H5N1

Molecular evidence for SARS-CoV-2 in samples collected from patients with morbilliform eruptions since late 2019 in Lombardy, northern Italy

Via ScienceDirect, a report in Environmental Research that could change the origin story of SARS-CoV-2: Molecular evidence for SARS-CoV-2 in samples collected from patients with morbilliform eruptions since late 2019 in Lombardy, northern Italy. The abstract:

As a reference laboratory for measles and rubella surveillance in Lombardy, we evaluated the association between SARS-CoV-2 infection and measles-like syndromes, providing preliminary evidence for undetected early circulation of SARS-CoV-2. 

Overall, 435 samples from 156 cases were investigated. RNA from oropharyngeal swabs (N = 148) and urine (N = 141) was screened with four hemi-nested PCRs and molecular evidence for SARS-CoV-2 infection was found in 13 subjects. Two of the positive patients were from the pandemic period (2/12, 16.7%, March 2020–March 2021) and 11 were from the pre-pandemic period (11/44, 25%, August 2019–February 2020). 

Sera (N = 146) were tested for anti-SARS-CoV-2 IgG, IgM, and IgA antibodies. Five of the RNA-positive individuals also had detectable anti-SARS-CoV-2 antibodies. No strong evidence of infection was found in samples collected between August 2018 and July 2019 from 100 patients. 

The earliest sample with evidence of SARS-CoV-2 RNA was from September 12, 2019, and the positive patient was also positive for anti-SARS-CoV-2 antibodies (IgG and IgM). Mutations typical of B.1 strains previously reported to have emerged in January 2020 (C3037T, C14408T, and A23403G), were identified in samples collected as early as October 2019 in Lombardy. One of these mutations (C14408T) was also identified among sequences downloaded from public databases that were obtained by others from samples collected in Brazil in November 2019. 

We conclude that a SARS-CoV-2 progenitor capable of producing a measles-like syndrome may have emerged in late June-late July 2019 and that viruses with mutations characterizing B.1 strain may have been spreading globally before the first Wuhan outbreak. Our findings should be complemented by high-throughput sequencing to obtain additional sequence information. 

We highlight the importance of retrospective surveillance studies in understanding the early dynamics of COVID-19 spread and we encourage other groups to perform retrospective investigations to seek confirmatory proofs of early SARS-CoV-2 circulation.

Genomic epidemiology of the first two waves of SARS-CoV-2 in Canada

Via eLife: Genomic epidemiology of the first two waves of SARS-CoV-2 in Canada. The abstract:

Tracking the emergence and spread of SARS-CoV-2 lineages using phylogenetics has proven critical to inform the timing and stringency of COVID-19 public health interventions. We investigated the effectiveness of international travel restrictions at reducing SARS-CoV-2 importations and transmission in Canada in the first two waves of 2020 and early 2021. 

Maximum likelihood phylogenetic trees were used to infer viruses’ geographic origins, enabling identification of 2263 (95% confidence interval: 2159–2366) introductions, including 680 (658–703) Canadian sublineages, which are international introductions resulting in sampled Canadian descendants, and 1582 (1501–1663) singletons, introductions with no sampled descendants. 

Of the sublineages seeded during the first wave, 49% (46–52%) originated from the USA and were primarily introduced into Quebec (39%) and Ontario (36%), while in the second wave, the USA was still the predominant source (43%), alongside a larger contribution from India (16%) and the UK (7%). 

Following implementation of restrictions on the entry of foreign nationals on 21 March 2020, importations declined from 58.5 (50.4–66.5) sublineages per week to 10.3-fold (8.3–15.0) lower within 4 weeks. Despite the drastic reduction in viral importations following travel restrictions, newly seeded sublineages in summer and fall 2020 contributed to the persistence of COVID-19 cases in the second wave, highlighting the importance of sustained interventions to reduce transmission. Importations rebounded further in November, bringing newly emergent variants of concern (VOCs). 

By the end of February 2021, there had been an estimated 30 (19–41) B.1.1.7 sublineages imported into Canada, which increasingly displaced previously circulating sublineages by the end of the second wave. Although viral importations are nearly inevitable when global prevalence is high, with fewer importations there are fewer opportunities for novel variants to spark outbreaks or outcompete previously circulating lineages.

See also this CTV report on the study.

