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.
Here, we show evidence of how fast the VOC P.1 has spread in the most populated city in South America – Sao Paulo. From March 1st to March 15th, 427 nasopharyngeal samples were collected from 245 HP and 125 from HCW outpatients (25.5% and 23.2% of positivity rate, respectively). We then selected 60 samples with Ct value ≤ 30 (38 samples from HP, and 22 from HCW). All HCW presented only mild symptoms and did not need hospitalization.
Of the 60 selected samples, 52 whole genome sequences were generated (30 from HP and 22 from HCW) following the sequencing protocol using the Illumina MiSeq platform and the analysis pipeline described by Resende et al (8). The SARS-CoV-2 lineages were classified by the PANGO lineages nomenclature (9). Genome sequences generated have been deposited at the EpiCoV database on GISAID https://www.gisaid.org/) under accession numbers EPI_ISL_1464630 to EPI_ISL_1464677.
Of the 52 sequenced samples, 44 (84.4%) were identified as VOC P.1; 5 (9.2%) as VOI P.2; 1 (1,9%) as B.1.1.7, and 2 (3,8%) B.1.1.28.
The most notable variants circulating in the second wave, including B.1.1.7 (detected first in the United Kingdom) and B.1.1.351 (detected first in South Africa), and P.1, are related to an increase of transmissibility (2,10). Interestingly, the P.1 variant was first identified in the State of Amazonas, about 3,800 kilometers apart from São Paulo (5). It is evident that the P.1 variant prevailed during the first two weeks of March, showing a regular distribution among HP and HCW with no difference in terms of age, sex, vaccination, and outcome (Table). From the first to the second weeks of March, we observed a higher frequency of P.1 (78.6% and 91.7%, respectively). In this survey, only one sample from a HP was identified as VOC B.1.1.7. The other two samples were identified as B.1.1.28, a widely spread lineage during the first wave in Brazil.
There is a broad discussion about whether the available vaccines against SARS-CoV-2 will be less effective at preventing infection with the emerging variants (10). In this work, 14 samples (26.9%) of the 52 sequenced samples were from individuals that had received at least one dose of vaccine, ChAdOx1-S/nCoV-19 (n=2) or SINOVAC (n=26). Although they were vaccinated, they could not be considered immunized, regarding the days after vaccination.
Among the hospitalized patients, 19 (63%) were admitted to the intensive care unit, from which nine were discharged and ten died. Comparing the RT-PCR Ct values of all attended patients since the first wave, we did not observe any difference in the Ct mean values with those of P.1 (data not shown). May 2020 registered the peak of number of positive cases with a Ct mean of 23.6. Now, as of April 2021, we are facing a rise in the number of cases. However, the Ct mean was 24.9, which may indicate that the spread of P.1 does not contribute to an actual increase in the viral load.
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.”
12th March 2020 – Boris Johnson: “many more people will lose loved ones to coronavirus” (Guardian).
13th April 2021 – Boris Johnson: “sadly we will see more hospitalisation and deaths” (Guardian)
We report a cluster of two sequences characterized by a unique array of 18 mutations, including new non-synonymous changes in the same critical spike amino acid positions, E484Q and N501T. This lineage seems to have emerged independently from the nationally widespread B.1.1.28, as previously reported for P.1 and P.2, and adds up to the composition of a complex epidemiological scenario of the SARS-CoV-2 pandemic in Brazil.
Our analysis revealed the circulation of a putative new variant derived from lineage B.1.1.28, and represented by two genome sequences in our dataset, LBI215 (complete, 99.81% 10x genome coverage, 98.07% 100x genome coverage, average sequencing depth: 1532x, pangolin original classification: B.1.235) and LBI218 (partial, 76.20% 10x genome coverage, 57.45% 100x genome coverage, average sequencing depth: 595x, pangolin original classification: B.1.1.94). These two sequences form a well-supported (SH-aLRT = 100) monophyletic clade characterized by a unique set of 18 nucleotide mutations.
Beyond harboring multiple exclusive synonymous (C1627U, A10888G, C12664U, C24904U, C27807U, A28271U) and non-synonymous (G5180A: ORF1ab D1639N, G9929A: ORF1ab D3222N, G23012C: Spike E484Q, A23064C: Spike N501T, C24374U: Spike L938F, G24410A: Spike D950N, C28311U: Nucleocapsid P13L) SNPs, this lineage also possesses mutations present in other VOCs: deletion 11288-11296 (ORF1ab 3675-3677 SGF; shared by P.1, B.1.1.7 and B.1.351), C21614U (Spike L18F, P.1) and C28253U (Synonymous, P.2). Two additional deletions are present in these sequences: deletions 28881-28889 (Nucleocapsid 203-206 RGTS(T)) and 29581, which causes a frameshift mutation in ORF10. Additional mutations covered only in the LBI215 genome include: G3617A, ORF1ab V1118I; C21846T, spike T95I; deletion 21986-21991, Spike 142/143 GV; T23542C, synonymous. To ascertain that these mutations were not assembly artifacts, we confirmed their presence in the raw sequencing data .
