COVID-19: Scientific Updates

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The pandemic of the coronavirus is advancing. Fortunately, the scientific studies and evidence on the virus (SARS-CoV-2) and the disease (COVID-19) are also advancing at great speed.   

In this section, which we regularly update, we summarise the most relevant emerging information on SARS-CoV-2.

 

[Evidence published between 07/07/2022 and 20/07/2022]

Microbiota and COVID-19

A study with pre-pandemic blood samples reveals pre-existing T cells that recognise common microbes in the gut and skin and can also recognise the Spike protein. These cells could shape our response to SARS-CoV-2, helping explain the great diversity of symptom severity upon infection.

Omicron immunity

Three studies from Qatar shed more light on immunity against Omicron subvariants. Effectiveness of hybrid immunity (infection plus vaccination) against BA.2 infections was >70%, compared with 3 mRNA doses (52%) or infection alone (46%). In people infected during the first Omicron wave, protection against reinfection with BA.4/BA.5 was 76%, compared to 15% in people that were infected with a pre-Omicron variant. And, among unvaccinated people, protection against reinfections wanes to under 10% by month 32, but protection against severe disease remains strong, irrespective of the variant (the last two studies have not yet been peer-reviewed).

Nose up

A nasal spray containing nitric oxide accelerated nasal virus clearance in patients recently infected with SARS-CoV-2 (3 days vs 7 days in placebo group), according to a clinical trial in India which included unvaccinated people at high risk of severe disease.

Four for the elderly

A Swedish study confirms that, compared with a third dose, a fourth dose of an mRNA COVID-19 vaccine administered during the Omicron era reduced the risk of death in the oldest and residents of long-term care facilities during the first two months (71%), after which the protection became slightly lower.

Ex aequo

The COVID-19 vaccines that most saved lives in 2021 were the AZ-Oxford and the Pfizer-BioNTech vaccines (6-7 million each), according to estimates by The Economist.

The way to go

A vaccine containing nanoparticles with the Spike receptor-binding domains from SARS-CoV-2 and 7 other animal sarbecoviruses elicited strong immune responses and protected mice and macaques upon challenge with SARS-CoV-2 and SARS. The vaccine induced antibodies against conserved epitopes, suggesting they could be used to protect against future sarbecovirus spillovers.

Increasing risk

Zoonotic outbreaks in Africa are up 63% from 2012 to 2022 compared to 2001–2011. A clear example of this are Ghana’s first two cases of Marburg virus disease.

Collateral damage

In 2021, 25 million children failed to get vaccinated against diphtheria, tetanus and pertussis, the biggest backslide in 3 decades, according to WHO /UNICEF.

Monkeypox outbreak

Viral DNA was frequently found in saliva, semen, and other biological fluids from 12 patients with confirmed infection, and up to 16 days after symptom onset, according to a study in Barcelona. The next step is to determine whether the samples contain infectious virus.

Data from previous studies suggest that a single dose of the monkeypox vaccine produced by Bavarian Nordic protects well against monkeypox, and that the second dose mainly serves to extend the durability of protection. Applying one single dose would allow to stretch the currently limited global supply of vaccine.

 

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[Evidence published between 15/06/2022 and 06/07/2022]

To watch closely

A new Omicron subvariant (BA.2.75) is under close surveillance – it has 8 additional mutations in Spike compared to its parent BA.2, some of which could enhance antibody escape and/or enhance ACE2 affinity. Over 80 sequences have been detected in countries across the world, but it is still unclear if it will be able to compete with BA.5.  

Genetic factors

Two studies identify genetic factors underlying severe COVID-19 and that affect the type 1 interferon response (our first-line of immune defence). The first one found enrichment of mutations in genes involved in type I and III IFN immunity. The second one found high titers of antibodies against type I interferons in about 10% of patients with severe COVID-19 pneumonia.  

Omicron and long Covid

People infected with Omicron were less likely to experience long COVID as compared to those infected with Delta (4% among Omicron cases vs 10.8% among Delta cases), according to a study in the UK. However, given the high number of cases during the Omicron peak, the absolute number of people with long Covid will inevitably rise, warn the authors.  

Blood clots, virus persistence, immune dysregulation are three non-mutually exclusive leading hypothesis on the causes of long Covid.  

Women, those with poor overall health, and those aged 50 to 60 are more likely to report symptoms of long Covid, according to another UK study.  

Only for those at high risk

Paxlovid did not significantly reduce the risk of hospitalization in unvaccinated patients without a high risk of developing COVID-19 or in vaccinated persons with risk factors, according to a clinical trial by Pfizer. The company said it will focus efforts on generating further data of its pill in vulnerable populations, including longer treatments in immunocompromised individuals. 

Shifting treatment options

The monoclonal antibody Sotrovimab, which was reported to be effective against BA.1, is much less effective in neutralising BA.2, BA.2.12.1, and BA.4/BA.5 subvariants, whereas cilgavimab maintains substantial activity against all omicron subvariants except BA.1 and bebtelovimab neutralises all subvariants with similarly high efficacy, according to a study.

Life-saving vaccines

COVID-19 vaccines prevented 14.4 million deaths since December 2020 (19.8 when including excess mortality), according to a modelling study. The study also estimates that 1 in 5 COVID deaths in low-income countries could have been prevented if the WHO’s global vaccination targets had been met. 

Updated vaccines?

Moderna reported that its bivalent mRNA vaccine (expressing original and BA.1 Spike) still showed a strong neutralizing antibody response against the BA.4 and BA.5 subvariants, even if 3-fold lower than against BA.1.  

And BioNTech- Pfizer announced they will begin testing a universal coronavirus vaccine, but provided no more details.  

Monkeypox outbreak

 Europe is the epicentre of the outbreak accounting for 90% of confirmed cases, which have tripled over the past 2 weeks. WHO Europe called on governments to ramp up efforts to prevent monkeypox from establishing itself on the continent.  

German researchers examined surfaces in hospital rooms occupied by two monkeypox patients. Infectious virus was successfully isolated from certain surfaces (towels, soap operating dispenser, examiner gloves), underlining the importance of adhering to recommended protective measures.

 

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[Evidence published between 25/05/2022 and 14/06/2022]

When did it start?

No SARS-CoV-2 specific neutralising antibodies were detected in over 40,000 samples from blood donors in Wuhan, China between September and December 2019, indicating the virus was not spreading widely until 2020.

Omicron subvariants

Laboratory experiments show that BA.2 replicates more efficiently in nasal and bronchial tissues than BA.1, which would explain why it outcompeted BA.1. However, as data from the USA and Germany confirm, Omicron’s (BA.1 or BA.2) intrinsic virulence is lower than Delta’s: the odds of hospitalisation and death were up to 80% lower with Omicron (BA.1 or BA.2) as compared to Delta, even among those unvaccinated.

Regarding BA.4/BA.5, they seem to have a growth advantage over the BA.2.12.1 subvariant, and are neutralised 2-3 fold less efficiently by serum from triple vaccinated people. Thus, more breakthrough infections and reinfections are likely to occur as BA.4/BA.5 outcompete BA.2. 

