“During July 2021, 469 cases of COVID-19 associated with multiple summer events and large public gatherings in [Provincetown] were identified,” the Centers for Disease Control and Prevention (CDC) reported.1 “Approximately three-quarters (346; 74%) of cases occurred in fully vaccinated persons.”


The CDC added the caveat that data “from this report are insufficient to draw conclusions about the effectiveness of COVID-19 vaccines against SARS-CoV-2, including the delta variant, during this outbreak.”

The outbreak prompted the CDC to call for a return to indoor masking among the vaccinated and raise a warning that even vaccinated people can transmit SARS-CoV-2 if they are shedding sufficient virus for transmission.

“[On] rare occasions, some vaccinated people infected with the delta variant after vaccination may be contagious and spread the virus to others,” CDC Director Rochelle Walensky, MD, MPH, said at a press conference before the report was released. “This new science is worrisome and, unfortunately, warrants us to update our recommendations. Vaccinated individuals continue to represent a very small amount of transmission occurring around the country.”

This science was not fully elucidated in the report, but it does mention that “cycle threshold values” of viral loads were similar among specimens from patients who were fully vaccinated and from those who were not vaccinated.

“High viral loads suggest an increased risk of transmission and raise concern that, unlike with other variants, vaccinated people infected with delta can transmit the virus,” Walensky said in a statement when the report was released. “This finding is concerning and was a pivotal discovery leading to the CDC’s updated mask recommendation [on July 27, 2021].”

The Right Decision?

Although delta had emerged in India in October 2020 and was being reported in other parts of the world, the CDC made the decision to lift mask requirements for vaccinated people on May 13, 2021, a time when cases were dropping and the pandemic had lulled in the United States. The potential for the delta variant to spread to the United States, become the predominant strain, and undermine vaccine efficacy was not anticipated by the nation’s leading public health agency.

“This [recommendation to mask again] doesn’t undo that serious error that the CDC made earlier,” said Larry Gostin, JD, a professor at Georgetown University Law Center in Washington, DC. “I understand why the CDC did that. It was not an unreasonable scientific decision, but it was a really poorly thought-out public health decision because it was entirely foreseeable at the time that both the vaccinated and unvaccinated would unmask. And that’s what happened — on day one.”

Of course, CDC scientists also were shocked to find delta could mount sufficient viral loads in the vaccinated to actually transmit the virus. A study published recently in preprint found that delta replicates to viral loads a thousand times higher than the original SARS-CoV-2 strain.2 That could in part explain its shorter incubation period, high transmissibility, and ability to cause breakthrough infections in the vaccinated.

Another study in Singapore documented breakthrough infections, but encouragingly found less serious infections and saw viral titers drop more quickly in vaccinated people.

“Of 218 individuals with B.1.617.2 [delta] infection, 84 had received a mRNA (messenger ribonucleic acid) vaccine, of which 71 were fully vaccinated, 130 were unvaccinated, and four received a non-mRNA [vaccine],” the authors reported.3 “Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination. PCR (polymerase chain reaction) cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals.”

According to a Yale Medicine report, delta spreads 50% faster than the first Alpha variant, which itself was about 50% more transmissible than the original SARS-COV-2 strain.4 The question of enhanced virulence still is somewhat unresolved, but a CDC internal meeting slide set says delta is “likely more severe.”5

The CDC cites three studies in the meeting materials that report indicators of increased virulence, with one from Canada finding higher odds of hospitalization, intensive care unit (ICU) admission, and death.6 Another study from Singapore cites higher odds of oxygen requirements, ICU admission, pneumonia, and death.7 Finally, a study from Scotland reports higher odds of hospitalization with the delta variant.8

In the meeting slides, the CDC emphasizes that “vaccines prevent > 90% of severe disease [caused by delta] but may be less effective in preventing infection or transmission. Therefore, more breakthrough and more community spread [may occur] despite vaccination.”

Breakthroughs always were expected at some level with coronavirus and, in general, the higher the vaccination rate of a given population, the greater proportion of infections will represent breakthroughs.

