In what seemed like an instant, COVID-19 became an inevitable aspect of everyday life more than two years ago — with no signs to suggest that we’ll ever see otherwise again.
As we look at our lives ahead with waves of new variants and “stealth” sub-variants, and seasonal vaccine boosters to match, it begs the question: Should we fear reinfection?
Doctors have recently confirmed that those infected with an earlier Omicron variant, which first appeared and spread rapidly last summer, can indeed test positive again for the new sub-variant.
Last week, as the latest strain — BA.2 or BA2.12.1 — made its presence known in New York City and clusters throughout the Northeast and Midwest, the US crossed a grim milestone: 1,000,000 COVID deaths. Globally, we’ve lost more than 6,000,000.
The Post spoke to NYU Langone Health infectious diseases expert Dr. Michael Phillips about what we can expect from life with COVID as we know it.
Can you get infected with COVID twice — and who’s at risk?
There is no such thing as perfect immunity from COVID. Regardless of severity or immunization, someone who tests positive for the virus can become infected again at some point.
“Our hospitalizations have crept up over the past several weeks, particularly with this newer variant of Omicron,” Dr. Phillips told The Post. “But thankfully, the vast majority of people [who] get the infection tend to recover without too much problems.”
But there’s more at stake for some. People who have not received two doses of the mRNA vaccine, as well as those with weakened immune systems due to age, medications, preexisting illness or other clinical factors, such as poor physical fitness, are at a higher risk of reinfection and becoming severely sick with COVID-19.
But Phillips warns against us “develop[ing] a laissez faire attitude about it.” While some relatively young, healthy and vaccinated individuals may become reinfected with only a mild case, the person they pass it to — potentially, someone with a weakened immune system due to age, medications, preexisting illness or other clinical factors, such as poor physical fitness — may not fare so well.
Omicron is “very, very different from prior waves of Delta,” Phillips added. “I think it shifted our game plan for sure.” Now more than ever the focus of prevention efforts is on protecting those the ones at a greater risk of severe illness — and protecting yourself from COVID reinfection means also “protect[ing] the vulnerable.”
Can you be reinfected with the same COVID variant?
It’s certainly possible, particularly in those who are not vaccinated. Unlike earlier variants, Omicron has rapidly evolved into several sub-types, prompting simultaneous localized outbreaks. Meanwhile, there’s no telling how many positive cases of COVID-19 go unreported, whether due to lack of testing or symptoms to warrant alarm. So whether to fear reinfection with the same niche strain may not be a pragmatic question to ask — because, by the time it’s answered, a new strain may already be here.
“There are so many of these other variants within that big family of coronaviruses, and we’re typically infected with three to four a year,” Phillips explained, most of which present as a mild cold.
Ideally, SARS-CoV-2 could fade into coronavirus obscurity like many of the others — but we aren’t there yet, and it’s too soon to say whether that’s a feasible outlook. “It’s still severe enough that that we have to be pretty mindful about,” said Phillips. “We just don’t know enough about future variants for us to take our guard down yet.”
How long after getting COVID can you be reinfected?
This is another complicated question — especially for sufferers of long COVID, who appear to harbor low, even undetectable levels of the virus for weeks and months. For mild to moderate cases, people who test positive for COVID can expect their infection to clear within five to 10 days after their symptoms arose, or since their confirmed test result.
Nascent research suggests that the average immune system can fend off COVID reinfection for three to five months after the previous bout. That’s why, according to the Centers for Disease Control and Prevention, people who had a confirmed infection within the previous 90 days are not expected to quarantine after coming in contact with another infected individual.
But all bets are off about six months later, when antibodies are known to start waning — regardless of vaccination.
How long do COVID antibodies last?
Experts don’t know exactly. While those survive COVID appear to be largely protected from repeat or severe illness for up to five months after the previous infection, there isn’t enough data available yet to be certain how long those COVID-specific antibodies linger, or even to confirm that the presence of antibodies guarantees immunity, according to the Food and Drug Administration.
Immune system B cells give rise to COVID-specific antibodies, designed to attack the virus on sight, before it can penetrate tissue cells and reproduce. They begin to form within the first few days infection or vaccination, and continue to build for several weeks until they peak at around three months thereafter — when your COVID defenses are at their strongest.
The good news is that waning antibodies doesn’t mean we’re totally defenseless, as some B cells will remember the tools it previously took to create COVID antibodies during re-invasion. (Boosters, furthermore, helps our immune system remember how. to fight.) Meanwhile, our killer T-cells, the immune system’s backup line of defense, may not so good at preventing the virus from entering the body, but they can spot an infected host cell — and destroy before it multiplies to another cell. And while they’re more difficult to track, they do appear to be more faithful than fleeting antibodies.
“Those appear to stay be much more robust,” said Phillips, adding, that “the T cell response is probably more important for response to viral infections” in the long run.
Are COVID vaccines still effective?