A mammal pathogen

An analysis of SARS-CoV-2 samples isolated from deer and mink finds that minimal adaptation was required for the virus to transmit itself efficiently in these animals, supporting the notion that the virus can infect a wide range of mammals.

Sniffing out Covid

Dogs were able to identify Covid-positive individuals by smelling sweat samples, with an overall sensitivity of 97% (up to 100% in asymptomatic individuals) compared with PCR tests.

Vaccines and Long Covid

According to a study using electronic healthcare databases of US Veterans, vaccination reduced the risk of Long Covid (at 6 months after infection) by around 15%, instead of the estimated 50%. However, the study was performed when Delta was dominant and on a population with a relatively high age (around 65).

Preventive treatment

A single intramuscular dose of AstraZeneca’s monoclonal antibody cocktail (Evusheld) in immunocompromised persons can reduce the risk of infection, hospitalization and death up to 70-80%, according to a study with US veterans and a multi-country trial. 

Future treatments?

A study identifies three drugs that could target biological pathways that were found to be overactivated in Covid patients who did not survive.

Variant-adapted vaccines

A trivalent viral vector vaccine expressing Spike of the original, beta and delta variants (NDV-HXP-Spike) substantially increased protection against distant variants, including Omicron, in mice.

Moderna announced that its bivalent booster (expressing the original and Omicron Spike) demonstrated superior antibody responses against Omicron, as compared to the original vaccine. The company expects its bivalent shot to be ready in the late summer.

Monkeypox outbreak

Over 1300 cases have been reported by 30 countries where monkeypox is not endemic, most of them in Europe. In addition, since the beginning of the year, there are 1536 suspected cases reported from eight countries in the WHO African Region, of which 59 cases have been confirmed and 72 deaths reported, according to WHO’s latest situation update.

Scientists warn that the virus may find animal reservoirs outside Africa, which could lead to repeated outbreaks in humans and the emergence of new variants.

Viruses from the current outbreak have almost 50 mutations as compared to the closest sequence from a 2018 outbreak, which is more than expected in a DNA virus. A possible explanation involves mutations introduced by action of a host enzyme (APOBEC3), which would suggest the virus has been circulating at low levels since 2017.

 

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[Evidence published between 11/05/2022 and 24/05/2022]

Consequences of hospitalisation

A study in China estimates that half of COVID-19 patients hospitalised during the first wave have at least one persistent symptom 2 years after infection (down from 68% at 6 months). The most common symptoms were fatigue and muscle weakness and sleep difficulties.

Another study in the UK, with data from more than 8 million adults, shows that the risk of developing anxiety, dementia, psychotic disorder, and bipolar disorder was increased in adults hospitalised for COVID-19 but also in those hospitalised for other severe acute respiratory infections. This suggests that disease severity, rather than the pathogen, is associated with neuropsychiatric consequences.

Antivirals in the real-world

First real-world data on early antivirals against Omicron are starting to emerge. Paxlovid and the monoclonal antibody sotrovimab were more effective than molnupiravir both in hospitalised and high-risk non-hospitalised patients.

Studying immunity to Omicron subvariants

Omicron subvariants BA.4/5 and BA.2.12.1 share a mutation with the Delta variant, which could help explain why antibodies from Delta-infected patients are more efficient in neutralising these variants than antibodies patients infected with the BA.1 Omicron subvariant, according to a study that has not yet been peer-reviewed. 

However, antibodies from vaccinated people who were subsequently infected with Omicron BA.1 can broadly neutralise previous and current circulating variants.

And a study in healthcare workers confirms once again that T cells induced by mRNA vaccines recognise well the Omicron Spike protein, with no difference between 2 and 3 doses.

Hybrid power

Omicron BA.1 breakthrough infections induce neutralizing antibodies against BA.1 and BA.2 in the nasal mucosa which are not observed in those vaccinated but not infected. The study, not yet peer reviewed, also identified a potent antibody that is unaffected by any of the mutations in the different Omicron subvariants and is therefore a strong candidate for clinical development.

Better boosters?

A live attenuated virus vaccine developed by German researchers induces robust immunity in hamsters, including stronger systemic and mucosal humoral responses as compared to mRNA or adenoviral-vectored vaccines, This type of vaccine may offer advantages over current vaccines for containing the pandemic, particularly when applied as booster.

A trial performed with individuals vaccinated with the Chinese Coronavac vaccine (inactivated virus) shows that an orally administered adenovirus-based vaccine (Ad5-nCoV) is safe and highly immunogenic.

Three for the youngest

Pfizer-BioNTech announced early promising clinical trial results indicating that a third shot increases the efficacy of its mRNA vaccine in children under five years of age. Three doses of 3ug each (1/10th that given to adults) induced a strong immune response and had an efficacy of around 80% against Omicron infections.

Getting ready for the fall

Germany announced it will buy two new Covid vaccines in preparation for next fall: an Omicron-specific vaccine from Pfizer-BioNTech and a bivalent vaccine (original and Omicron Spike) from Moderna.

Monkeypox outbreak

Over 150 monkeypox cases have now been reported across 12 countries.

Sequences uploaded so far to the nextstrain platform are closely related, suggesting there was one single introduction.

The virus is considered endemic only in a dozen countries in West and Central Africa, where human infections occur sporadically. The natural reservoir is still not known but some rodents are suspected. The ECDC warns it could become endemic in Europe if the current outbreak continues and the virus spills back into susceptible animals.

The risk of monkeypox for the broader population is low, while the overall risk in persons having multiple sexual partners is moderate, according to the latest ECDC’s risk assessment.

 

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[Evidence published between 27/04/2022 and 10/05/2022]

Omicron and its subvariants

The Omicron BA.2 subvariant is around 40% more transmissible relative to BA.1 and, according to experiments in hamsters, may be slightly more pathogenic. In turn, BA.2 has given rise to other subvariants that seem to be even more transmissible: the BA.4 and BA.5 subvariants in South Africa, and the BA2.12.1 subvariant in the US, estimated to be 25% more transmissible than BA.2.

Studies indicate that vaccinated people who have been infected with Omicron BA.1 should be protected against BA.2, other Omicron subvariants and even other variants of concern such as Delta. In contrast, infection with BA.1 alone offers limited cross-protection against other variants.

The infected majority

In the US: As of February 2022, almost 60% of people (75% of children and adolescents) had evidence of previous SARS-CoV-2 infection, with approximately one third becoming infected since December 2021.

In Europe: 60%–80% of the EU’s population has been infected with the virus, according to the European Commission.

In Valencia, almost half of the population has been infected by SARS-CoV-2 and 96% of them have virus-specific antibodies due to infection and/or vaccination. The study also showed that at least 75% of people have virus-specific memory T cells.

The bright side of asthma

Allergic asthma is associated with higher levels of an immune mediator called interleukin-13 in the airways, which was shown to decrease SARS-CoV-2 cell entry, replication and cell to cell transmission. This would help explain why people with allergic asthma are less susceptible to severe disease.

Good news for Long COVID?

Among adults with two vaccine doses, the odds of reporting long COVID symptoms 4-8 weeks after a first infection were 50% lower with Omicron BA.1 than with Delta, according to the latest data from England. Three doses further lowered the probability of Long COVID for Delta infections (but not for Omicron).

