Category: COVID

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Modelling Suggests COVID Will Reach Endemic Stage by 2024

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COVID heat map. Photo by Giacomo Carra on Unsplash

A new study on coronavirus transmission in rats suggests that COVID will enter the endemic stage in about two years. The study also suggested that infections from high-risk conditions such as close contact with infected individuals produced more robust immunity than by exposure in low-risk settings.

The study, published in PNAS Nexus, made use of rats to determine when and how SARS-CoV-2 would eventually become endemic. Rats, like humans, are susceptible to coronaviruses. By collecting data on coronaviral reinfection rates among rats, the researchers were able to model the potential trajectory of COVID.

SARS-CoV-2 is just one of many coronaviruses, and there are several that cause the common cold. Many livestock animals live with endemic coronaviruses, too, and a key factor identified in the spread of animal and human coronaviruses alike is their tendency to evoke non-sterilising immunity.

“It means that initially there is fairly good immunity, but relatively quickly that wanes,” explained the study’s senior author, Caroline Zeiss, a professor of comparative medicine at Yale School of Medicine. “And so even if an animal or a person has been vaccinated or infected, they will likely become susceptible again.”

Over the past two years, scientists have come to see that SARS-CoV-2 yields non-sterilising immunity as people become re-infected.

The strong similarities between animal and human coronaviruses, animal data helps improve the understanding of SARS-CoV-2, said Prof Zeiss.

“There are many lessons to be learned from animal coronaviruses,” she said.

In this study, Prof Zeiss and her colleagues observed how a coronavirus similar to one that causes the common cold in humans was transmitted through rat populations. The team modelled the exposure scenario to resemble human exposures in the US, where a portion of the population is vaccinated against COVID and where people continue to face natural exposure to SARS-CoV-2. They also reproduced the different types of exposure experienced by people in the US, with some animals exposed through close contact with an infected rat (high risk of infection) and others exposed by being placed in a cage once inhabited by an infected rat (low risk of infection).

Infected animals contracted an upper respiratory tract infection and then recovered. Three to four months later, the rats were then reorganised and re-exposed to the virus. The rates of reinfection showed that natural exposure yielded a mix of immunity levels, with those exposed to more virus through close contact having stronger immunity, while those exposed to lower virus levels by (being placed in a contaminated cage) having higher rates of reinfection.

The takeaway, said Prof Zeiss, is that with natural infection, some individuals will develop better immunity than others. People also need vaccination, which is offered through a set dose and generates predictable immunity. But with both vaccination and natural exposure, the population accumulates broad immunity that pushes the virus toward endemic stability, the study showed.

Mathematical models using the data predicted that the median time for SARS-CoV-2 to become endemic in the United States is 1437 days, or just under four years from the start of the pandemic in March 2020.

In this model’s scenario, 15.4% of the population would be susceptible to infection at any given time after it reaches endemic phrase.

“The virus is constantly going to be circulating,” said Prof Zeiss. So it will be important to keep more vulnerable groups in mind. “We can’t assume that once we reach the endemic state that everybody is safe.”

Four years is the median time predicted by the model, she said, so it could take even longer to reach the endemic stage. And this doesn’t take into account mutations that could make SARS-CoV-2 more harmful.

“Coronaviruses are very unpredictable, so there could be a mutation that makes it more pathogenic,” said Prof Zeiss. “The more likely scenario, though, is that we see an increase in transmissibility and probable decrease in pathogenicity.” That means the virus would be easily transmitted between people but less likely to cause severe illness, much like the common cold.

There is precedent for this trajectory. In the late 1800s, the ‘Russian flu’ killed approximately one million people around the world. Researchers now think that virus was a coronavirus that originated in cattle, which eventually evolved into one of the common cold viruses still in circulation. Reduced pathogenicity associated with the transition from epidemic to endemic status has also been observed in pig coronaviruses. And almost all commercial chicken flocks across the globe are vaccinated for an endemic respiratory coronavirus that has been present since the 1930s.

Longstanding experience with coronaviral infections in other animals can help navigate a pathway to living with SARS-CoV-2.

However, endemic stability in the United States also depends on what happens to the virus elsewhere.

“We are one global community,” Zeiss said. “We don’t know where else these mutations are going to arise. Until we reach endemic stability around the entire globe, we are vulnerable here to having our US endemic stability disrupted by introduction of a new variant.