Outcomes of SARS-CoV-2 reinfection

Via Research Square, a preprint: Outcomes of SARS-CoV-2 Reinfection. This is a disturbing finding. The abstract, re-formatted and with my bolding:

First infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in the pulmonary and extrapulmonary organ systems. However, whether reinfection adds to the risk incurred after the first infection is not clear. 

Here we use the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes. 

We show that compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders); 

the risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection; 

the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection. 

Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. 

The constellation of findings shows that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death

Via Nature Scientific Reports:SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death. The abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accompanied by chronic neurological sequelae such as cognitive decline and mood disorder, but the underlying mechanisms have not yet been elucidated. We explored the possibility that the brain-infiltrating SARS-CoV-2 spike protein contributes to the development of neurological symptoms observed in COVID-19 patients in this study. 

Our behavioral study showed that administration of SARS-CoV-2 spike protein S1 subunit (S1 protein) to mouse hippocampus induced cognitive deficit and anxiety-like behavior in vivo. These neurological symptoms were accompanied by neuronal cell death in the dorsal and ventral hippocampus as well as glial cell activation. Interestingly, the S1 protein did not directly induce hippocampal cell death in vitro. Rather, it exerted neurotoxicity via glial cell activation, partially through interleukin-1β induction. 

In conclusion, our data suggest a novel pathogenic mechanism for the COVID-19-associated neurological symptoms that involves glia activation and non-cell autonomous hippocampal neuronal death by the brain-infiltrating S1 protein.

A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada

Thanks to Norman Spector for sending the link to this report in Genome Medicine: A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada. The abstract:

Background  

Québec was the Canadian province most impacted by COVID-19, with 401,462 cases as of September 24th, 2021, and 11,347 deaths due mostly to a very severe first pandemic wave. In April 2020, we assembled the Coronavirus Sequencing in Québec (CoVSeQ) consortium to sequence SARS-CoV-2 genomes in Québec to track viral introduction events and transmission within the province.  

Methods  

Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec. We report 2921 high-quality SARS-CoV-2 genomes in the context of > 12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatiotemporal spread of the virus.  

Results  

Conservatively, we estimated approximately 600 independent introduction events, the majority of which happened from spring break until 2 weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (> 50 sequenced cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and “snowbird” destinations, most of the introductions were inferred to have originated from Europe via the Americas.  

Once introduced into Québec, viral lineage sizes were overdispersed, with a few lineages giving rise to most infections. Consistent with founder effects, the earliest lineages to arrive tended to spread most successfully. Fewer than 100 viral introductions arrived during spring break, of which 7–12 led to the largest transmission lineages of the first wave (accounting for 52–75% of all sequenced infections). These successful transmission lineages dispersed widely across the province.  

Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travellers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order.  

Conclusions  

Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.

Coronaviruses with a SARS-CoV-2-like receptor-binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula

Via Research Square, a preprint, not yet peer reviewed: Coronaviruses with a SARS-CoV-2-like receptor-binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula.

The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affinis, RaTG13. Several studies have suggested the involvement of pangolin coronaviruses in SARS-CoV-2 emergence. 

SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 pathway have not yet been identified, though they would be key in understanding the origin of the epidemics. 

Here we show that such viruses indeed circulate in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula. We found that the RBDs of these viruses differ from that of SARS-CoV-2 by only one or two residues, bind as efficiently to the hACE2 protein as the SARS-CoV-2 Wuhan strain isolated in early human cases, and mediate hACE2-dependent entry into human cells, which is inhibited by antibodies neutralizing SARS-CoV-2. 

None of these bat viruses harbors a furin cleavage site in the spike. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic

Via bioRxiv: Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic. The abstract:

The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud, and reconstruct partial sequences of 13 early epidemic viruses. 

Phylogenetic analysis of these sequences in the context of carefully annotated existing data suggests that the Huanan Seafood Market sequences that are the focus of the joint WHO-China report are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.

ECDC rapid risk assessment: Assessing SARS-CoV-2 circulation, variants of concern, non-pharmaceutical interventions and vaccine rollout in the EU/EEA, 15th update

ECDC has published Rapid risk assessment: Assessing SARS-CoV-2 circulation, variants of concern, non-pharmaceutical interventions and vaccine rollout in the EU/EEA, 15th update. Excerpt:

Although SARS-CoV-2 transmission remains widespread in large parts of the EU/EEA, most countries report declining trends in 14-day COVID-19 notification rates, hospital and intensive care unit (ICU) occupancy, and mortality. Many countries have initiated partial lifting of different non-pharmaceutical interventions (NPIs) that aim to reduce the degree of citizens physical contact and mobility. 

