Virus World

SARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown. We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period. Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24). These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021. This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.

Preprint available at medRxiv (August 17, 2022):

https://doi.org/10.1101/2022.08.16.22278820 

The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.

Preprint available in medRxiv (Feb. 22, 2022):

 https://doi.org/10.1101/2022.02.19.22271112 

British scientists on Monday launched a trial which will deliberately expose participants who have already had COVID-19 to the coronavirus again to examine immune responses and see if people get reinfected.  In February, Britain became the first country in the world to give the go-ahead for so-called "challenge trials" in humans, in which volunteers are deliberately exposed to COVID-19 to advance research into the disease caused by the coronavirus. read more The study launched on Monday differs from the one announced in February as it seeks to reinfect people who have previously had COVID-19 in an effort to deepen understanding about immunity, rather than infecting people for the first time. "The information from this work will allow us to design better vaccines and treatments, and also to understand if people are protected after having COVID, and for how long," said Helen McShane, a University of Oxford vaccinologist and chief investigator on the study.  She added that the work would help understanding of what immune responses protect against reinfection.

An analysis of millions of coronavirus test results in Denmark suggests that natural infection with SARS-CoV-2 protects against reinfection in most people — but this protection is significantly weaker in those aged 65 years or older. Steen Ethelberg and his colleagues at the Statens Serum Institut in Copenhagen mined data from polymerase chain reaction tests, which are the gold-standard method for detecting SARS-CoV-2 infection, conducted in Denmark (C. H. Hansen et al. Lancet https://doi.org/gjg8qk; 2021). The team focused on people who tested positive for the coronavirus during one or both of Denmark’s two surges of infection — from March to May and from September to December — in 2020. The team found that, at about 6 months after initial infection, protection against repeat infection was approximately 80%, with no significant difference in reinfection rates between men and women. But this protection was reduced to 47% for those aged 65 years or older, emphasizing the need to prioritize vaccinations for this group.

Findings published in the Lancet (March 17, 2021)"

https://doi.org/10.1016/S0140-6736(21)00575-4

Two new studies in macaques offer hope that humans could develop protective immunity against SARS-CoV-2, either as the result of a natural infection or by way of a vaccine. While there are differences between SARS-CoV-2 infection in macaques and humans, these findings - some of the first to show that non-human primates can develop protective immunity to SARS-CoV-2 - are promising in light of the ongoing efforts around the world to develop a vaccine and antibody treatments for COVID-19. An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure; there is currently no data on whether humans are protected from re-exposure in this way. 

Earlier this year, research investigating cynomolgus macaques found these animals to be promising models for testing COVID-19 therapeutics. Here, in two new studies in rhesus macaques, researchers explored whether initial exposure to SARS-CoV-2 protected against reinfection and whether vaccination protected against infection, respectively. In a macaque model of SARS-CoV-2 infection they developed, and which recapitulated certain aspects of human SARS-CoV-2 infection, Abishek Chandrashekar, Ralph Baric, Dan Barouch and colleagues tested whether 9 adult animals who had cleared the virus were immune to viral re-challenge 35 days later. All 9 animals showed little to no symptoms after re-challenge and exhibited immune responses that protected against the second infection (given at the same doses as the first). Additional research will be required to define the durability of natural immunity shown here, the authors note. "Rigorous clinical studies will be required to determine whether SARS-CoV-2 infection effectively protects against SARS-CoV-2 re-exposure in humans," they say....

Original Studies  Published in Science (May 20, 2020):

https://doi.org/10.1126/science.abc4776

https://doi.org/10.1126/science.abc6284

Monkeys infected with SARS-CoV-2 were protected from subsequent exposures, a finding that has vital implications for vaccine design. 

Concerns about SARS-CoV-2 infection have reached an all-time high in the United States and around the globe. With increasing numbers of COVID-19 cases, hospitalizations, and deaths—and “social distancing” now a household word—the possibility of being infected is on everyone’s mind. As if that weren’t enough to worry about, the surfacing of multiple personal accounts—primarily out of China and Japan—of patients who recovered after infection only to fall ill a second time, have some worried about the possibility of reinfection. Now, a collaboration of Chinese scientists has dug deeper into whether or not reinfection with SARS-CoV-2 is possible with a small monkey study. The team looked at whether or not non-human primates, rhesus macaques, can become reinfected with SARS-CoV-2. The work was posted on the preprint server bioRxiv on March 14 in a paper titled, “Reinfection could not occur in SARS-CoV-2 infected rhesus macaques.” Their conclusion: there may be no reason to worry about reinfection.

The study used four, adult Chinese rhesus macaques. After intratracheal infection, the monkeys were analyzed on schedule, including measurements such as body weight, body temperature, lung x-rays, sampling of sera, nasal/throat/anal swabs, and primary tissues. The rhesus monkeys were successfully infected, as measured by weight loss, viral replication mainly in the nose, pharynx, lung, and gut, as well as moderate interstitial pneumonia....

