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Category Archives: Covid-19
Is it time to rethink COVID-19 boosters? New study dives into variant-specific vaccines – News-Medical.Net
Posted: October 16, 2023 at 6:45 am
A recent study published in the journal Science discussed variant-adapted boosters for coronavirus disease 2019 (COVID-19).
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have decreased the burden of the COVID-19 pandemic. Nevertheless, the waning of neutralizing antibodies (nAbs) and the emergence of variants of concern (VOCs) have reduced the efficacy of vaccines, prompting the need for boosters. Some SARS-CoV-2 variants exhibit greater antigenic distances from the ancestral strain, driving the development of variant-specific vaccines.
Further, the interplay of waning protection and SARS-CoV-2 variants, the selection of variants in updated vaccines, their effectiveness, and when to change variants in vaccine updates remain unknown. Immunization with the primary vaccine series induced high antibodies against the viral spike but declined substantially after a few months. This decay of antibodies was accompanied by the emergence of SARS-CoV-2 Delta.
Study: Variant-adapted COVID-19 booster vaccines. Image Credit:Crystal Eye Studio/ Shutterstock
Plasmablasts, the terminally differentiated B-cell subset, are responsible for the initial antibody response. These antibodies have a half-life of weeks and decline slowly after vaccination. Nonetheless, spike antibodies in serum plateau six to nine months post-vaccination, suggesting that bone marrow plasma cells were induced, which can persist throughout the host's lifetime.
Serum nAb titers strongly correlate with protection from symptomatic COVID-19. Waning nAbs increase the probability of breakthrough infections, particularly with new mutants. Serum antibodies increased with the rollout of booster vaccines and plateaued at a higher baseline than pre-boost levels.
Thus, a third dose may be critical for durable protection and could be deemed a part of the primary series. Exploring the basis of waning protection due to immune evasion by emergent variants is vital. The Delta VOC triggered breakthrough infections but did not have a direct strong immune-evasive phenotype relative to the contemporary Beta VOC.
The Delta variant showed efficient replication in the upper airways and had shorter incubation periods. This meant increased viral shedding, implying that exposed subjects inhaled higher viral loads, which may overwhelm pre-existing immunity. However, it was clear that the Omicron variant would exhibit extensive immune escape as many epitopes targeted by nAbs had changed.
Furthermore, Omicron and its sub-variants have shorter incubation periods than Delta. Due to the decay of vaccine-induced serum nAbs against Omicron, updated vaccines with spikes from the ancestral strain and Omicron BA.5 were approved in autumn 2022. Clinical trials revealed that updated vaccines, i.e., monovalent BA.1 vaccine and bivalent ancestral-BA.1 vaccine, had better nAb profiles against Omicron BA.1 than ancestral vaccines.
The monovalent BA.1 vaccine performed better than the bivalent ancestral-BA.1 counterpart. The main concern after bivalent ancestral-BA.5 vaccines were introduced, which were not evaluated in clinical trials pre-licensure, was whether they would induce nAbs against BA.5 and other newer sub-variants.
Some studies reported marginal titer increases with these updated vaccines, while others noted substantial differences. The timing of sampling may have complicated these comparisons. Samples were obtained from monovalent booster recipients in early 2022 and in autumn 2022 from bivalent booster vaccinees.
Moreover, breakthrough infections may have occurred between these two points in bivalent recipients, which may introduce bias in comparisons. However, the vaccine rollout allowed direct comparison of bivalent boosters in Europe. Studies demonstrated that bivalent BA.5 vaccine response was skewed toward BA.5.
In contrast, the response of bivalent BA.1 was not skewed toward BA.1. This highlighted potential intrinsic differences in immunogenicity between spikes, which would be critical in selecting variants for future vaccines. Moreover, bivalent vaccinees lacked BA.5-specific responses, suggesting that BA.5 vaccination mainly recalls responses against shared epitopes.
