough at the Duke Human Vaccine Institute in the US has shown the vaccine protected mice against Covid-19, severe acute respiratory syndrome (Sars) and Mers the Middle East respiratory syndrome first identified in Saudi Arabia in 2012.
The research offers hope that a pan-coronavirus vaccine could one day be developed further to protect human beings from numerous viruses.
The single nanoparticle vaccine included components of a previous vaccine that protected mice and primates against variants of Sars-CoV2, the virus that causes Covid-19.
This study demonstrates proof-of-concept that a single vaccine that protects against Mers and Sars viruses is an achievable goal
Kevin Saunders, Duke Human Vaccine Institute.
Scientists in the US built the tri-valent vaccine using a nanoparticle loaded with a key fragment called a receptor binding domain from each of the three viruses.
That fragment acts as a docking site on each virus, boosting immunity by enabling it to infiltrate the bodys cells to protect them against actual coronaviruses that may enter the body.
Further tests are planned on human subjects next year in the hope a vaccine can be developed that carries immunogens to attack several coronavirus strains.
We are making important progress toward a broadly protective coronavirus vaccine, said Kevin Saunders, author of the study and associate director of the Duke Human Vaccine Institute.
These are pathogens that cause or have the potential to cause significant human infections and loss of life, and a single vaccine that provides protection could slow down or even prevent another pandemic.
Sars is a viral respiratory disease similar to Covid-19.
It was first identified in February 2003, during an outbreak that emerged in China and then spread to four other countries in Asia.
In the following months, the illness spread to more than 24 countries, including in the Americas and Europe before it was contained later that year.
During the 2003 outbreak, the World Health Organisation reported 8,098 cases of illness and 774 deaths.
Symptoms were similar to influenza, with a dry cough after several days, with most sufferers developing pneumonia.
While the worlds attention has been focused on the coronavirus in recent years, a related pathogen -- the Middle East Respiratory Syndrome (MERS) -- has been continuing to circulate and cause deaths. Reuters
Since the disease emerged a decade ago, there have been 2,605 confirmed cases, about 84 per cent of them in Saudi Arabia. AFP
Ulrich Wernery, scientific director of the Central Veterinary Research Laboratory in Dubai, takes samples from a camel to assist with a study of Mers. Pawan Singh / The National
Passengers walk past a thermal scanner at Manila International Airport in the Philippines. The country is one of 18 that have reported cases of the MERS coronavirus. AP
Camel owners do not want to vaccinate their herd because the animals themselves do not become ill.
Saudi Arabia has urged its citizens and foreign workers to wear masks and gloves when dealing with camels. AFP
Better hygiene and other virus control measures have helped to reduce the number of people infected with the virus from camels. Pawan Singh / The National
Almost a decade later a similar virus emerged in the Middle East.
Since Mers was first reported in 2012, there have been more than 2,600 confirmed laboratory cases, with the majority in Saudi Arabia.
Of those, there have been 856 related deaths from Mers, the virus believed to be passed on from dromedary camels.
A man in the UAE tested positive for the Mers virus this year.
The WHO said the man, 28, an expatriate living in Al Ain, was admitted to hospital on June 8.
It said 108 contacts were identified and monitored for 14 days from the last date of exposure to the patient.
No further cases were detected.
The research by the Duke Human Vaccine Institute could pave the way for a human vaccine to protect against all three deadly viruses.
This study demonstrates proof-of-concept that a single vaccine that protects against Mers and Sars viruses is an achievable goal, Mr Saunders said.
Given that one Mers and two Sars viruses have infected humans in the last two decades, the development of universal coronavirus vaccines is a global health priority.
Updated: October 19, 2023, 8:50 AM
People with HIV were more likely to have been vaccinated and boosted.
October 18, 2023, 12:13 PM ET
4 min read
People with HIV are at increased risk of being reinfected with the virus that causes COVID-19, according to new federal data.
Researchers from the Centers for Disease Control and Prevention and the Chicago Department of Public Health followed adult residents in Chicago from their first reported infection from March 2020 through the end of May 2022, according to the report published Wednesday by the CDC.
The team compared COVID test laboratory data and COVID vaccine administration data to Chicago's Enhanced HIV/AIDS Reporting System.
About 5% experienced reinfection among more than 453,000 Chicago residents who tested positive for the virus.
Rates of reinfection were higher among people with HIV (6.7%) than among people without HIV (5.2%).
People with HIV are more likely to have completed a primary COVID vaccine series plus a booster before their reinfection -- 31.8% versus 27% for those without HIV.
Reinfection rates were consistently higher throughout the pandemic for people with HIV and were highest during the original omicron variant phase, according to the report.
"Understanding if persons with HIV have a higher risk for SARS-CoV-2 reinfection may help tailor future COVID-19 public health guidance," the authors wrote. "[Persons with HIV] should follow the recommended COVID-19 vaccine schedule, including booster doses, to avoid SARS-CoV-2 reinfections."