“We don’t have to be paranoid about the emergence of a new strain … but we have to be thoughtful and ready for that.”
Dr. Michael Phillips, MD, NYU Langone Health
More or less. Vaccines remain the best way to build-up antibodies, the body’s primary line of defense against severe COVID-19 illness. While allowing oneself to become infected can also give rise to antibodies, it’s not worth the risk.
“I’m strongly pro vaccine, because of the the problems that happen when you don’t get it,” said Phillips, who hinted at alternative forms of vaccination technology on the horizon as well.
Regardless of type, antibodies are known to wane afer about six months since last infection or booster, making reinfection more likely to occur.
How often can you get a COVID booster?
For those on the two-dose regimen, a second round should be completed about six weeks after the first. However, it’s been well over a year since the vaccine was introduced, which means many patients completed those two rounds back in 2021.
Doctors expect that annually, even seasonally redesigned boosters against COVID-19 could become the norm — kind of like influenza, only different, and more troubling: One flu season sees just one or two major strains globally, allowing researchers time to prepare vaccines. “It’s not this, sort of, constant changing during a ‘season’,” said Phillips, like COVID-19 has done.
Currently, only those who have a weakened immune system and people age 50 or older are being recommended for a third shot by the CDC — which is, altogether, a good sign.
Said Phillips, “We don’t have to be paranoid about the emergence of a new strain … but we have to be thoughtful and ready for that.”
Authors: Madison Muller, May 13,2022 Bloomberg News
As a stealth wave of Covid makes its way across the U.S., those who have so far evaded the virus are now falling ill — while others are catching Covid for a second, third or even fourth time.Several factors have conspired to make the state of the pandemic harder than ever to track. The rise of at-home tests, which rarely make it into official case numbers, have made keeping accurate count of positive cases impossible. Additionally, many U.S. states and jurisdictions are now reporting Covid data only sporadically to the Centers for Disease Control and Prevention. Earlier this week, Washington, D.C., reported case data to the agency for the first time since April.This has happened just as new, more contagious subvariants of omicron are making their way through the U.S. population, leading not only to rising first-time Covid cases but also frequent reinfections. The latest versions of the virus appear particularly adept at evading the body’s immune response from both past Covid infections and vaccines. Studies suggest most reinfection cases aren’t even being reported, giving little insight into how often they occur. All this makes it especially difficult to gauge what percentage of the population is presently vulnerable to Covid — and how the pandemic might evolve. “The reality is that things are really not going well at the moment,” said Jacob Lemieux, an infectious disease doctor at Massachusetts General Hospital, speaking at a Harvard Medical School Covid briefing on Tuesday. “We all thought that we were in for a reprieve after the devastating omicron wave. And that was clearly the case until a few weeks ago.”The result is that coworkers are calling in sick, friends are posting snapshots of positive Covid tests on social media and school contact tracing programs are blasting out exposure alerts, even as official Covid case counts suggest the numbers are only creeping back up slowly. On Tuesday, the CDC reported more than 98,000 new cases. The true number is almost certainly higher. “There’s so much less visibility about what’s happening,” said Rick Bright, a virologist and CEO of the Rockefeller Foundation’s Pandemic Prevention Institute.Experts say that it’s difficult to know what the next few months will bring. While vaccines are still doing a good job at keeping most people out of the hospital, the virus is not behaving the same way it has in the past and the majority of the country is living like the pandemic is over. In December and January, during the first wave of omicron infections, case levels skyrocketed before dropping almost as quickly. That’s because widespread infections at the start of the outbreak soon gave the virus fewer people to infect. Public health measures, like masking, also helped reduce the spread. That may not be what happens this time.
“It’s likely that we won’t see the same fast downturn of cases we’ve seen in other surges,” said Bob Wachter, chief of medicine at the University of California, San Francisco.Early evidence suggests omicron has not only made Covid reinfection more likely, but also shortened the window in which a past infection provides protection against the virus. There was hope that the hundreds of thousands of omicron infections this past winter would help bolster population immunity and protect against future surges in coming months. According to CDC data, about a third of the country had caught Covid prior to the omicron wave, a figure that has since increased to more than half. But how effective those antibodies are is now dependent on what variant a person gets.
Delta immunity, for example, doesn’t hold up well against other variants, according to a study recently published in Nature. And there is now evidence that some omicron subvariants can even evade the immune defenses imparted by omicron variants that came before them. One recent study published as a preprint by researchers in Beijing found that several omicron subvariants—BA.2.12.1, BA.4 and BA.5—could get past the defenses of immunity from infection with another version of omicron, BA.1.