“But I think overall the picture’s hopeful. I think we will be in endemic stability within the next year or two.”

Source: Yale University

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A Nose for COVID: Sniffer Dogs Outperform Antigen Tests

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Since the start of the COVID pandemic, dogs have been found to be able to sniff out signs of the virus in infected individuals, with some countries deploying the dogs at border posts to quickly check incoming travellers. Now, a new study published in PLOS One shows that they can be faster than rapid antigen tests, and in some instances even more sensitive than PCR testing.

Applications for medical sniffer dogs have been increasingly studied in recent years, and with the arrival of the COVID pandemic, they provided a quick, efficient way to test for SARS-CoV-2 infection. A number of studies demonstrated their effectiveness, with one study reporting a 94% accuracy. Now, this new study shows that can be as accurate as antigen tests, especially in asymptomatic individuals.

The researchers conducted a prospective cohort study in two community COVID screening centres, with 143 symptomatic and 192 asymptomatic adults. Participants were tested with two nasopharyngeal swabs (NPS), one saliva and one sweat sample. The dog handlers (and the dogs…) were blinded to the individuals’ COVID status. The dogs’ sniff tests were compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing.

Overall, 109 of the 335 participants tested positive on nasopharyngeal RT-PCR, 78 symptomatic and 31 asymptomatic. The overall sensitivity of canine detection was 97% and even reached 100% in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91%, reaching 94% for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97%), but the specificity was lower (90% versus 97%).

The researchers concluded that using dogs’ sense of smell to detect SARS-CoV-2 infection could be a speedy alternative to NPS RT-PCR when rapid testing is necessary when antigenic tests are the standard for mass screening.

Categories : COVIDTags :

Long COVID Risk only Slightly Lower after Vaccination

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Man wearing mask with headache
Source: Usman Yousaf on Unsplash

Vaccination only reduces the risk of long COVID after infection by only about 15%, according to a study of more than 13 million people published in Nature Medicine. That’s the largest cohort that has yet been used to examine how much vaccines protect against the condition, but it is unlikely to end the uncertainty as other studies have produced conflicting results.

Studying long COVID has been challenging not least because of how hard it is to define from its constellation of symptoms. Even its prevalence has been hard to determine, with some studies suggesting it occurs in 30% of people after COVID infections. But nephrologist Ziyad Al-Aly and colleagues conducted a study of about 4.5 million people treated at US Department of Veterans Affairs (VA) hospitals, and the findings suggested that the number is 7% overall and lower than that for those who were not hospitalised.

Another mystery has been whether long COVID is less likely to occur after a breakthrough infection. But Al-Aly’s team now looked at VA health records from January to December 2021, including those of about 34 000 vaccinated people who had breakthrough SARS-CoV-2 infections, 113 000 people who had been infected but not vaccinated and more than 13 million people who had not been infected.

These results indicated only 15% a reduction of Long COVID in vaccinated individuals, a marked contrast to previous, smaller studies which suggested much higher protection rates. It’s also a departure from another large study, which used self-reported data from 1.2 million UK smartphone users and found that vaccination halved the risk of long COVID.

The authors of the latest study also compared symptoms such as brain fog and fatigue in vaccinated and unvaccinated people for up to six months after they tested positive for SARS-CoV-2. The team found no difference in type or severity of symptoms between those who had been vaccinated and those who had not. “Those same fingerprints we see in people who have breakthrough infections,” Al-Aly said.

In the US alone there have been over 83 million COVID infections, he noted. If even a small percentage of those turn into long COVID, “that’s a staggeringly high number of people affected by a disease that remains mysterious”.

Such limited protection means putting vulnerable people such as the immunocompromised at risk if measures such as masking are withdrawn. “We’re literally solely reliant, now almost exclusively, on the vaccine to protect us and to protect the public,” said Al-Aly. “Now we’re saying it’s only going to protect you 15%. You remain vulnerable, and extraordinarily so.”

“Generally speaking, this is horrifying,” said David Putrino, a physical therapist at Mount Sinai Health System in New York City who studies long COVID. While he praises the study, he notes that it is limited because it does not break the data down by key factors, such as medical history. “These are very important questions we need answers to,” Putrino says. “We don’t have any really well constructed studies just yet.”