Further, only six out of 378 memory B-cell-derived monoclonal antibodies from the recipients of monovalent BA.1 booster recognized the BA.1 spike, while the remainder identified spikes from both the ancestral strain and BA.1. Cross-reactive B cells may produce nAbs that bind with high or low affinity to the new variant.
Low-affinity nAbs may undergo further affinity maturation for enhanced binding. Further, subsequent exposure to Omicron-related variants may improve the low frequency of de novo responses in the memory compartment. The evolution of SARS-CoV-2 has been ongoing. The BQ.1.1 variant has been outcompeted by the XBB lineage, demonstrating a potent immune escape phenotype.
Several international health bodies recommend updating vaccines for autumn 2023, with annual boosters adapted to the newest variants. Including the ancestral strain in updated vaccines is not practical. Nevertheless, whether annual variant-specific vaccine updates are the best solution remains unclear.
Likewise, whether mRNA technology or other platforms are best suited for boosters is unknown. However, the influenza model may not be optimum in the long term for COVID-19. As such, broadly protective vaccines offering durable immunity irrespective of antigenic changes are needed for SARS-CoV-2.
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In a recent review published in the journal Cellular & Molecular Immunology, researchers discussed the important virological, immunological, and clinical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in human immunodeficiency virus (HIV) patients.
This included the severity and outcomes of coronavirus disease 2019 (COVID-19) and the response to vaccines.
People with HIV have varying levels of immune suppression, viral control, and immune reconstitution, depending on the stage of HIV infection and whether they are on antiretroviral therapy. HIV infections affect the immune system, and often, people with HIV are vulnerable to respiratory infections such as pneumococcal pneumonia and influenza.
With the onset of the COVID-19 pandemic, the United States (U.S.) Centers for Disease Control and Prevention (CDC) indicated that people with HIV infections were at a greater risk of COVID-19 complications than the general population.
The immune competence of people with HIV varies substantially based on whether the individual is on antiretroviral therapy or remains untreated. The HIV infections and the state of immunity in HIV patients have been remarkably well-managed with the use of antiretroviral therapy.
However, the response to antiretrovirals often varies between individuals, and studies report that despite sustained viral suppression, the CD4 cell counts are not normalized in close to 30% of the HIV patients undergoing treatment. This incomplete immune recovery could impact immune response to SARS-CoV-2 infections and COVID-19 vaccinations.
While early studies reported conflicting results about the incidence of SARS-CoV-2 infections among people with HIV as compared to people without HIV, recent evidence suggested that the HIV infection itself does not increase the susceptibility to SARS-CoV-2 infections.
Instead, the health status and social inequalities faced by people with HIV were suggested to be the factors that increase the susceptibility of people with HIV to SARS-CoV-2 infections.
Examination of clinical outcomes and disease severity in people with HIV and SARS-CoV-2 coinfections indicated that the crude mortality rates associated with COVID-19 were higher among people with HIV as compared to those without HIV.
However, the status of the HIV infection also seemed to play a significant role in the COVID-19 outcomes. Individuals with uncontrolled HIV infections, indicated by low CD4 counts and detectable levels of HIV viral loads, were at an increased risk of severe COVID-19 outcomes and mortality.
Other studies reported that although antiretrovirals did reduce the risk of severe COVID-19 outcomes and mortality risk in people with HIV, they continued to be at greater risk of severe SARS-CoV-2 infections than individuals without HIV.
Furthermore, it has been suggested that people with HIV on antiretroviral therapy also face other health problems, such as diabetes, hypertension, and cardiovascular disease, which increase the risk of severe COVID-19 outcomes.
The findings on the impact of HIV infections on innate immunity continue to remain inconclusive.
Studies have reported that severe lymphopenia that occurs when HIV infections are left untreated, or the inadequate elevation of the CD4 cell counts in patients undergoing antiretroviral therapy can impact the ability of HIV patients immune systems to mount a strong T-cell response against SARS-CoV-2 infections.
