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Covid-19 Breakthrough Infections in Vaccinated Health Care Workers



Breakthrough infections

Of 11,453 fully vaccinated healthcare workers, 1,497 (13.1%) underwent RT-PCR testing during the study period. 39 breakthrough cases were found among the workers tested. For each positive case found, more than 38 people were tested for a test positive of 2.6%. Thus, this percentage was much lower than the test positive rate in Israel at the time, as the ratio between positive results and the extensive number of tests performed in our study was much lower than in the national population.

Of the 39 breakthrough patients, 18 (46%) were nurses, 10 (26%) were administrative or maintenance personnel, 6 (15%) were related health professionals, and 5 (13%) were physicians. The mean age of the 39 workers infected was 42 years and the majority were women (64%). The median interval from the second vaccination dose to the detection of SARS-CoV-2 was 39 days (range 11 to 102). Only one infected person (3%) had immunosuppression. Other comorbidities are listed in Table S1.

For all 37 case patients for whom data on the source of infection were available, the suspected source was an unvaccinated person; in 21 patients (57%) that person was a member of the household. These case patients included two married couples where both spouses worked at Sheba Medical Center and had an unvaccinated child who had tested positive for Covid-19 and was suspected to be a source. In 11 of 37 case patients (30%), the suspected source was an unvaccinated health care worker or patient; in 7 of the 11 case patients the infection was caused by a nosocomial outbreak of variant B.1.1.7 (alpha). These 7 patients, who worked in different hospital sectors and wards, were found to be all related to the same suspected unvaccinated index patient who had received non-invasive positive pressure ventilation prior to being infected.

Of the 39 cases of infection, 27 occurred in workers who were tested solely for exposure to a person with a known SARS-CoV-2 infection. Of all workers with breakthrough infection, 26 (67%) had mild symptoms at some point and none had to be hospitalized. The remaining 13 workers (33% of all cases) were asymptomatic for the duration of the infection; 6 of these workers were defined as borderline cases because they had an N-Gen-Ct value of more than 35 when tested again.

The most commonly reported symptom was upper airway congestion (36% of all cases), followed by myalgia (28%) and loss of smell or taste (28%). Fever or chills were reported in 21% (Table S1). In the follow-up survey, 31% of all infected workers stated that they still had residual symptoms 14 days after diagnosis. 6 weeks after their diagnosis, 19% said they had “long-term Covid-19” symptoms, including persistent loss of smell, persistent cough, fatigue, weakness, dyspnoea, or myalgia. Nine workers (23%) were taken off work beyond the 10 days of required quarantine; of these workers, 4 returned to work within 2 weeks. One worker had not returned after 6 weeks.

Verification tests and secondary infections

Repeated RT-PCR assays were performed on specimens collected from most infected workers and for all patients with an initial N-Gen Ct greater than 30 to ensure that the first test was not performed too early before the worker became infectious. A total of 29 case patients (74%) had a Ct value below 30 at some point during their infection. Of these workers, however, only 17 (59%) had positive results with simultaneous Ag-RDT. Ten workers (26%) had an N-Gen-Ct value of over 30 over the entire period; 6 of these workers had values ​​over 35 and were probably never contagious.

Of the 33 isolates tested for a variant of concern, 28 (85%) were identified as a B.1.1.7 variant by either multiplex PCR assay or genome sequencing. At the time of this study, variant B.1.1.7 was the most widespread variant in Israel and accounted for up to 94.5% of the SARS-CoV-2 isolates.1,16 Since the end of the study, the country has had a flood of cases caused by the delta variant, like many other countries worldwide.

Thorough epidemiological investigations of the data on contact tracing in the hospital revealed no transmission by infected nursing staff (secondary infections) in the 39 primary infections. No secondary infections were detected among the 31 cases for which household transmission data (including symptoms and RT-PCR results) were available, including 10 case patients and their 27 household members where the healthcare professional was the only index case patient.

Data on N-specific IgG antibodies after infection were available for 22 of 39 case patients (56%) on days 8 to 72 after the first positive result in the RT-PCR test. Of these workers, 4 (18%) had no immune response, as evidenced by negative results in N-specific IgG antibody tests. Of these 4 workers, 2 were asymptomatic (Ct values ​​32 and 35), 1 was not examined serologically until day 10 after diagnosis and 1 had immunosuppression.