Steven Deeks, an HIV researcher at the University of California, San Francisco, points out that the study includes no data from people infected during the period when the Omicron variant was causing the majority of infections. “We have no data on whether Omicron causes long COVID,” he says. The findings, he adds, “apply to a pandemic that has changed dramatically”.

Deeks added, that the results do highlight the need for more research on long COVID, and for accelerated development of therapies. “We don’t have a definition, we don’t have a biomarker, we don’t have an imaging test, a mechanism or a treatment,” he said. “We just have questions.”

Source: Nature

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Omicron Viral Load Shedding May Be Unaffected by Vaccination

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SARS-CoV-2 virus
SARS-CoV-2 virus. Source: Fusion Medical Animation on Unsplash

A small study published in the New England Journal of Medicine has found that viral load shedding of the omicron variant is similar to other strains, and is not significantly affected by vaccination status.

The SARS-CoV-2 omicron variant has a shorter incubation period and a higher transmission rate than previous variants. Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons from 10 days to 5 days after symptom onset or initial positive test, followed by 5 days of masking. However, the viral delay kinetics and load shedding of omicron is still unclear.

Using nasal swabs to measure viral load, sequencing, and viral culture, they enrolled 66 participants, including 32 with delta variant and 34 with omicron. Participants who received COVID–specific therapies were excluded; only one participant was asymptomatic.

The characteristics of the participants were similar in the two variant groups except that more participants with omicron infection had received a booster vaccine than had those with delta infection (35% vs 3%). After adjustments for age, sex, and vaccination status, the number of days from an initial positive polymerase-chain-reaction (PCR) assay to a negative PCR assay and the number of days from an initial positive PCR assay to culture conversion were similar in the two variant groups.

The median time from the initial positive PCR assay to culture conversion was 4 days in the delta group and 5 days in the omicron group; the median time from symptom onset or the initial positive PCR assay, whichever was earlier, to culture conversion was 6 days and 8 days, respectively. There were no appreciable between-group differences in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision in the estimates.

In these participants with nonsevere COVID, the viral decay kinetics were similar with omicron infection and delta infection. No large differences in the median duration of viral shedding was seen among participants who were unvaccinated, vaccinated but not boosted, and those who were vaccinated and boosted.

Discussing limitations, the authors cautioned that the small sample size limits precision, and there are possible residual confounding variables. Further studies are need to properly correlate culture positivity with infectivity.

They conclude by saying: “Our data suggest that some persons who are infected with the omicron and delta SARS-CoV-2 variants shed culturable virus more than 5 days after symptom onset or an initial positive test.”

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Long COVID Cognitive Impairment More Widespread than Thought

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Scientists following COVID patients up to 12 months after diagnosis have found that mild cognitive impairment is common even after mild to moderate COVID. The study results, currently in preprint on the medRxiv server awaiting peer review, suggest that cognitive impairment, though barely noticeable, may affect large portions of the global population.

The finding comes as the US Centers for Disease Control reported that up to 1 in 5 Americans experienced at least one symptom that could be attributable to Long COVID.

SARS-CoV-2 is believed to cause lasting cognitive impairment in some cases, though the exact nature of it was not clear. Severe COVID cases risk damage through hypoxia, stroke, as well as the immune and inflammatory response to SARS-CoV-2. Mild to moderate COVID cases are still at risk of brain dysfunction, and cognitive deficits, providing a window into the potential mechanisms of brain injury without the confounding role of severe disease and its complications. Given the large numbers of people who had mild to moderate COVID disease, there would be significant implications for public health.

To assess the effects of the disease, the researchers studied 128 SARS-CoV-2 positive patients, assessing cognition and olfaction at set intervals after COVID diagnosis, along with lung capacity and blood biomarkers including the kynurenine pathway (KP).

After correcting for demographics, mild to moderate cognitive impairment was present in 26% on year post diagnosis, respectively. Overall cognitive performance declined mildly, but was statistically significant. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly associated with cognitive decline.

“The immune system reacts first with the virus … tries to basically get rid of the virus,” she said to ABC News. “Then it goes a little bit into overdrive and this overdrive does not fully calm down.”

The KP pathway was seen to be disturbed similarly to the way inflammation is caused by viruses such as HIV.