However, the present review found that overall, people with well-controlled HIV infections had a comparable immune response to SARS-CoV-2 infections as people without HIV.
Studies also suggested that the severe immune dysfunction that occurs in people with HIV caused prolonged SARS-CoV-2 infections and significantly longer viral shedding consisting of high SARS-CoV-2 levels.
Furthermore, the protracted SARS-CoV-2 infection resulted in the accumulation of multiple mutations that could confer the virus with resistance to neutralizing antibodies.
However, research also indicated that the initiation or resumption of antiretroviral therapy played a significant role in accelerating SARS-CoV-2 clearance, highlighting the fact that complete immune restoration was not imperative to SARS-CoV-2 clearance.
Although people with HIV have been largely underrepresented in clinical trials that test the efficacy of COVID-19 vaccines, a few trials have included people with HIV on stable antiretroviral therapy.
The findings suggested that although the COVID-19 vaccines were effective in protecting HIV patients against fatal SARS-CoV-2 infections, the efficacy of various COVID-19 vaccines is lower in people with HIV as compared to those without HIV.
Furthermore, the incidence of breakthrough SARS-CoV-2 infections was higher among people with HIV than among those without HIV, and the CD4 cell counts were negatively associated with the risk of breakthrough SARS-CoV-2 infections.
One study reported that a third dose of the COVID-19 vaccine did reduce the risk of breakthrough SARS-CoV-2 infections among people with HIV.
Overall, the review indicated that people with HIV, especially those with advanced or untreated HIV and low CD4 cell counts, were at a greater risk of severe COVID-19 outcomes. Furthermore, the cellular and humoral immune responses against SARS-CoV-2 infections were suboptimal in people with HIV who had incompletely recovered immunity. SARS-CoV-2 infections were also more prolonged in people with HIV, but antiretroviral therapy was seen to help in clearing infections.
Additionally, the incidence of breakthrough infections was higher among people with HIV, although a third dose of the vaccine was effective in reducing the risk of breakthrough infections.
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The coronavirus disease 2019 (COVID-19) pandemic overwhelmed the healthcare systems in many countries with large numbers of acutely ill patients. However, as months passed, chronic sequelae came to be recognized.
A new paper in Scientific Reports examines lung complications in COVID-19 survivors in order to provide a tentative guideline for future monitoring of COVID-19 patients.
By June 2023, over 700 million cases of COVID-19 were documented worldwide, and it was calculated that about one in a hundred people died of the disease. Between 30 to 50% of hospitalized COVID-19 patients had severe or critical disease, as shown by their admission to intensive care units (ICU) or death.
Among COVID-19 survivors, cough and breathlessness have been reported, along with other respiratory symptoms, even after three months from infection. Some earlier research suggested that these might result from structural and functional lung damage. This included lung fibrosis and restricted gas diffusion, reported in almost one in three survivors at one year from infection.
Similarly, 30 to 70% of survivors also report reduced mental health and a lower quality of life. In view of this, survivorship clinics were set up to manage those with lung-related symptoms after discharge from ICU care. However, there was little guidance on how many other non-ICU patients might need such follow-up and for how long.
The current study aimed to provide prospective evidence to guide such decisions by helping to understand what to expect and how best to manage such clinics.
The scientists conducted a single-center cohort study including 46 COVID-19 survivors (almost all Delta variant) from May 1, 2020, to April 31, 2022. Patients were prospectively enrolled. There were 17 participants with a history of severe to critical COVID-19.
None of the participants were pregnant, had uncontrolled hypertension or a recent heart attack, or had cognitive impairment. Only those who could understand English well enough to take the tests were recruited. The mean age was 52 years, and 80% were males.
About 75% had never smoked nor had pre-existing chronic lung disease. Of the rest, that is, six patients, four had asthma, one had obstructive sleep apnea, and one had chronic obstructive pulmonary disease (COPD).