Case-control analysis

The results of periinfection-neutralizing antibody tests were available for 22 groundbreaking cases. This group included 3 health care workers who participated in the serological study and who had a test in the week prior to the discovery; In 19 other workers, neutralizing and S-specific IgG antibodies were determined on the detection day. Of these 19 case patients, 12 were asymptomatic at the time of discovery. For each case, 4 to 5 controls were matched as described (Fig. S1). A total of 22 breakthrough cases and their 104 matching controls were included in the case-control analysis.

Table 1. Table 1. Population characteristics and results in the case-control study. Figure 2. Figure 2. Neutralizing antibody and IgG titers in cases and controls, depending on the point in time.

Among the 39 fully vaccinated health care workers who had a breakthrough infection with SARS-CoV-2, the neutralizing antibody titers are during the peri-infection phase (within a week before SARS-CoV-2 detection) (Panel A) and the peak Titer within 1 month after the second dose (panel B) compared to the corresponding controls. Also shown are IgG titers during the peri-infection period (Panel C) and peak titers (Panel D) in the two groups. Each breakthrough infection was compared with 4 to 5 controls according to gender, age, immunosuppression status and time of serological testing after the second vaccine dose. In each panel, the horizontal bars show the geometric mean titers and the bars show 95% confidence intervals. Symptomatic cases, all of which were mild and did not require hospitalization, are highlighted in red.

Figure 3. Figure 3. Correlation between neutralizing antibody titer and N-gene cycle threshold as an indication of infectivity.

The results of the antigen-detecting (Ag) rapid diagnostic tests for the presence of SARS-CoV-2 are shown along with neutralizing antibody titers and N-gene cycle thresholds (Ct) in 22 fully vaccinated healthcare workers with breakthrough infection for whom data were available ( Slope of the regression line, 171.2; 95% CI, 62.9 to 279.4).

The predicted GMT of the periinfection neutralizing antibody titre was 192.8 (95% confidence interval [CI], 67.6 to 549.8) for cases and 533.7 (95% CI, 408.1 to 698.0) for controls, for a predicted case-to-control ratio of neutralizing antibody titers of 0.361 (95% – KI, 0.165 to 0.787) (Table 1 and Figure 2A). In a subgroup analysis in which the borderline cases were excluded, the ratio was 0.353 (95% CI, 0.185 to 0.674). Periinfection-neutralizing antibody titers in the breakthrough cases were associated with higher N-gene Ct values ​​(i.e., lower viral RNA copy number) (slope of the regression line, 171.2; 95% CI, 62.9 to 279.4)Figure 3).

A peak in neutralizing antibody titer within the first month after the second dose of vaccine was only available for 12 of the breakthrough cases; the maximum neutralizing antibody titre predicted by GEE was 152.2 (95% CI, 30.5 to 759.3) in 12 cases and 1027.5 (95% CI, 761.6 to 1386.2) in 56 controls, for one Ratio of 0.148 (95% CI, 0.040 to 0.548) (Figure 2B). In the subgroup analysis, in which borderline cases were excluded, the ratio was 0.114 (95% CI, 0.042 to 0.309).

The observed and predicted GMTs of peri-infection S-specific IgG antibody levels in breakthrough infection cases were lower than controls, with a predicted ratio of 0.514 (95% CI, 0.282-0.937) (Figure 2C). The observed and predicted IgG GMT peak values ​​were also slightly lower in the cases than in the controls (0.507; 95% CI, 0.260 to 0.989) (Figure 2D).

In order to assess whether our approach to measuring antibodies on the day of diagnosis led to biases due to the recording of anamnestic reactions to the current infection, we examined 13 patients in whom both values ​​were present. In all cases, the periinfection titers were lower than the previous peak titers, suggesting that the titers obtained on the day of diagnosis were likely representative of the periinfection titers (Fig. S2).

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Opinion: The good news about J&J’s Covid-19 vaccine



Put yourself back to the February 2021 mindset. We had a desperate shortage of vaccines, and I and other medical and public health officials were encouraging people to “get the first vaccine you are offered”. At this point, J&J felt like a game changer.

It could dramatically increase capacity and reduce supply chain challenges. Its reported effectiveness was slightly less than that of the Moderna or Pfizer mRNA vaccines, but was still strong; Clinical studies showed it to be 66% effective in preventing moderate to severe illness, 85% effective in serious illness, and 100% effective in preventing death.

