Photo Courtesy/WV Legislative Photography Del. Bob Fehrenbacher reads reports proving the success of vaccination efforts in his floor speech opposing a bill loosening school vaccine requirements and allowing religious exemptions.
CHARLESTON The West Virginia House of Delegates passed an update to public and private school vaccination requirements to allow for religious exemptions after a passionate debate about the merits of immunizations.
House Bill 5105, eliminating the vaccine requirements for public virtual schools, passed the House in a 57-41 vote after nearly two hours of discussion. The bill now heads to the state Senate.
HB 5105 would eliminate vaccine requirements for school students for those participating in one of the two statewide virtual public schools or future county-level virtual public charter schools except when those students are participating in activities supervised by the West Virginia Secondary School Activities Commission.
The House Judiciary Committee amended HB 5105 last week to expand vaccine exemptions to students attending private or parochial schools in the state. And after lengthy debate Friday, the House adopted an amendment from Del. Todd Kirby, R-Raleigh, to create a religious exemption for all vaccines in public and private schools as long as a parent or guardian presents a letter stating the reasons for the religious exemption request.
The stated reason to require most vaccinations of children for public safety which can only be achieved through herd immunity is disingenuous, illogical, and ultimately contrary to what we claim to be most important, said Del. Laura Kimble, R-Harrison, the lead sponsor of the bill. How we arrived to the point we can defend freedom in so many other contexts but unable to defend it in the face of mandatory vaccinations is a question we should all be asking ourselves.
State Code requires children attending school in West Virginia to show proof of immunization for diphtheria, pertussis, tetanus, polio, measles, mumps, rubella, varicella, and hepatitis B unless proof of a medical exemption can be shown. West Virginia does not provide a religious exemption.
These diseases, other than polio, are still prevalent in this world, said Del. Bob Fehrenbacher, R-Wood. Without knowing what percentage of the children are not going to be vaccinated, I think the prudent thing that is going to influence my vote and the vote is going to be no is to safeguard other children in this state.
According to the National Conference of State Legislatures, 15 states offer what they call philosophical exemptions to immunization requirements. Ohio and Pennsylvania allow for personal belief exemptions, while Kentucky, Virginia, and Maryland allow for religious exemptions. West Virginias vaccine requirements are considered to be some of the most robust in the nation.
Del. J.B. Akers, R-Kanawha, said he supported the amendment Friday adding a religious exemption for vaccine requirements. But he said he would vote against the bill due to an unintended loophole that would require vaccines for students participating in WVSSAC activities but not for students participating in West Virginia Christian Athletic Association activities. Student-athletes in public and Christians schools in the state often compete.
I think we are potentially creating an equal protection problem among schools, because we will have a situation where if a parent can afford to send their child to a private or parochial school, they will not have to be immunized, Akers said. Ive seen no states that allow exemptions based upon whether you can afford to send your child to private school, but Ive seen where private schools can be forced to immunize if they dont want to.
House Minority Leader Sean Hornbuckle, D-Cabell, also raised issues with requiring students participating in WVSSAC activities to be immunized but not requiring students participating in secondary school sports from private or Christian schools to be immunized.
They will play each other, Hornbuckle said. If theyre not vaccinated, theyre still going to spread it to the kids who members of the WVSSAC. This is an incomplete piece of legislation.
There have been several attempts by some Republican lawmakers since taking the majority in the Legislature in 2015 to introduce bills to weaken or eliminate vaccine requirements for school-age children, though most of these bills never make it through the 60-day legislative session. But since the COVID-19 pandemic hit the nation in March 2020 and COVID vaccine came available at the end of 2020, some GOP lawmakers across the country have upped the rhetoric against vaccines.
Freedom is scary to those who are used to being subservient, said Del. Eric Brooks, R-Raleigh. This goes to the root of who we are and what we say we believe.
You have the opportunity to actually make history for the State of West Virginia, said Del. Todd Kirby, R-Raleigh. I would submit to this body to ignore the scare tactics and the fearmongering because you will have the same number of unvaccinated kids under this bill when it goes into effect than the year before this bill goes into effect.
Some of the rhetoric appears to be having an effect on national vaccination rates. According to the Kaiser Family Foundation, there was a decline in vaccinations for measles, mumps, rubella (MMR) among kindergarteners, from a 95% vaccination rate in 2019-2020 to a 93% vaccination rate during the 2021-2022 school year. The U.S. Centers for Disease Control sent out notices earlier this year warning about measles outbreaks, including in Florida.
Were number one in childhood immunizations, Hornbuckle said. That should be very important to us. We shouldnt chip away at that. I would suggest to you if youd like to indulge yourself to a race to the bottom not be number one, Id suggest you buy a red cap and put on it Make Measles Great Again.'
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Global measles cases are on the rise, in spite of the widespread availability of a life-saving vaccine. It's an ominous reflection of waning vaccine confidence, experts say.
In the United States, multiple children from Broward County were sick with the disease this month, school officials in Florida confirmed. However, the state's Surgeon General Joseph Ladapo continued to make statements that could appear to diminish, if not discredit, the use of vaccines. In a Feb. 20 letter to school officials, Ladapo wrote that Florida's Department of Health "is deferring to parents or guardians to make decisions about school attendance," citing the "high immunity rate in the community" and "the burden on families and the educational costs of healthy children missing school."
Critics say high-profile statements like Ladapo's make it easier for people to feel validated in not getting their kids vaccinated against measles. Epidemiologist Katelyn Jetelina called the surgeon general's message "unprecedented" on X, the platform formerly known as Twitter.
"Unvaccinated kids need to stay home for 21 days during an outbreak" to avoid the "very real chance of infection, hospitalization, death or serious damage to the immune system," Jetelina wrote.
Vaccine exemption rates above 5 percent limit the level of achievable vaccination coverage, which increases the risk for future outbreaks of preventable diseases. Chart by Megan McGrew/PBS NewsHour
Weeks earlier, on Jan. 25, the Centers for Disease Control and Prevention alerted clinicians to be on the lookout for measles after 23 cases were counted across the nation, including seven tied to international travel and two separate outbreaks made up of more than five patients. Most cases were identified in children and adolescents who had not been vaccinated against measles, the alert said.
Experts "are seeing measles everywhere," said Dr. Natasha Crowcroft, the World Health Organization's senior technical adviser on measles and rubella. "We've got a perfect storm coming this year."
"We're not just seeing cases, we're seeing transmission, which means vaccine levels aren't what we'd like them to be," said Saskia Popescu, an assistant professor of epidemiology and public health at the University of Maryland School of Medicine.
Measles is a highly contagious viral infection, spread through contact with mucus that has been coughed or sneezed, or through breathing the same air as an infected person hours after they have left a room. In 2000, U.S. health officials had declared the end of the disease's endemic spread, eliminated by decades of vaccination campaigns. In the years since, the measles vaccine has saved an estimated 57 million lives worldwide, according to the CDC.
READ MORE: As COVID cases rise, doctors worry about the consequences of misinformation
But now, data show a dangerous decline in vaccination among schoolchildren, both in the U.S. and in Europe.
"That is a huge wakeup call," said Dr. Syra Madad, an epidemiologist, senior director at New York City Health + Hospitals and fellow at the Harvard Kennedy School's Belfer Center for Science and International Affairs. She said when it comes to vaccination rates, each percentage point "can translate into thousands of children."
"We're not just seeing cases, we're seeing transmission, which means vaccine levels aren't what we'd like them to be."
So far, Europe has seen a far more dramatic rise of the disease cases grew nearly 45-fold in 2023 compared to a year earlier, according to WHO. In late January, British health officials urged parents to get their children vaccinated against measles after hundreds of cases were confirmed.
Public health experts say 95 percent or more of children should be vaccinated against the disease to foster sufficient herd immunity within a community, protecting people with weakened immune systems, such as cancer patients and babies. According to data from the United Kingdom's National Health Service, 85 percent of children there have received both doses by age 5, giving the disease an opening.
Experts point in part to the negative effects of COVID-era misinformation about the safety and efficacy of vaccines. But when it comes to measles, there's actually a longer history that helped set the stage for the broader decline in vaccination confidence.
Researchers developed the measles vaccine in 1963, and U.S. children have received this scheduled vaccine before they start school ever since. According to a report from the CDC, 93 percent of kindergartners for the 2022-2023 school year got their two doses to prevent measles, mumps and rubella a combination that has been safe, effective and available since 1971.
However, misinformation has chipped away at hard-won gains. In 1998, Andrew Wakefield published a study in the journal Lancet that claimed a thoroughly debunked connection between the measles-mumps-rubella vaccine and autism. The study ignited a media firestorm, despite being founded on misleading research and unethical practices, and fueled celebrity-fronted, anti-vaccine campaigns.
