Happy New Year everyone and a thought for today

Happy New Year everyone and a thought for today

Happy New Year everyone and a thought for today, at definitely my fave time of year. Christmas is over and we have arrived at a time that is nominally still the holidays, but also the opposite of a holiday, a blank space stretching between Christmas and New Year’s Eve when very little makes sense and time loses its meaning; well to me.  A bit ephemeral even. Nice word, and happens in this case, to be true:

But I also think that for many of us like me, this is the only time of year when it feels possible, and even encouraged, to do nothing. I look forward to it all year long in fact. Strange but true. And in some ways now, stranger than contemplating when we’ll receive our 4th shot, and with what type of vaccine (the same as before, Omicron-specific, or heterologous boosting using a different product?).

During earlier stages of the pandemic, most of my friends were spared a direct brush with the virus. Perhaps they used to be much more careful. Or perhaps they were just lucky. Whatever the reason, their good fortune has now run out. Quite a few friends all over the world recently told me they had tested positive along with their kids and so on. Several more strongly suspect they have COVID but are unable to get their hands on a test, or presume they have it and can’t be bothered to test. Thankfully, everyone has decidedly mild symptoms (no doubt in part because they all are vaccinated and they are not in high-risk categories), if symptomatic at all. This S African data should greatly reassure more than most:

Further, Israeli health officials are reportedly considering aiming for herd immunity via mass coronavirus infection. This ‘Swedish model’ would move away from some anti-transmission measures and tolerate a rise in infection rates, with the assumption that the vast majority of the population will be spared from serious illness. Once a critical mass of the population has become infected, the logic says, widespread immunity will slam the brakes on infection:

https://www.timesofisrael.com/what-a-herd-immunity-policy-would-look-like-and-why-it-may-be-premature-for-israel/

At this time of year we seem to be in no man’s land, temporally speaking.  The time from December 26 until the afternoon of December 31 is generally considered part of the holidays. Kwanzaa, and very rarely Chanukkah, falls during this period. But for many of us, whether still celebrating holidays or having just finished Christmas festivities, this week is like a long hangover, regardless of alcohol intake. To some degree, I think all of society feels a little aimless during these few days and Covid is for some the best excuse not to broadly socialise. We’re also waiting for the new year, with all its resolutions and hopes for starting over, but we’re not quite done with the old one. In between the end of the old year and the beginning of the new one is this weird little stretch of unmarked time. For most people, this week isn’t even a week off from work, but at the same time it also isn’t a return to the normal rhythm of regular life. Nobody knows what to do with this leftover week, awkwardly stuck to the bottom of the year. It’s really ‘Dead Week’ to paraphrase the Atlantic, a time when nothing counts, and when nothing is quite real.

Here it’s an extension of the formal holiday Boxing Day; obviously this was a massive problem this year falling on a Sunday so in some ways many would feel they lost of holiday weekday as Sunday is kind of day off time anyway. Perhaps a touch unfair that Christmas day was Saturday and New Year’s Eve is tonight so we ‘lose’ days off. Boxing Day is an older tradition that some think stems from wealthy families giving presents to their household staff the day after Christmas; in its current form, it is a day to box up and get rid of extra stuff, or regift unwanted gifts. Boxing week I note has become an excuse for black Friday type sales and the accumulation of more stuff. In Norwegian, this week is known as romjul, a word that combines the Norse words for “room” or “space” and Jul, or “Yule”; it literally means “time and space for celebrating the yuletide.” But it also echoes the Old Norse word rumheilagr, which means “not adhering to the rules of any particular holiday”. I mean how do I know this; how do I know anything? It’s obvious, thanks Google, Wiki and so on.