As a “one and done” shot, it would also help the needle phobes, the mRNA hesitation, or just people who would never return for a second visit to protect themselves.

But then the floor fell out. For a combination of reasons, J&J was viewed by some as the third stage vaccine.

An extremely rare but severe blood clotting syndrome was identified as a possible side effect in mid-April. And just a few weeks earlier, millions of J&J cans had to be thrown away due to a production mix-up. Some vaccination centers across the country even started phasing out vaccination. The number of new people vaccinated with this vaccine slowed to a trickle.Many of the roughly 14.8 million Americans who received J&J probably and rightly felt like the forgotten. It was becoming increasingly rare for J&J to be the subject of major news updates while Pfizer and Moderna drew attention to the possibility of booster shots. My own guide for friends and neighbors evolved into that of New York Times writers David Leonhardt and Ian Prasad Philbrick: Proceed at your own risk. J&J recipients began to feel that instead of getting the first choice, they had received the scum. Then finally, this week, we got some good news about J&J. After a disappointing summer wave from Delta it was exactly what we needed. On September 16, a preprint study reported that the J&J vaccine maintained its effectiveness against both symptomatic disease and hospitalization between March and late July – despite the rise of the Delta variant.

This finding suggests that J&J is potent against this novel variant. In other words, J & J’s vaccine has staying power.

In a moment of tremendous uncertainty, this analysis enables J&J receivers to sleep more easily after receiving only a single shot.

Then, on September 21, a press release from Johnson and Johnson shared more promising data suggesting that protection against all forms of Covid-19 with a J&J booster shot is just superb. After an eight-week refresher, the vaccine’s effectiveness against severe or critical Covid-19 was almost 100% (albeit with large estimates: the confidence interval ranged from 33% to 100%) and protection against moderate to severe Covid-19 disease was in the USA at 94% (the confidence interval in this case was 58% – 100%). In a pandemic for which nothing is guaranteed, 100% sounds pretty good.

A six month booster dose showed preliminary signs that they were even better based on antibody measurements, although actual clinical results were not reported. The safety metrics for both the eight-week and six-month boosters are reportedly excellent.

What the Arizona sham audit really taught us

This press release gives hope for the future to our 14.8 million J&J recipients: if the second dose of J&J is approved by the U.S. Food and Drug Administration, they won’t be left behind when and when boosters hit the market.

I have to make the usual reservations, of course. This data was published in preprints and press releases. They haven’t been reviewed by the FDA. There are still many questions to answer about age, gender, race, and ethnicity. And most importantly, I want to see the data for security. While there is a slim chance of getting a very unusual type of blood clot from the J&J vaccine, there is also the possibility of developing a blood clot if you are hospitalized with a diagnosis of Covid-19. But we also need to see data on what happens after a second shot – the same caution I gave to boosters for Pfizer and Moderna.

Despite these warnings, the findings are positive.

For those who have already received J&J, I am now confident to tell you that you are just as protected as I am (having completed my Pfizer vaccine series more than eight months ago). Hold on for a booster. Feel better with your choice.

Equally important, if you have not yet been vaccinated, J&J is clearly a very good choice. In fact, I will now be suggesting this vaccine a little more strongly to my emergency room patients who have not yet been vaccinated and who often face barriers to initial two-shot treatment.

I also hope that this vaccine, which is easier to transport and administer, can help us meet the immense global need for vaccination – without making citizens feel like they are receiving a second-class choice.

The big picture? After all, with those stats in hand, J&J no longer looks like it’s a minor choice.

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Alaska reports nearly 1,800 new COVID-19 cases and 44 deaths, in part due to backlog



Alaska broke multiple daily records for COVID-19 case numbers, hospital admissions and deaths on Friday, but public health officials said the high numbers were at least partially due to a lack of data.

Due to backlogs in data entry, the roughly 1,800 new cases reported Friday have been bloated by several hundred older cases, health officials said.

“That doesn’t detract from the fact that we continue to see the tremendous spread of COVID in our communities,” said Dr. Anne Zink, Alaska Chief Medical Officer, on a call to the news media.

The 41 Alaskan deaths from COVID-19 reported on Friday occurred mostly in the past month, officials said. Some even took place earlier this year and hadn’t been added to the list due to a cyberattack that hampered the state’s system of recording deaths.

However, a record of 217 hospital admissions reported on Friday was not part of the backlog and represents the growing number of people suffering from COVID-19 in need of hospital treatment in Alaska.