Those who were reinfected were more likely to be male, older and Black or African American compared to those without HIV, the study found.
People with HIV were also less likely to have been unvaccinated at the time of their first infection compared to people without HIV.
The report notes the findings are a reminder about the risks of reinfection for those who are immunocompromised.
HIV can weaken the immune system, infecting and destroying CD4 cells, which causes the white blood cell count to drop and compromises the immune system.
This means that people with HIV are susceptible to COVID infection especially those who are not on antiretroviral therapy (ART).
ART is a combination of drugs that suppresses a person's viral load until HIV Is virtually undetectable. The ability of ART to control viral replication has been shown to greatly improve immune system function, studies show.
"Evaluating the association between HIV infection and SARS-CoV-2 reinfections using surveillance data can help strengthen public health recommendations including the need for extra doses as part of a primary series, booster doses of vaccine, and optimized ART in [persons with HIV]," the authors wrote. "Tailored guidance and prevention messaging for [persons with HIV] can help reduce the elevated risk we identified in this analysis and limit continued SARS-CoV-2 transmission."
Quinn Dombrowski / Flickr cc
A study yesterday in JAMA Network Open based on outcomes seen among Singaporean children ages 4 years and younger showed good protection for two doses of monovalent mRNA COVID vaccines during an Omicron surge.
The authors said the findings support vaccinating this age-group, despite low incidence of severe disease or hospitalization.
The study was conducted from October 1, 2022, to March 31, 2023, after all Singaporean children ages 1 to 4 had been vaccinated with mRNA two-dose vaccines in a community vaccination campaign following approval of vaccines for this age-group in August 2022.
The 6-month study period coincided with an Omicron XBB surge in Singapore, during which schools remained open, mask wearing was optional, and close contacts of COVID-19 cases were allowed to remain in school if well.
A total of 121,628 children (median age, 3.1 years) were included in the study, contributing 21,015,956 person-days of observation. A total of 45,693 children (37.6%) had a prior SARS-CoV-2 infection, with most having had prior infection during the earlier Omicron BA.1/2 wave, the authors said.
In kids with no previous COVID-19, vaccination was 63.3% effective in protecting against infection. Protection was higher, 74.6%, in those with a documented prior infection. Data were insufficient to assess vaccine effectiveness in fully vaccinated children with prior SARS-CoV-2 infection, the authors said.
There were no hospitalizations among fully vaccinated children, and no deaths were reported during the study.
Rapid increases in pediatric COVID-19 infections coinciding with periods of high community transmission may still place health care systems under strain.
Though vaccinating children under the age of 5 is debatable, the authors said, "Rapid increases in pediatric COVID-19 infections coinciding with periods of high community transmission may still place health care systems under strain."
The severe acute respiratory syndrome coronavirus 2; SARS-CoV-2 is responsible for coronavirus disease1,2. COVID-19 induced coagulopathy appears to be different from the traditional coagulopathy in many ways since it meets the criteria for the relatively newly defined entity of sepsis-induced coagulopathy (SIC) that is characterized, and quantified according to reduced platelet counts, increased international normalized ratio (INR), and higher organ dysfunction in SARS-CoV-2 patients3. The findings during the last few years after COVID-19 pandemic have suggested that SARS-CoV-2 has a connection with various blood disorders, including a higher risk of clot formation and sometimes bleeding problems in acutely infected patients4,5,6,7. During infection, the frequently observed micro- and macro- thrombotic events are due to the perpetuation of a state of hypercoagulability that has been termed as the COVID-19-associated coagulopathy (CAC) and, in fact, it is different from the regular clotting problems8. The so-called CAC represents a key aspect for the development of multi-organ damage in patients. In CAC the changes are represented by high levels of D-dimer and fibrinogen; however, CAC also has some common features with disseminated intravascular coagulation (DIC) and SIC, but there are differences between these clinical observations. It appears that the pathogenesis of CAC is more complex and is influenced by an interconnection between the inflammatory system and coagulation, in the phenomenon of immuno-thrombosis and thrombo-inflammation. In CAC many factors come into play including the neutrophils, inflammatory cytokines, complement system as well as fibrinolytic system. Finally, changes in platelet function coupled with endothelial dysfunction also play roles in CAC. Though we are still piecing together exactly how it happens, several factors such as problems with endothelial lining, inflammation, and an intense immune system response affects in raising the risk of clotting. Moreover, in severely acute infection, the immune system can go off the track. This can lead to additional issues with a part of the immune system called the complement system, which can also damage blood vessels making clotting problems worse9.