The week has neither the religious gravity of Christmas nor the flat-out party atmosphere of New Year’s Eve (Omicron aside), but is stuck halfway between one and the other. This week is a holiday without expectations, which are how we usually understand holidays. We know we won’t get especially demanding work e mails typically. We are not expected to work but markets are open, and work is happening, which is a strange limbo-esque time. Elsewhere, romjul traditions include general holiday activities such as partying, eating a lot, visiting family, and resting. Our culture doesn’t have an official name for this time but most don’t spend time looking at calendars or clocks; we can enjoy forgetting what day it is, wearing outfits that make no sense, ignoring our phones, and falling into a pointless internet rabbit hole for hours, one of my personal specialties. Lots of people have either just returned from family visits or are still there, stuck in the half-familiarity of being an adult in the spaces of childhood. We celebrate by having no idea what to do during this time and, within that confusion, quietly luxuriating in what might be the only collective chance for deep rest all year. Rest clearly doesn’t just mean the absence of work: it means not worrying about getting ‘that e mail’.

Most people do work during this week in the United States. In recent years, some companies to giving employees the entire week off, a tacit admittance that it is both still part of the holidays and a useless time to expect any kind of productivity. But far more workers have no possibility of taking this time off; in retail, for instance, this is one of the busiest and most hellish weeks of the year.

Even so, it is still the closest thing we have in our society to some kind of a communal pause. Nothing is ever as quiet as it is during those few days, cities emptied out and small towns sleepier than usual, people drifting around not interested in accomplishing anything. There is a collective sense that, for these few days, we are not going to do any more than we must. It doesn’t really matter if you don’t brush your hair, if you stay up all night, if you don’t send that work email. Many people aren’t checking email anyway, and nobody wants to be asked to do more work than they absolutely have to. But, this week isn’t a week off for everyone, or at least the thing it is a week off from isn’t work. Rather, it is a week off from the forward-motion drive of the rest of the year. It is a time against ambition and against striving. Whatever we hoped to finish is either finished or it’s not going to happen this week, and all our successes and failures from the previous year are already tallied up. It’s too late for everything; this week is the luxurious relief of giving up.

These five days are the purest unit of nothing time that the year offers. Nothing time is different from free time; the week is not a vacation and not a holiday, but we are afforded so little truly unmarked and nonurgent time that five days when nothing really matters can feel like something more precious than either one. In society, we spend most of the year receiving the message that we are supposed to try harder, do better, achieve more than the person next to us, rack up a bigger pile of stuff and a longer list of accomplishments. For once, the insistent push to hustle and climb grows quiet, and there is a break from the screeching sense that every day must be optimized for efficiency.

My favourite part of this week is getting up early, drinking coffee, and looking ahead to the long stretch of nothingness that fills the day. The nothingness doesn’t have to be slothful; sometimes I leave the house and sometimes I don’t, but the point is that it doesn’t matter. If I don’t go outside, I don’t feel bad about it, and if I do, everybody else I encounter looks equally confused and at loose ends, frittering away these leftover days. It is the only time of year when the days feel slow to me, when the time outside of whatever tasks I have to do does not somehow vanish into further worry and busyness. It is the only time I don’t feel like I am perpetually late to my own life, and that easing of guilt offers a deeper rest than any vacation would.

This week also is forgiving, everyone loses track of time; everyone forgets; everyone decides not to worry about it until January. These days at the end of the year offer a kind of grace, a time when simply existing is enough, outside the records of success and failure. Now back to Covid. Again.

Although Omicron is very capable of evading antibodies and causing reinfections/breakthroughs, it barely evades T-cells at all, meaning vaxxed or recovered people are likely to retain very good protection against severe disease:

They studied neutralizing antibodies and T-cell responses to SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers (HCW) after immunisation with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralisation assays with authentic virus showed consistent cross-neutralisation of the Beta and Delta variants in study participants, but Omicron-specific responses were significantly lower or absent (up to a 34-fold decrease compared to D614G). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunisations or Ad26.COV.2 priming partially restored neutralisation of the Omicron variant, but responses were still up to-17-fold decreased compared to D614G. CD4+ T-cell responses were detected up to 6 months after all vaccination regimens; S-specific T-cell responses were highest after mRNA-1273 vaccination. No significant differences were detected between D614G- and variant-specific T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations may be needed to further restore Omicron cross-neutralisation by antibodies:

A report shows the Johnson&Johnson vaccine demonstrates 85% effectiveness against hospitalisation in South Africa when Omicron was dominant. A second, separate analysis of the immune response to different vaccine regimens, conducted by Beth Israel Deaconess Medical Center (BIDMC), demonstrated that a heterologous booster (different vaccine) of the JNJ COVID-19 vaccine in individuals who initially received the Pfizer vaccine generated a 41-fold increase in neutralizing antibody responses and a 5-fold increase in CD8+ T-cells to Omicron by four weeks following the boost. While a homologous boost with Pfizer generated a 17-fold increase in neutralizing antibodies and a 1.4-fold increase in CD8+ T-cells by four weeks following the boost. Thus, both neutralizing antibodies and CD8+ T-cells were higher four weeks after the boost with the Johnson & Johnson vaccine than with the Pfizer vaccine.

Whether the BNT162b2 vaccine (Pfizer–BioNTech), which was previously shown to have 95% efficacy against COVID-19 will effectively neutralize infection with the omicron variant is unclear. Thus a group compared neutralisation of omicron-infected cells in serum samples obtained from participants who had received two doses of vaccine with neutralisation in samples obtained from participants who had received three doses. Microneutralisation assays with wild-type virus and B.1.351 (beta), B.1.617.2 (delta), and omicron variant isolates were performed with the use of serum samples obtained from two groups of 20 health care workers. One group comprised participants who had received two doses of the BNT162b2 vaccine (mean, 165.6 days since receipt of the second dose), and the second group comprised those who had received three vaccine doses.

Receipt of three vaccine doses led to better neutralisation of the wild-type virus and the three variants than receipt of two vaccine doses. A significantly lower neutralisation efficiency of the BNT162b2 vaccine against all the tested variants of concern (beta, delta, and omicron) than against the wild-type virus was observed in samples obtained from participants who had received two doses than in those obtained from participants who had received three doses. The lower neutralisation efficiency against the beta and omicron variants than against the wild-type virus was similar in samples obtained from participants who had received two doses and in those obtained from participants who had received three doses. The third dose of the BNT162b2 vaccine efficiently neutralized infection with the omicron variant (geometric mean titre, 1.11 after the second dose vs. 107.6 after the third dose). They found low neutralisation efficiency with two doses of the BNT162b2 vaccine against the wild-type virus and the delta variant, assessed more than 5 months after receipt of the second dose, and no neutralisation efficiency against the omicron variant. The importance of a third vaccine dose is clear, owing to the higher neutralisation efficiency (by a factor of 100) against the omicron variant after the third dose than after the second dose; however, even with three vaccine doses, neutralisation against the omicron variant was lower (by a factor of 4) than that against the delta variant. The durability of the effect of the third dose of vaccine against Covid-19 is yet to be determined:

https://www.nejm.org/doi/full/10.1056/NEJMc2119358?

In the NEJM an SA group published a piece using data from Discovery Health, a South African managed care organisation, they estimated the vaccine effectiveness of two doses of the BNT162b2 vaccine (i.e., full vaccination) against hospitalisation for Covid-19. They analyzed 133,437 PCR test results that had been obtained during the comparator period, of which 38,155 (28.6%) had been obtained at least 14 days after the patient had received the second dose of vaccine. For the proxy omicron period, they analyzed 78,173 PCR test results, of which 32,325 (41.4%) had been obtained at least 14 days after the second dose (tables below). The overall test positivity was 6.4% during the comparator period and 24.4% during the proxy omicron period, whereas the Covid-19 admission rate was 10.8% and 2.2%, respectively, as a percentage of positive PCR test results.  During the proxy omicron period, we found a vaccine effectiveness of 70% (95% confidence interval [CI], 62 to 76), a finding that was supported by the results of all sensitivity tests. This measure of vaccine effectiveness was significantly different from that during the comparator period, when the rate was 93% against hospitalisation for Covid-19. Thus, during the proxy omicron period, they saw a maintenance of effectiveness of the BNT162b2 vaccine (albeit at a reduced level) against hospital admission for Covid-19 that was presumed to have been caused by the omicron variant as compared with the rate associated with the delta variant earlier in the year. The addition of a booster dose of vaccine may mitigate this reduction in vaccine effectiveness:

https://www.nejm.org/doi/full/10.1056/NEJMc2119270?