Original Study available at bioRxiv  (March 14, 2020):

https://doi.org/10.1101/2020.03.13.990226

BACKGROUND:  The SARS-CoV-2 Omicron (B.1.1.529) variant has two main sub-lineages, BA.1 and BA.2 with significant genetic distance between them. This study investigated protection of infection with one sub-lineage against reinfection with the other sub-lineage in Qatar during a large BA.1 and BA.2 Omicron wave, from December 19, 2021 to February 21, 2022. METHODS: Two national matched, retrospective cohort studies were conducted to estimate effectiveness of BA.1 infection against reinfection with BA.2 (N=20,197; BA.1-against-BA.2 study), and effectiveness of BA.2 infection against reinfection with BA.1 (N=100,925; BA.2-against-BA.1 study). Associations were estimated using Cox proportional-hazards regression models.

RESULTS: In the BA.1-against-BA.2 study, cumulative incidence of infection was estimated at 0.03% (95% CI: 0.01-0.07%) for the BA.1-infected cohort and at 0.62% (95% CI: 0.51-0.75%) for the uninfected-control cohort, 15 days after the start of follow-up. Effectiveness of BA.1 infection against reinfection with BA.2 was estimated at 94.9% (95% CI: 88.4-97.8%). In the BA.2-against-BA.1 study, cumulative incidence of infection was estimated at 0.03% (95% CI: 0.02-0.04%) for the BA.2-infected cohort and at 0.17% (95% CI: 0.15-0.21%) for the uninfected-control cohort, 15 days after the start of follow-up. Effectiveness of BA.2 infection against reinfection with BA.1 was estimated at 85.6% (95% CI: 77.4-90.9%).

CONCLUSIONS: Infection with an Omicron sub-lineage appears to induce strong, but not full protection against reinfection with the other sub-lineage, for at least several weeks after the initial infection.

Preprint in medRxiv (Feb. 25, 2022):

https://doi.org/10.1101/2022.02.24.22271440 

The risk of reinfection from the omicron coronavirus variant is three times higher than for any previous strain, according to a South African study of infections since the start of the pandemic. 

The finding provides evidence of omicron’s “ability to evade immunity from prior infection,” according to the authors, Juliet Pulliam of the South African Center for Epidemiological Modelling and Analysis and Harry Moultrie of the National Center for Communicable Diseases. The study was based on data collected through South Africa’s health system on about 2.8 million confirmed coronavirus infections between March 2020 and Nov. 27, including 35,670 suspected reinfections, the authors wrote in an emailed statement. They detected a significant increase in reinfections since the first known cases of omicron. “The reinfection risk profile of omicron is substantially higher than that associated with the beta and delta variants during the second and third waves, with observed numbers of reinfections falling well beyond the prediction intervals,” they wrote. “Our most urgent priority now is to quantify the extent of omicron’s immune escape for both natural and vaccine-derived immunity, as well as its transmissibility relative to other variants and impact on disease severity.” 

That strain has rapidly taken hold in Africa’s most-industrialized nation. New cases exceeded 11,000 on Thursday, compared with 585 two weeks ago, according to government data. In Gauteng, the nation’s richest province and its Covid-19 epicenter, each infected person on average is able to pass on the virus to another 2.33, according to the National Institute for Communicable Diseases. The beta or delta variants spread “primarily from increased transmissibility, rather than immune escape,” according to the research paper, which hasn’t been peer reviewed. South Africa announced the discovery of a new variant, later named omicron, on Nov. 25 as cases began to spike and the strain spread across the globe. National daily cases almost doubled on Wednesday, days after countries across the world halted flights to and from southern Africa. “This virus may be similar to delta in its ability to spread or in being contagious,” Anne von Gottberg, a clinical microbiologist at South Africa’s National Institute for Communicable Diseases, said at a briefing on Thursday. “However, it’s the susceptibility of the population that is greater now because previous infection used to protect against delta and now, with omicron, it doesn’t seem to be the case.”

Preprint available at medRxiv (Dec. 02, 2021):

https://doi.org/10.1101/2021.11.11.21266068

Although antibodies induced by SARS-CoV-2 infection are largely protective, they do not completely protect against reinfection in young people, as evidenced through a longitudinal, prospective study of more than 3,000 young, healthy members of the US Marines Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published April 15 in The Lancet Respiratory Medicine.  "Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common" says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. "Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission."

The study, conducted between May and November 2020, revealed that around 10 percent (19 out of 189) of participants who were previously infected with SARS-CoV-s (seropositive) became reinfected, compared with new infections in 50 percent (1.079 out of 2,247) of participants who had not been previously infected (seronegative). While seronegative study participants had a five times greater risk of infection than seropositive participants, the study showed that seropositive people are still at risk of reinfection. The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were assessed for baseline SARS-CoV-2 IgG seropositivity (defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent [ELISA] assays.) The presence of SARS-CoV-2 was assessed by PCR at initiation, middle and end of quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three bi-weekly PCR tests in both seronegative and seropositive groups once recruits left quarantine and entered basic training. Recruits who tested positive for a new second COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralising antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.  Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45%) new infections during the study. Among the seropositive participants, 19 (10%) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48%) became infected during the study.