Not good for prevention

Pfizer’s Paxlovid pill failed to prevent symptomatic infections, according to a controlled trial of around 3,000 participants who had household exposure to the virus, including Omicron.

To be confirmed

A randomized trial of almost 2000 mostly vaccinated high-risk people in Brazil showed a 50% reduction in need for hospitalization if they received a single shot of peginterferon lambda (a modified form of a molecule produced by the innate response) within 7 days of symptom onset, according to the company. Although promising, the detailed results must be peer-reviewed. 

Climate change and pandemics

Climate change will greatly increase the risk of viruses jumping from one species to another by pushing animals to other habitats and encounter other species for the first time. Around 4,000 new virus transmission events between mammal species (including humans) are expected to occur in the following 50 years, mostly in Africa and Asia, even if warming is held under 2 °C.

 

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[Evidence published between 06/04/2022 and 26/04/2022]

Two years into the pandemic, the world has surpassed 500 million confirmed COVID-19 cases.

No signals of herd immunity

Until November 2021 (before Omicron), 44% of the global population had been infected at least once, according to estimates. The proportion of infected population varied greatly between countries (>70% in 40 countries to <20% in 39 countries), but even in those with high immunity levels (80%), no abrupt drop in transmission rates was observed, indicating that there is not a clear herd immunity value.

Delta 2, Omicron 3

Two doses of vaccine were enough to significantly reduce infectious viral loads in people who had a Delta breakthrough infection, as compared to unvaccinated individuals. For Omicron three doses were necessary. The study also shows that the amount of viral RNA in the nose is not always correlated with the amount of infectious virus.

A third mRNA vaccine dose not only expands memory B cells that were already present after the second dose but also generates new ones, thereby increasing the potency and breadth of Spike-specific memory B cells. More than 50% of the analysed neutralizing antibodies in the memory compartment after a 3rd dose were capable of neutralising Omicron.

Take a breath

The US FDA authorised the first diagnostic test that detects SARS-CoV-2 infections using breath samples. The test can correctly detect 91.2% of positive cases and 99.3% of negative cases and can provide results in less than 3 minutes, but it requires a rather big machine and needs to be performed by a qualified operator.

One year after

Only 30% of patients hospitalised for COVID-19 reported full recovery one year after hospital discharge. Female sex, obesity and invasive mechanical ventilation were factors associated with suffering from post-COVID sequelae.

Around half of COVID-19 patients shed SARS-CoV-2 RNA in faeces one week after infection, and 4% still shed faecal RNA 10 months after diagnosis, suggesting that prolonged SARS-CoV-2 infection in the gastrointestinal tract could play a role in long COVID.

New treatments ahoy

• China's Kintor Pharmaceutical said its drug, which blocks the receptor for the sex hormone androgen, reduced the risk of hospitalization and death by 50 to 70% in patients with mild to moderate COVID-19 symptoms.
• A pill developed by Shionogi, Japan, which inhibits the 3CL protease, showed rapid clearance of SARS-CoV-2 when given within the first five days of symptoms. And another oral protease inhibitor (camostat mesylate) resulted in more rapid resolution of symptoms when given during the first seven days.
• The antidepressant fluvoxamine reduces the risk of hospitalization in symptomatic COVID-19 adult patients when taken early, and could be an option in resource-limited settings, according to a review of three clinical trials.
• A single intramuscular dose of AstraZeneca’s antibody cocktail Evusheld reduced by 76% the risk of COVID-19 hospitalisation among high risk populations. It is one of the few monoclonal antibody cocktails that still work against Omicron.

And new vaccine candidates

• Arcturus therapeutics announced preliminary results for its self-amplifying mRNA COVID-19 vaccine (2 doses, 5ug each). The study, conducted in Vietnam when Delta and Omicron were circulating, shows 55% efficacy against symptomatic disease and 95% efficacy against severe disease. The vaccine requires less RNA and should be cheaper and easier to distribute than other mRNA vaccines.
• Moderna announced that a booster shot (50ug) with its bivalent COVID-19 vaccine (with Spike from the original and the Beta variant) induced higher titers of neutralising antibodies against Omicron (as compared to a boost with the original formulation). The company is also evaluating a bivalent shot combining original and Omicron Spike.

 

 

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[Evidence published between 23/03/2022 and 05/04/2022]

Watching closely

The WHO said it is monitoring recombinant viruses, including a BA.1-BA.2 version (XE) that was first observed in the United Kingdom and appears to be about 10% more transmissible than the BA.2 subvariant.

A one and only experiment

The first results of the SARS-CoV-2 human challenge in young adults were published. 34 volunteers without previous infection or vaccination were exposed to the original SARS-CoV-2 variant. 18 (53%) of them became infected (2 were asymptomatic). Virus was first detected in the throat but rose to higher levels in nose, regardless of symptoms. Viable virus was recoverable from the nose up to 10 days after infection.

Neurological effects depending on the variant?

Monkeys infected with the original SARS-CoV-2 variant showed inflammation, microhemorrhages and hypoxia in the brain, even in animals that did not develop severe respiratory disease. However, a preprint study in hamsters shows that, while the original variant results in invasion and inflammation of the olfactory bulb, this was hardly observed with Delta or Omicron BA.1.

Risk in children remains low

A large study in England found no difference in risk of hospitalization with Alpha or Delta in children, while another study found that, in children under 5, Omicron led to around 7-fold more infections but substantially less severe outcomes as compared to Delta.

Not surprisingly

COVID-19 patients coinfected with influenza virus had a 4-fold risk of receiving invasive mechanical ventilation and twice the risk of dying, compared to those who only had COVID-19. Hence, the importance of vaccinating vulnerable groups against flu and COVID-19.

Better late than never

A study in Italy that followed patients hospitalised for COVID-19 suggests that vaccination within the following months after infection conferred protection against long COVID.

Hybrid is better

A Swedish study concludes that the risk of SARS-CoV-2 reinfection and hospitalisation in previously infected individuals remained low for up to 20 months, although vaccination further decreased the risk of both outcomes. This study adds to the evidence that vaccination reinforces natural immunity.

Similarly, an Omicron BA.1 infection in people who were not vaccinated elicits antibodies that can cross-neutralise BA.2 or BA.3 subvariants, but not previous variants of concern. In contrast, a BA.1 breakthrough infection in previously vaccinated people results in strong neutralising activity not only against Omicron subvariants but also against previously circulating variants (studies not yet peer-reviewed).

A new kind of inhibitor

TMPRSS2 is a protein at the surface of our cells that SARS-CoV-2 uses to facilitate its entry into the cell. A molecule that binds to TMPRSS2 was shown to prevent and treat infections by different SARS-CoV-2 variants, when given to mice as an intranasal spray.

In case there was any doubt

The largest controlled trial yet confirms that early treatment with ivermectin does not result in lower risk of hospitalisation due to COVID-19. 

Similar, but not identical

A detailed comparison of antibodies induced by the two approved mRNA vaccines (Pfizer-BioNTech and Moderna) reveals some differences: Moderna seems to induce more IgA antibodies of a certain type, and more antibodies that activate the innate immune system.