Survivors of severe or critical COVID-19 took much longer for complete resolution of their chest X-ray findings, at an average of ~130 days, compared to a week for those with mild or moderate disease.
All participants were monitored with pulmonary function tests (PFTs) at 6, 9, and 12 months, along with a health survey using the Short Form-36 (SF-36) tool. Any participant whose PFT showed abnormalities could undergo a computed tomography (CT) scan of the chest.
Among the PFT abnormalities, diffusion capacity of the lung for carbon monoxide (DLCO) was the most common, observed in 15 of 23 patients. Restrictive lung defects hindering lung expansion were present in 13 of 23 patients, with 10 patients showing overlapping DLCO and restrictive ventilatory defects.
Restrictive ventilatory defects could be due to obesity more than fibrotic lung changes because of COVID-19, as earlier studies show. Obstructive PFT results were due to pre-existing obstructive conditions.
The differences in outcome became most apparent at the six-month follow-up. The findings revealed a higher risk of DLCO defects among survivors of severe or critical COVID-19 compared to those who had mild or moderate illness. These may reflect ventilatory loss, damage to the alveolar membrane, or the microvascular bed caused by the cytokine storm that characterizes this condition.
People with DLCO defects had a higher proportion of severe disease with acute respiratory distress syndrome (ARDS) requiring ventilation. They also had lower SF-36 scores. In particular, the physical performance in the first group showed a significantly lower summary score, at 45, vs 52 in those with mild to moderate illness.
Risk factors for lung deterioration included older age, higher levels of inflammatory markers, and the presence of widespread infiltrates in the lungs seen on chest radiographs.
In most cases, the earliest PFT showed the abnormality. Encouragingly, patients with normal PFTs had a low risk of future lung complications. New abnormalities were rarely reported on their chest X-rays, and they were unlikely to need repeat PFTs.
This was also the case with the mild to moderate COVID-19 survivors, who showed little change in either DLCO or SF-36 scores over the period of monitoring. However, in the group with DLCO abnormalities, 8 of the 23 patients had another PFT at 18 months, with normal scores in half the cases.
Notably, 9 of 23 patients with PFT abnormalities had either asthma or COPD or suffered from morbid obesity. These conditions must be ruled out before attributing such changes to COVID-19-related lung damage.
Of the 13 patients who had a chest CT, nine had DLCO defects. The observed subpleural bands, ground glass opacities, and reticulate markings might explain most. Another cause was morbid obesity in five patients.
The researchers also found that patients with severe or critical COVID-19 tended to have the lowest quality of life, corroborating the findings of earlier studies.
The study indicates the need to follow up with patients who have survived severe or critical COVID-19, especially if they presented with severe and widespread inflammation and had X-ray or CT changes.
However, PFT should be conducted no earlier than six months or so from the infection to give time for acute injury to resolve, leaving room for the detection of chronic sequelae.
The most common findings on PFT in this group were, as expected, DLCO defects, as expected from earlier studies. DLCO defects may resolve slowly, even when other PFT measures show considerable improvement. Significant lung fibrosis was rare.
In conclusion, any severe or critical COVID-19 survivor with an abnormal PFT at six months from infection should be monitored using 6-monthly PFTs until the results stabilize, with no new lesions and resolution of earlier findings. If the PFTs continue to show abnormalities, the possibility of other etiologies should be duly excluded.
CT scans may be reserved for those with severe disease if there is sufficient reason to suspect pulmonary fibrosis or pulmonary embolism.
Following severe or critical COVID-19, survivors must be recognized to be at risk for lung damage, mental ill-health, and poor quality of life, all of which may be improved by proper pulmonary rehabilitation.
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DES MOINES More than $11 billion in federal funding was sent to Iowa via multiple aid packages designed to help Americans and local governments weather the effects of the COVID-19 pandemic.
More than $2.4 billion remains unspent by Iowa, according to a recent state report. But how was the rest of it spent? And whats planned for the remaining funds? Those questions were recently posed to The Gazette by a curious Iowan.