When platelets get activated, they stick together and release chemicals that promote inflammation. This makes blood clot formation more easily. In regular clotting, the making of thrombin helps turn fibrinogen into fibrin the material that makes up clots. Conditions like hemophilia, where some clotting factors are missing, or DIC, where too much of this process happens, lead to standard clotting problems. So, the main differences between CAC and regular clotting problems lie in how they happen. In regular clotting problems, making of thrombin is important for clotting to occur but in CAC, the risk of blood clots arises from a mix of inflammation, problems with blood vessel lining, platelet activation, and issues with the immune systems response9. The spike protein or SP also interacts with the clotting process. This contributes to the unique clotting situation seen in CAC. Understanding these aspects of CAC is crucial for devising care for COVID-19 patients, especially for people with weakened immune systems like diabetics, who face clotting-related problems more often than those without diabetes10,11,12,13,14,15,16.
Briefly, the coronaviruses that cause severe acute respiratory syndrome (SARS), such as SARS-CoV, MERS-CoV (responsible for the middle east respiratory syndrome), and SARS-CoV-2, need transmembrane serine protease 2 (TMPRSS2) for their entry into the host cells. Subsequent studies have also shown that SARS-CoV-2 requires the angiotensin-converting enzyme 2 (ACE2) as the main receptor together with TMPRSS2 for infecting the host cells productively17,18,19. SARS-CoV-2 is a single-stranded ribonucleic acid (RNA) virus that encodes a variety of proteins, including 4 structural proteins such as (1) Membrane/Matrix (M), (2) Envelope (E), and (3) Spike (S) proteins that assemble around (4) Nucleocapsid (N) and its RNA. As mentioned above, the virus infects host cells upon binding to ACE2 receptor, and subsequent action of proteases, including the transmembrane protease serine 2 (TMPRSS2). The virus exhibits a high infectious rate and can provoke a wide array of symptoms beginning with the cytokine storm20,21. The recent pandemic is the third outbreak due to a highly pathogenic -coronavirus in only just two decades. Thus, there is a tremendous need to acquire in-depth knowledge of the virus infection cycle, as well as the cellular and molecular pathways that are involved in the viral replication and mounting of the innate and adaptive immune responses in the host. We believe that answers to these fundamental questions will help us in the development of safer, and efficient therapeutics and pan--coronavirus vaccines against emerging SARS-CoV-2 variants and their subvariants of concern22. ACE turns angiotensin I into angiotensin II, which has multiple effects throughout our body such as increase in blood pressure. Angiotensin I is cleaved by angiotensin-converting enzyme (ACE) to produce angiotensin II, and then Angiotensin II binds to its receptors and exerts its effects in the brain, kidney, adrenal, vascular wall, and the heart. Although SARS-CoV-2 spike protein (SP) masks the ACE2, but it increases the availability of angiotensin (Ang II; 18) and decreases the Ang (17), suggesting a role in hypertension23,24,25,26. Although COVID-19 has been linked to orthostatic tachycardia (OT), again the mechanisms are largely unknown. The heart rate of the patient increases by ~30 beats/min; however, the blood flow to the brain decreases that causes hypoperfusion, and vascular contributions to cognitive impairment and dementia (VCID). This also suggests a role of vascular coagulopathy, and thrombosis for the decrease in the blood flow to brain27. Since so many complications are associated with COVID-19 including the vascular coagulopathy/thromboembolism, endothelial dysfunction, stiffness, fibrosis, and extracellular matrix (ECM) fragmentation9,28,29,30,31,32,33,34,35,36, but the underlying mechanisms of these events are unclear.
The ongoing research in our laboratory is based on our previous studies that have shown activation of inflammatory M1 macrophages with renal infiltrates in the hACE2 mice administered with SP, intranasally37. In COVID-19 patients there is an elevated level of neopterin (NPT)38,39. Because NPT is generated by activated pro-inflammatory macrophages (M1) in response to COVID-19 via inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and peroxinitrite (ONOO-) along with activation of proteinases. We are of the opinion that iNOS generates NPT and decreases BH4, eNOS activity and a disintegrin and metalloproteinase thrombospondin 13 domain (ADAMTS13), anti-thrombosis/anti-coagulant but at the same time activates urinary neutrophil gelatinase associated lipocalin2 (NGAL2, pro-thrombosis/pro-coagulant), and transmembrane serine proteinase S2 (TMPTSS2, proteolytic factor processing of COVID-19) and matrix metalloproteinases (MMPs), leading to renal dysfunction and failure18,40,41,42,43. NGAL and FGF23 (vascular hypertrophic factor) are high and ADAMTS13 is low post COVID-19 sequelae44,45,46,47,48. Again, the recognition of endothelial dysfunction within the realm of COVID-19 is emerging as a pivotal and defining aspect of SARS-CoV-2 infection, and its post infection implications especially against the background of the intricate interplay between endothelial cells and immune constituents, exemplified by the dynamic interaction with neutrophils in the context of thromboembolism, assumes paramount significance. This alliance between endothelial cells lining and immune effector molecules that our work has reported earlier prompts a series of inquiries that underscore the pivotal role of endothelial cells in the intricate landscape of thromboembolic events37. A further deeper exploration into the mechanisms underpinning endothelial dysfunction can unravel its contribution to the disruption of coagulation equilibrium, particularly within the intricate milieu of CAC. This knowledge will enhance our comprehension of the pathophysiological mechanisms at play but also to pave the way for the identification of strategic interventions aimed at safeguarding our patients during the throes of acute infection. Hence, by delving into the nuanced of how endothelial dysfunction precipitates coagulation dysregulation, particularly within the context of COVID-19 related coagulopathic manifestations, a potential roadmap might emerge via an understanding of the molecular interactions that could hold the promise of unveiling therapeutic avenues designed to shield afflicted patients during the critical phase of acute infection49.