READ MORE: Why experts worry more pet owners may skip rabies shots over vaccine hesitancy
His fraudulent claims led Wakefield to lose his medical license in the U.K., but the damage endures. Two decades later, measles gained a foothold in pockets of the U.S., including parts of southern California and New York City, leading to one of the largest measles outbreaks in recent history with nearly 1,300 cases confirmed in 2019. According to the CDC, a majority of cases were among those who were unvaccinated against the virus.
Chart by Megan McGrew/PBS NewsHour
Now, experts say, the climate for misinformation is even worse.
During and even before the COVID pandemic, the public health community was overwhelmed by crisis, budget cuts and staffing shortages, and it initially dismissed the threat of anti-vaccine attitudes, said Heidi Larson, who directs the Vaccine Confidence Project. Those factors meant they fell behind in the fight against the technology being used to spread misinformation and disinformation.
False claims were fanned by people who genuinely believed vaccines were unsafe, but also by people with financial or political motives for using fear to control people's behavior, she noted. With the COVID vaccines developed and deployed faster than ever before, the people who protested their use found a "a huge stage with any vaccine grievance anyone had," Larson said.
Misinformation about the new virus shaped people's perceptions of the need to get vaccinated against other diseases, like measles, Larson said, and may leave more long-lasting effects on public health.
In addition to stirring a new falsehood fever pitch, the COVID pandemic disrupted general health services. People avoided sitting in waiting rooms or exam rooms in health care facilities, delaying preventative care. Childhood vaccination rates fell around the world. According to the CDC, the pandemic erased years of progress toward greater global vaccine protection against measles, with an increase in cases and deaths, particularly among children.
Today, some states face a greater threat of outbreaks than others. For example, during the 2022-2023 school year in Idaho, 84 percent of kindergartners were vaccinated against measles, compared to Mississippi, where 98 percent of kindergartners had received both doses.
All U.S. states require certain vaccines for schoolchildren, but some have adopted or expanded exemptions to go beyond medical concerns to include religious and philosophical beliefs, according to the National Conference on State Legislatures.
Since 1979, Mississippi had vaccinated nearly all schoolchildren against measles. That state, one of the poorest in the nation with some of the worst health outcomes, earned praise for its efforts to slow the spread of preventable illness. In July, Mississippi began for the first time to offer religious exemptions for routine childhood vaccinations, which followed a ruling from U.S. District Judge Sul Ozerden that it had to offer exemptions like most other states.
Through these exemptions, Madad said more parents are opting their children out of vaccinations, influenced by misinformation. She expects use of these exemptions to expand because "because this is not just a public health issue, it's also a political issue."
Such exemptions have further hobbled outreach efforts by public health departments that have struggled for years due to other strains. Dr. Jesse Ehrenfeld, president of the American Medical Association that has opposed religious-based vaccine exemptions, echoed that these dispensations are informed by misinformation, which "continues to drive vaccine hesitancy."
To prevent more measles outbreaks, Ehrenfeld said the U.S. must improve vaccine coverage and strategies to combat these untruths. While lawmakers have considered regulations to reduce the spread of harmful messages, focusing on regulation alone is not the answer, Larson believes. The people and groups who generate them have "become incredibly sophisticated," she said, jumping to platforms with less regulation or going offline altogether, showing up at town halls, playgrounds and on billboards. The misinformation ecosystem only gets more complicated with the introduction of text generators and deepfakes powered by artificial intelligence.
"Because they don't see it and because of how well vaccines have worked, they have forgotten what humanity has gone through."
One solution seems deceptively simple and low-tech: For patients with questions about what to do about vaccination, Ehrenfeld urged them to ask their doctor.
Health officials and public leaders must pay "attention to trust building," Larson said. "People turn to this stuff when they feel they're not getting the answers to their questions."
To bring people back to official sources of public health information, Larson added, "there needs to be a much bigger investment from public health institutions to be there, where people are. If they don't," she warned, "the gap between official information and where people are going is going to get bigger and bigger."
That will also require health care providers, many of whom have reported record-high burnout, to listen to patients and "to come from a place of empathy," Popescu said. She also said health workers need training in how to respond effectively when a patient seems influenced by misinformation.
READ MORE: COVID made health care burnout worse. Here's what those workers need now
Madad has faced this challenge in her personal life. During the 2018-2019 measles outbreak that spread to hundreds of children, Madad said a friend of hers had not vaccinated their children against measles because they believed the disease "is not around."
After listening to their logic for avoiding vaccination, Madad told her friend that the vaccine is 97-percent effective and very safe. But in that instance, she realized those statistics were less helpful than telling the person how the vaccine would benefit them.
She then described what life was like before the measles vaccine existed. She described how an estimated 500,000 children were sick in the U.S. and how hundreds died each year. She showed them photos of measles patients.
"Because they don't see it and because of how well vaccines have worked, they have forgotten what humanity has gone through," Madad said. "Do you want to put your child through something like that?"
YF17D vaccination induces similar neutralizing antibody titers but expands a poor-neutralizing IgG response in TBEV-pre-vaccinated individuals
To investigate the effects of pre-existing cross-reactive immunity on the response to the live YF17D vaccine, we examined a longitudinal cohort of 250 YF17D healthy young vaccinees grouped based on their previous immunization with the inactivated TBEV vaccine (cohort-1). Given that TBEV vaccination is recommended in the region where this study was conducted, a representative fraction of participants self-reported ahistory of TBEV vaccination prior (>4 weeks) to study inclusion (n=162; 64.8%). TBEV pre-immunity was verified through positive results for TBEV neutralization by plaque reduction neutralization assay (PRNT) and positive detection of anti-TBEV-DIII IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Individuals with discrepancies between self-reported vaccination status and serological assays were excluded from the analysis. The final study cohort-1 comprised 139 participants pre-vaccinated against TBEV and 56 TBEV-unvaccinated individuals. Different sexes, ages, and BMI values are equally distributed in both subgroups (Fig.1; TableS1). The exact strain, number of doses, and timing of TBEV vaccinations had not been documented. Consequently, TBEV-experienced donors showed heterogeneity in their TBEV neutralizing titers prior to YF17D vaccination (Fig.2B).
A Diagram representing the longitudinal PBMC, serum, and plasma sample collection of 250 participants. Samples were collected at baseline (immediately before vaccination) and on days 7, 14 and 28 post vaccination. Prepared with Biorender (www.biorender.com) B Flow chart of cohort members grouping according to TBEV pre-vaccination status. 139 individuals self-reported having received at least one TBEV-vaccine dose and contained neutralizing antibodies and anti-TBEV IgG at baseline. 56 TBEV-unvaccinated individuals were classified based on a self-reported negative vaccination history validated by the absence of detectable anti-TBEV IgG and neutralizing capacity at baseline C Histogram depicting the age distribution of the 139 TBEV-vaccinated participants (in orange) and the 56 TBEV-unvaccinated donors (in blue). D Table summarizing cohort-1 characteristics for all 250 individuals and separated according to TBEV-pre-vaccination status.
A YF17D 80% neutralization titer at day 28 post-vaccination for TBEV-vaccinated (n=137) and unvaccinated (n=56) individuals. B TBEV 80% neutralization titer before and 28 days after YF17D vaccination for TBEV-vaccinated individuals (n=137) and TBEV-unvaccinated individuals (n=56). C Longitudinal YF17D virion-specific IgM response in TBEV pre-vaccinated (baseline, n=132; day 7, n=128; day 14, n=128; day 28, n=129) and TBEV unvaccinated donors (baseline, n=54; day 7, n=54; day 14, n=54; day 28, n=53). D YF17D virion-specific IgM titer on days 14 and 28 in IgG-depleted serum for TBEV pre-vaccinated (n=56) and TBEV unvaccinated donors (n=28). E Longitudinal YF17D anti-E protein-specific IgG titers for TBEV-vaccinated (baseline, n=136; day 7, n=131; day 14, n=132; day 28, n=133) and TBEV-unvaccinated donors (baseline, n=52; day 7, n=52; day 14, n=52; day 28, n=52). F, G Plasmablasts and total sE-specific longitudinal B-cell response quantified by ELISpot and depicted as spot-forming units (SFU) in 100,000 PBMC (n=10 TBEV-vaccinated and n=9 TBEV-unvaccinated donors). Spot pictures are shown for a representative example of a TBEV-pre-vaccinated and unvaccinated individual. Significance compares B cell counts between groups on days 14 (F) and 28 (G). H, I Spearman correlation between the YF17D polyclonal neutralizing titer of sera on day 28 with the IgG titer (TBEV-vaccinated n=133 and TBEV-unvaccinated donors n=52) and IgM titer (TBEV-vaccinated n=129, TBEV-unvaccinated donors n=53). J Neutralization curves of undepleted polyclonal serum and IgG or IgM-depleted serum (in grey) for TBEV-pre-vaccinated (n=45 and 26, respectively) and unvaccinated individuals (n=19 and n=22, respectively). Quantification of the 80% neutralization cutoff before and after IgG (K) and IgM (L) depletions shown in J. TBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue. Boxplots show a horizontal line indicating the median and lower and upper hinges corresponding to the first and third quartiles. The lower and upper whiskers extend to 1.5x IQR (interquartile range) from the respective hinge. The curve fitting in J was done with local regression with a 0.95 confidence interval. Statistical significance between TBEV-vaccinated and unvaccinated individuals is shown above every comparison and was estimated with a two-sided Mann-Whitney test. Statistical significance between undepleted and depleted samples (K and I) and between timepoints (D) was calculated with a two-sided Wilcoxon signed-rank test. P values above 0.05 are considered non-significant (ns).