New estimates

Latest UK data show that vaccine effectiveness against Omicron was underestimated due to incidental hospitalisations, especially for adults 18-65. When redefining hospitalisation cause, vaccine effectiveness was of 82% more than 6 months after the second dose and of 90% up to 4 months after a booster. Another study in Germany confirms the high protection conferred by boosters against hospitalization (>90%), across all ages.

Deer, deer

A study shows that white-tailed deer can transmit the virus through nasal and oral secretions and aerosols for up to 5 days after infection.

 

 

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[Evidence published between 09/03/2022 and 22/03/2022]

The real death toll

An analysis of excess mortality in 74 countries estimates that 18.2M people died worldwide because of the pandemic between January 2020 and December 2021. The excess mortality rate was highest in Russia and Mexico (with 375 and 325 deaths per 100,000 people, respectively). 

Reducing the risk of viral variants

A couple of studies point to the need of closely monitoring immunocompromised patients to reduce the risk of emerging viral variants. In 4 patients treated with sotrovimab, viral mutations were detected within 6 to 13 days after treatment. In another immunocompromised patient treated with remdesivir, a mutation conferring resistance to the drug was detected.

The risk of emerging variants can be reduced if the rate of vaccination is fast and social distancing is maintained during vaccination, according to a modelling study.

Mother to child- possible but rare

An analysis of several studies concludes that mother to child transmission of SARS-CoV-2 occurs very rarely (about 1.8% of the time), and that vaginal births and breastfeeding do not raise the risk to the baby.

Sugar levels post-infection

An analysis following over 35,000 individuals diagnosed with Covid in Germany shows an increased incidence of type-2 diabetes compared with controls (15.8 vs 12.3 per 1000 person-years). Another study with US veterans confirms a 40% increase in the risk of developing diabetes in the year following the infection. These findings underline the need to actively monitor glucose levels in patients after they recover from mild or severe COVID-19.

Another promising treatment in the pipeline?

A Chinese team developed an antibody that can simultaneously recognise and bind to two highly-conserved regions on Omicron and all other variants. The antibody can reach the lung via inhalation and proved to be very effective in mice.

Replacing Sputnik’s second jab

In case of supply problems, the second shot of the COVID-19 Sputnik V vaccine (which uses an Adenovirus 5 vector) can be replaced by a mRNA vaccine dose, or to a lesser extent, by a dose of the Oxford-AstraZeneca vaccine, according to a trial performed in Argentina.

Vaccine power

Vaccinated persons infected with Omicron BA.1 develop robust neutralizing antibody titers against the BA.2 subvariant, suggesting a good degree of cross-protective immunity. The study also confirms that a third dose of the Pfizer-BioNTech vaccine was needed for generating sufficient neutralizing antibodies against either BA.1 or BA.2. The efficacy of a third dose against Omicron was also confirmed by a series of recent studies: 

A study in Finland concludes that vaccine effectiveness against severe COVID-19 among the elderly wanes slightly after 2 doses, but a third dose restores protection, which remained high for at least two months, even against Omicron. 

A study in Qatar shows that mRNA vaccines offer similar protection against BA.1 and BA.2, and that protection against severe disease remained at 68% or higher for at least 7 months in people who had only received two doses, and rose to over 80% after a booster dose.

Data from the US show the risk of invasive mechanical ventilation or death after Omicron infection was reduced in 79% after two shots and 94% after three shots, as compared with unvaccinated individuals.

And recent data from the UK show vaccine protection against death rose from 59% (several months after the second dose) to 95% several weeks after the third dose.

On the other hand, the efficacy of a fourth dose against symptomatic Omicron infections seems modest in young people, according to a small Israeli study with healthcare workers.

Reminder

11 billion doses have been administered globally, but only 14.4% of people in low-income countries have received at least one dose.

 

 

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[Evidence published between 23/02/2022 and 08/03/2022]

As close as it gets?

Three new studies (not yet peer-reviewed) provide new evidence that the SARS-CoV-2 outbreak started in Wuhan’s Huanan market and was linked to wildlife trade. The first study detected SARS-CoV-2 in samples collected from cages, stalls and drains in the market section where live animals are sold. The other shows geospatial clustering of the earliest cases near to or within that market section, linking several cases to a single stall. The third shows the presence of two distinct viral lineages (A and B) prior to February 2020, suggesting that SARS-CoV-2 emergence resulted from at least two spill-over events which occurred late November or early December 2019. The studies do not provide evidence as to what type of animal harboured the virus, but racoon dogs are suspected. Many experts think this is the closest evidence we may get on the origins of the virus.

Deer surveillance

A Canadian team identified a new and highly divergent lineage of SARS-CoV-2 in white-tailed deer. Its mutations are quite different from those in Omicron and other variants of concern, suggesting it has evolved independently. The study (not yet peer-reviewed) also suggests there could have been deer to human transmission of the variant.

Close look at Omicron

Two new studies (in Nature and Science) using electron microscopy and X-ray analysis reveal how Omicron can bind tightly to the human ACE2 receptor and reduce recognition by monoclonal antibodies. The findings may inform design of vaccines effective against all variants.

The WHO has declared that Omicron's subvariant BA.2 does not cause more severe disease than the original but urged countries to continue monitoring it separately.

A novel site of viral replication

A study in macaques (not yet peer-reviewed) shows SARS-CoV-2 can replicate in testicular and penile tissue, which can lead to severe pathology. This may explain erectile dysfunction reported by some Covid patients.

Genetic factors and severe disease

Two new studies identify genetic factors that may increase the risk of developing severe COVID-19. One genomic analysis examining more than 3000 blood proteins identified 11 markers, including the ABO protein that determines blood group, associated with hospitalization and need for respiratory support or death. Another whole genome study identified 16 new gene variants associated with severe disease, and that are involved in the control of viral replication or in pulmonary inflammation and intravascular coagulation.

Brain changes?

A study comparing brain scans before and after SARS-CoV-2 infection in over 400 cases (and 300 controls) detected certain changes in brain structure, including reduction in grey matter thickness and markers of tissue damage in regions connected to olfactory cortex. It remains to be seen whether this effect is reversed with time.

One more treatment for severe COVID

The RECOVERY trial shows that baricitinib (an anti-inflammatory drug used for rheumatoid arthritis) reduced the risk of death by 13%, when given to hospitalised patients with severe COVID-19, in addition to standard treatment.

One less against BA.2

Laboratory experiments using 19 monoclonal antibodies (including sotrovimab), show that only the recently authorized bebtelovimab (by Eli Lilly) is capable of neutralizing all three sublineages of the Omicron variant (BA.1, BA.1+R346K, and BA.2).

Vaccines in teens

Vaccines are reducing 180-fold the risk of hospitalization by COVID among adolescents aged 12-17, according to latest CDC data. Furthermore, only 1 case per million vaccinated adolescents developed multisystem inflammatory syndrome (MIS-C) versus 200 cases per million unvaccinated.

The arrival of protein-based vaccines

Health Canada has authorized Medicago's Covid-19 virus-like particles vaccine produced in plants. The vaccine demonstrated efficacy of 75.3% against COVID-19 of any severity for the Delta variant and 88.6% against Gamma.