“I think we’re seeing something a bit akin here, where this low level of inflammation is more and more understood as being able to traffic to the brain, or even being within the brain and affecting those regions of the brain where we process information that demand speed, extra attention and extra cognitive demands,” she explained.

Dr Cysique emphasises that the cognitive decline recorded among most participants in the study is mild and they may not even notice it.

The researchers suggested that as a unique biomarker, the KP offers a potential therapeutic target for COVID-related cognitive impairment.

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How Effective was Masking for SA in Preventing COVID?

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COVID restrictions have finally come to an end altogether in South Africa, as Health Minister Joe Phaahla gazetted a number of changes to the rules, as reported by BusinessTech. This means the end of mask use requirements, social gatherings restrictions and COVID border testing. Prof Shabir Madhi was welcoming of the move in a recent tweet, having criticised SA’s lockdowns as overly harsh and economically damaging. Around the world, many had questioned the widespread use of masks, or their use by some subset of the population, such as children – and even questioned locally by a scientist who argued that it didn’t and wouldn’t work in a South African setting, where people are less adherent to regulations.

Professor Salim Abdool Karim likened such a viewpoint to saying Africans with HIV can’t use ARVs because they didn’t have watches to take them at the right time, reminiscent of “a colonial mentality”.

The case for public mask use is well established. Experiments had shown that even simple cloth masks were moderately effective at hindering the transmission of SARS-CoV-2–containing aerosol particle from infected individuals, though they were less effective at protecting a wearer against infection. Predictably, N95 masks and others are better at doing the job than simple cloth face coverings.

There are no real-world studies for South Africa comparing mask use vs non-mask use as mask wearing was compulsory from the early stages of the outbreak. It would have been downright unethical to ask people to not wear masks, although some people may have had exemptions due to medical conditions or other important reasons. There is a country with good COVID surveillance and a distinct division in mask wearing – the United States. Implementation of mask mandates in the US was down to local authorities, which provides a basis for comparison.

One US study, published in Health Affairs, found that, compared to nonmasking counties, masking counties saw a daily case incidence decline by 25% at four weeks, 35% at six weeks after introduction of masking mandates. The reductions were strongest in Republican-leaning counties, which is notable since Republican voters were less in favour of lockdowns and mask mandates.

Another study found a 16.9% drop in cases four weeks after counties introduced masking mandates. Real-world data also show mask use was effective in preventing infection. A case-and-control study done in California by the CDC showed a 29% drop for surgical mask/respirator use “some of the time” and a 56% drop for “all of the time”.

While a direct comparison between a wealthy country like the US and South Africa as a middle-income country is impossible, it is easy to believe that masking mandates reduced cases by a significant percentage, perhaps saving tens of thousands of lives especially against the country’s possible true COVID death toll of 300 000.

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Chinese Study Finds Children More Likely to Spread COVID

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By gaining access to a high quality COVID transmission data from a northern Chinese city which enforced stringent lockdowns, scientists concluded that young people were most responsible for an increase in direct and secondary infections, and also determined that county-wide lockdowns proved effective in limiting the virus’s spread.

The research study, led by Professor of Sociology Zai Liang at University of Albany, was given rare access to patient profiles and contact tracing data from every case accompanying the outbreak of the virus in Shijiazhuang from January to February in 2021. “Because of universal testing and digital tracing, the data are of high quality,” said Prof Liang, who was assisted by Sociology PhD student and lecturer Han Liu. Liu is from Shijiazhuang and has connections with that city’s CDC research centre, which enabled them to get the data.

The two UAlbany researchers, joined by two colleagues from China, published their findings in the Journal of Urban Health.

Prof Liang wrote that while individual-level contact tracing studies on the virus’s transmission and mitigation efforts have been growing, “because of limited testing capacities and risks of infringing on privacy, surveillance data used in individual-level research usually have limited representativeness.” His Shijiazhuang study, whose analysis included 99.52 percent (1028 of 1133) of the transmitted cases in Shijiazhuang, is designed “to fill this gap in the literature.”

The research examined sociodemographic factors including age, gender and socioeconomic status, postulating that “certain sociodemographic characteristics may facilitate the spread of germs by exposing the host to more social contacts.” This would include children interacting in the classroom, females having more contact with their relatives than do males, and less affluent workers working or living in overcrowded settings.