All of these factors mean that huge swaths of the population once protected from infection may now be vulnerable.There are just too many holes in the data to be able to judge the state of the pandemic accurately. It’s unclear how frequently reinfections are occurring or which variants people are getting reinfected with. The CDC’s last update on reinfections was in January. The agency has not indicated whether it is tracking the cases and does not make such data available to the public.A handful of state health departments, though, have taken to diligently monitoring the repeat cases. That data suggests reinfections are now happening more frequently.The Colorado State Health Department, for example, has recorded more than 44,000 reinfections throughout the pandemic — 82% of which have occurred since omicron became the dominant variant in December. Reinfections are more common among the unvaccinated, but more than a third have happened to people who have completed their initial two-dose vaccine series, according to the data. Over 16% of reinfections in Colorado have been in people with at least one booster dose.Data from the North Carolina Department of Health and Human Services show reinfections in the state have been increasing since late March. Reinfections currently make up 8% of the state’s total infections for the week ending April 30. Repeat infections have been on the rise in Indiana, too, according to data, where they account for more than 12% of total cases, and in Idaho where they accounted for 18.5% of cases in the first quarter of 2022.A report from Washington state published Wednesday shows that some reinfections are also leading to hospitalization. The age group most likely to get reinfected is 18 to 34 year olds, but people 65 and older are the most likely to get hospitalized after reinfection, the data show.“It feels like the first time in two years that no matter if someone is really careful and does everything right, it won’t be surprising if they end up getting Covid,” said Wachter, at University of California, San Francisco. “We’re unquestionably in a surge.”
Authors: Yasmeen Abutaleb, Joel Achenbach May 6, 2022 The Washington Post
The Biden administration is warning the United States could see 100 million coronavirus infections and a potentially significant wave of deaths this fall and winter, driven by new omicron subvariants that have shown a remarkable ability to escape immunity.
The projection, made Friday by a senior administration official during a background briefing as the nation approaches a covid death toll of 1 million, is part of a broader push to boost the nation’s readiness and persuade lawmakers to appropriate billions of dollars to purchase a new tranche of vaccines, tests and therapeutics.
In forecasting 100 million potential infections during a cold-weather wave later this year and early next, the official did not present new data or make a formal projection. Instead, he described the fall and winter wave as a scenario based on a range of outside models of the pandemic. Those projections assume that omicron and its subvariants will continue to dominate community spread, and there will not be a dramatically different strain of the virus, the official said, acknowledging the pandemic’s course could be altered by many factors.
Several experts agreed that a major wave this fall and winter is possible given waning immunity from vaccines and infections, loosened restrictions and the rise of variants better able to escape immune protections.
Many have warned that the return to more relaxed behaviors, from going maskless to participating in crowded indoor social gatherings, would lead to more infections. The seven-day national average of new infections more than doubled from 29,312 on March 30 to nearly 71,000 Friday, a little more than five weeks later.
“What they’re saying seems reasonable — it’s on the pessimistic side of what we projected in the covid-19 scenario modeling run,” said Justin Lessler, an epidemiologist at University of North Carolina Gillings School of Global Public Health. “It’s always hard to predict the future when it comes to covid, but I think we’re at a point now where it’s even harder than normal. Because there’s so much sensitivity, in terms of these long-term trends, to things we don’t understand exactly about the virus and about [human] behavior,” Lessler said.
Another modeler, epidemiologist Ali Mokdad of the University of Washington’s Institute for Health Metrics and Evaluation, said in an email Friday that a winter surge is likely. His organization, which has made long-term forecasts despite the many uncertainties, just produced a new forecast that shows a modest bump in cases through the end of May and then a decline until the arrival of winter.
Shortly after he served on a jury in March, Gregg Crumley developed a sore throat and congestion. The retired molecular biologist took a rapid test on a Saturday and saw a dark, thick line materialize — “wildly positive” for the coronavirus.
Crumley, 71, contacted his doctor two days later. By the afternoon, friends had dropped off a course of Paxlovid, a five-day regimen of antiviral pills that aims to keep people from becoming seriously ill.
The day he took his last dose, his symptoms were abating. He tested each of the next three days: all negative.
Then, in the middle of a community Zoom meeting, he started feeling sick again. Crumley, who is vaccinated and boosted, thought it might be residual effects of his immune response to the virus. But the chills were more prolonged and unpleasant. He tested. Positive. Again.
Crumley, like other patients who have experienced relapses after taking Paxlovid, is puzzled — and concerned. On Twitter, physicians and patients alike are engaged in a real-time group brainstorm about what might be happening, with scant evidence to work with.
It is the latest twist — and newest riddle — in the pandemic, a reminder that two years in, the world is still on a learning curve with the coronavirus.
Infectious-disease experts agree that this phenomenon of the virus rebounding after some patients take the drug appears to be real but rare. Exactly how often it occurs, why it happens and what — if anything — to do about it remain matters of debate.