Interestingly, CAC in glomerular capillaries-microvascular wall, the interaction between macrophages, neutrophil and immune cells, causes build-up layers of damage endothelial via iNOS, NGAL2, eNOS, and ADAMTS13, sets the stage of pro-thrombotic and pro-coagulant processes. This also contributes to focal glomerulosclerosis lesions in COVID-19 patients50,51. The levels of transmembrane (TMPRSS2), EMMPRIN (CD147) and ECM proteinases are elevated post COVID-1918. These proteinases are associated with collagen/elastin breakdown during renal glomerular remodeling. However, because the turnover of collagen is rapid than elastin, the degraded elastin is replaced by collagen, causing fibrosis, stiffness, and thickening of the basement membrane in the glomeruli, instigating impaired glomerular filtration rate (GFR)52. Therefore, an increase in M1 macrophages iNOS decreases BH4 bioavailability to eNOS, causing glomerular capillary microvascular endothelial dysfunction. The oxidative peroxinitrite (ONOO-) activates NGAL2 and FGF23 and decrease in ADAMTS1353,54. The transmembrane serine (TMPRSS2), EMMPRIN and MMPs/TIMPs are activated, leading to renal dysfunction. Interestingly, there appears to be evidence of fibrosis with hypertrophy in the glomeruli of hACE2 mice administered with SP within 4 weeks post COVID-19 sequelae, as expected, since this will suggest that there is acute kidney injury (AKI) with preserved glomerular filtration rate (GFR), that can be reversed by iNOS blocker37. However, if there is chronic thickening of the basement membrane, post COVID-19, this will suggest that there is chronic kidney disease (CKD). In that situation an inhibitor of proteinases, such as TMPRSS2 will be able to mitigate the COVID-19 induced CKD. This is important and novel in the sense that post COVID-19 morbidities, and mortalities can be halted with a TMPRSS2 inhibitor.
Further, in the landscape of biomarkers linked to endothelial dysfunction, the circulating inflammatory coagulation markers assume a pivotal role, notably the fibrin(ogen), D-dimer, P-selectin, and von Willebrand Factor (VWF). These biomarkers, in their close relationship with endothelial cells, platelets, and erythrocytes, contribute significantly to the pathological progression observed in acute COVID-19 cases55. For example, the fibrin(ogen) and D-dimer are indicative of ongoing coagulation and fibrinolysis processes, exhibiting a dynamic connection with MMP-2, MMP-9, and MMP-1356. These MMPs can potentially modulate the stability of blood clots, thereby impacting both clot formation and dissolution. The interplay between these biomarkers might amplify the coagulopathic tendencies observed in severe COVID-19 patients, thus accentuating the pro-thrombotic environment. Interestingly, the Von Willebrand Factor (VWF) and P-selectin are integral to platelet adhesion and aggregation, and intersect with ADAMTS-13, a critical regulator of VWF cleavage57,58. Thus, a dysregulation of ADAMTS-13 in COVID-19 could lead to increased VWF activity, thereby fostering the microvascular thrombosis. This interaction, coupled with the intricate role of MMPs, might contribute to the endothelial activation and damage central to the disease pathogenesis. On the other hand, the renal NGAL, is a biomarker of kidney injury, and that usually reflects the broader systemic impact of inflammation and coagulation in COVID-19 patients59. Its interplay with MMP-7 or matrilysins (it was originally described as PUMP-1; putative uterine metalloprotease-1), and was long considered a third member of the stromelysin family, although it appeared only distantly related to the other stromelysins, and later dubbed MMP-7, a possible reference to ion transporters, underscores the systemic implications of electrolyte imbalance in severely ill patients, potentially affecting both coagulation and vascular health60,61. Furthermore, TMPRSS2, an enzyme facilitating viral entry, adds another layer to this complex narrative. Its interplay with these biomarkers might signify a feedback loop where the virus-induced dysregulation contributes to coagulopathic tendencies, potentially mediated by the interplay of endothelial cells, platelets, and erythrocytes62,63,64,65,66. In a nutshell, the interaction between fibrin(ogen), D-dimer, P-selectin, VWF, and biomarkers like MMPs, ADAMTS-13, renal NGAL, PUMP, and TMPRSS2 intertwine within the context of acute COVID-19. This intricate interplay encompasses endothelial dysfunction, platelet aggregation, coagulopathy, and systemic impact, collectively contributing to the complex pathogenesis observed in severe cases. Understanding these connections will aid not only in deciphering disease mechanisms but also in the identification of potential avenues for therapeutic intervention for the patients.