Among the study’s results are:

  • Children 0–17 years old had fewer close contacts than adults, but these led to more secondary infections: 32.1% infected children, 67.9% adults
  • Close contacts of children were 81% more likely to be infected than the contacts of those 18–49
  • Peasant workers, compared to non-manual workers, had 40% more secondary cases from the same neighbourhoods.

Prof Liang wrote, “While children have a low probability of having severe symptoms after being infected by COVID, they can seed the spread in the larger society by infecting their household members and other adults living in their neighbourhoods. These adults can then transmit the disease to their own social contacts. Future studies on how to control within-school infections are therefore urgently needed.”

Another major conclusion of the Shijiazhuang study is that timely non-pharmaceutical interventions, including restrictions on gatherings and school closures, effectively contained further infections via contact reduction, especially when implemented in small areas with the highest caseloads. Liang acknowledged that school closures did have negative ramifications for children’s education and socialisation.

Serendipitous data collection

How did Prof Liang and colleagues obtain comprehensive data not yet publicly available to others? “We heard of this COVID outbreak in this part of northern China early last year, when I was working on a proposal to study COVID. I asked Han Liu if we had connections in that city. It turned out that he is originally from Shijiazhuang and has connections with that city’s CDC research centre.

“The two researchers who collected the data agreed to join us in this effort. I am lucky to ask the right question at the right time.”

Source: University at Albany

Categories : COVID GenderTags :

Females ‘Significantly’ More Likely to Experience Long COVID

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A new study published in Current Medical Research and Opinion has revealed that females are “significantly” more likely to suffer from Long COVID than males and will experience substantially different symptoms.

Long COVID is a syndrome in which complications persist more than four weeks after the initial infection of COVID, sometimes for many months.

In a review of studies, researchers observed females with Long COVID are presenting with a variety of symptoms including ear, nose, and throat issues; mood, neurological, skin, gastrointestinal and rheumatological disorders; as well as fatigue.

Male patients, however, were more likely to experience endocrine disorders such as diabetes and kidney disorders.

“Knowledge about fundamental sex differences underpinning the clinical manifestations, disease progression, and health outcomes of COVID is crucial for the identification and rational design of effective therapies and public health interventions that are inclusive of and sensitive to the potential differential treatment needs of both sexes,” the authors explained.

“Differences in immune system function between females and males could be an important driver of sex differences in Long COVID syndrome. Females mount more rapid and robust innate and adaptive immune responses, which can protect them from initial infection and severity. However, this same difference can render females more vulnerable to prolonged autoimmune-related diseases.”

In their review, researchers gathered a total sample size amounting to 1 393 355 unique individuals.

While the number of participants sounds large, only 35 of the 640 634 total articles in the literature provided sex disaggregated data in sufficient details about symptoms and sequalae of COVID disease to understand how females and males experience the disease differently.

The findings showed that, with the initial onset of COVID, female patients were far more likely to experience mood disorders such as depression, ear, nose, and throat symptoms, musculoskeletal pain, and respiratory symptoms. Male patients, on the other hand, were more likely to suffer from renal disorders.

The authors note that this synthesis of the available literature is among the few to break down the specific health conditions that occur as a result of COVID-related illness by sex. Plenty of studies have examined sex differences in hospitalisation, ICU admission, ventilation support, and mortality. But the research on the specific conditions that are caused by the virus, and its long-term damage to the body, have been understudied when it comes to sex.

“Sex differences in outcomes have been reported during previous coronavirus outbreaks,” the authors added. “Therefore, differences in outcomes between females and males infected with SARS-CoV-2 could have been anticipated. Unfortunately, most studies did not evaluate or report granular data by sex, which limited sex-specific clinical insights that may be impacting treatment.” Ideally, sex disaggregated data should be made available even if it was not the researcher’s primary objective, so other interested researchers can use the data to explore important differences between the sexes.

Greater occupational exposure through traditionally female-dominated jobs may may complicate interpretation the COVID sequelae.

Source: EurekAlert!

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Substantially Lower Long COVID Risk from Omicron Infection

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SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Findings from a new study reported in The Lancet has found the risks of developing long COVID are greatly reduced (by ~50% to 75%) as a result of Omicron infection compared to Delta infection.