Last month the state had its “highest incidence of cases we have ever seen, weighing on our public health infrastructure, our hospitals, our businesses and our economy,” said Zink.

The majority of the 44 deaths reported Friday – including 41 residents and three non-residents – were deaths that occurred in August and identified through a standard death certificate check, officials said Friday.

[Alaska health workers face anger and threats from COVID patients and public, chief medical officer says]

Government agencies rely on death certificates to report COVID-19 deaths. If a doctor believes that COVID-19 infection contributed to a person’s death, it will be included on the death certificate and eventually counted in the state’s official toll, according to the DHSS.

Some deaths are reported directly to the state, while other deaths are less clear-cut than others and take longer to review, said epidemiologist Dr. Louisa Castrodale.

“Hospitals will call us and say, ‘Hey, we had this unfortunate death, we really think it’s COVID and we’re going to report it to you,'” she explained.

“Hospitals will also call us and say, ‘Hey, we have this person who died. There is a lot going on with this person, we are not sure what the provider will ultimately write on the death certificate. ‘ So that’s what we’re waiting for, ”she said.

Ultimately, every single COVID-19 death that the state reports has a death certificate listing COVID-19 as a contributing cause of death, and each one goes through a rigorous review process, Castrodale said.

[How do COVID-19 deaths in Alaska get counted?]

About a dozen of the deaths reported on Friday occurred in the spring; for these, reporting was delayed by a cyber attack in May that targeted the state health department and left many of its systems offline for months, officials said.

The continued high number of COVID-19 patients continues to overwhelm healthcare facilities across the state.

Record hospital stays – and long waiting times in the emergency room

As of Friday, a state dashboard reported a new record of 217 people hospitalized across the state with COVID-19 – higher than at any point in the pandemic and well above last winter’s high.

Hospitals say their numbers likely haven’t counted the true effects of COVID-19 enough, as they don’t include some long-term COVID-19 patients who have stopped testing positive but are still in need of hospital treatment.

Earlier this week, state officials announced that they would implement crisis standards for care nationwide, a worst-case scenario that forces hospitals to ration supplies due to resource and staffing constraints.

Hospitals across the state continue to report long emergency room waits, late procedures and limited transfers, and in at least one case, the death of a patient who was unable to receive timely care.

The vast majority of cases, hospitalizations, and deaths in Alaska have been in people who have not been vaccinated.

In August in Alaska, state data showed residents were 8.3 times less likely to be hospitalized if they were vaccinated than if they were unvaccinated, Zink said Friday.

The new record of 1,793 new virus cases on Friday – including 1,735 residents and 58 non-residents – followed Thursday’s previous record of 1,330 cases plus seven deaths.

Fall residue

A few hundred of the cases reported on Friday were from positive test results from the last week and the week before, and some even before that, Castrodale said. She estimated that once the state clears its backlog, it will expect around 1,000 cases a day.

Since the state found ways to automate newer cases, they have been able to examine and catch up on older case reports, Castrodale said.

The delays in data reporting make it difficult to compare daily numbers, and Zink said it may be more helpful to look at the overall trend each week. She stressed that throughout September, the state had the highest number of cases ever.

The delays are also coming from a variety of locations, officials said, including certain overwhelmed testing facilities all of which are sending their results for several days at a time, as well as a limited number of staff amid a host of new cases.

“We only have a limited number of people on the team, so we’re doing our best to get it,” said Zink.

Alaska’s per capita fall rate remains the highest in the country – and about three times the national average, according to a New York Times tracker.

Nationwide, 9.23% of the tests carried out last week gave positive results.

Among eligible Alaskans 12 and older, 62.8% had at least one dose of the COVID-19 vaccine, while 58.5% were considered fully vaccinated by Thursday.

The deaths involved residents from across the state, including 11 from Anchorage, six from Wasilla, four from Fairbanks, three from Ketchikan, three from Juneau, two from Soldotna, two from Bethel, one from Homer, one from North Pole, one from Tok, one from Big Lake, one from Petersburg, one from Palmer, one from Kenai, one from Willow, one from a small community in the northwest of the Arctic, and one from Sitka.

Fairbanks also recorded three deaths from non-residents.

Almost half of the deceased were over 70 years old. Fourteen were in their 50s or 60s, two were in their 40s, two were in their 30s, and two were in their 20s.

