A 39-year-old Brazilian man who died of COVID-19 last month was suffering from a second bout of the illness, researchers said on Tuesday, making it the country’s first confirmed death from coronavirus reinfection. Both episodes involved variants with the E484K mutation.
The man, from Campo Bom in the southern state of Rio Grande do Sul, had a history of chronic cardiovascular disease and diabetes. He first tested positive on November 30 but details about his symptoms – if any – are unclear. Genomic sequencing revealed the P.1 variant.
The patient fell ill a second time about 3 months later and tested positive on March 11, according to researchers at Feevale University. His initial symptoms were fatigue and respiratory distress, but his condition worsened and he was transferred to the ICU, where he was intubated and died on March 19.
Genomic sequencing of the sample from the second episode revealed the P.2 variant, which is classified as a Variant of Interest.
“We were the first to identify two independent events of co-infection caused by the occurrence of B.1.1.28 (E484K) with either B.1.1.248 or B.1.91 lineages. Also, clustering analysis revealed the occurrence of a novel cluster of samples circulating in the state (named VUI-NP13L) characterized by 12 lineage-defining mutations.”
ScienceDirect.com preprint: Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil
People in the UK have been infected with Covid-19 more than once thanks to catching different variants of the coronavirus. Dr Susan Hopkins, chief medical adviser for NHS Test and Trace, said there had been cases where people had become reinfected by different strains of the coronavirus. “We have seen some people who have had their first dose of vaccine who have had the South African variant and the variant that arose in Kent,” she told BBC’s the Andrew Marr show. “You can see that they’re not as good against the South African variant as they are against our own (variant) B117 at preventing infection and transmission.”
“Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common” says Stuart Sealfon, MD. The study, conducted between May and November 2020, revealed that around 10 percent of participants who were previously infected with SARS-CoV-2 became reinfected, compared with new infections in 50 percent of participants who had not been previously infected.
Lancet Respiratory Medicine study – SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study
Prof Paul Hunter, professor in medicine at the University of East Anglia, told the Guardian that the arrival of the India variant was potentially worrying. He said: “These two escape mutations working together could be a lot more problematic than the South African and Brazilian variants which have only got one escape mutation. “It might be even less controlled by vaccine than the Brazilian and South African variants.”
The variant featured two “escape mutations” – E484Q and L452R – that “are causing people to be concerned. “There’s laboratory evidence that both of these are escape mutations. Basically, applying what we know about other human coronaviruses would suggest that this is going to be even less controlled by vaccine. But we don’t know that for certain at the moment”
A paper to be published in May in the U.S. Centers for Disease Control and Prevention’s (CDC/US) journal Emerging Infectious Diseases (EID) shows that a first exposure to COVID-19 in mild or asymptomatic cases may not produce an immune response, and that a person can reinfect himself or herself with the same variant. The second infection can cause stronger symptoms than the first, the study indicates.
The data shows that for a portion of the population that has the disease in the mild form (in which hospitalization is not required) this does not mean that they will be immune or that a reinfection will evolve in a benign way. The study also indicates that reinfection may be more frequent than assumed.
The case of being infected by the same variant happens because the patient would not have built up an immunological memory. In the case of another strain, it would “escape” surveillance, it would not be recognized by the previously generated memory because it is a little different.
To reach these conclusions, the researchers followed a group of 30 people on a weekly basis from March 2020, at the pandemic start, until the end of the year. Of these, four contracted Sars-CoV-2, and some were infected with the same variant. The researchers then sequenced the virus genome in the case of the first infection and then in the second infection to be able to compare them.
“The gene sequencing method developed by MGI allowed us to detect the virus even in samples with low viral load. Today, Bio-Manguinhos [the Immunobiological Technology Institute] has some of these machines,” says Moreno.
In all four cases, the first infection occurred with mild symptoms. In the second, the symptoms were more frequent and stronger, but did not require hospitalization. “These people didn’t actually have detectable immunity until after the second infection. This leads us to believe that for a population part that had the disease in a mild form, one exposure to the virus is not enough, but more than one, to have a degree of immunity,” says Moreno. “This allows a portion of the population that has already been exposed to sustain a new epidemic.”