In the intricate landscape of biomarkers linked to endothelial dysfunction, certain circulating inflammatory coagulation biomarkers assume a pivotal role, notably the fibrin(ogen), D-dimer, P-selectin, and von Willebrand Factor (VWF). These biomarkers, in their close relationship with endothelial cells, platelets, and erythrocytes, contribute significantly to the pathological progression observed in acute COVID-19 cases. For example, the fibrin(ogen) and D-dimer are indicative of ongoing coagulation and fibrinolysis processes, exhibiting a dynamic connection with MMP-2, MMP-9, and MMP-13. These MMPs can potentially modulate the stability of blood clots, thereby impacting both clot formation and dissolution. The interplay between these biomarkers might amplify the coagulopathic tendencies observed in severe COVID-19 patients, thus accentuating the pro-thrombotic environment. Interestingly, the Von Willebrand Factor (VWF) and P-selectin are integral to platelet adhesion and aggregation, and intersect with ADAMTS-13, a critical regulator of VWF cleavage. Thus, a dysregulation of ADAMTS-13 in COVID-19 could lead to increased VWF activity, thereby fostering the microvascular thrombosis. This interaction, coupled with the intricate role of MMPs, might contribute to the endothelial activation and damage central to the disease pathogenesis. On the other hand, the renal NGAL, is a biomarker of kidney injury, and that usually reflects the broader systemic impact of inflammation and coagulation in COVID-19 patients. Its interplay with MMP-7 or matrilysins (it was originally described as putative uterine metalloprotease-1 (PUMP-1) in 1988, and was long considered a third member of the stromelysin family, although it appeared only distantly related to the other stromelysins, and later dubbed MMP-7, a possible reference to ion transporters, underscores the systemic implications of electrolyte imbalance in severely ill patients, potentially affecting both coagulation and vascular health. Furthermore, the TMPRSS2, an enzyme facilitating viral entry, adds another layer to this complex narrative. Its interplay with these biomarkers might signify a feedback loop where the virus-induced dysregulation contributes to coagulopathic tendencies, potentially mediated by the interplay of endothelial cells, platelets, and erythrocytes. In summary, the interaction between fibrin(ogen), D-dimer, P-selectin, VWF, and the mentioned biomarkers like MMPs, ADAMTS-13, renal NGAL, PUMP, and TMPRSS2 intertwines within the context of acute COVID-19. This intricate interplay encompasses endothelial dysfunction, platelet aggregation, coagulopathy, and systemic impact, collectively contributing to the complex pathogenesis observed in severe cases. Understanding these connections will aid not only in deciphering disease mechanisms but also in identifying potential avenues for therapeutic interventions.
A pair of cormorants thought to have died from H5N1 bird flu, found washed up on a beach in Chile earlier this year.Credit: Martin Bernetti/AFP via Getty
Researchers studying the evolution of the bird flu virus over the past 18 years have shown how the strain currently circulating worldwide, an extremely deadly form of the H5N1 subtype, has become increasingly infectious to wild birds. The strain emerged in Europe in 2020, and has spread to an unprecedented number of countries.
The study, published in Nature on 18 October1, looked at changes to the viruss genome over time and used data on reported outbreaks to track how it spread.
Why is bird flu so bad right now?
In 2020, the rate of spread among wild birds was three times faster than that in farmed poultry, because of mutations that allowed the virus to adapt to diverse species.
What was once very clearly a poultry pathogen has now become an animal-health issue much more broadly, says Andy Ramey, a wildlife geneticist at the US Geological Survey Alaska Science Center in Anchorage. That has implications for wildlife and domestic poultry as well as us humans that rely upon these resources.
H5N1, classified as a highly pathogenic avian influenza (HPAI) virus because of its high death toll in poultry, was first detected in birds in China in 1996. Outbreaks are usually seasonal, synchronizing with bird migration in Northern Hemisphere autumn. But since November 2021, they have become persistent. In 2022, the virus killed millions of birds across five continents and seeded outbreaks among farmed mink and various marine mammals.
Source: Ref. 1
To study changes in the viruss behaviour, the authors examined data reported to the Food and Agricultural Organization of the United Nations and the World Organisation for Animal Health between 2005 and 2022, and analysed more than 10,000 viral genomes.
Their work reveals that in mid-2020, a new H5N1 strain evolved from an earlier variety, called H5N8, which first emerged in poultry in Egypt between 2016 and 2017 and caused global flare-ups throughout 2020 and 2021 (see Bird flu outbreaks). The new H5N1 virus mutated through interactions with non-deadly varieties of bird flu, called low-pathogenic avian influenza (LPAI) viruses, that had been circulating among wild birds in Europe since 2019.