The neutralizing antibody titer against YF17D, commonly used as a correlate of vaccine-induced protection, was equally strong at day 28 post-vaccination (pv) in both flavivirus-nave and experienced individuals. This result indicates that TBEV-pre-immunity does not impair the neutralizing antibody response to YF17D (Fig.2A). Conversely, YF17D immunization did not alter the neutralizing activity against TBEV, indicating that the YF17D vaccine did not generate cross-neutralizing antibodies to TBEV (Fig.2B).
The presence of YF17D virion-specific IgM in serum was measured longitudinally by ELISA. The IgM titer reached a plateau between day 14 and 28 pv and was comparable in both groups of vaccinees as confirmed in IgG-depleted serum samples (Fig.2C, D). Unlike the IgM response, participants with a prior TBEV exposure had YF17D cross-reactive IgG antibodies already at baseline and, upon vaccination, the IgG titer was further boosted resulting in a 100-fold higher titer compared to the TBEV-unvaccinated group. The same dynamic was observed for E protein (Fig.2E) and full-virion specific IgG (Fig.S1B, C). The IgG titer continued to increase from day 14 to day 28 pv, at which timepoint all the study participants had seroconverted. While TBEV-pre-vaccinated donors showed an anti-E IgG response already at day 14 pv, only a fraction of the TBEV-unvaccinated participants generated detectable anti-E IgG levels at that timepoint, suggesting an earlier response to YF17D in individuals with immune experience (Fig.2E).
To assess the generation of vaccine-specific B cells, we implemented a soluble (s)E-specific ELISpot assay. The number of plasmablasts was quantified directly ex vivo and the total number of sE-specific B cells was measured following the differentiation of B cells into antibody-secreting cells. sE-specific IgG secreting plasmablasts peaked at day 14 pv in TBEV-pre-vaccinated participants but were below detection for unvaccinated donors (Fig.2F). The total amount of sE-specific B cells was in line with the IgG levels measured in serum with a significantly higher B cell number in flavivirus-experienced individuals. Likewise, sE-specific B cells were detected earlier, on day 14, in TBEV-pre-immunized individuals (Fig.2G).
Collectively, these results indicate that TBEV pre-immunization does not hinder the response to YF17D. TBEV-pre-immunized individuals have cross-reactive IgG antibodies to YF17D and experience an earlier and stronger IgG response.
The observed differences in the IgG titer did not correspond with the similar neutralization capacity between both groups of vaccinees. When groups were analyzed separately, the IgG titer at day 28 correlated weakly with neutralization (R=0.29, p 0.04 and R=0.34, p<0.0001), whereas there was a stronger association with the IgM levels (R=0.55, p<0.0001 and R=0.64, p<0.0001 for TBEV-unvaccinated and experienced individuals, respectively) (Fig.2H, I). We depleted serum of the IgM or IgG fractions in a subgroup of the study cohort-1 to precisely define the contribution of IgG and IgM antibodies to neutralization. We confirmed that depletions were successful, without loss of the alternative antibody fraction (Fig.S1D). We observed that the IgM fraction was the main mediator of virus neutralization, accounting for approximately 75% of the neutralizing titer on day 28 (Fig.2J, L). Consistently, IgG depletion led only to a 25% loss of neutralization capacity on days 14 and 28 (Fig.2J, K, and S1D,E). IgM-depleted sera of TBEV-pre-immunized individuals showed a significantly higher neutralizing capacity, indicating that the increased IgG titer contributed partly to virus neutralization (Fig.2L). There was no significant difference in the IgM antibody titers and IgM-mediated neutralization between groups (Fig.2D, J, K).
Thus, on day 28 the IgM fraction is primarily responsible for the neutralization capacity and is equally strong regardless of the pre-vaccination status. The IgG fraction can mediate neutralization, but the boosted response in TBEV-experienced individuals is predominantly directed towards poorly-neutralizing epitopes.
As reported by Chan et al. 2016, cross-reactive non-neutralizing or sub-neutralizing IgG antibodies can mediate FcR engagement and increase vaccine immunogenicity via ADE of YF17D virus infection20. Given that TBEV-pre-vaccinated individuals had YF17D cross-reactive antibodies at baseline, we measured whether they could facilitate YF17D infection of FcR expressing cell lines (THP-1 and K562). We observed an enhanced infection of a Venus-fluorescent YF17D virus in both cell lines in the presence of serum from TBEV-pre-immunized donors. ADE was IgG-dependent, as it was absent in IgG-depleted serum but not in IgM-depleted serum, and it was inhibited in the presence of FcR-blocking antibodies (Fig.3A and S2A, B, C). YF17D infection enhancement was observed exclusively with sera from TBEV-experienced individuals (Fig.3B) which showed the highest enhancing titer, calculated as area under the curve (AUC) (Fig.3C).
A Flow cytometric determination of venus-YF17D virus infection of THP-1 cells in the absence or presence of cross-reactive serum from a TBEV-vaccinated individual. The conditions tested include polyclonal serum alone or in combination with FcR-blocking antibodies and IgM or IgG-depleted serum. B ADE of YF17D mediated by study participants serum (n=132 TBEV-vaccinated, n=53 TBEV-unvaccinated individuals). Virus infection was quantified in combination with serially diluted serum and was normalized against the enhancement of a 1:20 diluted enhancing-serum control carried for all measurements. Thick dashed line indicates the mean of the different just-virus controls and dotted lines define +/ 1SD. The curve was fitted with local regression with a 0.95 confidence interval. C Quantification of the enhancing titer as AUC of the normalized virus infection across serial dilutions shown in B. D Comparison of anti-YF17D-DIII specific IgG titer at day 28 post-vaccination for both TBEV groups (n=36 TBEV-unvaccinated, n=117 TBEV-vaccinated individuals). Longitudinal quantification of anti-YF17D-DIII (E, n=97 donors) and anti-TBEV-DIII (F, n=114 donors) specific IgG in TBEV-experienced individuals. G Paired comparison of the DIII-specific IgG fold-change between day 28 and day 0 for TBEV and YF17D (n=76 pairs). H Spearman correlation in TBEV-experienced individuals of baseline anti-E IgG and enhancing titers versus YF17D vaccine-induced neutralizing antibody titer at day 28, anti-sE and anti-DIII IgG titers and baseline anti-YF17D-E and anti-YF17D-DIII IgG titers. Color intensity reflects the Spearman correlation coefficient. I Comparison of the first (n=34) and fourth (n=33) quartile group of YF17D-sE specific IgG at baseline and the anti-YFDIII IgG on baseline and day 28, the anti-YF17D-sE IgG titer on day 28 and the anti-YF17D neutralizing antibody titer on day 28 (high vs. low quartile n=24/23, 32/28, 33/32, 34/33 respectively). J Comparison of the first (n=33) and fourth (n=33) quartile group of the Enhancing titers at baseline and the anti-YFDIII IgG on baseline and day 28, the anti-YF17D-sE IgG titer at baseline and day 28 and the anti-YF17D neutralizing antibody titer on day 28 (high vs low quartile n=25/22, 28/30, 32/33, 32/33, 33/33, respectively). TBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue. Boxplots show a horizontal line indicating the median and lower and upper hinges corresponding to the first and third quartiles. The lower and upper whiskers extend to 1.5x IQR from the respective hinge. Statistical significance between TBEV-vaccinated and unvaccinated individuals (D) and between high and low quartiles (I, J) is shown above every comparison and was estimated with a two-sided Mann-Whitney test. Statistical significance in EG was calculated with a two-sided Wilcoxon signed-rank test. P values above 0.05 are considered non-significant (ns).