The high cost for children

5.2 million children worldwide are estimated to have lost a parent to COVID-19. Peru and South Africa saw the highest per capita rates of orphanhood.

And for women

As we celebrate InternationalWomensDay 2022, a comprehensive review concludes that the most significant inequalities between women and men (employment, schooling, gender-based violence) have been amplified by the Covid pandemic.

 

 

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[Evidence published between 09/02/2022 and 22/02/2022]

Searching for high-risk viruses

Viruses very similar to SARS-CoV-2 were isolated from bats in North Laos. These viruses bind strongly to the human ACE2 receptor and can efficiently replicate in human cells. While another study identified over 100 viruses (some of them new) in wild animals frequently sold in Chinese markets, including 21 viruses considered “high risk” to humans.

A mental health pandemic

A large cohort study of US veterans found that 4.4%-5.6% of those who survived COVID-19 were diagnosed with neuropsychiatric disorders. This means that the virus may have contributed to 2.8 million new cases of mental health disorders in the US and more than 14.8 million worldwide.

Long Covid and vaccination

Vaccinated individuals are less likely to develop long COVID in the short, medium and long-term, according to a review of current evidence. Studies also suggest that vaccination may improve long Covid symptoms in a majority of cases, particularly if the vaccination occurred soon after diagnosis. Some cases, however, reported worsening.

Paxlovid also as prevention?

Studies in hamsters show that prophylactic administration of Paxlovid completely protected them against intranasal infection with Beta and Delta variants, and that treating infected animals completely prevented transmission to untreated co-housed animals.

Getting better?

Merck’s molnupiravir reduced the risk of COVID-19 hospitalization by 65% according to a phase 3 trial in India with over 1200 patients with mild symptoms. This is higher than the 30% efficacy observed in a previous trial.

May work

Activation of the ACE2 receptors with two known drugs (imatinib and methzolamide) may help treat metabolic complications associated with COVID-19. Moreover, in the lab, these drugs directly reduce viral infection by inhibiting binding of the virus to ACE2.

Definitely not working

A trial performed in Barcelona shows that convalescent plasma does not reduce the risk of hospitalization in patients with mild COVID-19. And yet another randomized clinical trial (in Malaysia) shows that early treatment of high-risk patients with ivermectin does not prevent progression to severe disease.

‘Natural’ immunity needs a boost

Two studies with convalescent patients (one in UK and another in Israel, during the Delta wave) show that infection-acquired immunity boosted with vaccination offers robust, durable protection (> 1 year) against reinfection. In the Israeli study, reinfection occurred in 0.4% of infected plus vaccinated participants compared to 3.3% of infected but unvaccinated. Additional doses in those with prior infection made no difference.

A study (not peer-reviewed) finds that unvaccinated individuals infected by Omicron have low levels of cross-neutralising antibodies, suggesting they remain susceptible to infection by previous variants. In contrast, vaccination prior to Omicron infection considerably improves cross-neutralization of -and protection against- other variants.

More on boosters

Booster vaccinations may have prevented 105,600 people from being admitted to hospital with COVID-19 since mid-December according to a UK analysis. An analysis in Spain estimates that mRNA boosters reduce by half the likelihood of getting infected by Omicron (one month after the boost) and that effectiveness was higher when the booster was given 6 months or more after primary vaccination. And according to CDC data (US), the risk of death was reduced in 85% with 2 shots, and 95% with booster. People ages 65 and older benefited the most from receiving a booster dose. And individuals receiving 3 doses of current mRNA COVID vaccines have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of neutralising variants as diversified as Omicron.  

Measuring cellular immunity

A T cell-based assay allows to distinguish between infected and vaccinated individuals with high sensitivity and specificity. This assay could be an important tool for monitoring vaccination and establishing markers of immune protection.

mRNA tech expands

The WHO announced that Egypt, Kenya, Nigeria, Senegal, South Africa, and Tunisia will be the first African nations to receive the technology to produce mRNA vaccines, as part of a global effort to expand manufacturing in low- and middle-income countries.

 

 

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[Evidence published between 26/01/2022 and 08/02/2022]

In the 10 weeks since Omicron was discovered, there have been 90M Covid cases reported — more than in all of 2020, says the WHO

Omicron “sister”

The BA.2 Omicron sub-variant seems to be slightly more transmissible than the prevalent BA.1 sub-variant, according to data from UK and Denmark, but there is no indication of increased severity; and vaccine effectiveness against BA.2 remains unchanged, according to UK’s latest report. Both strains are as genetically distinct as earlier variants Alpha, Beta, and Gamma are from each other. Thus, it is still not clear whether infections by BA.1 will provide protection against BA.2 and to what extent.

Tracking variants in wastewater

Scientists have detected new SARS-CoV-2 variants in wastewater of New York City. These contain mutations that have not been observed in clinical samples, and share many mutations with Omicron.

Indirect damage

Cells infected by SARS-CoV-2 produce soluble mediators that cause neighbouring cells to lose their capacity to divide, even if they are not infected. This leads to an inflammatory response which continues even after the virus is no longer detectable. Similarly, SARS-CoV-2 infection was shown to induce the downregulation of olfactory receptors even if the olfactory neurons are not infected. These findings could help explain the loss of smell associated with COVID-19.

COVID-19 and mortality

Obesity was more strongly associated with the risk of dying from COVID-19 among racial minorities as compared to white patients, according to a study in England. And COVID-19 patients released from the hospital were more than twice as likely to be rehospitalised or die within the next months, as compared to the general population, and at increased risk of cardiovascular disease.

Risk of Long COVID

One study suggests that reactivation of latent viruses such as Epstein Barr Virus during acute SARS-CoV-2 infection could contribute to developing post-acute sequelae, and that type 2 diabetes, viral RNA levels, and certain autoantibodies are risk factors. Another study finds an antibody signature predicts the risk of sequelae, while yet another one finds a combination of inflammatory mediators is associated with Long Covid with an 80% accuracy. A Danish nationwide study of 37,522 children with SARS-CoV-2 infection concludes that Long Covid in children is rare and mainly of short duration.

Counting reinfections

According to UK data, which now includes reinfections, around 11% of current cases are reinfections by Omicron, as compared with 1.5% for Delta.

The order does not alter the result

A study shows that SARS-CoV-2 infection increases the quantity, quality, and range of vaccine-generated antibodies, whether it occurs before or after vaccination.

Omicron-adapted vaccines

Pfizer has launched a study to test its new updated Omicron version. However, preliminary data from Moderna show that boosting macaques with an Omicron-specific vaccine did not provide greater immunity or protection against Omicron as compared to a boost with the current vaccine. This suggests that, for the time being, individuals with immunity from vaccination or infection may not benefit from variant-adapted vaccines.

An intranasal boost

A study in mice (not yet peer-reviewed) shows that a “Prime and Spike” strategy consisting on a first mRNA intramuscular dose, followed by an intranasal boost with Spike protein, induced robust mucosal immune memory in the respiratory tract. By combining different Spike proteins, this strategy could confer broad cross-reactive immunity to different SARS-CoV-2 variants. 