It developed two subtypes in 2021 and 2022. One spread across the northern coastal regions of central Europe and was eventually carried to North America by birds migrating across the Atlantic Ocean. The other was carried around the Mediterranean Sea and into Africa.
How to stop the bird flu outbreak becoming a pandemic
Many bird flu outbreaks begin in poultry, but spillover into wild birds has spread the disease into larger areas, creating a global challenge that is difficult to manage, the study found.
Once its adapted to wild birds, we have no mechanism to control the virus. And I think thats the biggest impact that has changed now, says co-author Vijaykrishna Dhanasekaran, an evolutionary biologist and virologist at the University of Hong Kong.
Louise Moncla, an evolutionary virologist at the University of Pennsylvania in Philadelphia, agrees. Regardless of how much outbreak response you do in poultry, if its coming in from wild birds repeatedly, this is going to be really hard to manage.
This is really something that most of the world at this point has skin in the game, adds Ramey.
LPAI viruses often circulate freely in poultry and wild birds. Previous infection with these non-deadly strains is thought to encourage population immunity in wild birds. You can think of it as an imperfect vaccine, that doesnt stop infection, but it helps mitigate the effects of disease, says Ramey.
But theres probably two sides of the coin here, he adds. HPAI viruses can mutate through interactions with LPAI ones. In both, the genome is split into eight segments that can be mixed and matched. When two viruses co-infect the same cell, they could swap their genes when the virus is getting packaged, says Dhanasekaran.
Because of this, LPAI viruses especially a strain called H9N2 play a major part in the evolution of H5N1, he adds. But they are not well monitored. Eradication or elimination strategies that target these low pathogenic viruses would be a huge step forward in terms of controlling avian influenza itself, says Dhanasekaran.
Humanity is facing the worst bird flu crisis on record. Since the diseases resurgence in the 2020-2021 season, at least 250 million poultry have been culled around the world to nip outbreaks in the bud, according to data from epidemiologist Vijay Dhanasekaran of the University of Hong Kong. The figures are unprecedented: during this period, over 100,000 wild birds of 400 different species have died, with the disease making worrisome jumps to mammals, such as the one observed at an American mink fur farm in Galicia, Spain, and the massive deaths of sea lions on the beaches of Peru. The new avian influenza virus subtype is everywhere. Dhanasekarans team has investigated the pathogens evolution. On Wednesday, he warned that the epicenter of the crisis has shifted from Asia to Europe and Africa. Experts are bracing for the imminent onset of the typical November outbreaks caused by the arrival of migratory birds from the Arctic.
The current viruss lineage was detected in geese in Chinas Canton province in 1996. Avian influenza viruses have two characteristic proteins on their surface: hemagglutinin (H) and neuraminidase (N). There are 18 types of H and 11 types of N, with a multitude of possible combinations. The Guangdong Goose virus was an H5N1 that could be transmitted rapidly among poultry, causing a hemorrhagic disease with a very high mortality rate of over 40%.
Two different subtypes of influenza can coincide in the same cell of an animal, giving rise to a phenomenon called genetic reassortment, which generates a third subtype, a mixture of the previous ones. Dhanasekarans group has detected key episodes in the viruss evolution. In 2016, a particularly virulent strain of H5N8 originated in ducks in China. In 2020, a subtype of H5N8 classified as 2.3.4.4b emerged in African poultry. In 2021, the H5N1 2.3.4.4b subtype emerged through genetic reassortment in wild birds in Europe; since November of that year, it has caused unprecedented outbreaks in wild animals on five continents, according to Dhanasekarans study in the journal Nature.
The shift of the epicenter of these highly pathogenic viruses to new regions has increased the chances of them infecting a wider range of animals, including mammals, epidemiologist Dhanasekaran warns. The avian flu virus has already been detected in seals, foxes, raccoons, cougars, lynxes and bears, among other species. Exceptionally, humans have also been infected, as in the case of a 9-year-old girl who nearly died after living with sick chickens in a village in Ecuador in late 2022. Repeated infections in mammals, and in humans, increase the chances of the virus adapting, increasing the likelihood of a pandemic, Dhanasekaran warns.
The team analyzed the genomes of 10,000 viruses and investigated outbreaks recorded by the World Organization for Animal Health and the United Nations since 2005. The authors note that the viruss ubiquity in wild birds has accelerated the speed of the pathogens spread and multiplied the risk of genetic reassortment. There is a perpetual threat of the virus jumping to humans. This is mainly due to the viruss ability to evolve rapidly. It can acquire mutations that help it better attach to receptors on human cells, or it can acquire the ability to transmit via aerosols, Dhanasekaran explains. The biggest concern is the genetic reassortment of an H5 [bird] virus with human influenza viruses, which is what happened in previous pandemics, such as the ones in 1957 and 1968.