In addition, we quantified the IgG fraction targeting DIII. DIII is often used for serological diagnosis35 and although cross-reactive epitopes have been described36,37, responses to DIII are generally virus-specific38. As observed for anti-sE IgG antibodies, TBEV-pre-vaccinated individuals had a stronger IgG response against YF17D-DIII (Fig.3D). We then compared the fold change in anti-YF17D-DIII and anti-TBEV-DIII IgG titers between baseline and day 28 pv. Interestingly, the strong expansion of anti-YF17D-DIII-reactive IgG (10-100-fold) contrasted with the moderate increase in TBEV-DIII reactive IgG (<10-fold) (Fig.3EG). Since the IgG fraction targeting TBEV-DIII was not expanded to the same extent, we conclude that YF17D is not only boosting cross-reactive TBEV-induced memory responses but also triggers antibodies towards previously unseen, non-cross-reactive epitopes in DIII, potentially via enhanced immunogenicity.
The correlation between the baseline levels of sE-specific IgG and the baseline enhancing titer with the post-immunization IgG response to sE and DIII, as well as the post-vaccination neutralizing titers, suggests that ADE of YF17D infection could mediate an increase in vaccine immunogenicity (Fig.3H, S2D, E, F). To gain insight into the size effects of ADE of YF17D infection on vaccine immunogenicity, we grouped the vaccinees into quartiles based on their enhancing and baseline IgG titers. This approach removed individuals with intermediate TBEV-vaccine-induced IgG levels from the analysis and therefore improved the precise identification of true differences between the high and low vaccine enhancers. Participants in the highest quartile of the enhancing titer had significantly higher neutralizing titer and IgG levels against sE and DIII (Fig.3I) than the participants in the lowest quartile. The same associations were observed with baseline IgG quartiles (Fig.3J). Thus, within the TBEV-pre-vaccinated group, ADE of YF17D infection was associated with increased vaccine immunogenicity.
Altogether, in addition to an anamnestic response, these results suggest that TBEV-pre-immunity may increase the magnitude and breadth of the humoral response to YF17D vaccine facilitated by ADE of YF17D infection.
The IgG response in both groups was investigated for cross-reactivity with other members of the Flaviviridae family. Using an indirect immunofluorescence test, the IgG and IgM binding to ZIKV, JEV, WNV, TBEV, YFV, and all serotypes of DENV was measured in a cohort subset (Fig.4, S3). At baseline, TBEV pre-vaccination induced an IgG response cross-reactive with all flaviviruses at similar magnitude. This pan-flavivirus cross-reactive IgG signature was boosted upon vaccination with the YF17D vaccine. In contrast, the YF17D vaccine induced an IgG response that targeted uniquely YFV in unvaccinated individuals (Fig.4A). Consistent with previous studies, the IgM signature was YFV-specific and could not be detected at baseline (Fig.4B).
IgG (A) and IgM (B) subtype cross-reactivity evaluation before and after YF17D vaccination using an indirect immunofluorescent test for a panel of nine human-pathogenic flaviviruses: DENV 14, ZIKV, WNV, JEV, YFV and TBEV. A subgroup of n=39 individuals was tested (Fig.S3), out of which n=15 were TBEV-unvaccinated and n=24 TBEV-experienced. Bars indicate titer mean and dots reflect the antibody amounts as serum dilution end-point titers. TBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue.
These results highlight the capacity of the vaccine strain of YFV to prevent a cross-reactive response when administered to flavivirus-nave individuals.
Depending on previous flavivirus exposure, YF17D induces a differential cross-reactivity pattern while eliciting a comparable neutralizing response. We hypothesized that the neutralizing capacity is predominantly driven by antibodies targeting quaternary dimeric epitopes, equivalent to EDE (EDE-like), and the FL-proximal region, whereas cross-reactive antibodies target the immunodominant FLE. To better understand this change in the immunodominance, we designed a set of recombinant sE protein mutants for the study of the IgG response to different epitopes (Fig.5A). Besides the monomeric sE protein containing all three ectodomains and variants consisting of either only DI-II or only DIII, we designed constructs displaying quaternary dimeric epitopes to reproduce the epitope landscape of YF17D more realistically. The substitution S253C in DII allows the formation of an inter-protomer disulphide bond across the two sE protomers, generating a covalently bound dimer39. This construct (hereinafter referred to as breathing-dimer) retains the ability to oscillate and exposes EDE-like dimeric epitopes, FLE, and the FL-proximal region. Furthermore, a W101H substitution was introduced in the breathing-dimer setting to disrupt the FLE (breathing-dimerW101H) (Fig.5A). In addition, we produced a locked-dimer E protein by introducing a double substitution L107C and T311C following the strategy used by Rouvinski et al (2017) and Slon-Campos et al (2019) with DENV and ZIKV. This construct displays quaternary epitopes on a pre-fusion dimeric structure that is bridged with two disulfide bonds between DI and DIII of opposing protomer units (Fig.S4A, B). Correct folding and epitope exposure of the recombinant proteins were verified by binding with specific antibodies using ELISA and SEC analysis (Fig.S6). Both the FLE KO construct (breathing-dimerW101H) and the locked dimer failed to bind antibodies recognizing the FLE but were recognized by an antibody binding DII outside of the FL. Both sE monomer and the breathing-dimer were recognized by fusion loop specific antibodies (Fig.S6).
A Recombinant proteins for the dissection and functional analysis of different antibody specificities. The illustration depicts the envelope protein ectodomains (sE), DI-II, and DIII produced separately as well as recombinantly produced dimeric structures. The table summarizes the epitopes displayed by the protein antigens used. B IgG endpoint titer quantification for breathing-dimer and breathing-dimerW101H specificities by ELISA at baseline (n=23 TBEV-vaccinated donors) and day 28 (n=24 TBEV-vaccinated, n=20 TBEV-unvaccinated individuals). C Antibody binding competition to sE of participants serum with the FL-mab 4G2 at baseline (n=55 TBEV-vaccinated) and day 28 (n=55 TBEV-vaccinated and n=43 TBEV-unvaccinated donors). The percentage of remaining binding is calculated by comparing the binding signal with and without 4G2 as competitor D Spearman correlation between antibody binding loss estimated with the 4G2 competition assay (C) and with the breathing-dimerW101H (B) (n=23 pairs of baseline samples, n=23 pairs of TBEV-vaccinated and n=20 TBEV-unvaccinated of day 28 samples) E Longitudinal quantification of IgG-producing B-cells specific for breathing-dimer and breathing-dimerW101H (n=10 TBEV-vaccinated and n=9 TBEV-unvaccinated donors). Units represent spot-forming units per 100.000 PBMC. F Table describing the antigens used for antigen-specific IgG depletions and the expected specificities of the remaining undepleted fraction used for YF17D neutralization assays. G YF17D neutralization titers (50% cutoff) of IgM-depleted and antigen-specific-depleted sera as explained in F (n=9 TBEV-vaccinated and n=9 TBEV-unvaccinated participants). TBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue. Envelope structure accession number (PDB: 6IW4) was edited using Pymol. Individual selection is shown in Supplementary Fig.3 (SF3). Boxplots display a horizontal line indicating the median and lower and upper hinges corresponding to the first and third quartiles. The lower and upper whiskers extend to 1.5x IQR from the respective hinge. Barplots in C and G indicate the mean and the error bars the standard error of the mean. Statistical significance between TBEV-vaccinated and unvaccinated individuals (C) was estimated with a two-sided Mann-Whitney test. Statistical significance in B, E and G was calculated with a two-sided Wilcoxon signed-rank test. P values above 0.05 are considered non-significant (ns).
The comparison between the breathing-dimer and breathing-dimerW101H-specific IgG titers serves to measure the fraction targeting theFLE. For TBEV-experienced individuals, the antibody fraction targeting the breathing-dimer was significantly reduced in baseline samples and at day 28 by the W101H mutation (45 and 64% reduction respectively) whereas TBEV-nave individuals showed no significant difference (Fig.5B). Additionally, the sE-specific IgG titer was quantified in binding competition assays with 4G2 (pan-flavivirus FLE-specific mAb) and 2D12 (YFV-neutralizing, non-cross-reactive anti-E mAb) (Fig.5C, S5A). As anticipated, TBEV-pre-exposed vaccinees lost over 80% of the sE-IgG binding fraction at day 28 in competition with 4G2, while flavivirus-nave individuals ranged from 0 to 60% binding loss, demonstrating that FLE is a dominant binding site for the antibody response in TBEV-experienced individuals, but not in TBEV-unvaccinated individuals. Likewise, baseline antibodies also competed with 4G2 for binding (Fig.5C). Consistently, binding loss caused by the W101H mutation and competition with 4G2 correlated with each other (R=0.65, p=0.0012), serving as cross-validation of these assays to quantify FLE antibodies in serum (Fig.5D).