What’s clear is that patients should be warned it is possible so they don’t panic — and so that they know to test again if they start feeling ill. More data is needed to understand what is going on. Paxlovid, made by the drug giant Pfizer, remains a useful drug, even though it has sparked a new mystery.Biden administration boosts access to antivirals as covid cases rise
“I’m not negative on Paxlovid,” said Crumley, who lives in Philadelphia and whose last positive test was a week after his second wave of illness began. “I don’t know whether it’s just stopping [viral] replication for that five-day period of time, and it comes back.”
One of the top worries accompanying antiviral drugs is the threat of resistance, when the virus evolves to evade the treatment. A Food and Drug Administration analysis of Pfizer’s clinical trial of the drug showed the virus rebounded in several subjects about 10 to 14 days after their initial symptoms but found no reason and no evidence that their infections were resistant to the treatment.
Michael E. Charness, chief of staff at the VA Boston Healthcare System, published a detailed case study of one 71-year-old patient who had a relapse. The man, who was vaccinated and boosted, received Paxlovid and quickly felt better. When he developed cold symptoms a week after his case of covid had resolved, researchers sequenced the virus’s genetic code and found it was the same virus surging back. That ruled out a reinfection, the emergence of a variant or the virus becoming resistant.
Charness would like to see more data and other questions answered. Should antivirals be given longer, to assure the virus is cleared? Should people be treated a second time? What are the implications for people returning to their normal lives?
“If you have a resurgence of viral load, and that happens on day 10, when CDC says you’re back to work, no mask, what are you supposed to do about isolation? Is that a moment when you’re contagious again?” Charness said. “The person we studied, we advised to isolate until their viral load was gone the second time.”
Pfizer is collecting data, in clinical trials and in real-world monitoring of the drug’s use. The company’s trial data indicates there is a late uptick in viral load in “a small number” of people who take the drug, but the rates appear to be similar among study participants given a placebo, according to company spokesman Kit Longley. The people who experienced such increases also did not develop severe disease the second time around.
Those findings suggest that Paxlovid isn’t the reason people are relapsing, because that’s happening in untreated people, too.
If that turns out to be true, it raises the concern that some people — whether they have taken the drug or not — could be infectious long after they think they are in the clear, and after guidelines suggest they can stop taking precautions.
“Although it is too early to determine the cause, this suggests the observed increase in viral load is unlikely to be related to Paxlovid,” Longley wrote in an email. “We have not seen any resistance to Paxlovid, and remain very confident in its clinical effectiveness.”
The limited evidence leaves most physicians favoring the idea that Paxlovid knocks the virus down but doesn’t knock it out completely. It’s possible that by holding the virus in check, the immune response doesn’t fully ramp up, because it doesn’t see enough virus. Once the treatment ends, the virus can start multiplying again in some people.
Philip Bretsky, a primary care doctor in Santa Monica, Calif., said he has encountered two cases among patients, both of whom were vaccinated and boosted at least once.
A double-boosted 72-year-old who had chronic medical conditions that raised his risk for severe illness started to feel unwell at the end of March. He tested positive and began a course of Paxlovid. He felt better and tested negative. Then, 12 days later, he started feeling crummy again — and tested positive.
Reinfection seemed improbable, and Bretsky thought resistance was unlikely with a five-day course of treatment.
In well-vaccinated people, being reinfected so quickly would be “like getting struck by lightning or winning the lottery,” Bretsky said. “I don’t think this is reinfection. I think this is recrudescence of the original infection.”
Experts don’t know how common this phenomenon is. Many people may not test if they get sick again after their initial infection has receded, making it hard to track.
That almost happened to Holly Teliska, 42, of San Francisco. Teliska got sick shortly after returning home from a trip to New York. She has a risk factor for severe illness and got access to Paxlovid right away. When she finished her treatment course, she took a home PCR test that was negative and felt much better, though remained fatigued.
Four days later, she came down with a runny nose and cough. She assumed she had caught her daughter’s cold and powered through. Five days later, with plans to visit an immunocompromised friend, she took a test.
Teliska almost felt silly testing herself. She had been vaccinated and boosted, then infected.
“We’ve been saying I’m her safest friend now, now that I’ve had covid, so for three months, I can go spend time with her pretty safely,” Teliska said. “That really threw that narrative out the window. … This entire experience has been a real reminder there is still so much to learn.”
Paxlovid is new. It only began to be used in December, so reports people share on social media of resurgent illness may be the tip of the iceberg — or might simply reflect the eagerness to learn more about a rare, intriguing outcome.
If such cases turn out to be exceedingly rare, then these case reports may be a sporadic curiosity — something to warn patients could happen. If more common, it could lead to tweaks in treatment regimens.
The mounting anecdotes are compelling to many physicians, but it’s also possible the virus might rarely rebound. Yonatan Grad, an associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, has studied the viral loads of NBA players and staff during the course of an infection. That data, he said, shows that viral loads can bounce around.
What’s “exceptionally uncommon,” Grad said, is for the viral load to plunge for a few days to a level that suggests they are negative and then go up again.