Ornithologist Victor Gamarra notes that the current panzootic the animal equivalent of a pandemic has affected hundreds of thousands of wild birds around the world. The first case of H5N1 in Peru was detected in a pelican on November 13, 2022. The outbreak spread quickly along the coast and by mid-March at least 100,000 wild birds belonging to 24 species, some of which are endangered had been found dead, as Gamarras team described in a recent study. The pathogen killed 20% of the pelicans in Perus protected marine areas. The ornithologist emphasizes that the total numbers are much higher, because his estimates do not include what happened outside protected areas, where half a million birds could have died.
The virus has spread throughout South America. And its no longer just birds, but thousands and thousands of dead sea lions from the Pacific coast to the Atlantic, laments Gamarra, a researcher at the Natural History Museum of the National University of San Agustn in Arequipa, Peru. The situation could become even worse when the new bird migration begins soon. A recombination of the virus could occur, and we could possibly be talking about a second wave in South America, he warns. This virus spreads fairly quickly, so studies like Dhanasekarans may become outdated. Thats this viruss major threat: we are not prepared to be able to counteract how fast it [spreads].
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The gene edit also helped limit the spread of the virus. Four ordinary chickens were placed in the same incubator with the gene-edited birds that had already been exposed to high levels of the virus. Out of the four, only one became infected.
Researchers monitored the gene-edited birds over the course of two years and found that the gene changes had no adverse effects on their health or egg production.
This is showing a potential mechanism for reducing the susceptibility of chickens to avian flu, says Carol Cardona, a veterinarian and professor of avian health at the University of Minnesota College of Veterinary Medicine, who wasnt involved in the study. But even if we protected every single chicken on the globe, flu wouldn't go anywhere. Avian influenza has been identified in more than 100 different species of birds.
The fact that some breakthrough infections occurred means that the virus still has a chance to infect other birds, and could escape the vaccines effects by mutating away from using the ANP32A protein to reproduce. In fact, when the UK researchers took samples of the virus from the infected gene-edited chickens, they found some mutations in the part of the virus that this protein interacts with.The flu virus replicates rapidly, and every time it enters a new host, there's an opportunity for that virus to adapt and change, Cardona says.
During the press briefing, Barclay said those viral mutations didnt make the chickens any sicker. The team also wanted to make sure those changes wouldnt cause more severe infection in people, so they added the mutated viruses to human airway cells that had been cultivated in a dish. They found that the mutations didnt help the virus grow in a way that would pose an increased risk to people.
Its also not known how the gene-edited chickens will fare against the much more aggressive bird flu strains such as H5N1, which werent tested in the study. Barclay said they chose H9N2, considered a low pathogenicity virus that causes little to no signs of disease, in part because its more common. Also, deliberately infecting chickens with H5N1 raises animal welfare concerns, since it causes serious illness and is often fatal.
The authors identified two other related proteins, ANP32B and ANP32E, that they think would prevent virus replication. In chicken cells grown in the lab, they edited the genes that code for all three proteins and exposed them to the flu virus. The edits successfully blocked growth of the virus in the cells, but the researchers have not yet bred chickens with all three edits.
UAB physicians urge people to get flu shots early in the season.
UAB physicians urge people to get flu shots early in the season.The change of season in October and November brings in crisp, fall weather for the majority of the United States. Many begin to look toward the holiday season to come, but few think about the impending cold weather and subsequent sickness that pops up when winter arrives.
Physicians at the University of Alabama at Birmingham have their sights firmly set on influenza season, however, and want to encourage everyone to get a flu shot between now and early November. That is when the cold sets in for many in the United States, and flu germs historically begin to thrive.
The flu vaccine is the best protection for the flu and how to protect others from the flu as well, says Stephen Russell, M.D., professor in UABs Division of General Internal Medicine and physician at UAB Medicine Leeds. The vaccine prepares the immune system to see, recognize and fight off the flu virus.
Flu season starts in early October, and the reason is that, by the time we see more cases of flu and in the hospital which is usually at the beginning of November we want people to be protected, Russell shared. It takes about two weeks from the time you get your flu shot for your body to develop antibodies that fight the flu, which is why we recommend that everybody gets the flu shot in October or early November. That way, by the time we see more flu in the community, peoples bodies are ready to fight off the virus.
Russell has had patients ask if getting the flu shot actually means his patients are receiving the flu virus, but he says that is not the case. Some people believe that, if they get sick immediately after receiving the vaccine, they have the flu, he says.
We know from very good medical studies and science that the flu vaccine does not give you the flu, he said. If you experience body aches and have a low-grade fever 24 hours after you get a flu vaccine, we consider that a success because your immune system is revved up and ready to fight off the flu. We can almost guarantee that 48 hours after that you will feel normal, which means your immune system is ready to fight off the flu this season.