Vaccine power

Boosted adults are 97 times less likely to die of COVID-19 than unvaccinated individuals, according to data from the CDC until December 4. For every 100,000 people, 9.7 of those who were unvaccinated died from COVID-19, compared to 0.7 of those fully vaccinated and 0.1 of those boosted.

A study on households with unvaccinated children estimates that having one vaccinated parent reduced the risk of infection by Delta by 20%, while having two vaccinated parents reduced the risk by 58.1%.

Africa can

Researchers at Afrigen Biologics in South Africa have created a near copy of Moderna’s mRNA. The technology transfer hub, launched by the WHO, cannot yet produce enough vaccines to make a difference this year (or maybe even for this pandemic), but it lays the foundation for a more globally distributed mRNA vaccine industry in the future.

Prevention pays off

Three actions could minimize the impact of future pandemics: better surveillance of zoonotic pathogens; better management of wildlife trade; and substantial reduction of deforestation. These preventive actions cost less than 1/20th the value of lives lost each year to emerging viral zoonoses and has substantial benefits, concludes an analysis.

 

 

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[Evidence published between 12/01/2022 and 25/01/2022]

The travels of Omicron

According to data from wastewater surveillance in US, Omicron was probably present in New York City as early as November 21, four days before South Africa first announced cases by the variant. 

Investigating Omicron’s higher transmissibility

Omicron infections seem to have lower peak viral RNA titers and a shorter clearance phase than Delta infections – most individuals are no longer infectious after six days, according to a small study in Japan. Furthermore, vaccinated individuals with Omicron infection had comparable infectious virus titers than those with Delta infections. These results, not yet peer-reviewed, suggest that other mechanisms contribute to Omicron’s higher infectiousness.

The first structural analysis of Omicron’s Spike at the molecular level shows that overall binding strength to the ACE2 receptor is comparable to that of Delta, but cleavage of the Spike protein and viral replication seem to be enhanced by the S:655Y mutation, present in Omicron and Gamma.

And its lower pathogenicity

Two studies published in Nature with mice or hamster models point to decreased pathogenicity of Omicron as compared to prior variants.

In Portugal, Omicron was also associated with a 75% risk reduction of hospitalization compared with Delta, as well as a reduced length of hospital stay.

One boost for Omicron

Three studies published in Cell confirm that Omicron strongly evades neutralizing antibodies but that a booster dose rescues neutralization by increasing the magnitude and breadth of the antibody response.

Indeed, mRNA boosters decreased by 50% the risk of infection by Omicron as compared to two doses, and by 66% the risk of symptomatic infection. Boosters also increase vaccine effectiveness against hospitalization by Omicron: to 90% (compared to 57% for two doses) according to CDC data and remains above 85%-90% according to UK’s latest data.

Preliminary results give some idea on the duration of the booster effect: neutralizing antibodies against Omicron decrease gradually over the following four months after the third dose, but remain quite high.

And a small study in Israel finds that a fourth dose does not significantly enhance protection against infections by Omicron, despite an increase in antibody levels.

Pre-existing protection against infection?

Individuals who were not infected despite high exposure to the virus may be protected by memory T cells that cross-react with other viral antigens outside Spike. These results suggest that including non-spike antigens in second-generation vaccines may be a good idea.

COVID-19 and pregnancy

Unvaccinated pregnant women with COVID-19 are at much higher risk for complications from the disease and death, shows a Scottish study. The mortality rate for women who gave birth within 28 days of a COVID-19 diagnosis was 22.6 per 1,000 births, compared to 5.6 per 1,000 births. In addition, babies of pregnant women with COVID-19 have higher odds of adverse outcomes such as preterm birth and low birth weight, particularly when infections occur during the first and second trimester.

SARS-CoV-2 does not directly infect the placenta, but induces placental inflammation.

and adolescents

A single dose of Covid vaccine reduces the risk of multisystem inflammatory syndrome (MIS-C) in adolescents by > 90%, according to a French study. No adolescents with two doses of vaccine had MIS-C.

Fertility and vaccines

A cohort study of more than 2,000 women in the US and Canada indicates that COVID-19 vaccination does not impair fertility in men or women, but that men infected with SARS-CoV-2 may experience a short-term decline in fertility.

10 billion

Almost 10 billion vaccine doses have been administered worldwide. Of these, 1 billion doses have been delivered by COVAX to 144 countries.

But 118 countries (out of 195) – including Russia, and the United States – are not on track for the WHO's target of vaccinating 70% of their population by mid-2022.

 

 

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[Evidence published between 22/12/2021 and 11/01/2022]

Mutations beyond Spike

A study identifies mutations outside Spike may help boost the transmission potential of Alpha, Delta or Omicron variants. These mutations increase levels of ORF9b, a viral protein that suppresses the innate immune response.

More evidence on Omicron

Target cells and entry route. Studies show that Omicron’s Spike binds more strongly than other variants to the ACE2 receptor. In contrast, it is less efficiently cleaved by the TMPRSS2 receptor (a process that offers a second entry route), which may help explain why it causes milder disease, since TMPRSS2 is more common in lower airways.

Incubation period. This may also help explain why the time between exposure and symptoms has shortened to 3 days (versus 4 for Delta and 5 for the original variant).

Symptoms. Top symptoms for Omicron seem to be a runny nose, headache, fatigue, sneezing, and a sore throat. Only half of infected individuals reported fever or cough, and less than 21% reported a loss of taste or smell.

Disease severity. More evidence points to reduced severity of disease caused by Omicron. In South Africa, admission to intensive care was 18.5% in the Omicron wave, compared with 30% in the Delta wave. In the UK, those with confirmed Omicron infections were 15%-20% less likely to be hospitalized, compared with those with Delta, and those hospitalized with Omicron had shorter hospital stays. In the US, the risk of hospitalisation, ICU admission, and mechanical ventilation were significantly lower for those infected with Omicron as compared to those with Delta, across all age groups (including younger unvaccinated children). The risk of ICU admission fell by 50% (from 0.8% to 0.4%).

Studies in mice and hamsters also show that Omicron causes less severe disease.

Vaccine effectiveness. A study in Denmark finds that, in households struck by omicron, unvaccinated and fully vaccinated people had similar chances of getting infected, but a booster dose cut the risk of infection by half. Importantly, unvaccinated people were 40% more likely to infect another household member, regardless of the variant.

Latest data from the UK shows booster doses continue to provide high levels of protection against severe disease by Omicron among adults aged 65 or more: about 90% at 3 months after a booster dose, as compared to 70% for two doses at 3 months and 50% after 6 months. The data do not support for now the need for a fourth dose among the most vulnerable.

Time to shine for T cells. Several studies show that the majority of T cells induced by different vaccines  or  infection are capable of recognising Omicron, underscoring their key role as second line of defense. 

Vaccines and Long Covid

A study in Israel (not yet peer reviewed) shows that fully vaccinated individuals were 50-68% less likely than unvaccinated individuals to report post-acute COVID symptoms, including fatigue, headache, weakness, and persistent muscle pain.