Curious Iowa is a series from The Gazette that seeks to answer Iowans questions about the state, its culture and the people who live here. To answer that question, we took a look at a recent report from the nonpartisan Iowa Legislative Services Agency. It analyzed how much the state received in federal financial assistance during the pandemic, where the state has allocated funds, and how much it still has to spend.
LSA issued the report in early August, and the financial analysis within the report is accurate as of July 28. That means the figures in the report are likely slightly different as of mid-October. The report tracks funding from 87 different federal programs.
State agencies in Iowa have reported receiving federal assistance totaling $11.047 billion, according to the LSA report.
That federal assistance came from six pieces of federal funding legislation passed in 2020 and 2021, including the CARES Act and Paycheck Protection Program passed in 2020 under former President Donald Trump, and the American Rescue Plan Act passed in 2021 under President Joe Biden.
Broadly speaking, $7.9 billion was allocated directly to state agencies, nearly $3 billion was allocated to the states Coronavirus Fiscal Recovery Fund, and $152 million was dedicated to a capital fund for broadband internet expansion.
Broken down by program, Iowas unemployment insurance program received the largest chunk of federal financial assistance: nearly $3 billion, according to the LSA report.
During the peak of the pandemic, unemployment claims spiked in Iowa and across the country as businesses were forced to close either by public health mandate or because of a lack of business. A large portion of the federal financial assistance was designed to help employers and workers survive that disruption.
More than $1.1 billion went to Iowas Medical Assistance Program, which supports the states Medicaid program.
Roughly $650 million in federal assistance designed to help state and local governments was sent to Iowa.
And a trio of education programs each received roughly $400 million in federal funds.
Given those programs received the most pandemic assistance funding, it comes as no surprise that the three state agencies that received the most funding were Workforce Development with $3 billion, Health and Human Services with $1.6 billion, and Education with $1.1 billion.
Of that $2.4 billion that the state has not yet allocated, the biggest chunks are in the state public health department and the Iowa Finance Authority, which operates housing assistance programs for homeowners and renters and has spent less than a third of its allotted federal funding.
Most of the funds have deadlines by which the money must be spent, and those deadlines are staggered over the coming years, depending on the funding source. In some cases, the state has until 2027 to spend pandemic relief funds.
There is nearly $1.1 billion remaining in the Iowa Coronavirus Fiscal Recovery Fund, according to the LSA report. Those funds carry broad spending authority: they can be used to address emergency and economic effects of the pandemic, replenish lost government revenues, or invest in water, sewer and broadband infrastructure.
Funds from the fiscal recovery fund must be spent by the end of 2026, or they will revert back to the federal government.
The public health department, which is now under the Health and Human Services department with the recent reorganization of state government, is yet to spend more than $337 million, according to the LSA report. Thats 60 percent of the federal funds awarded to the department.
The majority of the public health departments unspent funds are for the Epidemiology and Laboratory Capacity for Infectious Diseases Program, according to the LSA report. Expenses for that program are ongoing and funding will remain available in future years, the report says.
The Iowa Finance Authority is yet to spend $208 million; thats 68 percent of its allotted financial assistance. The bulk of those unspent funds are for the Emergency Rental Assistance program, and those funds also will remain available in future years, according to the LSA report.
The workforce development agency had $415.5 million still unspent, but that is just 12 percent of the funding it received.