It’s really hard to work out case numbers just now with post-Xmas dumping of results and so forth. Even the US CDC has revised down its estimates for US infection by the Omicron variant, stating it accounts for approximately 59% of all Covid cases in the US, not 73% as it previously said.

Interesting survey results here. The FDA as we know granted emergency authorisation last week to the antiviral pill, which is called Paxlovid, a move some see as a significant step in combating the coronavirus. Only 72% of the adult population in the U.S. is fully vaccinated and just 24% have received a booster dose, according to the CDC. In studies, the pill reduced the risk of hospitalisation or death by 88% compared to a placebo among patients treated within five days of experiencing Covid-19 symptoms. Yet interest in the Pfizer pill varies significantly. Of those who were familiar with the Pfizer pill, the poll found 84% are likely to take it if they test positive for the coronavirus, with no large differences between generations, racial groups, or political affiliations. But there was one key difference: 91% of vaccinated people would take the pill, but only 52% of all unvaccinated Americans said they are very or somewhat likely to do so. The likelihood an unvaccinated person would take the pill dropped even further, to 35%, among those who said they would never get vaccinated, compared to unvaccinated people who said they will “wait and see.” To an extent, the findings seem to mirror the calcified views held toward Covid-19 vaccines for the past year. For instance, political affiliations do underscore somewhat differing perceptions of the Pfizer pill, not just vaccines. Nine in 10 Democrats who are familiar with the pill think it will effectively help manage the virus, compared with 79% of Republicans who knew about Paxlovid. Overall, 46% of all unvaccinated Americans indicated they are unwilling to receive a vaccine or the Pfizer pill. Breaking it down, nearly half of unvaccinated women, millennials, members of Gen X, and Republicans were unwilling to get vaccinated or take the pill, if they were to get infected. Slightly more than half of unvaccinated people living in rural areas and those identifying as politically independent would avoid both.

Yet some unvaccinated Americans who are familiar with the Pfizer pill would prefer it to a vaccine. Why? One in five believes the development of the vaccines was rushed, but not the development of the pill. A similar proportion find taking pills safer and also less invasive. I should note the poll occurred before the FDA authorized a pill from Merck that offers less effectiveness than Paxlovid and has generated less enthusiasm. By contrast, nearly six in 10 of those who are vaccinated believe the pill can supplement vaccines in the fight against the pandemic, compared with 31% of unvaccinated Americans who are aware of Paxlovid. However, nearly a quarter of those who are vaccinated wrongly believe the pill will reduce the need for vaccines and boosters, and that increases to 40% among those who are unvaccinated:

Now an interesting thought piece in the NEJM, paraphrasing here – who should decide to have kids vaccinated, parents or the kids themselves? Vaccinating children 12 to 17 years of age is important, both for their own mental and physical health and for public health; the benefits of vaccination vastly outweigh the small risk of adverse reactions. Yet according to the CDC, nearly 40% of U.S. adolescents haven’t received at least one dose of the Pfizer–BioNTech Covid-19 vaccine (as of December 2021, the only product that had been authorized by the FDA for this age group, with approval granted for those 16 or older). Although adolescents are at lower risk than adults for severe medical complications of Covid-19, they tend to be disproportionately affected by the instability that comes from school closures, social distancing, and other pandemic-related disruptions. Adolescents also make up a substantial portion of the population that is capable of spreading Covid-19. Vaccines, because of their role in keeping schools open and ending the pandemic, can address both problems, but only if they are widely administered.

