Three SARS-CoV-2 variants of global concern now are in the United States, threatening to erode vaccine efficacy, undermine treatment, and increase both hospitalizations and deaths. Current vaccines are expected to hold to varying degrees against these highly transmissible variant strains, although efficacy may be diminished. With vaccine supply limited, masking, social distancing, and hand hygiene will be critical over the next few months.

What does that mean for infection prevention in hospitals? In a word, vigilance.

This was a point of emphasis by Ann Marie Pettis, RN, BSN, CIC, FAPIC, president of the Association for Professionals in Infection Control and Epidemiology (APIC).

“Nothing is really changing in terms of what we are doing and what we are recommending in our healthcare system,” says Pettis, director of infection prevention at the University of Rochester, NY. “As I talk to my colleagues all over the country, that is pretty much true across the board.”

The Food and Drug Administration (FDA) has granted emergency use authorization (EUA) to two messenger ribonucleic acid (RNA) vaccines for COVID-19 in the United States made by Moderna and Pfizer, which have respective efficacies of 94% and 95% against the original wild SARS-CoV-2 strain.

“Even if there were no variants, and you have vaccines with efficacy of 95% you still have that 5% of cases that can occur,” Pettis says. “Even if the variants hadn’t rose their ugly heads, we were already recommending that nothing change in terms of pre-testing for procedures or any of that. So, nothing was really changing even then, and now with these variants, certainly nothing is changing. No one is really comfortable in backing off from the recommendations that have been made.

“In our organization, we have over 85% of our staff who are vaccinated at this point,” Pettis says. “Even with that high amount of folks vaccinated, we are still telling them we cannot relax with personal protective equipment [PPE] at this point. The message has not changed at all despite vaccinations.”

William Schaffner, MD, professor of health policy at Vanderbilt University in Nashville, concurred with Pettis.

“I wouldn’t relax an inch,” he says. “I think we have to continue our very comprehensive infection control personal behaviors and using our PPE exactly as we are doing and not looking to relax that. I actually think that at this time and this is just personal opinion the healthcare environment is much safer than the community. My sense is that the substantial majority of the COVID infections that are being reported in healthcare now are coming from the community not at work.”

In that regard, APIC is conducting a social media “take the pledge” campaign encouraging the public to not let up on masking and other measures, even as vaccines become more available.

FDA Reviewing Third U.S. Vaccine

In what could mean a considerable boost toward herd immunity, a third vaccine was awaiting emergency use approval in the United States as this report was filed. The FDA scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Feb. 26, 2021, to discuss the request for EUA for a COVID-19 vaccine from the Janssen Biotech Inc. division of Johnson & Johnson (J&J).

To induce an immune response, the J&J vaccine uses an attenuated adenovirus to carry deoxyribonucleic acid (DNA) encoding the spike protein of the SARS-CoV-2 virus. Although a full assessment of adverse reactions and side effects will be done by the FDA, those listed in preliminary data include fatigue, headache, and muscle aches. Janssen’s one-shot vaccine was 66% effective overall in preventing moderate to severe COVID-19 in research participants including those infected with emerging viral variants 28 days after immunization.

The overall level of protection against moderate to severe COVID-19 infection was 72% in the United States, 66% in Brazil, and 57% in South Africa. Thus, the new vaccine shows some protection against the two concerning variants from Brazil (P.1) and South Africa (B.1.351), more so if considering serious disease alone.

“The most important goal for any of the vaccines is whether it prevents serious disease,” Schaffner says. “Disease that requires hospital admission, perhaps intensive care unit admission, and dying. That’s the important part. We are less interested if it prevents less serious disease that just keeps you at home. The J&J vaccine was shown to prevent 89% of serious disease, which puts it in the same ballpark as the Pfizer and Moderna vaccines. The effectiveness on South African strains was the lowest, but even with those they did not have any serious disease.”

In addition to requiring only one shot, the J&J vaccine can be stored in normal refrigeration, and the company projects it could produce 100 million doses by this June.

“With the two vaccines we have and J&J which we think will get [FDA] EUA approval very shortly we can deploy those vaccines to the max and make substantial impact on hospitalizations,” Schaffner says.

That could ease the burden on hard-hit hospitals, and the J&J vaccine also would be a good candidate to use in ambulatory settings. But even with three vaccines, the continued mutation of SARS-CoV-2 likely will create more variants through relentless evolution. Over time, as the pandemic coronavirus persists and globally circulates, treatments and vaccines may have to be augmented to meet the threat of variant mutations.

A key message is that the variants make vaccination all the more important, since mutations will continue to arise if SARS-CoV-2 runs unchecked through large populations, said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, in a recent interview. “It is all the more reason why we should be vaccinating as many people as we possibly can. If you can suppress that by a very good vaccine campaign, then we can avoid this deleterious effect of mutations.”

Variants Emerge in United States

On Jan. 28, 2021, the Centers for Disease Control and Prevention (CDC) announced that the first U.S. documented case of the South African B.1.351 variant of SARS-CoV-2 had been detected in South Carolina. There were two unrelated cases of the strain in South Carolina with no history of travel, meaning the South African variant is spreading in the United States. Subsequently, three cases of the same strain were found in Maryland and another in Virginia.

Also, in January, the first two cases of the Brazil P.1 variant was detected in the Twin Cities metro area in Minnesota. One of the cases had traveled to Brazil and subsequently transmitted to a household contact. Another case was subsequently detected in Oklahoma.