The study, the first of its kind to report on long COVID risk associated with Omicron, highlights the speed with which app-based health surveillance can provide insights. These have further been shown to be consistent and replicable.

A major strength of the study was the ability to log a wide range of symptoms with the app. Limitations of the self-reported data include no direct testing of infectious variants (here assumed from national data) and no objective measures of illness duration. There was insufficient data to estimate the odds of long COVID in unvaccinated individuals. Finally, to enable swift reporting, the period of assessment of omicron cases was slightly shorter than for the delta variant, and assessment of longer durations of long COVID (eg, >12 weeks) was not possible.

In this case-control observational study, the researchers took self-reported data from the COVID Symptom Study app.

Participants were selected on a positive COVID test after SARS-CoV-2 after vaccination, at least one log per week in the app for at least 28 days after testing positive, and no previous SARS-CoV-2 infections before vaccination. The researchers identified 56 003 UK adults first testing positive between Dec 20, 2021, and March 9, 2022, when the Omicron variant became dominant. Similarly, researchers identified 41 361 UK adult cases first testing positive between June 1, 2021, and Nov 27, 2021, during the period of Delta dominance.

Both symptomatic and asymptomatic infections were considered, and, for the Omicron period, only participants testing positive before Feb 10, 2022, were included, to ensure all participants had at least 28 days for symptom reporting after testing positive. The researchers adjusted for socioeconomic deprivation and other factors.

In both periods, female participation was higher than male participation (55% for Omicron and 59% for Delta cases). Delta and Omicron cases had similar age (mean age 53 years) and prevalence of comorbidities (around 19%). Among Omicron cases, 2501 (4.5%) of 56 003 people experienced long COVID and, among Delta cases, 4469 (10.8%) of 41 361 people experienced long COVID. Cases were stratified by time from vaccination to first infection. They found that, for all vaccine timings, Omicron cases were less likely to experience long COVID, with an odds ratio ranging from 0.24 to 0.50.

However, the researchers noted that the the absolute number of people with long COVID at a certain time depends on the pandemic curve. Considering the UK Omicron peak of more than 350 000 new symptomatic COVID cases per day estimated on March 26, 2022, by the ZOE app model, with 4% of cases being long COVID, future numbers with long COVID will inevitably rise.

Source: The Lancet

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Few Patients get ‘Rebound COVID’ after Paxlovid Treatment

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Mayo Clinic researchers studied the outcomes of 483 high-risk patients  treated for COVID with a five-day oral regimen of Paxlovid, a combination of nirmatrelvir and ritonavir. Only a handful developed COVID rebound symptoms, something which the researchers say needs further investigation. Their findings appear in the journal Clinical Infectious Diseases.

All of the patients benefited from Paxlovid and recovered, including the patients who developed rebound symptoms, which were generally mild.

“We found that rebound phenomenon was uncommon in this group of patients,” says senior author Aditya Shah, MBBS, an infectious diseases physician and researcher at Mayo Clinic. “The four individuals who experienced rebound [symptoms] represent only 0.8% of the group, and all of them recovered quickly without additional COVID-directed therapy.”

Most of the patients had been vaccinated, and many had received booster vaccinations. The median age was 63. While these patients were high-risk for COVID, none was immunocompromised. Only two patients were admitted to the hospital, and it was for reasons other than COVID.

The study focussed on four patients with rebound symptoms:

  • A 75-year-old man with coronary artery disease who had increased cough and muscle aches 19 days after treatment.
  • A 40-year-old woman with obesity, hypertension and kidney disease who developed fatigue and sore throat six days after treatment.
  • A 69-year-old man with hypertension and obesity who exhibited nasal discharge and cough 10 days following therapy.
  • A 70-year-old man with a history of prostate cancer, obesity, hypertension and high cholesterol, who developed significant sinus congestion 10 days after treatment.

Why did some rebound?

Researchers think one explanation could be that a replication of SARS-CoV-2 could have triggered a secondary immune response, which showed up as mild COVID symptoms. This question could be answered by prospective studies could answer the question. They also note that all four patients with rebound symptoms had many serious health problems known as comorbidities — a factor shown to complicate recoveries. And all four patients had been vaccinated more than 90 days before becoming infected with COVI.

Source: Mayo Clinic