Low Covid-19 vaccination rates among U.S. adolescents can be partly explained by some parents’ decision not to consent to vaccination for their children. In a November 2021 survey conducted by the Kaiser Family Foundation, 50% of parents reported that they had already had their adolescent children vaccinated, but 4% said they would vaccinate their children only if vaccination was required for school attendance, and 13% said they would “wait and see” before having their children vaccinated. The most worrisome finding was that 30% of parents said they were definitely opposed to vaccination for their children. Given the importance of Covid-19 vaccination, we believe adolescents should be able to independently consent to vaccination, even when their parents don’t want them to be vaccinated.

The ability of adolescents to consent to Covid-19 vaccination is complicated by inconsistent regulations. Adults are legally presumed to have medical decision-making capacity. Whether an adolescent legally has medical decision-making capacity depends on the state — and in some cases, the local jurisdiction. All but a few states consider 18 years to be the age of majority (at which people are granted full personal legal responsibility). Nine states and the District of Columbia, however, allow younger adolescents who are capable of giving informed consent to make general medical decisions on their own behalf. Four states and the District of Columbia have age thresholds that are lower than 18 years, whereas the other half don’t specify a minimum age for independent medical decision making. Complicating matters further, some local jurisdictions have established their own regulations — San Francisco, for example, allows children as young as 12 to consent to receiving Covid-19 vaccines.

In most states, parental permission is still required for the vaccination of an adolescent under 18. The scope of child-welfare protections allows parents substantial discretion to make medical decisions for their children according to their own values. In nearly all these states, however, there are statutory exceptions to this general standard. Current exceptions to parental-consent requirements include allowing adolescents to seek contraceptive and abortion services and treatment for substance use disorders, mental health disorders, and sexually transmitted infections (STIs) without parental permission. In a few states, adolescents can also receive diagnostic services and treatment for reportable and other communicable diseases (other than STIs) without a parent’s permission. In even fewer states, they can receive preventive services for these conditions; these states can actively encourage adolescents to consent to Covid-19 vaccination.

One approach to increasing adolescent-vaccination rates would be to increase the number of states that allow adolescents to independently consent to general medical treatment when treatment is in their best interest. A more feasible strategy would involve encouraging all states that already have laws allowing some statutory exceptions to parental-consent requirements (e.g., exceptions for the detection and treatment of STIs) to expand their lists of exceptions to include the prevention, diagnosis, and treatment of reportable diseases and other diseases of public health importance. This approach would be focused primarily on states that don’t allow exceptions to parental-consent requirements for most reportable diseases, but do have exceptions for substance use disorders, mental health disorders, or STIs. If these states expanded their lists of exceptions, at least some adolescents in every or nearly every state could independently consent to being vaccinated against infectious diseases, including Covid-19.

When it comes to the most common exceptions to parental-consent requirements (contraceptive and abortion services and treatment for substance use disorders, mental health disorders, or STIs), the primary justification for allowing adolescents to independently consent to care is that being denied access to any of these forms of care could negatively affect an adolescent’s life. The same is true of Covid-19 vaccines. Adolescents may want to be vaccinated to protect themselves, their family, and their friends and to participate in in-person events. A requirement for parental permission could also lower the chances that an adolescent will seek desired treatment and preventive services. Just as adolescents may be uncomfortable bringing up topics such as contraception and substance use disorder treatment with their parents, raising the topic of Covid-19 vaccination (including expressing an intention to be vaccinated) may be uncomfortable when adolescents know their parents are opposed to Covid-19 vaccination more generally.