Additionally, we performed an ELISpot assay to quantify the number of epitope-specific circulating B cells. We observed that the number of breathing-dimer-specific B cells was larger for TBEV-pre-immunized compared to TBEV-unvaccinated participants. Approximately 50% of the specific-B cells in TBEV-pre-immunized donors (100 cells/100.000 lymphocytes) required the unmutated FL for binding (Fig.5E). Consistently with serum antibody levels, TBEV-unvaccinated individuals had lower numbers of breathing-dimer specific B cells, although a relevant fraction produced antibodies requiring FL for binding. These B cells secrete antibodies that may be binding dimeric structures or FL-proximal regions whose binding site includes amino acids located in the FL (Fig.5A, E). The locked-dimer-specific IgG and B cell response was in line with the findings showing increased responses in TBEV-experienced individuals (Fig.S4C, D).
Taken together, these results show that the IgG fraction targeting the FLE is dominant in TBEV-pre-immunized but not in TBEV-unvaccinated participants. However, the fusion loop region is a binding site for antibodies elicited in both groups.
To assess the neutralizing capacity of antibodies with different specificities, we performed antigen-specific IgG depletion from serum samples that had been pre-depleted of IgM antibodies (Methods and Fig.5F, G). Depleting the IgM fraction allowed for a more precise dissection of the main neutralizing sites targeted by the long-term, durable, IgG response. As expected, IgM removal greatly reduced the neutralizing capacity of the sera (Fig.2G). Further depletion with the breathing-dimer protein resulted in a remarkable loss of neutralizing capacity in both TBEV-experienced and nave individuals. The neutralizing titers of sera depleted with the breathing-dimerW101H antigen remained high, demonstrating that neutralizing epitopes include the FL as a binding site (Fig.5G, left panels). In fact, the main chain of the FL is part of the EDE epitope in DENV10. Depletions performed with the locked-dimer construct resulted in only a slight decrease in neutralizing capacity (Fig.S4E). Despite the occlusion of the FL in the locked-dimer, we thought this construct would deplete antibodies with dimeric specificities and would reduce greatly the serum neutralization activity. However, the direct modification of the FLE by the L107C mutation of this construct also had an impact on the integrity of the dimer epitope, affecting the ability to deplete antibodies targeting dimeric specificities. A comparable construct for dengue40, although able to bind most of the dengue EDE antibodies, showed a reduction in binding for selected EDE. Similarly, the YF17D E locked-dimer construct may have failed to deplete the principal antibody fraction responsible for the virus neutralization (Fig.S4).
sE monomer cannot be used to deplete exclusively monomer-specific IgG antibodies as dimer-specific antibodies may assemble sE monomers together into dimers and therefore, this construct would also deplete antibodies with dimer-specificities41. To ensure the removal of antibodies with monomeric but not dimeric specificities, we then performed subsequent depletions with DI-II and DIII. Even though the depletions resulted in a clear loss of neutralizing capacity, especially in TBEV-experienced individuals, monomeric specificities only made up a minor fraction of the polyclonal neutralizing antibody response when compared to the breathing-dimer depleted sera (Fig.5G right panels).
Altogether, these results highlight the importance of dimer epitopes as the main YFV neutralizing sites and reveal that the FL is a critical component of the binding site for potent neutralizing dimeric antibodies.
Given that in TBEV-experienced individuals YF17D boosts a pan-flavivirus cross-reactive IgG response, we examined whether sera from these individuals mediate ADE of DENV and ZIKV infection using viral reporter replicon particles (VRP)42.
Interestingly, the antibody response induced by TBEV immunization was sufficient to enhance DENV and ZIKV infection. The enhancing capacity was further increased after YF17D vaccination. As expected, flavivirus-nave individuals did not facilitate DENV and ZIKV infection in vitro at baseline and the YF17D vaccine did not induce antibodies with enhancing potential. This is consistent with the absence of cross-reactive antibodies in these individuals (Fig.6A).
A Antibody-dependent enhancement of infection with DENV-2 (16681) VRPs at baseline and day 28 post-YF17D vaccination (n=23 TBEV-vaccinated, n=15 TBEV-unvaccinated individuals) B Antibody-dependent enhancement of infection with ZIKV (MR-766 African strain) VRPs at baseline and day 28 post-YF17D vaccination (n=16 TBEV-vaccinated, n=8 TBEV-unvaccinated individuals). C Dengue ADE for TBEV-vaccinated and unvaccinated individuals driven by: undepleted serum (n=22 per group), IgM-depleted serum (n=22 per group), and, as detailed in Fig.5F, IgM & antigen-specific-IgG-depleted serum (n=9 per depletion group). Relative infectivity is estimated as the normalized fold-increase of infection to an internal control carried for all the assays. Curves were fitted with local regression. In A and BTBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue.
To explain the antibody specificities mediating ADE, we first removed the IgM fraction and then measured the enhancing capacity after antigen-specific depletions of the remaining IgG fraction. ADE to DENV was lost in serum depleted of antibodies binding to the breathing-dimer, sE monomer (DI-II and III) or DI-II. In contrast, samples depleted with breathing-dimerW101H or locked-dimer constructs retained antibodies mediating ADE (Fig.6B, S5F). These results point to FLE-antibodies as responsible for cross-reactivity and ADE.
In conclusion, the YF17D vaccine expands FLE-antibodies with the potential to mediate ADE of DENV and ZIKV infection in vitro in TBEV-pre-immunized individuals, but not in the flavivirus-nave population.
The B cell response to the YF17D vaccine continues to mature for 6 to 9 months after vaccination29. Likewise, as the immune response advances, the antibody response undergoes diversification in terms of epitope recognition and binding affinity43. To extend our findings beyond day 28 post-vaccination, we analyzed serum samples from an independent cohort of 20 individuals collected one year after YF17D vaccination (cohort-2). Although baseline samples were unavailable, a review of the vaccination records identified that 16 individuals had received at least one TBEV vaccine dose before YF17D vaccination, while 4 were TBEV-nave. Additionally, two individuals who received the YF17D vaccine 9 and 11 years before sample collection, with no record of TBEV vaccination, were part of this cohort (Fig.7A, B).
A Diagram representing the serum sample collection of 22 participants. Prepared with Biorender (www.biorender.com). B Table summarizing cohort-2 characteristics and TBEV-pre-vaccination status. The table indicates the age at the time of vaccination. C YF17D anti-E protein-specific IgG titers in relative units (RU). D Neutralization curves of undepleted polyclonal serum and IgG- or IgM-depleted serum (in grey) for TBEV-pre-vaccinated or unvaccinated individuals. E Quantification of the 80% neutralization cutoff before and after IgM depletion. F Antibody binding competition to sE of participants serum with the FL-mAb 4G2. Percentage of remaining binding is calculated by comparing the binding signal with and without 4G2 as competitor. G Antibody-dependent enhancement of infection with DENV-2 VRPs. TBEV-vaccinated participants (n=16) are depicted in orange and unvaccinated (n=6) in blue. One-year pv samples are represented with circles and over 9 years pv with triangles. All individuals are included in every assay except for D and E (n=15 TBEV-vaccinated donors). Curve fitting in D and G was calculated with local regression. Boxplots display a horizontal line indicating the median and lower and upper hinges corresponding to the first and third quartiles. The lower and upper whiskers extend to 1.5x IQR from the respective hinge. Barplots in F indicate the mean and the error bars the standard error of the mean. Statistical significance between TBEV-vaccinated and unvaccinated individuals (C, E and F) was estimated with a two-sided Mann-Whitney test. Statistical significance between undepleted and IgM-depleted serum samples in E was calculated with a two-sided Wilcoxon signed-rank test. P values above 0.05 are considered non-significant (ns).
Similar to cohort 1, TBEV-pre-vaccinated individuals had significantly higher IgG antibody titers against the YF17D sE protein than TBEV-unvaccinated participants (Fig.7C). Of note, the difference in titers was approximately one order of magnitude, lower than what we observed on day 28. Moreover, flavivirus-nave individuals exhibited increased IgG levels compared to those at day 28 (Fig.7C). Both subgroups efficiently neutralized YF17D one-year pv, with the IgM fraction retaining significant neutralizing potential in participants sera. Surprisingly, we observed a trend of improved neutralizing titers in TBEV-unexperienced individuals compared to TBEV-pre-vaccinated individuals for both undepleted and IgM-depleted serum (Fig.7D, E). While the TBEV-unvaccinated sample size is limited, these results suggest that TBEV-pre-vaccinated individuals expanded a high titer of sE-specific antibodies with limited neutralizing potential, while flavivirus-nave individuals generated a more efficient IgG response for virus neutralization (Fig.7D, E).
In serum samples from TBEV-pre-vaccinated individuals one-year pv, the sE-IgG binding fraction competed with 4G2 mAb by over 80%. In contrast, flavivirus-nave individuals retained between 50% and 100% of sE-IgG binding in the presence of 4G2. This result, consistent with the analysis of cohort-1, confirms that the FLE is still a dominant target of the IgG response in TBEV-pre-vaccinated individuals but not in TBEV-unvaccinated donors after one-year pv (Fig.7F). Moreover, one year after YF17D vaccination, serum from TBEV-experienced donors was still capable of mediating ADE of DENV infection in vitro, while flavivirus-nave individuals did not elicit an IgG response with enhancing potential (Fig.7G).