To understand why these reinfections occurred, the authors studied the reinfected and not infected participants' antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels against the SARS-CoV-2 virus than those who did not become reinfected. In addition, in the seropositive group, neutralising antibodies were less common (neutralising antibodies were detected in 45 (83%) of 54 uninfected, and in six (32%) of 19 reinfected participants during the six weeks of observation). Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection. The authors note that this will need further investigation. In the study, most new COVID-19 cases were asymptomatic—84% (16 out of 19 participants) in the seropositive group vs 68% (732 out of 1,079 participants) in the seronegative group—or had mild symptoms and none were hospitalised. The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very love antibody levels following their past infection. They strongly suggest that even young people with previous SARS-CoV-2 infection be a target of vaccination since efforts must be made to prevent transmission and prevent infection amongst this group.

Study cited was published in The Lancet Respiratory Medicine (April 15, 2021):

https://doi.org/10.1016/S2213-2600(21)00158-2

Large study of UK health-care workers suggests that most people are immune for months after catching COVID-19 for the first time. Most people who catch and recover from COVID-19 are likely to be immune for several months afterwards, a study of more than 20,000 health-care workers in the United Kingdom has found.  The study — called SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) and published on the preprint server medRxiv on 15 January1 — concluded that immune responses from past infection reduce the risk of catching the virus again by 83% for at least 5 months. Over the course of the past year, reports of repeat infections with SARS-CoV-2 have shaken confidence in the immune system’s ability to sustain its defences against the virus. The interim results from the study assuage some of those fears, said SIREN lead investigator Susan Hopkins, a senior medical adviser at Public Health England in London, at a press briefing. The data suggest that natural immunity might be as effective as vaccination, she added, at least over the five-month period the study has covered so far.  The data suggest that repeat infections are rare — they occurred in fewer than 1% of about 6,600 participants who had already been ill with COVID-19. But the researchers also found that people who become reinfected can carry high levels of the virus in their nose and throat, even when they do not show symptoms. Such viral loads have been associated with a high risk of transmitting the virus to others, said Hopkins. “Reinfection is pretty unusual, so that’s good news,” says immunologist John Wherry at the University of Pennsylvania in Philadelphia. “But you’re not free to run around without a mask.”

Regular screening

SIREN is the largest study of coronavirus reinfection that systematically screens for asymptomatic infections, said Hopkins. Every two to four weeks, participants undergo blood tests for SARS-CoV-2 antibodies as well as PCR tests to detect the virus itself. Over the 5 months, the team found 44 possible reinfections. In the group of 14,000 participants who had not been previously infected, 318 people tested positive for the virus. Some of the reinfections are still being evaluated, Hopkins said. All 44 are considered ‘possible’ reinfections, and were classified on the basis of PCR tests combined with screening measures to reduce the risk of re-detecting virus from the initial infection. So far, only 2 of these 44 cases have passed more stringent tests to be classified as ‘probable’. The study did not assess whether symptoms were better or worse during the second infection than during the first, but Hopkins notes that only about 30% of the people with possible reinfections reported any symptoms, compared with 78% of participants with first-time infections.  At the moment, the team does not have enough data to tease out who might be most at risk of reinfection. And immunologist George Kassiotis at the Francis Crick Institute in London notes that participants in the study were mainly women, and mostly under the age of 60. “This group is unlikely to experience the most severe form of COVID-19,” he says, “and may not be representative of the population as a whole.” Investigators are still collecting data; they hope to get a sense of how long immunity lasts and to investigate the effects of a SARS-CoV-2 variant called B.1.1.7 that emerged in 2020 and has rapidly spread across the country. Although there are many reasons to suspect that existing protection should cover new variants, it is possible that immune responses raised against one variant will be less effective against another, says Kassiotis. “It is still an open question.”

Preprint available in medRxiv (Jan. 15, 2021):

https://doi.org/10.1101/2021.01.13.21249642 

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes.

Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.

Published in Science (July 2, 2020):

https://science.sciencemag.org/content/early/2020/07/01/science.abc5343

South Korean officials on Friday reported 91 patients thought cleared of the new coronavirus had tested positive again. The KCDC’s Jeong raised the possibility that rather than patients being re-infected, the virus may have been “reactivated. Kim also said patients had likely “relapsed” rather than been re-infected. False test results could also be at fault, other experts said, or remnants of the virus could still be in patients’ systems but not be infectious or of danger to the host or others.

“There are different interpretations and many variables,” said Jung Ki-suck, professor of pulmonary medicine at Hallym University Sacred Heart Hospital. “The government needs to come up with responses for each of these variables”. South Korea on Friday reported 27 new cases, its lowest after daily cases peaked at more than 900 in late February, according to KCDC, adding the total stood at 10,450 cases....