Paul Sax, an infectious-diseases specialist at Brigham and Women’s Hospital in Boston, recently shared the story of a patient who became infected and then relapsed after taking Paxlovid. He has heard from lots of colleagues with similar stories. But the anecdotes raise more questions than they answer.
Even if the virus has not been shown to develop resistance to the treatment during a resurgence, that’s doesn’t mean it won’t happen, he points out. Does the treatment knock the virus down so successfully that people aren’t generating a robust immune response? That could have implications for understanding whether being infected acts as a potent booster.
The phenomenon is so new that many doctors aren’t aware of it. Jennifer Charness, a 31-year-old nurse who lives in Brookline, Mass., had the benefit of knowing about her father’s work at the Boston VA.
Charness started sneezing in early April and got a blaringly positive coronavirus test. She has a history of asthma and was prescribed Paxlovid. As she took the drug, she saw her positive test line grow fainter and her symptoms resolve. She swabbed to make sure she was negative before going back to work, as a precaution. Then, two days later, she felt the symptoms come back and tested positive — again.
“I’m so frustrated,” Charness said. “I don’t think I’m going to get very sick. It’s the concern of what does this mean for my viral load, and how contagious am I? And when will I not be contagious? I’m stuck back in my home again.”
Charness’s primary concern is that she doesn’t pose a risk to anyone else. She consulted a doctor via telemedicine Friday. The practice hadn’t heard of any cases like hers and decided to treat it as a reinfection and reset the isolation clock.
By the numbers: Overall, cases dropped 5% across the U.S. to an average of about 28,700 cases from an average of more than 30,000 cases two weeks ago.
Three states — Alaska, Vermont and Rhode Island — had more than 20 new cases per 100,000 people.
Nine states — Utah, Montana, South Dakota, Kansas, Louisiana, Iowa, Arkansas, Indiana and Tennessee — had three or fewer new cases per 100,000 people.
Between the lines: Deaths fell to an average of 600 a day, down 34% from just over 900 a day two weeks ago.
What we’re watching: While U.S. officials have said they aren’t expecting a significant rise in hospitalizations or deaths, there have been signs of hospitalizations rising among older individuals in the U.K., the Guardian reported.
Since those numbers lag behind new cases, we won’t have a clear view of that impact in the U.S. for a few weeks.
Weekly / January 28, 2022 / 71(4);125–131 January 19, 2022, this report was posted online as an MMWR Early Release.
Authors: Tomás M. León, PhD1; Vajeera Dorabawila, PhD2; Lauren Nelson, MPH1; Emily Lutterloh, MD2,3; Ursula E. Bauer, PhD2; Bryon Backenson, MPH2,3; Mary T. Bassett, MD2; Hannah Henry, MPH1; Brooke Bregman, MPH1; Claire M. Midgley, PhD4; Jennifer F. Myers, MPH1; Ian D. Plumb, MBBS4; Heather E. Reese, PhD4; Rui Zhao, MPH1; Melissa Briggs-Hagen, MD4; Dina Hoefer, PhD2; James P. Watt, MD1; Benjamin J. Silk, PhD4; Seema Jain, MD1; Eli S. Rosenberg, PhD2,3
What is already known about this topic?
Data are limited regarding the risks for SARS-CoV-2 infection and hospitalization after COVID-19 vaccination and previous infection.
What is added by this report?
During May–November 2021, case and hospitalization rates were highest among persons who were unvaccinated without a previous diagnosis. Before Delta became the predominant variant in June, case rates were higher among persons who survived a previous infection than persons who were vaccinated alone. By early October, persons who survived a previous infection had lower case rates than persons who were vaccinated alone.
What are the implications for public health practice?
Although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for averting future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death. Primary vaccination, additional doses, and booster doses are recommended for all eligible persons. Additional future recommendations for vaccine doses might be warranted as the virus and immunity levels change.
By November 30, 2021, approximately 130,781 COVID-19–associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30–November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for >50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change.