For example, Singapore has vaccinated about 75% of its population. In a recent report of about 1,000 recent infections, 44% were fully vaccinated. None of them became seriously ill.9

Independence and Illness

None of the aforementioned factors about delta were widely known or suspected — certainly not among the general public — when a large gathering of gay men went to Provincetown recently for the annual of Fourth of July week celebration.

“Most cases occurred in males (85%); median age was 40 years,” the CDC reported. “Persons with COVID-19 reported attending densely packed indoor and outdoor events at venues that included bars, restaurants, guest houses, and rental homes. [D]emographics of cases likely reflect those of attendees at the public gatherings, as events were marketed to adult male participants. Further study is underway to identify other population characteristics among cases, such as … underlying health conditions, including immunocompromising conditions.”

That raises the issue of human immunodeficiency virus (HIV) infection, which possibly could undermine vaccine efficacy.

“There is that issue, and there are all kinds of subsidiary issues, like people with undiagnosed HIV infections — are they the same [as those diagnosed]?” says William Schaffner, MD, an epidemiologist at Vanderbilt University in Nashville, TN. “Are they more or less likely to be vaccinated? When were they vaccinated? There are a lot of potential confounding variables here that are not acknowledged in this [CDC] report.”

It should be noted that most men attending events in Provincetown were fully vaccinated and, again, had been given the green light by the CDC in May 2021 that they could remove masks if immunized. A fully vaccinated man who attended the Provincetown festivities and came down with COVID-19 upon return to his hometown described the experience in a published account. Upon testing positive for SARS-CoV-2, he went into quarantine and kept hearing from gay friends — about two dozen — who also were in Provincetown and now were sick despite being vaccinated.

“This was to be our government-approved ‘hot vax summer,’ when masks came off and inhibitions could finally breathe again,” he wrote. “… For months, the CDC had advised us that breakthrough cases among the vaccinated were rare events.”10

Although there have been no reports of the pandemic respiratory virus being transmitted sexually in the traditional understanding of that term, the spatial closeness of intimate encounters at the gathering could have led to some transmission of the delta variant, Schaffner says. It could be that maskless encounters in public and private over several days made the highly transmissible variant a kind of opportunistic infection among this population.

Cases Surge Nationally

The general thinking is that breakthrough infections and transmission by vaccinated people still are relatively rare. However, the Provincetown outbreak raises the question of whether they may become more common with the delta variant now the dominant strain in the United States.

“Those [breakthrough] numbers seem inflated because it’s a relatively isolated [outbreak], if you will,” says Ann Marie Pettis, president of the Association for Professionals in Infection Control and Epidemiology (APIC) “We need a lot more data before we can really decide, can you spread the virus if you are vaccinated, as readily as you might believe, if you just looked at this one report? The jury’s out in my mind.”

Meanwhile the delta surge is driving cases nationally, with those hospitalized still primarily the unvaccinated. “In late June, our seven-day moving average of reported cases was around 12,000,” the CDC reported.11 “On July 27, the seven-day moving average of cases reached over 60,000.”

Shockingly, the latter case rate looks more like the toll of infections seen before the COVID-19 vaccines were widely available, the CDC noted.

“We’re seeing a lot younger people becoming infected, as well as hospitalized,” says Pettis, director of infection prevention for the University of Rochester (NY). “I know IPs (infection preventionists) like myself all over the country are really struggling with this right now — some areas worse than others. In my own area, just this last week, we more than doubled our number of cases. In our hospital, we went to zero cases to 15 in the matter of a day or two.”

On the other hand, the silver-lining effect of delta is that it may finally push some of the hesitant population to be vaccinated. “All of this attention that has been devoted to delta, including having to change the CDC guidelines, I think may have conspired in a positive way to drive up vaccine acceptance,” Schaffner says. “We are still nowhere near where we want to go, but in my own state — which has been very vaccine-reluctant — I’ve seen an increase in vaccinations.”