A total of 514 residents and 18 non-residents in the state have died of COVID since the pandemic began.

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Booster shot or not? Mixed messaging creates distrust during COVID-19 pandemic



CLEVELAND, Ohio – Don’t wear masks; wear them. Masks protect you; Masks protect others. The only thing that was consistent about the masking of health professionals at the start of the pandemic was the inconsistency that left many Americans confused and skeptical.

Now the public is experiencing a similar whiplash injury from having the COVID-19 vaccine booster. First, President Joe Biden released a plan to bring Pfizer boosters to everyone. An advisory body to the US Food and Drug Administration rejected the plan.

Then an advisory panel from the U.S. Centers for Disease Control and Prevention changed the game again on Thursday, recommending boosters for people 65 and over, people with pre-existing conditions and residents of nursing homes. And late at night, CDC director Dr. Rochelle Walensky prompted the committee’s decision to exclude frontline workers at increased risk of exposure.

What are the implications of all of the rapidly changing health policies and conflicting messages? Another type of pandemic – an increase in conspiracy theories, disinformation and a lack of confidence in the system that was created to protect us.

“The uncoordinated news that has occurred may be the biggest public health failure we’ve seen with COVID-19,” said Scott Frank, director of the public health program at Case Western Reserve University School of Medicine. “In public health, the first rule of a pandemic is always to present a single message.”

Frank said the idea that the booster was ready for a widespread release is premature and a good example of what he calls “news drift”.

Frank said it was important to come up with a coordinated response. Advances in science have helped the medical community fight COVID-19 in unprecedented ways, but it’s not without its consequences.

“Before, we wouldn’t have had the science that would have allowed us to change course in the middle of the stream. We would have stayed with our original plan and had a consistent message, ”said Frank. “But it would have been the wrong message. The fact that we had a change in science doesn’t mean scientists are upset; it means we are discovering new information that will enable us to take a more effective course in fighting the virus. “

Raed Dweik, a Cleveland Clinic doctor and a member of the hospital’s COVID-19 response team, said one of the most troubling aspects of the pandemic had been uncertainty.

“This uncertainty has been tough for a lot of people not only in the community but also in the medical field because we have to understand it ourselves so we can convey it to the public,” said Dweik. “I know it is awkward for people not to have definitive answers, but this is a sign of the times.”

For ethnic and ethnic minority populations, the insecurity and fear caused by inconsistent messaging are compounded by a lack of trust stemming from years of public health inequalities while being disproportionately affected by COVID-19, Frank said .

And since the early days of the pandemic, the interface between politics and medicine created a power dynamic that led to contradicting messages. Around the world, each country set its own safety plan, while here in the US, states advanced with different approaches, each backed by unique scientific research working with a variety of medical experts.

“The push-and-pull between science and politics has contributed most to the distrust,” said Frank. “Scientists have been asked to justify or rationalize some policy decisions that were not based on rational science.”

As this decision and scientific information evolves, the Internet provides a breeding ground for misinformation and disinformation – arguably more damaging as it is shared with the intent to deceive. Although the problem plagued online platforms long before the pandemic, COVID-19 exacerbated the problem as disinformation was turned into weapons to serve individual agendas rather than serve the health of the community.

“It can land on ears that may have a basic distrust of vaccines, healthcare, government, or science,” Frank said. “These messages are amplified by people on social media who have a tendency to believe these messages and convey them to others. It is quite painful to see people you know and trust spread messages that actually harm their neighbors and the people we care about. “

The challenge for the public health system is to maintain the public’s beliefs while mixed messages increase suspicion. For Frank and Dweik the answer is simple: create trust through coordinated and systematic communication.

The Cleveland Clinic has developed a strategy of communicating quickly and frequently while their experts share their knowledge of COVID-19 – and most importantly, what they don’t know – based on the latest data.

“A lot of things come out that are speculation or guesswork,” said Dweik. “It is not easy for us as doctors to say that we do not know. But it’s better … than saying something that isn’t backed up or supported by science and evidence. “

Cuyahoga County Health Department will decide its recommendations and the timing of their release based on the best possible way to prevent hospitalizations and death. However, these decisions can be at the expense of public opinion, according to Terry Allan, health commissioner for Cuyahoga County.

“Information comes out quickly, and a fog can build up when people try to understand the steps,” Allan said. “Sometimes it’s not popular. That comes with every emergency and we have to live with it. “

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