Four cohorts of persons aged ≥18 years were assembled via linkages of records from electronic laboratory reporting databases and state-specific immunization information systems.† Persons were classified based on whether they had had a laboratory-confirmed SARS-CoV-2 infection by March 1, 2021 (i.e., previous COVID-19 diagnosis)§; had received at least the primary COVID-19 vaccination series¶ by May 16, 2021; had a previous COVID-19 diagnosis and were fully vaccinated**; or had neither received a previous COVID-19 diagnosis by March 1 nor received a first COVID-19 vaccine dose by the end of the analysis period. The size of the unvaccinated group without a previous diagnosis was derived by subtracting the observed groups from U.S. Census estimates.†† To maintain each defined cohort, persons who received a COVID-19 diagnosis during March 1–May 30, 2021, or who died before May 30, 2021, were excluded (to maintain eligibility for incident cases for all cohorts on May 30, 2021),§§ as were persons who received a first vaccine dose during May 30–November 20, 2021. During May 30–November 20, 2021, incident cases were defined using a positive nucleic acid amplification test (NAAT) result from the California COVID-19 Reporting System (CCRS) or a positive NAAT or antigen test result from the New York Electronic Clinical Laboratory Reporting System. In California, person-level hospitalization data from CCRS and supplementary hospitalization reports were used to identify COVID-19–associated hospitalizations. A lifetable method was used to calculate hazard rates (average daily cases during a 7-day interval or hospitalizations over a 14-day interval), hazard ratios, and 95% CIs for each cohort. Rates were age-adjusted to 2000 U.S. Census data using direct standardization.¶¶ Supplementary analyses stratified case rates by timing of previous diagnoses and primary series vaccine product. SAS (version 9.4; SAS Institute) and R (version 4.0.4; The R Foundation) were used to conduct all analyses. Institutional review boards (IRBs) in both states determined this surveillance activity to be necessary for public health work, and therefore, it did not require IRB review.
Approximately three quarters of adults from California (71.2%) and New York (72.2%) included in this analysis were vaccinated and did not have a previous COVID-19 diagnosis; however, 18.0% of California residents and 18.4% of New York residents were unvaccinated with no previous COVID-19 diagnosis (Table 1). In both states, 4.5% of persons were vaccinated and had a previous COVID-19 diagnosis; 6.3% in California and 4.9% in New York were unvaccinated with a previous diagnosis. Among 1,108,600 incident COVID-19 cases in these cohorts (752,781 in California and 355,819 in New York), the median intervals from vaccination or previous COVID-19 diagnosis to incident diagnosis were slightly shorter in California (138–150 days) than in New York (162–171 days).
Before the Delta variant became predominant in each state’s U.S. Department of Health and Human Services region (June 26 in Region 9 [California] and July 3 in Region 2 [New York]),*** the highest incidence was among unvaccinated persons without a previous COVID-19 diagnosis; during this time, case rates were relatively low among the three groups with either previous infection or vaccination and were lowest among vaccinated persons without a previous COVID-19 diagnosis (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/113253) (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/113253). During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; rates were 7.2-fold (California) and 9.9-fold (New York) lower among unvaccinated persons with a previous COVID-19 diagnosis and 9.6-fold (California) and 8.5-fold (New York) lower among vaccinated persons with a previous COVID-19 diagnosis (Table 2).
As the Delta variant prevalence increased to >95% (97% in Region 9 and 98% in Region 2 on August 1), rates increased more rapidly among the vaccinated group with no previous COVID-19 diagnosis than among both the vaccinated and unvaccinated groups with a previous COVID-19 diagnosis (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/113253) (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/113253). For example, during the week of October 3, compared with rates among unvaccinated persons without a previous COVID-19 diagnosis, rates among vaccinated persons without a previous diagnosis were 6.2-fold lower (95% CI = 6.0–6.4) in California and 4.5-fold lower (95% CI = 4.3–4.7) in New York (Table 2). Further, rates among unvaccinated persons with a previous COVID-19 diagnosis were 29-fold lower (95% CI = 25.0–33.1) than rates among unvaccinated persons without a previous COVID-19 diagnosis in California and 14.7-fold lower (95% CI = 12.6–16.9) in New York. Rates among vaccinated persons who had had COVID-19 were 32.5-fold lower (95% CI = 27.5–37.6) than rates among unvaccinated persons without a previous COVID-19 diagnosis in California and 19.8-fold lower (95% CI = 16.2–23.5) in New York. Rates among vaccinated persons without a previous COVID-19 diagnosis were consistently higher than rates among unvaccinated persons with a history of COVID-19 (3.1-fold higher [95% CI = 2.6–3.7] in California and 1.9-fold higher [95% CI = 1.5–2.3] in New York) and rates among vaccinated persons with a history of COVID-19 (3.6-fold higher [95% CI = 2.9–4.3] in California and 2.8-fold higher [95% CI = 2.1–3.4] in New York).
COVID-19 hospitalization rates in California were always highest among unvaccinated persons without a previous COVID-19 diagnosis (Table 2) (Figure). In the pre-Delta period during June 13–June 26, for example, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates were 27.7-fold lower (95% CI = 22.4–33.0) among vaccinated persons without a previous COVID-19 diagnosis, 6.0-fold lower (95% CI = 3.3–8.7) among unvaccinated persons with a previous COVID-19 diagnosis, and 7.1-fold lower (95% CI = 4.0–10.3) among vaccinated persons with a previous COVID-19 diagnosis. However, this pattern also shifted as the Delta variant became predominant. During October 3–16, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates were 19.8-fold lower (95% CI = 18.2–21.4) among vaccinated persons without a previous COVID-19 diagnosis, 55.3-fold lower (95% CI = 27.3–83.3) among unvaccinated persons with a previous COVID-19 diagnosis, and 57.5-fold lower (95% CI = 29.2–85.8) among vaccinated persons with a previous COVID-19 diagnosis.