Since January 2021, EU/EEA countries have reported an increase in the number and proportion of SARS-CoV-2 cases of variants of concern (VOC) associated with increasing transmissibility and/or severity, with Alpha (B.1.1.7) the current dominant variant across the EU/EEA. 

Estimates across the region show that a large proportion of the population across Europe still remains susceptible to SARS-CoV-2 and that population immunity is far from being reached. As of 3 June, the median cumulative vaccine uptake in the EU/EEA adult population (aged 18 years and older) had reached 46.2% for at least one vaccine dose and 22.3% for the full vaccination course. The highest level of vaccine uptake was observed among the elderly aged over 80, in which the uptake reached 80.5% for at least one dose and 66.3% for full vaccination coverage. For healthcare workers, the median level of at least one dose uptake was 87% and the median uptake for the full vaccination course was 65.2%. Increased vaccine supply has allowed countries to expand eligibility for vaccination to younger age groups.

Investigation of a severe SARS-CoV-2 outbreak in a long-term care home early in the pandemic

Via CMAJ: Investigation of a severe SARS-CoV-2 outbreak in a long-term care home early in the pandemic. The abstract:

BACKGROUND: The implementation of outbreak management measures has decreased the frequency and severity of SARS-CoV-2 outbreaks in Ontario long-term care homes. We describe the epidemiological and laboratory data from one of the first such outbreaks in Ontario to assess factors associated with its severity, and the impact of progressive interventions for infection control over the course of the outbreak. 

METHODS: We obtained line list and outbreak data from the public health unit to describe resident and staff cases, severity and distribution of cases over time and within the outbreak facility. Where available, we obtained data on laboratory specimens from the Public Health Ontario Laboratory and performed whole genome sequencing and phylogenetic analysis of viral specimens from the outbreak. 

RESULTS: Among 65 residents of the long-term care home, 61 (94%) contracted SARS-CoV-2, with a case fatality rate of 45% (28/61). Among 67 initial staff, 34 (51%) contracted the virus and none died. When the outbreak was declared, 12 staff, 2 visitors and 9 residents had symptoms. Resident cases were located in 3 of 4 areas of the home. Phylogenetic analysis showed tight clustering of cases, with only 1 additional strain of genetically distinct SARS-CoV-2 identified from a staff case in the third week of the outbreak. No cases were identified among 26 new staff brought into the home after full outbreak measures were implemented. 

INTERPRETATION: Rapid and undetected viral spread in a long-term care home led to high rates of infection among residents and staff. Progressive implementation of outbreak measures after the peak of cases prevented subsequent staff cases and are now part of long-term care outbreak policy in Ontario. 

First-ever image of COVID-19 variant supports faith in current vaccines, UBC says

Via The Globe and Mail, a report by The Canadian Press: First-ever image of COVID-19 variant supports faith in current vaccines, UBC says.

The first images of a mutation on a COVID-19 variant of concern have been captured by researchers at the University of British Columbia who say the photos offer some reassurance about how the virus strain may react to current vaccines. 

The University of B.C. says the researchers are the first to publish structural images of the mutation found on one portion of the SARS-CoV-2 spike protein.

The spike protein is the part of the virus that opens the door to infection, while the mutation is the change believed partly responsible for the rapid spread of the variant first identified in the United Kingdom. 

 A team led by Dr. Sriram Subramaniam, professor in the department of biochemistry and molecular biology at UBC’s faculty of medicine, found the images show localized placement of the mutation allows it to enter human cells more easily. 

The team’s analysis, recently published in PLOS Biology, reveals that, once inside, the mutation can still be sidelined by antibodies from current vaccines. 

Researchers say that adds to growing evidence that most antibodies generated by existing vaccines are likely to remain effective in preventing mild and severe cases of the B.1.1.7 variant. 

The statement says its researchers are also using beams of supercooled electrons in powerful microscopes to visualize the detailed shapes of other COVID-19 variants that are 100,000 times smaller than a pinhead. 

“It’s important to understand the different molecular structures of these emerging variants to determine whether they’ll respond to existing treatments and vaccines and ultimately find ways to control their spread more effectively,” the statement says.