Given the evidence regarding the individual and public health benefits associated with Covid-19 vaccination, should adolescents who are interested in being vaccinated need to forgo vaccination because their parents have the legal authority to withhold permission? Allowing adolescents to bypass their parents or override their parents’ refusal of consent probably won’t sit well with affected parents. Given the implications for personal and public health, however, we believe parents’ desire to refuse vaccination shouldn’t be sufficient justification for preventing willing adolescents from receiving Covid-19 vaccines. Some people argue that adolescents aren’t competent to make their own decisions about vaccines and therefore shouldn’t be allowed to independently consent to vaccination. When peer pressure and emotional arousal are minimized, however, adolescents over 14 years of age are “just as mature as adults” when it comes to medical decision making. The past year has seen extensive advocacy by adolescents promoting vaccination. One teen-run website (vaxteen.org), for example, provides teenagers with relevant information about vaccines and consent laws by state to encourage and facilitate teenage vaccination. Moreover, vaccines are clearly beneficial for adolescents individually and for society more generally; the favourable risk–benefit profile of Covid-19 vaccination tips the balance in favour of facilitating adolescents’ access to vaccination.

There is a need for research on the frequency with which adolescents who are interested in Covid-19 vaccination encounter barriers and whether requirements for parental permission limit their access to vaccines or lead them to resort to deception in seeking vaccination. If future research shows that adolescents make decisions about Covid-19 vaccination thoughtfully and with a clear understanding of the risks and benefits involved, it will be evidence of their capacity to make decisions regarding vaccination against Covid-19 and will strengthen the case that they should have the legal authority to independently consent to vaccination.

Allowing adolescents to independently consent to Covid-19 vaccination could substantially increase vaccine uptake in this population. The process of obtaining consent from adolescents doesn’t have to mirror the consent process for adults. Since adolescents may be more susceptible to peer pressure and emotional influences than adults, conversations about consent could occur only in private encounters with medical professionals delivering vaccines (whether in private offices, clinics, pharmacies, or schools). We believe that allowing adolescents to independently consent to Covid-19 vaccination is on par with allowing independent consent to any intervention that is in adolescents’ best interest and supports an important public health goal:

https://www.nejm.org/doi/full/10.1056/NEJMp2116771?

 

Snippets:

Last year’s efforts by public health authorities to ward off a “twindemic” of COVID-19 and influenza appear to have paid off in the form of increased flu vaccinations, according to a CDC report. Recent data from 10 states and New York City show that overall, flu vaccinations increased by 9% during the last quarter of 2020 compared with the same time period in 2018 and 2019. Driving the increase were adolescents, who received about 13% more vaccine doses, and adults aged 18 to 64 years, whose vaccinations rose by about 15%. A more modest 9.5% increase occurred in those aged 65 years or older. The number of doses administered to children and adolescents aged 5 to 12 years was similar during all 3 time periods, but it declined considerably among the youngest children in late 2020. Clinicians administered almost 14% fewer doses to infants and toddlers aged 6 to 24 months and 12% fewer to children aged 2 to 4 years during 2020’s last quarter compared with the 2 previous flu seasons. Data from the National Immunisation Survey-Flu and the Behavioral Risk Factor Surveillance System documented similar flu vaccination trends, the authors noted. They pointed out that even though it doesn’t protect against COVID-19, influenza vaccination was part of a public health strategy during the 2020-2021 flu season to flatten the overall curve of respiratory illnesses, protect essential workers from the flu, and conserve medical resources for patients with COVID-19. During the current flu season, “Influenza vaccination among all age groups could help reduce the spread of influenza…and reduce the potential burden that influenza cases could place on health care systems already overburdened by COVID-19,” the authors wrote:

https://www.cdc.gov/mmwr/volumes/70/wr/mm7045a3.htm?s_cid=mm7045a3_w

Lung autopsy studies, which include analyses of plasma samples from 6 of the patients, demonstrate how SARS-CoV-2 not only spreads in the lungs and damages them, but also how it affects immune system responses. The researchers determined that SARS-CoV-2 infected respiratory epithelial cells, which aid in generating and repairing lung tissue, via a different process than influenza. According to the authors, fatal influenza often results from secondary bacterial copathogenesis, unlike fatal COVID-19, which produces pulmonary damage and associated immune responses so severe that coinfection isn’t necessary for the disease to become deadly. Individuals who died more than 20 days following initial COVID-19 symptoms exhibited high levels of pulmonary fibrosis. Furthermore, several individuals had widespread thrombosis, and each had diffuse alveolar damage—a potentially fatal condition that prevents adequate oxygenation of the blood and ultimately stiffens the lungs, according to the study. All autopsied individuals died between March and July 2020, within 3 to 47 days of symptom onset; they were also diagnosed with at least 1 high-risk factor associated with severe COVID-19. The researchers concluded that their findings may help to predict case severity and recovery among people who are elderly or have obesity or diabetes when they develop COVID-19. The authors noted that the links they uncovered between disease processes and patients’ comorbidities such as diabetes may provide insight into tailoring existing COVID-19 therapeutics based on the stage of the illness:

https://www.science.org/doi/10.1126/scitranslmed.abj7790

It is not fully understood why COVID-19 is typically milder in children. To examine differences in response to SARS-CoV-2 infection in children and adults, a group analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy paediatric airways, they observed cells already in an interferon-activated state, that upon SARS-CoV-2 infection was further induced especially in airway immune cells. They postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression. The systemic response in children was characterised by increases in naive lymphocytes and a depletion of natural killer cells, while in adults cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. They provide evidence that dendritic cells initiate interferon signalling in early infection, and identify novel epithelial cell states that associate with COVID-19 and age. Their matching nasal and blood data showed a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were massively reduced in paediatric patients. Together, they provide several mechanisms that explain the milder clinical syndrome observed in children:

https://www.nature.com/articles/s41586-021-04345-x

Next, researchers show that the Omicron spike confers very significant evasion of vaccine elicited neutralising antibodies that is more pronounced for ChAdOx-1 adenovirus vectored vaccine versus BNT162b2 mRNA vaccine. Indeed neutralisation of Omicron was not detectable for the majority of individuals who had received two doses of ChAdOx-1. Third dose mRNA vaccination rescues neutralisation in the short term. Despite three mutations predicted to favour spike S1/S2 cleavage, observed cleavage efficiency is lower than for wild type Wuhan-1 D614G and Delta. They demonstrate significantly lower infectivity of lung organoids and Calu-3 lung cells expressing endogenous levels of ACE2 and TMPRSS2 but similar infection as compared to Delta when using H1299 lung epithelial cells. Importantly, fusogenicity of the Omicron spike is impaired, leading to marked reduction in syncitia formation. These observations indicate that Omicron has gained immune evasion properties whilst possibly modulating properties associated with replication and pathogenicity:

https://www.biorxiv.org/content/10.1101/2021.12.17.473248v1

A team evaluated the relative performance of saliva and mid-turbinate swabs as RT-PCR samples for the Delta and Omicron variants. The positive percent agreement (PPA) of saliva swabs and mid-turbinate swabs to a composite standard was 71% (95% CI: 53-84%) and 100% (95% CI: 89-100%), respectively, for the Delta variant. However, for the Omicron variant saliva and mid-turbinate swabs had a 100% (95% CI: 90-100%) and 86% (95% CI: 71-94%) PPA, respectively. This finding supports ex-vivo data of altered tissue tropism from other labs for the Omicron variant. Reassessment of the diagnostic testing standard-of-care may be required as the Omicron variant become the dominant variant worldwide:

https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1

Is substantial weight loss achieved with weight loss surgery associated with improved risk and severity of COVID-19 infection in patients with obesity? In this cohort study of 11,809 patients with obesity, the rates of positive SARS-CoV-2 test results were comparable among patients in the surgical group and control group. However, previous weight loss surgery was significantly associated with a 49% lower risk of hospitalisation, 63% lower risk of need for supplemental oxygen, and 60% lower risk of severe disease during a 12-month period after contracting COVID-19 infection. The findings from this study show an association between weight loss achieved with surgery and improved outcomes of COVID-19 infection, suggesting that obesity can be a modifiable risk factor for the severity of COVID-19 infection:

https://jamanetwork.com/journals/jamasurgery/fullarticle/2787613

What is an ideal balance between alternative care modalities implemented during the COVID-19 pandemic and traditional care in the post-pandemic care model? This survey study of 1529 chronically ill adults found that patients would choose alternative care (ie, teleconsultations, symptom-checkers, and remote monitoring) over the traditional care equivalent for 22% to 52% of their future needs. The study identified 67 care activities, patient characteristics, and characteristics of alternative care modalities for which patients considered it appropriate to replace traditional with alternative care. Alternative care modalities implemented during the pandemic could be used to deliver nearly half of patients’ post-pandemic care:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787586