Among the two cohorts with a previous COVID-19 diagnosis, no consistent incidence gradient by time since the previous diagnosis was observed (Supplementary Figure 3, https://stacks.cdc.gov/view/cdc/113253). When the vaccinated cohorts were stratified by the vaccine product received, among vaccinated persons without a previous COVID-19 diagnosis, the highest incidences were observed among persons receiving the Janssen (Johnson & Johnson), followed by Pfizer-BioNTech, then Moderna vaccines (Supplementary Figure 4, https://stacks.cdc.gov/view/cdc/113253). No pattern by product was observed among vaccinated persons with a previous COVID-19 diagnosis.
This analysis integrated laboratory testing, hospitalization surveillance, and immunization registry data in two large states during May–November 2021, before widespread circulation of the SARS-CoV-2 Omicron variant and before most persons had received additional or booster COVID-19 vaccine doses to protect against waning immunity. Rate estimates from the analysis describe different experiences stratified by COVID-19 vaccination status and previous COVID-19 diagnosis and during times when different SARS-CoV-2 variants predominated. Case rates were initially lowest among vaccinated persons without a previous COVID-19 diagnosis; however, after emergence of the Delta variant and over the course of time, incidence increased sharply in this group, but only slightly among both vaccinated and unvaccinated persons with previously diagnosed COVID-19 (6). Across the entire study period, persons with vaccine- and infection-derived immunity had much lower rates of hospitalization compared with those in unvaccinated persons. These results suggest that vaccination protects against COVID-19 and related hospitalization and that surviving a previous infection protects against a reinfection. Importantly, infection-derived protection was greater after the highly transmissible Delta variant became predominant, coinciding with early declining of vaccine-induced immunity in many persons (5). Similar data accounting for booster doses and as new variants, including Omicron, circulate will need to be assessed.
The understanding and epidemiology of COVID-19 has shifted substantially over time with the emergence and circulation of new SARS-CoV-2 variants, introduction of vaccines, and changing immunity as a result. Similar to the early period of this study, two previous U.S. studies found more protection from vaccination than from previous infection during periods before Delta predominance (3,7). As was observed in the present study after July, recent international studies have also demonstrated increased protection in persons with previous infection, with or without vaccination, relative to vaccination alone†††, §§§ (4). This might be due to differential stimulation of the immune response by either exposure type.¶¶¶ Whereas French and Israeli population-based studies noted waning protection from previous infection, this was not apparent in the results from this or other large U.K. and U.S. studies**** (4,8). Further studies are needed to establish duration of protection from previous infection by variant type, severity, and symptomatology, including for the Omicron variant.
The findings in this report are subject to at least seven limitations. First, analyses were not stratified by time since vaccine receipt, but only by time since previous diagnosis, although earlier studies have examined waning of vaccine-induced immunity (Supplementary Figure 3, https://stacks.cdc.gov/view/cdc/113253) (2). Second, persons with undiagnosed infection are misclassified as having no previous COVID-19 diagnosis; however, this misclassification likely results in a conservative bias (i.e., the magnitude of difference in rates would be even larger if misclassified persons were not included among unvaccinated persons without a previous COVID-19 diagnosis). California seroprevalence data during this period indicate that the ratio of actual (presumptive) infections to diagnosed cases among adults was 2.6 (95% CI = 2.2–2.9).†††† Further, California only included NAAT results, whereas New York included both NAAT and antigen test results. However, antigen testing made up a smaller percentage of overall testing volume reported in California (7% of cases) compared with New York (25% of cases) during the study period. Neither state included self-tests, which are not easily reportable to public health. State-specific hazard ratios were generally comparable, although differences in rates among unvaccinated persons with a previous COVID-19 diagnosis were noteworthy. Third, potential exists for bias related to unmeasured confounding (e.g., behavioral or geographic differences in exposure risk) and uncertainty in the population size of the unvaccinated group without a previous COVID-19 diagnosis. Persons might be more or less likely to receive testing based on previous diagnosis or vaccination status; however, different trajectories between vaccinated persons with and without a previous COVID-19 diagnosis, and similar findings for cases and hospitalizations, suggest that these biases were minimal. Fourth, this analysis did not include information on the severity of initial infection and does not account for the full range of morbidity and mortality represented by the groups with previous infections. Fifth, this analysis did not ascertain receipt of additional or booster COVID-19 vaccine doses and was conducted before many persons were eligible or had received additional or booster vaccine doses, which have been shown to confer additional protection.§§§§ Sixth, some estimates lacked precision because of sample size limitations. Finally, this analysis was conducted before the emergence of the Omicron variant, for which vaccine or infection-derived immunity might be diminished.¶¶¶¶ This study offers a surveillance data framework to help evaluate both infections in vaccinated persons and reinfections as new variants continue to emerge.