“Spike analysis reveals that the current SARS-CoV-2 variants of concern have sampled only 36% of the possible spikes changes which have occurred historically in Sarbecovirus evolution. It is likely that new SARS-CoV-2 variants with changes in these regions are compatible with virus replication and are to be expected in the coming months, unless global viral replication is severely reduced.”
“The more global analysis of spike regions in SARS-CoV-2 genomes revealed the changes that have occurred across the Sarbecovirues. Combined with the current VOC spike changes, the patterns suggest that SARS-CoV-2 has a great deal of evolutionary possibilities to avoid immune pressure.”
“Spike changes in SARS-CoV-2 compared to a large set of known Sarbecovirus indicate that the immediate zoonotic source of SARS-CoV-2 is yet to be identified and reinforces the unique nature of the SARS-CoV-2 genome.”
Biorxiv Preprint – Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses
The VOI 19B / 501Y (lineage A.27) has been detected infrequently but regularly in France since January 2021. It represented 1.8% of the interpretable sequences during the Flash # 4 survey versus 0% during the Flash Inquiry # 3. In weeks 10 and 11, respectively 48 and 47 detections of this variant were reported by the 4 national sequencing platforms.
However, several points of attention should be note and justify continuing the reinforced surveillance of this variant. First, it was detected during several clusters, a priori all closed, affecting schools, healthcare (including centers hospitals, SSR and Ehpad) or military, with for some a high number of COVID-19 cases (more around sixty), particularly in Ile-de-France (2 hospital clusters and 8 intra-family clusters), Pays de la Loire (3 clusters), Brittany (1 cluster in Morbihan) and Nouvelle-Aquitaine (6 clusters in Dordogne).
Community transmission of this variant is suspected in at least two departments (Seine-et-Marne et Dordogne), and additional investigations are currently being carried out by the ARS concerned, in conjunction with SpF and CNR, to characterize this signal. In addition, three cases considered as probable re-infections were identified with confirmation of infection with this variant during the second episode, without it being possible to date to estimate the frequency of re-infections with this variant, nor to compare it with that of other viral strains circulating in France.
Data is still lacking at this stage on the clinical features of infection with this variant, but we did not detect a signal in favor of significant impact on its transmissibility or increased severity of infection caused by this variant. The strengthening of the surveillance of this variant should be able to more precisely document its characteristics, which will be noted to you when additional data becomes available.
French Health Department – Risk analysis related to emerging variants of SARS-COV-2 (PDF)
One year after the first confirmed case of coronavirus infection, experts in the Czech Republic recorded 1,400 cases of reinfection, in which people in both cases had symptoms of Covid-19. In the last month, the number of reinfections increased ninefold, a month ago the SZÚ registered 158. According to the SZÚ, the increase is related to the large number of those infected in the autumn wave.
Protection against repeat infection was 80·5%. Among those aged 65 years and older, observed protection against repeat infection was 47·1%.
“During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51–0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22–3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155–0·246]). Protection against repeat infection was 80·5% (95% CI 75·4–84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179–0·251], estimated protection 78·8% [74·9–82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7–62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1–83·2] vs female 79·1% [73·9–83·3]) or evidence of waning protection over time (3–6 months of follow-up 79·3% [74·4–83·3] vs ≥7 months of follow-up 77·7% [70·9–82·9]).”
There are just over half a dozen cases of Covid-19 reinfections worldwide among the millions who have caught the disease. Cases in which the second reinfection is more severe than the first are rarer. Yet one of them is Ramon Valls, 62, a rheumatologist at Palamós Hospital, and a sportsman who has suffered no previous illnesses.
“I’m still on sick leave. I was reinfected in August and was hospitalised for 20 days. I was discharged on September 18 and I hope to be able to start working after the Christmas holidays. With the first infection in March I only had mild symptoms, and worked from home tending to my patients by phone. The second time was not the same.”
“They do all kinds of tests on me and they’ve been able to sequence the virus that reinfected me, and it’s not the same strain that I had in March.”
“Findings on B.1.351 [South Africa variant] are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
The immune plasma of COVID-19 convalescent blood donors had 6-fold less neutralizing capacity against the P.1 than against the B-lineage. Moreover, five months after booster immunization with CoronaVac, plasma from vaccinated individuals failed to efficiently neutralize P.1 lineage isolates.
Interpretation: These data indicate that the P.1 lineage may escape from neutralizing antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2.