Collectively, these results confirm our observations at day 28 post-vaccination in cohort 1 in an independent cohort sampled one year after YF17D vaccination. In conclusion, TBEV-pre-exposed donors develop a cross-reactive FLE-directed IgG response capable of mediating ADE of DENV infection. However, in flavivirus-nave individuals, YF17D primes for a non-cross-reactive yet effective neutralizing antibody response.
Were four years into the pandemic, and by this point, most Americans have had Covid at least once. But when the virus comes for us (again), it can still feel just as alarming as your first bout.
Heres a guide to what Covid looks like now and how to treat it.
The most common Covid symptoms havent changed much since the start of the pandemic, and they remain consistent for the latest dominant variant, JN.1, said Dr. Soniya Gandhi, the associate chief medical officer at Cedars-Sinai Medical Center in Los Angeles. They include fatigue, sore throat, congestion, runny nose, headache, body aches and cough.
All or any of those in isolation can still be Covid, Dr. Gandhi said.
Some people may develop conjunctivitis, also known as pink eye, or experience gastrointestinal issues, like nausea, vomiting and diarrhea, but those symptoms are rarer. Anecdotally, experts said, one of the most notable symptoms early in the pandemic the loss of taste and smell also appears to be less common these days.
The biggest change is that people are having milder symptoms overall, said Dr. Amanda Casto, an acting assistant professor of allergy and infectious diseases at the University of Washington. Thats because virtually everyone has some pre-existing immunity from vaccines, a prior infection or both.
While Covid is mild for most people, it can be dangerous and even fatal for some. Data from the Centers for Disease Control and Prevention indicated that, as of mid-February, more than 21,000 people were hospitalized with Covid, and there had been roughly 10,000 Covid-related deaths in 2024.
Severe illness is a lot less prevalent now than during the first few years of the pandemic, but were still seeing it, said Dr. Stuart Ray, a professor in the division of infectious diseases at Johns Hopkins Medicine in Baltimore. The people who are getting sickest tend to be those with compromised immune systems and underlying health conditions, such as heart disease, diabetes or lung problems. Adults over age 65 are also at higher risk for severe infections.
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Virginia Tech researchers are working on device that would let people sample air for the presence of COVID-19, before deciding whether to enter a location.
Researchers at Virginia Tech are working on a device that would let people sample air for the presence of COVID-19, before deciding whether to enter a business or facility.
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Here's what you should know about detecting COVID in the air
Were trying to make it possible that someone could walk into a space, and within 15 minutes, do something like a rapid test of the air, to find out if theres virus in the air, said Linsey Marr, professor of civil and environmental engineering at Virginia Tech, and leader of the project.
The research would enable a person, utilizing a consumer-ready portable testing device, to detect the presence of potentially harmful coronavirus.
You might be going out to eat at a restaurant, or youre going to a movie theater, or basketball game or shopping, and you might be concerned, Am I exposing myself to the virus here? Do I need to be concerned? Should I get out of here, or put on a mask?,' said Marr.
Air sampling for COVID-19 is possible currently, using a noisy pump, approximately the size of a microwave, said Marr, that yields a sample which a scientists could bring to a laboratory, and learn the results in a day or two: Thats too late, if you want to take action now, Marr said.
To conduct the test, first we try to capture a large amount of air lets say the amount inside your car, Marr offers. We use a big bag, like a big garbage bag, and you unfurl it, shake it around to capture enough air, seal it, then push out the air through a filter that would capture all the particles in the air.
While the specifics of the user experience are still in the works, Marr envisions a strip, like a rapid test, maybe you put a few drops of liquid on it, wait 1 minutes for the answer, and maybe a color change on the strip if theres enough virus there to potentially make you sick.
Marr said portability and ease of use are important: You need to be able to do this with just what youre carrying. With the current test, she envisions the capture bag would be reusable, but the other aspects of the test would be disposable after one use.
In the future, were interested in trying to build this into a less-obstructive sampling device, said Marr. Maybe something built into your shoes, so as youre stepping and pushing air through the sample device but were not there yet.
Marr said researchers have been able to identify when there are potentially harmful levels of the COVID-19 virus present.
Were able to do them and demonstrate them in the laboratory, but Id say were still a few years about from this becoming something that you could go buy in the store, said Marr.
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February 28 marks four years since COVID-19 was first reported in Aotearoa New Zealand. Many of us are probably surprised this virus is still causing a pandemic.
The World Health Organization refers to COVID-19 as a continuing pandemic. As Scientific American put it recently, it has been the elephant in every room sometimes confronted and sometimes ignored but always present.
It wasnt meant to be like this. The main wave of the 1918 influenza pandemic swept through New Zealand in eight weeks, killing 9,000 people almost 1% of the population. Then it was largely gone, returning as a new seasonal flu virus.
In doing so, it defined how pandemics were expected to behave. This model was written into pandemic plans and collective thinking across the globe.
But COVID is still circulating four years after New Zealand reported its first case, and more than two years after the Omicron variant arrived and infection became widespread.
Constantly present, it is also occurring in waves. Unexpectedly, the current fifth wave was larger than the fourth, suggesting we cant rely on the comforting assumption that COVID will get less severe over time.
These waves are driven by the interaction of the organism (SARS CoV-2 virus), the host (human characteristics such as immunity and behaviour), and environmental factors (such as indoor ventilation).
Continuing viral evolution is a major contributor to the changing dynamic. The virus has demonstrated an ability for large, unpredictable evolutionary shifts that dramatically alter its genome and spike protein.
The result is an enhanced ability to evade prior immunity and infect more people. This jump was seen with the highly mutated BA.2.86 subvariant in mid-2023.
Its offspring, JN.1, has acquired additional changes and is causing such a wave of new infections it could potentially be the next variant of concern, with its own Greek letter. It is now driving epidemic increases across the globe, including in New Zealand. This dominance by a single subvariant takes us back to the first year of Omicron in 2022.
Read more: I have COVID. How likely am I to get long COVID?
The pandemic continues to have a large, visible health impact. It is a leading cause of serious illness and death, mainly in older populations and those with existing long-term health conditions.
In 2023, it caused more than 12,000 hospitalisations and 1,000 deaths in New Zealand.
But COVID-19 also has an important and largely unmeasured burden of disease as the cause of long COVID, which may become its biggest health impact. A growing number of studies are describing an estimated incidence of long COVID of 5% to 15% of all infections.
For example, a recent large study of almost 200,000 Scottish adults reported that, after adjustment for factors that might confuse the results, long COVID prevalence following an infection was 6.6% at six months, 6.5% at 12 months, and 10.4% at 18 months.
These findings illustrate an important feature of long COVID: recovery can take two years or more, with symptoms that fluctuate over time.
New Zealand now needs a strong, integrated response to COVID-19 and other respiratory infections.
The major pandemic interventions have not changed: vaccination, public health and social measures to prevent infection, and antivirals for more vulnerable groups. The evidence has firmed up that long COVID risk is reduced by vaccination, but research is less certain for antivirals.
Read more: Vaccination, testing, clean air: COVID hasn't gone away here's where Australia needs to do better
But growing pandemic complacency from political leaders and the public has changed things. Some of this apparent indifference can be put down to understandable fatigue with response measures. But it remains dangerous in the face of a continuing pandemic.
One way to keep a focus on prevention and control would be to include these measures in an integrated respiratory infectious disease strategy. This would combine COVID-19 control measures with those used to protect against influenza, respiratory syncytial virus (RSV), and other respiratory infections.
Measles could be added to the list, given the rising threat to New Zealand from a global resurgence of the disease.
This integrated strategy would include vaccination, promoting testing and self-isolation when sick, and measures to reduce transmission in critical indoor environments such as healthcare, public transport and education settings.
Read more: Long COVID stemmed from mild cases of COVID-19 in most people, according to a new multicountry study
Such a programme would need to be supported with community engagement, education, surveillance and research.
Structural inequalities mean Mori, Pacific peoples, and those living in relative deprivation, are less vaccinated, less protected from infection, less tested and less likely to have antivirals.
Consequently, they are more likely to be hospitalised and die from COVID-19. These inequities are currently not being systematically tracked and acted on.
Read more: COVID: there's a strong current of pandemic revisionism in the mainstream media, and it's dangerous
As we enter the fifth pandemic year, we need a change in thinking about COVID-19. This infection has pathological features in common with the other severe coronaviruses (SARS and MERS).
It is wishful thinking to imagine it will suddenly transform into a common cold coronavirus. As a recent review article concluded:
Transition from a pandemic to future endemic existence of SARS-CoV-2 is likely to be long and erratic [] endemic SARS-CoV-2 is by far not a synonym for safe infections, mild COVID-19 or a low population mortality and morbidity burden.