Early treatments for high-risk patients

A controlled clinical trial shows that a 3-day course of remdesivir (which must be given intravenously) reduced by 87% the risk of hospitalization or death among non-hospitalized patients who were at high risk of progressing to severe COVID-19.

And the US FDA approved use of Pfizer's Paxlovid, the 1st oral pill to treat mild-to-moderate COVID-19 infection in patients who are at high risk of progressing to severe illness.

Vaccine safety in children

A total of 12 cases of myocarditis have been reported among 8.7 million Pfizer doses given in children aged 5-11 in the US. The rate in boys is 4 in 1M (10 times lower than that observed in teens).

A gift for the world

India granted emergency approval to Corbevax, a protein-based COVID-19 vaccine developed by researchers from the Baylor College of Medicine in Houston and manufactured by Biological E. The vaccine was more than 80% effective against symptomatic disease, but the data have not been yet published. Importantly, the vaccine is shared patent-free and represents an effective and low-cost alternative for developing countries.

 

 

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[Evidence published between 15/12/2021 and 21/12/2021]

Omicron

Very rapid spread: Omicron is likely to become the dominant variant in Europe by the first month of 2022, said the ECDC. It has already become dominant in the US, where it makes up 73% of diagnosed infections.

Disease severity: still unknown A study by Hong Kong University (not yet peer reviewed), performed in “tissues on a dish”, shows that Omicron replicates much faster in human bronchus, which may explain why it transmits more than Delta. The study also suggests that it has a reduced capacity to infect lung tissue, which may be an indicator of lower disease severity.

In South Africa, hospitalisations have not increased at the same rate than in previous waves. Researchers are testing whether the previous infections by the Beta variant (which spread in the country) could be providing extra protection. 

In contrast, a study by the Imperial College London finds no evidence of lower severity by Omicron as compared to Delta.

Immune evasion from antibodies but not T cells. The same study by Imperial College estimates that vaccine protection (against symptomatic infection) falls to 0-20% for 2 vaccine doses and is restored to 55-80% after a booster dose. According to Moderna, a booster of its COVID-19 vaccine (half dose) increases neutralising antibodies 37-fold. Protection against severe disease and death is expected to remain relatively high, since T cells seem to be relatively unaffected by the mutations in Omicron, according to data presented by scientists at a WHO meeting. Indeed, early data from South Africa suggests that, with 2 vaccine doses, protection from severe disease remains around 70%. 

Children and COVID

Analysis of 820,404 symptomatic paediatric COVID-19 cases reported by 10 European countries between August 2020 and October 2021 concludes that case and hospitalisation rates in children rose as transmission increased, but severe outcomes were rare: 1.2% were hospitalised, 0.08% required intensive care and 0.01% died.

Breakthrough infections

A study with healthcare workers shows that infections in those fully vaccinated further boosted humoral immunity despite predominantly mild disease. People with breakthrough delta infections showed improved neutralising activity against delta as compared to controls.

A study in Scotland and Brazil shows that, in people vaccinated with two doses of AstraZeneca-Oxford, protection against hospitalizations and deaths also declines after several months, confirming the need for a booster dose.   

A monoclonal antibody against Omicron

The EMA recommends the authorisation of sotrovimab (Xevudy), the drug developed by GSK-VIR for treating COVID-19 in adults and adolescents who are at increased risk of severe disease. It is one of the few monoclonal antibodies that remain effective against Omicron.

More vaccines to come

A fifth vaccine for Europe: EMA has approved Novavax’s protein-based COVID-19 vaccine for people from 18 years of age. The results of the clinical trials show a vaccine efficacy of around 90% at a time when alpha and beta were the most common variants circulating. The version of the vaccine made by Serum Institute of India was also approved by the WHO.

Another protein-based vaccine candidate: Medicago announced positive efficacy and safety results for the phase 3 trial of its COVID-19 vaccine, made of virus-like particles and grown in plants. The vaccine demonstrated a 75.3% efficacy against COVID-19 of any severity for delta.

Broader protection against variants? A needle-free COVID-19 vaccine developed by Cambridge University and DIOSynvax entered phase 1 trials. The vaccine, delivered to the skin through a jet of air, targets a wider range of predicted coronavirus antigens, and is expected to give more protection against SARS-CoV-2 variants and other coronaviruses.

 

 

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[Evidence published between 1/12/2021 and 14/12/2021]

Omicron: the emerging picture

Early laboratory and epidemiological data are starting to give a clearer picture of how this variant may behave.

• Transmissibility: Early data from the UK indicates that Omicron has a growth advantage over Delta: the risk of household transmission from an Omicron index case is 3-fold compared to a Delta index case, and the risk of a close contact becoming a secondary case is double. This growth advantage could be in part due to a better ability of the variant to evade immunity.
• Immune evasion: Preliminary data from South Africa and the UK strongly suggest that Omicron has an increased ability to evade immunity from prior infection (a reinfection rate of 7% for Omicron, compared to 0.4% for delta, according to first UK estimates). In terms of vaccine protection, several laboratories have posted first results showing a sharp decrease in the capacity of sera from convalescent or fully vaccinated individuals (2 doses) to neutralise omicron as compared to other variants. Sera from individuals with hybrid immunity (infected and vaccinated or vaccinated and infected) or from those who had received a booster shot had good neutralizing activity against Omicron. Accordingly, UK’s latest report shows an almost complete drop in protection against symptomatic disease after 2 AstraZeneca-Oxford doses, and a significant drop (to around 30%) for 2 doses of Pfizer-BioNTech. Boosters increased protection to 75% (within one month after a Pfizer booster). Vaccines are still expected to protect against severe disease, but it is too early to know.
• Regarding treatments based on monoclonal antibodies, sotrovimab (developed by GSK/VIR) remains effective against Omicron while the mAb cocktails by Lilly and Regeneron, and one of the two mAbs by AstraZeneca, are no longer effective.
• Disease severity: In South Africa, infections seem to be milder. However, there is no clear picture yet on the severity of disease caused by this variant, particularly in older populations or in people without previous immunity.

Detecting infections faster

A rapid antigenic test that amplifies the signal can be used to detect virus in saliva with high sensitivity.

Japanese researchers develop a mask that can detect traces of SARS-CoV-2 by spraying it with a fluorescent dye containing virus-specific antibodies extracted from ostrich eggs.

Fat tissue

SARS-CoV-2 can infect certain cells in the adipose tissue, and this results in a highly inflammatory response, according to a study that has not yet been peer-reviewed. These findings may explain the link between obesity and severe COVID-19.

Mucosal immunity is the thing

Individuals who were previously infected by SARS-CoV-2 develop a strong mucosal response (with high levels of IgA antibodies detected in saliva) after mRNA vaccination, which may help explain the robust protection against infection in this group (infected and vaccinated). Another study shows that intranasal administration of a flu vaccine in mice boosts local IgA secretion and protects against different flu viruses, underscoring the potential of intranasal vaccines against SARS-CoV-2 variants.

More treatments developed or approved

A drug (4′-fluorouridine) which blocks viral replication could be used as a broad-spectrum antiviral against respiratory viruses, including SARS-CoV-2, according to experiments in cells and animals. Oral treatment of ferrets infected with different SARS-CoV-2 variants was highly efficacious in reducing viral burden.