The CDC’s renewed emphasis on masking has brought that issue back, not only for people in public but now recommended by the agency for all school children this fall, he adds. “There has been a fair amount of chatter among the ID (infectious disease) docs in my community, and so far I haven’t found anyone who is against wearing masks in school,” he says. “We all think that it ought to be a standard practice across the country.”

Mandates Inevitable

There still is the question if vaccinated people will start donning masks again, although the delta variant certainly appears to warrant the measure.

“This time around, people are not quite as willing to pick up their cross and carry it, if you will,” Pettis says. “We are seeing more skepticism and reluctance in some people, but that is why it is important to keep sharing the data and the messaging.”

Unfortunately, the CDC complicated its new message by recommending a return to indoor masking for fully vaccinated people in areas with “substantial or high transmission” of COVID-19, Gostin says.12 The CDC referred to a map of U.S counties for determining whether any given local area has high or substantial transmission.13 Overall, about 89% of U.S. counties were designated as high or substantial transmission as of August 8, 2021.

“The current guidance, while better, is still confusing to the public,” Gostin says. “It differentiates in a different way — between communities with higher case rates and lower case rates. Well, no ordinary person is going to know whether they are in a high or low area. The data are changing every day. Guidance to the public has to be consistent and simple — a simple message like ‘mask up if you are indoors irrespective of vaccination.’ That should have [remained] the guidance all along. It’s very hard to turn the spigot on and off. When people throw away their masks, it is going to be hard to get them to put them back on.”

The lack of a national identification system to verify vaccination status remains a problem, and Gostin thinks the Biden administration should move on this issue. “You can’t set a guideline that sharply distinguishes between the vaccinated and unvaccinated and then give cities and states no guidance on how to make that differentiation,” he says.

The Department of Health & Human Services vaccine cards “are being procured, forged, and stolen,” he says. “It is not a credential within a system in any sense of the word. It should be reliable and confidential. A lot of countries have done this — Israel, France. I think they are resisting it [in the United States] because anything with any whiff of mandatory vaccination is ultimately going to fail. There is no scientific or public health reason for it — it is purely political.”

Yet, with the delta variant proving to be a game-changer, vaccination mandates of various kinds are looking inevitable.

“We’re seeing the federal government mandating vaccine for federal workers and contractors. California has done it and New York City has done it,” he says. “More and more businesses are doing it every day, from Facebook and Google to Microsoft.”

The nation is at a tipping point on mandates, as more companies and universities require them, he adds.

“Hospitals and health systems should have had mandates months ago, and any one of them that doesn’t have a mandate now is acting recklessly,” Gostin says.

REFERENCES

  1. Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings — Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep 2021;70:1059-1062.
  2. Li B, Deng A, Li K, et al. Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 delta variant. MedRxiv 2021; July 23. doi: https://doi.org/10.1101/2021.07.07.21260122. [Preprint].
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  6. Fisman DN, Tuite AR. Progressive increase in virulence of novel SARS-CoV-2 variants in Ontario, Canada. MedRxiv 2021; Aug. 4. doi: https://doi.org/10.1101/2021.07.05.2126005. [Preprint].
  7. Ong SWX, Chiew CJ, Ang LW, et al. Clinical and virological features of SARS-CoV-2 variants of concern: A retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). SSRN 2021; June 7. doi: 10.2139/ssrn.3861566. [Preprint]. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3861566
  8. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397:2461-2462.
  9. Aravindan A, Lin C. Vaccinated people make up 75% of recent COVID-19 cases in Singapore, but few fall ill. Reuters. Published July 23, 2021. https://www.reuters.com/world/asia-pacific/vaccinated-people-singapore-make-up-three-quarters-recent-covid-19-cases-2021-07-23/
  10. Rozen J. I was part of the July Fourth Provincetown “breakthrough” COVID cluster. It’s been a sobering experience. Slate. Published Aug. 2, 2021. https://slate.com/human-interest/2021/08/provincetown-delta-variant-cluster-diary.html
  11. Centers for Disease Control and Prevention. Delta variant: What we know about the science. Updated Aug. 6, 2021. https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html
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