Vaccination protected against COVID-19 and related hospitalization, and surviving a previous infection protected against a reinfection and related hospitalization during periods of predominantly Alpha and Delta variant transmission, before the emergence of Omicron; evidence suggests decreased protection from both vaccine- and infection-induced immunity against Omicron infections, although additional protection with widespread receipt of booster COVID-19 vaccine doses is expected. Initial infection among unvaccinated persons increases risk for serious illness, hospitalization, long-term sequelae, and death; by November 30, 2021, approximately 130,781 residents of California and New York had died from COVID-19. Thus, vaccination remains the safest and primary strategy to prevent SARS-CoV-2 infections, associated complications, and onward transmission. Primary COVID-19 vaccination, additional doses, and booster doses are recommended by CDC’s Advisory Committee on Immunization Practices to ensure that all eligible persons are up to date with COVID-19 vaccination, which provides the most robust protection against initial infection, severe illness, hospitalization, long-term sequelae, and death.***** Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change.
Dana Jaffe, California Department of Public Health; Rebecca Hoen, Meng Wu, New York State Department of Health; Citywide Immunization Registry Program, New York City Department of Health and Mental Hygiene.
1California Department of Public Health; 2New York State Department of Health; 3University at Albany School of Public Health, SUNY, Rensselaer, New York; 4CDC.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.
† Statewide immunization databases in California are the California Immunization Registry, Regional Immunization Data Exchange, and San Diego Immunization Registry; the laboratory system is the California COVID Reporting System (CCRS). In New York, immunization information systems include Citywide Immunization Registry and the New York State Immunization Information System; the laboratory system is the Electronic Clinical Laboratory Reporting System (ECLRS). California data were matched between the immunization and case registries using a probabilistic algorithm with exact match for zip code and date of birth and fuzzy match on first name and last name. New York data were matched to the ECLRS with the use of a deterministic algorithm based on first name, last name, and date of birth. In California, person-level hospitalization data from CCRS and supplementary hospitalization reports were used to identify COVID-19–associated hospitalizations.
§ For both classification into cohorts of persons with previous COVID-19 diagnoses and for measuring incident cases, laboratory-confirmed infection was defined as the receipt of a new positive SARS-CoV-2 nucleic acid amplification test (NAAT) or antigen test (both for New York and NAAT only for California) result, but not within 90 days of a previous positive result.
¶ Fully vaccinated with the primary vaccination series is defined as receipt of a second dose of an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) or 1 dose of the Janssen (Johnson & Johnson) vaccine ≥14 days before May 30, 2021.
** Because of the timing of full vaccination, the cohort definitions, and analysis timeframe, this cohort consisted nearly exclusively of persons who had previously received a laboratory-confirmed diagnosis of COVID-19 and later were fully vaccinated (California: 99.9%, New York: 99.7%), as opposed to the reverse order.
†† Whereas vaccinated cohorts were directly observed in the immunization information system databases, unvaccinated persons without a previous COVID-19 diagnosis were defined using U.S. Census population estimates minus the number of persons partially or fully vaccinated by December 11, 2021, and unvaccinated persons with a previous laboratory-confirmed infection before May 30, 2021. In California, the California Department of Finance population estimates were used for 2020, and the 2018 CDC National Center for Health Statistics Bridged Race file for U.S. Census population estimates were used in New York, consistent with other COVID-19 surveillance reporting.
§§ In California, a person-level match was performed to exclude deaths in each cohort before May 30, 2021. In New York, COVID-19 deaths were removed in aggregate from the starting number of unvaccinated persons with a previous COVID-19 diagnosis on May 30, 2021.
Grant R, Charmet T, Schaeffer L, et al. Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France. Lancet Reg Health Eur 2021. Epub November 26, 2021. https://doi.org/10.1016/j.lanepe.2021.100278external icon
Health Ministry data cited by Channel 13 suggests the Delta variant may be more effective at causing COVID reinfection among recovered patients than earlier strains of the coronavirus.
According to the data, 4,811 Israelis have been reinfected with coronavirus, accounting for 0.47 percent of the total recoveries. (The data provided refers to over 900,000 recovered Israelis, though the figure has since surpassed a million).
However, just 0.08% of the reinfection cases were recorded in 2020, while the number climbed to 0.71% in 2021 when the Delta variant became the dominant strain in Israel. In the past month, 2,702 recovered patients contracted the coronavirus again, or some 1.8%, the report says. It is unclear to what extent the Delta variant is more effective and to what extent the reinfections are the result of waning antibodies.
The majority of reinfections are among the young, according to the report.
Findings: In an international multi-center study inpatients without anti-HCoV OC43 NP antibodies had an increased risk of critical disease.•
Meaning: Prior infections with seasonal HCoV OC43 have a protective effect against critical COVID-19.
The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality.
To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed.
We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1.
Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 – 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.
Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.