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Accelerating into Immunization Agenda 2030 with momentum from … – Infectious Diseases of Poverty – BioMed Central
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IA2030 has seven strategic priorities: integration of immunization with primary care, country commitment to immunization fulfilling people-centered demand for vaccines, ensuring high and equitable coverage, vaccinating throughout the life course and integrated with essential services, management of outbreaks and emergencies, sustainable supplies of vaccines, and research and innovation. The COVID-19 vaccination campaign was well aligned with all seven of IA2030s strategic priorities. The priorities that can impart the most momentum to the program and support the global IA2030 vision are ones that increase the number of vaccines in the routine program (Strategic Priority 2, Commitment and Demand) and broaden the age groups recommended for routine vaccination (Strategic Priority 4, Life Course & Integration). Another strategic priority with long-term benefit for China and the world is Strategic Priority 7, Research & Innovation. The COVID-19 campaign relied heavily on research and innovation, as exemplified by rapid and successful development of new and innovative COVID-19 vaccines, new vaccine delivery techniques, and new vaccination strategies in a fully digitalized immunization program that harnessed big data and artificial intelligence for monitoring and analyzing vaccine safety, effectiveness, and coverage.
IA2030 talks about breadth of protection, meaning implementing and sustaining high coverage with all WHO-recommended vaccines. The COVID-19 vaccination campaign conclusively proved that Chinas immunization program can rapidly develop and introduce a new vaccine and achieve high vaccine coverage. The COVID-19 vaccination campaign was an astonishing eight times the size of the annual routine immunization program. This momentum and experience can be used to facilitate introduction of the vaccines that are recommended by WHO for all national programs but are not currently in Chinas program. Recent [8, 9] and earlier  analyses of Chinas national immunization program have recognized the disparity between the vaccines recommended by WHO and the vaccines included in Chinas program and have recommended strategies to introduce new vaccines. A legislatively supported mechanism, the National Immunization Advisory Committee (NIAC), now exists that can recommend to government non-program vaccines that should be moved into the program based on evidence of preventable burden of disease and vaccine effectiveness, safety, cost effectiveness, and supply security . Just as NIAC supported COVID-19 vaccination strategy, it can support evidence-based introduction of other vaccines. Moving human papillomavirus (HPV), pneumococcal conjugate (PCV), influenza, Haemophilus influenzae type b (Hib), varicella, and rotavirus vaccines into the national program would bring equitable and high coverage of these vaccines to well over 100 million young children and adolescents, preventing suffering from these infectious diseases while saving society money. Using domestically developed and produced vaccines will strengthen Chinas vaccine industry and foster innovative development of new vaccines for use in China and for WHO prequalification and global use. For example, combining Chinas Sabin-strain inactivated poliovirus vaccines into diphtheria, tetanus, acellular pertussis-, Hib-, and hepatitis B-containing combination vaccines could make space in the domestic routine immunization schedule for other vaccines while maintaining high polio vaccine coverage well into the future, for as long as is needed in China and elsewhere .
A thrust of IA2030 is life course vaccination. With its target population of everyone over the age of 3years, Chinas COVID-19 vaccination campaign exemplified life-course vaccination. COVID-19 vaccination was vigorously promoted to the elderly , people with comorbidities, health care workers and other working age adults, and school-age children. These are the same target populations for seasonal influenza vaccine. China CDC has recommended influenza vaccination of these populations for years , however uptake has been low except in several leading cities that have embraced influenza vaccination of these key target populations. The COVID-19 vaccination campaign proved that these populations can be reached to achieve high and equitable coverage. The COVID-19 vaccination experience can be used to make progress on influenza vaccination of these important target populations.
The maximum age for eligibility of National Immunization Program vaccines was recently raised from 14 to 18years of age. This age range expansion can provide adolescents the opportunity to catch up on any program vaccinations they missed and to receive HPV vaccine once it is included in the program. But why stop at 18years of age? The IA2030 vision is for the entire life course, as was the COVID-19 campaign. Program eligibility across all ages would enable immunization clinics, community health centers, and primary care providers to bring "everyone, everywhere, at all ages the full benefits of vaccines. For adults, this could include not only influenza vaccine, but also pneumococcal and zoster vaccines in a comprehensive program integrated with primary care. Innovative financing of adult vaccines, as was done for COVID-19 vaccines with the Medical Insurance Fund, could support universal immunization program eligibility that would lead to equitable and high coverage for allin good alignment with IA2030.
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