Virological.org preprint : Increasing frequency of SARS-CoV-2 lineages B.1.1.7, P.1 and P.2 and identification of a novel lineage harboring E484Q and N501T spike mutations in Minas Gerais, Southeast Brazil
Original press story: UFMG scientists announce they have discovered a new variant of the coronavirus
Brazil’s coronavirus catastrophe has deepened further after more than 4,000 daily deaths were reported for the first time since the outbreak began in February last year. At least 4,195 people were reported to have died on Tuesday taking Brazil’s total death toll – the world’s second highest after the US – to nearly 337,000.
Its health ministry also reported 86,979 new infections. Experts fear a record 100,000 Brazilians could lose their lives this month alone if nothing is done.
“It’s a nuclear reactor that has set off a chain reaction and is out of control. It’s a biological Fukushima,” Miguel Nicolelis, a Brazilian doctor and professor at Duke University, who is closely tracking the virus told Reuters
We sequenced the SARS-CoV-2 genome from 688 positive samples collected from December 28 2020 to March 13 2021 in Arizona, USA. 638 high-quality complete genomes were successfully sequenced that included variants such as B.1.1.7, B.1.427/429 and P.2. We detected 7 genomes associated with a common B.1.243 variant that had acquired an E484K mutation in the spike protein.
The novel variant had 11 lineage-defining mutations including V213G and E484K in the spike gene, a 9-nt deletion in ORF1ab (ΔSGF3675-77), a 3-nt insertion in the non-coding intergenic region upstream of the N gene and other synonymous substitutions (Figure 1A, Supplementary Table 1). These 11 conserved mutations are distinct from the mutations associated with the parental lineage, B.1.243. The parental B.1.243 lineage is a common circulating variant in the US that was first observed at the start of the pandemic as early as March 2020 (Figure 1B, 96.9%). The B.1.243 parent lineage encodes the spike gene D614G substitution, but none of the other concerning mutations (Figure 1A, Supplementary Table 2). Therefore, we designate the new E484K harboring variant the provisional name of B.1.243.1.
We report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North and Northeast regions.
The SARS-CoV-2 epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. Two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved within lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North and Northeast regions.
In December, 2020, 95 (89%) of 107 sequenced cases contained mutations of concern, rising to 102 (98%) of 104 in January, 2021. The identified variants included the previously reported B.1.351 (501Y.V2) and A.23.1 variants, along with a novel variant under investigation.
Prospective surveillance of SARS-CoV-2 by genome sequencing in Zimbabwe between December, 2020, and January, 2021 (the period of the so-called second wave), has identified that variants with concerning mutations are prevalent in sequenced samples. In December, 2020, 95 (89%) of 107 sequenced cases contained mutations of concern, rising to 102 (98%) of 104 in January, 2021. The identified variants included the previously reported B.1.351 (501Y.V2) and A.23.1 variants, along with a novel variant under investigation.
The B.1.1.7, B.1.525, P.1, and P.2 and variants were not identified in Zimbabwe. Variants with concerning mutations have all replaced previously identified lineages in Zimbabwe
In August 2020, Brazilian researcher Lucas Ferrante warned authorities of a 2nd wave of coronavirus in Manaus, Brazil in this article – an event which subsequently occurred and has been widely reported.
Now Ferrante has warned Manaus of a devastating 3rd wave of Covid-19 which could potentially allow the P.1 and P.2 Sars-Cov-2 variants to mutate and spread worldwide in this article: “Manaus City Hall ignores researchers’ warnings about 3rd wave of covid”
‘..a third wave could drag on until 2022 and Manaus will be the world epicenter. “If no initiative is taken, as in the past, the third wave will be longer and will kill many more people. The alternative is a lockdown with more than 90% isolation and vaccination for the entire population of Manaus,”’.
We report the first case of reinfection from genetically distinct SARS-CoV-2 lineage [P.2] presenting the E484K spike mutation in Brazil, a variant associated with escape from neutralizing antibodies.