Researchers found that patients with covid-19 admitted to hospital and those managed in the community had higher GP consultation rates for most symptoms and diseases, received more prescriptions, and were more likely to use healthcare resources after covid-19 than in the 12 months before infection, although the rates in the two groups differed. For example, although the rates for primary care consultations for symptoms such as fatigue, breathlessness, and palpitations were similar between the two groups, patients in the community were more likely to consult their GP because of loss of taste and smell and muscle pain; patients admitted to hospital were more likely to report ongoing problems related to nausea and delirium. Although healthcare use increased in both groups after covid-19 relative to levels before the pandemic, the increase was higher in patients admitted to hospital for all types of healthcare use. Nevertheless, healthcare use in the group managed in the community increased by 18% after covid-19 compared with levels before the pandemic, highlighting the need for adequate ongoing provision of care for this population. They also found that some outcomes improved after vaccination in the cohort managed in the community, giving hope that with time and increased vaccination rates most sequelae will resolve. We also saw a decrease over time in drug prescriptions, in particular for bronchodilators. Whether fewer prescriptions was a consequence of lack of improvement in symptoms with bronchodilators or increased recognition of dysfunctional breathing after covid-19 needs further investigation:

Above is incidence of healthcare use outcomes after covid-19 infection compared with 12 months before covid-19 infection, in patients admitted to hospital with covid-19, in patients managed in the community, and in the influenza cohort:

https://www.bmj.com/content/375/bmj-2021-065834

The objective of a study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir in Columbia. In a large randomised trial, the combined use of all the drugs reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use:

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00523-X/fulltext

A group describe how they used Twitter to investigate vaccine-induced side effects:

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(21)00378-1/fulltext

A group show that vaccine effectiveness is significantly reduced against the Omicron variant in association with neutralising antibody responses from dual and triple recipients of the BNT162b2 (Pfizer), ChAdOx1 (Astra Zeneca) and mRNA-1273 (Moderna) COVID-19 vaccines. Further, using live virus culture and viral pseudotypes, we describe an altered entry pathway that favours endosomal fusion over the TMPRSS2-dependent, cell surface fusion utilised by all previous variants of SARS-CoV-2. In summary, Omicron exhibits significant antigenic and biological changes that underpin immune evasion and hyper-transmissibility and could affect the pathogenesis and clinical severity of disease:

Omicron infects lung cells less well too:

https://www.gla.ac.uk/media/Media_829360_smxx.pdf

Graphs:

Hospitalisation in Gauteng:

Source: National Institute for Communicable Diseases

Time series of primary series/booster vaccinations (top), new COVID cases (middle) and current hospitalisations due to COVID (bottom) in the US:

Emerging hot spots in the US. The x-axis is growth rate of new cases compared to last week, the y-axis is the new case per hundred, and z is the latitude. Each state is colour coded by vaccination rate:

Back to Work Chart and Upcoming Vaccine Catalysts:

Percentage of hospital bed utilisation by US State:

US vaccinations:

Daily vaccinations in key regions:

Vaccinations vs Deaths in various countries:

Vaccine orders by country. The number on top of each bar shows the % of the population that the orders in place can cover. Note that countries whose orders cover <25% of their population were excluded:

Google search interest of three terms regarding COVID vaccines over the past 3 months:

Daily vaccinations in the US and Google trends of keywords around vaccination:

 

Variant for children development timeline:

 


Justin Stebbing
Managing Director

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