The United Kingdom (U.K.) B.1.1.7 variant has been in the United States for some time and is projected to become the predominant strain in America by March of this year. Researchers in England are warning that in addition to be being highly transmissible, there is “a realistic possibility” the variant may cause infections with higher rates of mortality.1

Based on limited genetic sequencing which the CDC is rapidly ramping up as of Feb. 7, 2021, there were 690 cases of COVID-19 in 33 states caused by the U.K. B.1.1.7 variant. Fortunately, both approved vaccines in the United States are effective against U.K. B.1.1.7.2

However, Moderna is concerned that the South African variant could diminish the effect of its vaccine and is preparing a one-time booster shot genetically coded to the B.1.351 variant, should it be necessary.

“For the South African strain, we still see a very high level of antibody, but it is lower than the traditional strain and B.1.1.7,” Moderna CEO Stephane Bancel said in a recent interview.3 “We believe our vaccine will be protective in the short term. What is unknowable right now is what will happen in six months, in 12 months, especially to the elderly, because they have a weakened immune system and the immunity might go down over time.”

Out of an “abundance of caution,” the company will test a single-dose booster shot targeting the South African strain. The shot will use the same RNA-messenger platform of the approved vaccines but will genetically target the B.1.351 strain. Working with the FDA, the booster could be deployed this spring if there are signs of waning immunity in the elderly, he said.

“We cannot fall behind this virus,” said Bancel. “We just wanted to be cautious, not for now, but for the future.”

A recent preprint study found that both the Moderna and Pfizer vaccines protected sufficiently against the U.K. and South African strains but warned that encoded genetic mutations can diminish efficacy to some degree.

“Taken together, the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy,” the authors concluded.4

Another study looked at whether unvaccinated patients who were convalescing or completely recovered from COVID-19 infection had immunity to the South African variant.5 “Of the 44 that they tested, 22 didn’t neutralize the virus,” Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview. “There were a handful of sera that did neutralize the virus completely. Those were obtained from people who had more severe disease and had higher titers and neutralizing antibodies. The vaccine may induce higher, longer-lasting titers than from people who are convalescent, which could have broader range of neutralizing titers just because they had different levels of disease.”

Moreover, the Brazil variant appears to have the ability to re-infect people who previously have acquired it, suggesting that vaccine will be critical to contain it if antibody protection wanes.

The Brazil variant has 17 unique mutations, including three in the receptor binding domain of the spike protein.

“There is evidence to suggest that some of the mutations in the P.1 variant may affect its transmissibility and antigenic profile, which may affect the ability of antibodies generated through a previous natural infection or through vaccination to recognize and neutralize the virus,” the CDC reports.6

Brazilian researchers published a paper recently about the disturbing implications of the outbreak in the city of Manaus.

“A study of blood donors indicated that 76% of the population had been infected with SARS-CoV-2 by October 2020,” they noted.7 “The estimated SARS-CoV-2 attack rate in Manaus would be above the theoretical herd immunity threshold (67%), given a basic case reproduction number of 3.4. In this context, the abrupt increase in the number of COVID-19 hospital admissions in Manaus during January 2021 … is unexpected and of concern.”

What Happened to Flu?

Another interesting development is that the SARS-CoV-2 strains have either driven seasonal influenza out of its ecological niche, or all the masking and mitigation efforts for COVID-19 have simply blocked flu.

“To date in my hospital and even in my system which is large, with a wide variety of hospitals you can count on one hand how many patients with flu we have had this season,” Pettis says. “We know that Australia and the Southern Hemisphere experienced the same thing. We are still not 100% confident that we couldn’t start seeing more flu, but it does seem that perhaps we won’t.”

In contrast, there are reports of other healthcare-associated infections (HAIs) increasing as so much focus shifts to COVID-19, causing a kind of collateral damage as IPs are focused on the pandemic.

“Many of us are seeing an increase in our other HAIs, particularly with central line associated bacteremia and Clostridium difficile,” she says. “When you have got so many plates spinning at once, it is very difficult to keep your eye on all of them. But we are aware of it and everybody is trying to refocus. The data [do not] lie, and we are paying renewed attention. Because when all is said and done, overall patient safety is the ultimate goal of every IP.”

That said, surprisingly, some IPs have been displaced and overlooked during the chaotic pandemic response, although most are taking a leading role.

“There are some IPs believe it or not, because it makes no sense to me who feel they have been pushed away from the table instead of being invited to the table or being at the head of the table,” Pettis says. “I don’t think it is widespread.”

On the other hand, IPs have been preaching for years that infection control is the responsibility of the entire hospital staff often to little avail.

“I’ve been doing this for 35 years and our mantra is that infection prevention is everyone’s business,” Pettis says. “Quite honestly, that was a struggle. Now, I’ve really never seen anything like it I watch people wash their hands incessantly and be very conscious of not coming to work when they have symptoms. So, I do think infection prevention has become everybody’s business. That is exciting.”

REFERENCES

  1. Horby P, Huntley C, Davies N, et al. NERVTAG note on B.1.1.7 severity. Published Jan. 21, 2021. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/955239/NERVTAG_paper_on_variant_of_concern__VOC__B.1.1.7.pdf
  2. Centers for Disease Control and Prevention. US COVID-19 cases caused by variants. Updated Feb. 8, 2021. https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html
  3. CNBC. CNBC transcript: Moderna CEO Stephane Bancel speaks with CNBC’s “Squawk Box” today. Jan. 25, 2021. https://www.cnbc.com/2021/01/25/cnbc-transcript-moderna-ceo-stephane-bancel-speaks-with-cnbcs-squawk-box-today.html
  4. Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv 2021; Jan 19. doi: 10.1101/2021.01.15.426911. [Preprint].
  5. Wibmer CK, Ayres F, Hermanus T, et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv 2021; Jan 19. doi: 10.1101/2021.01.18.427166. [Preprint].
  6. Centers for Disease Control and Prevention. Emerging SARS-CoV-2 variants. Updated Jan. 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html
  7. Sabino EC, Buss LF, Carvalho MPS, et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet 2021;397:452-455.