In the face of this continuing pandemic threat, we need a response that is evidence-informed rather than evidence-ignored.
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What to do when you test positive for COVID-19 can depend on factors such as your symptoms and your risk of complications. Anyone who has COVID-19, even if they test positive but don't have symptoms, can spread the illness to others. Protecting others with measures such as isolation and masking is very important.
This article will discuss steps to follow after testing positive for COVID-19, communicating with others about being positive, what to avoid while positive, and steps to take for long COVID-19 symptoms.
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It's important to note that while this article will discuss what to do after testing positive for COVID-19, it is possible to have COVID-19 and test negative, particularly on home tests and/or early on in the infection. If you have symptoms, have been exposed to COVID-19, or have reason to believe you might have it, follow the proper protocols even if you get a negative result.
Here are some steps to take if you find out you have COVID-19.
Call your healthcare provider and let them know you have tested positive for COVID-19. They can let you know, based on your health history and symptoms, if they need to see you, or if further actions are needed.
Treatments work best when started early. So, call your healthcare provider even if you are feeling OK if you have underlying health conditions and symptoms that your healthcare provider may feel warrant treatments.
Risks are higher in people who are:
If your healthcare provider has determined you would benefit from antiviral treatment, they may prescribe a medication such as:
Follow your healthcare provider's instructions carefully, and inform them of any other medications or supplements you take.
Unless otherwise specified by your healthcare provider, home is typically the best place to be when you have COVID-10.
General recovery steps to take include:
If you have a fever:
If you have a cough:
If you are feeling breathless:
First, determine if you need medical attention. Difficulty breathing can be serious. If you think you need medical attention, or you aren't sure, talk to a healthcare provider, get emergency treatment, or call 911 or your local emergency number.
If you are feeling breathless and do not need medical attention, you can try measures such as:
Isolate from others, whether you have symptoms or not. Do not leave your home unless you absolutely need to, such as for a medical visit. Steps to take include:
If you live with others, try to isolate alone in a room, and if there is more than one bathroom, keep one for only you to use.
Take measures such as:
If you must share a bathroom:
If you are living in a shared space (such as a dorm room in college or university), or you are living with a vulnerable person (such as someone who is immunocompromised, pregnant, or an older adult), it may be best to relocate while you are isolating, if possible.
If you live alone, try to have someone check in with you regularly (virtually or from a safe distance) to make sure you are doing okay.
If you must be around others, whether at home or in public, wear a high-quality mask.
Even if you have ended isolation, you should continue wearing a mask through day 10, or with two sequential negative tests 48 hours apart. If your antigen test results are positive, you may need to continue wearing a mask past day 10 as you could still be contagious. Continue testing every 48 hours until you get two negatives 48 hours apart.
Choose a mask that:
For more detailed information on choosing a mask, check the CDC's guide on types of masks.
While some people have a higher risk, anyone can have severe COVID-19 symptoms.
In some cases, COVID-19 can signal a medical emergency.
Call 911, or your local emergency number, or seek emergency medical treatment if you, your child, or someone else is showing emergency COVID-19 signs such as:
This is not a complete list. Seek medical attention for any symptoms that are concerning you.
How Isolation Days Are Counted
If you have had no symptoms:
If you have had symptoms:
How Long to Isolate
If you test positive for COVID, whether or not you had symptoms, you need to isolate from others for at least five days, as you are likely most infectious during these five days.
When you can end isolation depends on the severity of your symptoms, as follows:
However, if you had symptoms and severe illness (you were hospitalized) or you have a weakened immune system:
If you aren't sure about the severity of your symptoms or when you can end isolation, talk to your healthcare provider.
If your symptoms worsen or recur after you end isolation, start your isolation again at day 0.
No matter when you end isolation, until at least day 11:
These are general guidelines. Always follow the advice of your healthcare provider.
It's still important to get vaccinated and stay updated with boosters, even if you have had COVID-19. It's typically recommended to wait about 90 days after recovering from COVID-19 to get the vaccine. Talk to your healthcare provider about when to resume your COVID-19 vaccination schedule.
Positive results for COVID-19 on polymerase chain reaction (PCR) tests and on antigen (rapid) tests are very accurate and reliable.
Occasionally, some tests, particularly PCRs, may continue to show a positive test result for some time (up to 90 days), which can make it difficult to know if a new infection has occurred after a previous infection.
Negative tests, especially antigen tests, are less reliable. If you are going to take a single test, get a PCR test as it can give a more reliable negative result. If you get a negative antigen test result, that alone does not rule out having COVID-19. If you get a negative antigen test result, it's recommended you take another one in 48 hours (and a third one 48 hours after that if you don't have symptoms) to confirm a negative result.
If you test positive for COVID, it is important to inform your close contacts so they can monitor themselves and take precautions.
A close contact is someone who you have been around for at least 15 cumulative (added together) minutes within 24 hours.
You are considered contagious from two days before your symptoms started until 10 days after they started. If you have no symptoms, your contagious period is considered to be two days before your test sample was collected until 10 days after your test sample was collected.
Notify any close contacts you had during this time, as well as people whom you:
Let them know they need to follow guidelines for what to do if you have been exposed to COVID-19.
You should also call ahead if you need to be somewhere, such as a healthcare appointment, so they can prepare for you.
The main thing to avoid while COVID-19-positive is putting others at risk.
Avoid:
Long COVID broadly refers to signs, symptoms, and conditions that continue or develop after having an acute COVID-19 infection. It can have a range of health problems and is not one single illness.
There is no test for long COVID, a diagnosis is considered based on health history (including prior COVID-19 infection), and health examination. Symptoms can last weeks, months, or years, and may go away and come back.
There is no single treatment for long COVID. Treatments and therapies depend on symptoms, overall health, and more. A range of specialists may be included in your care, such as pulmonary specialists, cardiologists, gastroenterologists, and neurologists.
Examples of treatments that may be recommended include:
Talk to your healthcare provider if you are experiencing problems after a COVID-19 infection.
Most people will recover from COVID-19 with rest, fluids, and over-the-counter medication. Visit an emergency room or urgent care if you feel significantly ill. When sick, take steps to protect others, such as masking, hand washing, and social distancing.
Steps to take after receiving a positive COVID-19 test include calling your healthcare provider, starting treatments if necessary, staying home and recovering, isolating from others, wearing a mask, following steps for ending isolation, and getting vaccinated after an appropriate time has passed.
It is important to let anyone who may have been exposed know so they can take precautions.
There is no single treatment alone for long COVID, but rather treatment plans are based on individual needs.
On the menu today: Todays newsletter is a little bit about the Covid-19 lab-leak theory, a little bit about those social-media stories about notes left for waitresses, and a whole lot about what our culture deems newsworthy and important (and how the president of the United States shapes the worlds perceptions of what is important). Oh, and its also a little bit about the worst Commander in Washington since Daniel Snyder.
Ignoring Chinas Covid Role . . . to Our Detriment
We now know that prominent U.S. virologists did not want DARPA and the U.S. government to know what kind of gain-of-function experiments were being done on coronaviruses found in bats at the Wuhan Institute of Virology. James Meigs, writing over at Commentary:
The December breakthrough came when the medical watchdog group U.S. Right to Know unearthed an early draft of a 2018 grant proposal for a Project DEFUSE. The proposal outlines a joint project between [Ralph] Barics UNC lab and a team headed by WIV senior scientist Zhengli Shi, the famous Bat Lady of the Wuhan lab. The proposal was drafted under the supervision of Peter Daszak whose EcoHealth Alliance would funnel the hoped-for grant money to the researchers and was addressed to the U.S. Defense Advanced Research Projects Agency (DARPA). In the end, DARPA declined to fund the project. But many experts suspect the Wuhan lab conducted research along these lines using other funding sources. . . .
Some of the most telling passages in the newly released documents show how EcoHealths Daszak and UNC researcher Baric planned to evade this oversight. . . .
Daszaks and Barics deceptiveness about how and where their research would take place is all the more stunning when you consider how dangerous their proposal was. The project called for combining various bat-borne coronaviruses, modifying them by adding a furin-cleavage site that might help the virus bind to human cells, and then testing the supercharged virus on mice bred to have human-like cells in their lungs. When SARS-CoV-2 surged out of Wuhan in early 2020, it featured this exact type of furin-cleavage site, something never before seen in this family of viruses. This was the genetic quirk that alarmed many virologists who thought the virus looked engineered.
So, while DARPA didnt fund the DEFUSE project, its hard to escape the conclusion that Wuhan scientists followed this general roadmap (perhaps without the Americans knowledge). . . .