Russell notes that, if you actually have the flu, you can expect to experience seven days of aches, along with several days of feeling bad overall, including experiencing cough and fever. With the flu shot, your mild symptoms will last less than 48 hours.
If people are unable to or forget to get the flu shot early in the season, the Centers for Disease Control and Prevention says you can still get the shot for ample protection through January. However, when there are higher numbers of reported cases of the flu, your immune system is more susceptible to acquiring the flu if you are unprotected.
Members of the community can find out where they can get a flu shot in their area by visiting the CDCs vaccine finder.
An outbreak of avian flu a highly contagious viral infection that affects wild birds as well as poultry has hit poultry farms in South Africa. Two different strains are causing outbreaks in the country A(H5N1) and influenza A(H7N6). A specialist in poultry health, Shahn Bisschop, answers some questions put to him by The Conversation Africa.
The outbreak caused by a highly pathogenic (HPAI) strain of H7N6 avian influenza is causing the most concern at present. The strain was first confirmed in chickens near Delmas north of Johannesburg at the beginning of June 2023.
This virus is a novel mutation of a strain which originated from wild birds at or near the location of the original outbreak.
The strain is well-adapted to chickens it infects them easily and replicates effectively in them, in preference to other avian species and spreads very easily between birds and farms. An estimated 10 million have become infected while 6 million died from the H7N6. A further 1.7 million died from H5N1 earlier in the year.
The conventional control measures (collectively known as biosecurity) have been less effective than usual in limiting the spread of the disease. The main measures taken on poultry farms include strictly limiting human and vehicle movement. People entering farms will typically take further measures to limit disease transmission such as showering, changing clothes and disinfecting footwear when moving between different parts of the farm.
Because wild birds are associated with the spread of avian flu, measures are taken to ensure they are completely excluded from all chicken sheds.
For at least the past nine years, HPAI H5 viruses of the 2.3.4.4 clade have been spread across the globe principally by wild bird migrations and infect a range of avian and mammalian species. The first recorded cases caused by viruses belonging to this clade were reported in South Africa in 2017. A second outbreak occurred in 2020. It was anticipated that the next outbreak would probably also be caused by these viruses and indeed the first reported cases of HPAI in 2023 in the coastal regions were associated with H5 strains.
Local experts are working on the theory that the present outbreak of H7N6 HPAI was created when a low pathogenicity AI (LPAI) virus circulating without causing disease in wild birds underwent a mutation to become an HPAI strain adapted to causing serious disease in chickens. This mutation occurred locally.
Mutation from LPAI to HPAI has been described in poultry in various parts of the world but was considered less likely than the return of the H5 clade 2.3.4.4 viruses previously encountered.
Avian influenza is a controlled disease. That means its placed under strict government control with the aim of eradication as quickly as possible when outbreaks are detected. All outbreaks on farms are immediately reported to the state veterinary service, which takes responsibility for the disease.
The protocol for HPAI control is that all affected farms are placed under strict quarantine and all surviving birds are destroyed and disposed of as quickly as possible in order to limit the further spread of the disease.
But there are weaknesses in the system.
The biggest is that the state veterinary services dont have sufficient resources to manage the outbreaks effectively.
Secondly, because the state doesnt compensate farmers for their losses, they have difficulty getting farmers to comply with orders to cull. This has meant that outbreaks have spread out of control. Infected birds have been moved off infected farms for sale taking the disease with them.
Farmers in the EU and US are compensated when culling happens. This used to be the case in South Africa but no longer happens.
As a result, South Africa has struggled to contain HPAI outbreaks. In 2017 and 2020/21 the outbreaks gradually slowed and eventually stopped.
HPAI outbreaks tend to be seasonal. In Europe, they occur principally in winter months. In South Africa, there is a similar but less clear trend to more cases in the winter and fewer in summer. This may be related to reduced viral survival in hotter summer weather.
New and innovative thinking is needed to deal with the reality on the ground in South Africa.
One possible solution is the introduction of appropriate vaccines. This would reduce the losses associated with outbreaks and would slow the spread of the disease between farms. Like all vaccines, they cant prevent birds from becoming infected but they can manage the level of infection and spread. But they cant eradicate the disease.
But there are limited options in terms of available vaccines. And South Africa would need to ensure that the vaccines registered for use in the country were effective against the local strain. If vaccines are poorly matched to outbreak strains, they wont be effective.
All of this will take time, even with the best effort of government and industry.
The South African Poultry Association has made it clear that poultry products are safe for consumption. It has been collaborating with the University of Pretoria to make sure poultry products are indeed safe. Together with leading scientists they have sequenced the current field strain of H7 avian influenza virus. In a recent paper scientists reported that none of the amino acid markers were present that afford the virus the ability to bind to mammalian cells.
This shows that infection of humans with the current virus is highly unlikely.