I said what I had to say in that cover piece back in 2022, that the natural-origin theory requires us to believe a series of coincidences so unlikely that it becomes effectively impossible:
In the autumn of 2019, there were three institutions in the entire world that were doing gain-of-function research on novel coronaviruses found in bats. One was in Galveston, Texas, one was in Chapel Hill, N.C., and the third was in Wuhan, China.
In theory, the pandemic could have started with some random Chinese person who didnt have any connection to the bat coronavirus research conducted at the Wuhan Institute of Virology or the Wuhan CDC. This person would have a spectacularly unlucky run-in with a bat or other animal, and that random Chinese person caught the exceptionally rare naturally occurring animal virus that infects, sickens, and spreads among human beings like wildfire. This same hyper-contagious bat virus would have the exceptionally unusual trait of being extremely difficult to find in bats.
This extraordinarily unlucky person would then travel to the metaphorical doorstep of one of the three labs in the world doing gain-of-function research on novel coronaviruses found in bats and start infecting other people in the city of Wuhan. Under the natural-origin theory, the Wuhan laboratories just happen to be mind-bogglingly unlucky that events played out in a way that so closely mimics the consequences of a lab accident.
And, at least in the venue of American public opinion, those of us who thought a lab leak was a more likely cause of the pandemic won the argument. Back in 2023, a Quinnipiac University poll showed that 64 percent of Americans believed the pandemic started from a lab leak, compared to 22 percent who believed it had a natural origin. And the Economist/YouGov poll showed similar numbers: 66 percent believed in the lab-leak theory, compared to just 16 percent who believed in the natural-origin theory.
Though we won the argument in the realm of public opinion . . . nothing happened. There have still been few real consequences for the Chinese government, and certainly no consequences commensurate to unleashing a plague that killed about 7 million people officially and anywhere from 18 million to 32 million if you count all the suspiciously high excess deaths in places such as China and Russia, among others.President Biden assures us that U.S.China relations are in a thaw.
Stories dont get any bigger than the origin of a virus that caused a global pandemic, effectively shut down the world for a year, and changed the lives of every human being on the planet. Were still dealing with the learning loss; were still living with the consequences of missed cancer diagnoses; were dealing with an explosion of skepticism about the value of all kinds of vaccines thanks a lot, mandate advocates; and were dealing with an estimated financial cost of $14 trillion. (For perspective, all U.S. federal government spending in fiscal year 2023 was $6.1 trillion.)
And yet, when we wake up every morning, most of us choose to think about other topics and hey, there are a lot of other important priorities in this world. But sometimes it feels like vast swaths of American society chose to forget about the pandemic at the first opportunity and chose to not keep asking how and why the pandemic started, because they and some of our leaders didnt like the probable answers. Holding the Chinese government accountable for setting off the pandemic would just be too difficult. Theres still $575 billion in trade between the two countries. Mustnt upset the applecart.
To quote the late wise philosopher Dennis Green, They are who we thought they were, and we let them off the hook.
Instead, we think about other things, often much less consequential things. I generally dont like stories that bubble up into the news cycle from the realm of rarely verifiable social media, and few make me roll my eyes more than the you wont believe what this customer wrote on her check to her waitress! stories. (I guess I dont mind the stories about customers leaving generous tips and sweet or inspiring notes, but I still wonder whether theyre really news.)
First, these stories are often hoaxes. Second, assuming what happened is true . . . alas, the world has rude customers and service employees often bear the brunt of their antipathy. I wish that wasnt the case, but it is, and it has always been so. I doubt the value of these anecdotes as news. I dont think the actions of one particular jerk make any grand or revealing statement about our society.
There are times when it can seem that the focus on who wins the presidency is an unhealthy obsession, a saga that now effectively goes on for two years, vacuums up tons of money that could be put to better use elsewhere, dominates the news cycle, and often brings anything resembling actual governing to a halt.
And yet, the presidency has awesome power, even in the hands of an 81-year-old who has lost something off his fastball, to use the most generous euphemism. One of those powers is the ability to influence what the news covers, and what Americans discuss.
Biden has decided that forgiving student-loan debt is the great cause of our time, or at least one of them. Never mind that these were loans that were taken out voluntarily, and with full knowledge of the consequences for not paying them back on time. This is a demographic that voted heavily for Joe Biden; therefore, the power of the state must be used to alleviate its financial burdens.
Best that I can determine, Biden has not spoken publicly about the origin of Covid-19 since August 2021. After receiving a report from the intelligence community that amounted to, Eh, we dont know, boss, Biden declared, We will do everything we can to trace the roots of this outbreak that has caused so much pain and death around the world, so that we can take every necessary precaution to prevent it from happening again. . . . The world deserves answers, and I will not rest until we get them. Of course, this was right around the time when the Taliban was reconquering Kabul.
Apparently, President Biden will spend a portion of the State of the Union Address talking about shrinkflation the sense that youre paying the same price for a bag of chips that has more air and fewer chips than when the inflation rate hit 9.1 percent in July 2022. Rich calls it Bidens War on Packaging.
If Biden wanted to talk about the unresolved questions about the origin of Covid-19, and the Chinese governments refusal to cooperate with international inquiries, he could. Biden could discuss:
Chinese government reports and officials described ongoing equipment problems and inadequate safety training that in some cases resulted in lab animals being illegally sold after being used in experiments, and contaminated lab waste getting flushed into sewers. The problems were exacerbated, they reported, by a secretive, top-down bureaucracy that sets demanding goals while reflexively covering up accidents and discouraging any public acknowledgment of shortcomings.
Biden could talk about how, in the crucial early days of the pandemic, the Chinese government silenced and arrested doctors who tried to sound the alarm and insisted the new virus was not contagious among human beings, effectively dooming the world.
All of this is reported in places like this publication and the Washington Post and other independent Western journalistic institutions; this isnt classified information.
But President Biden hasnt said anything about the origin of Covid in more than two years. It just isnt that important to him.
In the modern era, the federal government and the man atop the executive branch focus their attention on the easy and popular stuff forgiving student-loan debt and the amount of air in your bag of chips. The real challenges of our time are just too difficult to focus upon, apparently.
ADDENDUM: Last week, over in that other Washington publication I write for, I wrote that the news that Commander, President Bidens German shepherd, was involved in at least 25 biting incidents in less than a year illuminated a deeper problem around the president and his team: The presidents dog pulling a Cujo is an abnormal situation, but it seems that in this White House, everyone just has to pretend that something that is obviously, glaringly, undeniably not right is totally unremarkable.
The usual suspects then decided that I was historys greatest monster for writing this.
This morning, Jill Abramson writes a review of recently released Secret Service records. Abramson is a former executive editor of the New York Times, a columnist for the Washington Post, and far from a reflexive Biden-basher. She concludes, But as I waded through the gory details of all these biting incidents, my empathy for the Bidens faded. Put plainly, these documents are a harrowing narrative of pet ownership in high places run dangerously amok. Two dogs belonging to the same family were both serial biters and had to be exiled. At some point, the trouble is not the animals its the owners.
Well, I guess she gets to be historys greatest monster this week.
TAMPA, Fla. Theres now new research giving insight into long COVID and how the virus is affecting peoples health, long after the initial COVID-19 infection.
A lot of people, I think, at the start, were thinking that long COVID wasnt real, said Dr. Jill Roberts, Associate Professor for the USF College of Public Health.
But health officials said there are now years of concrete evidence showing that long COVID is real.
Theres been so many pathology studies showing that we can get real data that shows that there are inflammation responses occurring months later to the COVID antigens, said Roberts.
According to the CDC, one in nine adults in the United States whove had a COVID-19 infection continues to experience long COVID, and the symptoms are wide-ranging, affecting all different parts of the body that vary from person to person.
All of these things that seem unrelated in terms of the different disease manifestations are actually caused by the same thing, said Dr. Thomas Unnasch, public health expert and researcher.
Some of the symptoms include shortness of breath, brain fog, depression, anxiety and fatigue.
A new study also shows that insomnia could be linked to long COVID, too.
Sleep disorder type of things, issues with long-term sadnesstheyre calling it the COVID sadness, in fact, said Roberts.
Another recent study said about one in 10 pregnant women will develop long-term symptoms if they get infected during pregnancy. A new pediatrics report found that up to six million children have developed COVID.
Long COVID in children, which we didnt really expect to be a thing, said Roberts.
The data suggest that most young people who have long COVID eventually recover.
Overall, health officials said vaccines help the severity of COVID-19 symptoms, which could help with long COVID.
I think its really important that finally, were really recognizing this is a long-term syndrome that a lot of people are going to be affected by, said Unnasch.
However, only time will tell the extent to which the virus is affecting people long-term and if a full recovery is possible for everyone.
Weve had tracking data for a couple of years now. Some people are recovering. So some of those common symptoms like brain fog and things like that are disappearing over time. So Im hopeful that that will be the case for most people, said Roberts.