The FDA has approved Evushield, an antibody designed for long-term protection against COVID-19 infection in people not adequately protected by COVID-19 vaccines, such as transplant recipients and cancer patients. Experiments are ongoing to determine whether it remains effective against Omicron.

After a final analysis of the data, Pfizer announced that its antiviral Plaxovid retained an 89% efficacy in preventing hospitalization and death among high-risk COVID-19 patients. 

Testing vaccine combinations

The COV-boost study in UK tested seven different COVID-19 vaccines (AstraZeneca-Oxford, Pfizer-BioNTech, Moderna, Janssen, Novavax, Curevac and Valneva) as third dose in individuals who had received either 2 doses of AstraZeneca-Oxford or two doses of Pfizer-BioNTech. The response varied according to the booster and age group, but all vaccines boosted antibody and neutralising responses (except Valneva in individuals primed with Pfizer).

Hippos too

Two hippos have tested positive for SARS-CoV-2 at Antwerp Zoo in Belgium, the first cases reported in this species.

Rising inequalities

2020 saw the steepest increase in billionares’ wealth, according to the latest World Inequality Report: the richest 10% of the world own 76% of the wealth while the poorest half owns 2%. Meanwhile, 100 million more children fell into poverty in 2020 (a 10% increase since 2019), says Unicef.

 

 

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[Evidence published between 17/11/2021 and 30/11/2021]

A new variant called Omicron

A cluster of cases infected by a variant with a high number of mutations was identified some days ago in South Africa. It does not originate from delta, but from the original virus (named B.1) and accumulates more mutations than any other variant described (over 30 mutations only in Spike), many of which are potentially associated with immune evasion or higher transmissibility. Some experts believe it may have evolved within a chronically infected immunocompromised person. It is still not clear whether it is more transmissible, more vaccine resistant, or more virulent than delta. Researchers are conducting studies to better understand the impact of these mutations. It has now been detected in several regions of the world, including USA, Canada, Europe, Israel, and Australia.

The lower the vaccination rate, the higher the risk that new viral variants will emerge and spread. In Africa, only 1 in 4 healthcare workers have been fully vaccinated against COVID-19. Less than 10% of people living in Africa have received both doses of the vaccine.

Understanding lung damage

A close analysis of lungs from 18 patients who died from COVID-19 shows that the virus directly infects epithelial cells within the lungs, impeding their capacity to repair damaged tissue. This in turn prevents proper oxygen flow and induces excessive thrombosis.

High diversity of T cell targets

An analysis of around 56 million T cells from 55 COVID patients reveals that virus-specific T cells can recognise many protein fragments (or epitopes) across the entire viral proteome. Of the 85 epitopes identified in Spike, only five of them would be affected by mutations in delta.

Milder future?

A study in Qatar shows that people with reinfections had a 90% lower risk of hospitalization or death than those infected for the first time. One third of reinfections were caused by the beta (B.1.351) variant. These findings suggest that the virus could adopt a more benign pattern of infection when it becomes endemic.

Good, but not that good

Updated data from Merck’s trial shows that molnupiravir is 30% effective in reducing COVID-19 hospitalisations and deaths instead of the 50% initially announced.

RNA as treatment?

A single dose of a small RNA molecule was shown to prevent SARS-CoV-2 infection and disease in mice through the rapid triggering of the innate immune system. This molecule (called SLR-14) is easy to produce and could be used as early post-exposure treatment and for treating immunosuppressed patients.

A T cell vaccine candidate

German researchers publish phase 1 results for a peptide-based vaccine candidate, that induces broad, potent and variant-independent T cell responses, higher to those detected after SARS-CoV-2 infection or vaccination with approved vaccines. A phase 2 trial for patients who cannot generate antibodies is currently underway.

25X

Among those aged 60-80, the risk of dying from COVID-19 is 25 times higher if unvaccinated, as compared to fully vaccinated, according to data released by Spanish authorities.

Half a million

COVID-19 vaccines have saved almost half a million lives in Europe over the last year, among those aged over 60, according to WHO Europe.

Fuelling antibiotic resistance

Countries in the Americas reported a surge in drug-resistant infections due to misuse of antimicrobials during the pandemic, warns the Panamerican Health Organisation (PAHO). More than 90% of hospitalized COVID patients in the Americas were given antimicrobials, while only 7% required them to treat a secondary infection.

Unequal recovery

The Gates Foundation predicts that, in 2022, average incomes will return to their pre-pandemic levels in 90% of advanced economies, compared with only 30% of low- and middle-income economies.

 

 

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[Evidence published between 03/11/2021 and 16/11/2021]

28 million years of life

28 million years of life were lost to COVID-19, in 2020 in 31 countries. This is more than five times higher than those lost with the seasonal influenza epidemic in 2015. The years of life lost were relatively low in people aged under 65 years, except in Russia, Bulgaria, Lithuania, and the US.

Spain’s COVID-19 death toll

Spain’s COVID-19 death toll in 2020 was 80,000 people (including those who died from comorbidities complicated by COVID), according to updated estimates. This makes COVID the first cause of death in Spain during 2020.

Studying mutations beyond Spike

Four mutations found in the nucleocapsid protein of Delta increase viral RNA delivery and expression in the cell by 10-fold, according to a study using a new system to create virus-like particles, developed by Nobel laureate Jennifer Doudna.

Neurons: affected but not infected?

A procedure which allows to visualise replicating virus in nasal tissue of deceased COVID-19 patients shows ciliated cells are the main target for SARS-CoV-2 in respiratory mucosa. The study found no evidence of infection of olfactory neurons suggesting it is not a neurotropic virus and that olfactory neurons may be affected without getting infected.

A high-risk gene identified

A variant of a gene called LZTF1 may confer a higher risk of developing severe COVID-19. This high-risk version of the gene, carried by 60% of people with South Asian backgrounds and 15% of people of European ancestry, could make lung cells more susceptible to infection.

Mortality data in children

A clinical review of deaths in the UK during the first pandemic year shows that 99.995% of children and adolescents with a positive SARS-CoV-2 test survived. Of the 61 deaths registered, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to COVID and 3 due to pediatric inflammatory syndrome.

Protective pre-existing T cells

A study with healthcare workers who were continuously exposed to the virus but repeatedly negative by PCR or serology shows that some of them displayed an expanded population of T cells that target the proteins responsible for viral replication, and which could help clear infections before antibodies are generated. The sequence recognised by these T cells is common to all human seasonal coronaviruses and could represent a target for pancoronavirus vaccines.

Time to reinfection

Antibody levels associated with protection against reinfection are likely to last 1.5-2 years on average, while protection from severe infection may last for several years, according to a study in the UK with over 7,500 participants. However, 24% of participants did not develop anti-Spike antibodies.

More antiviral treatments

An oral antiviral drug developed by Pfizer reduced the risk of COVID hospitalization by 89%, according to a press release by the company. The drug inhibits viral replication by interfering with a viral enzyme (or protease). Results published this week show the drug has good antiviral activity against different coronaviruses including MERS, SARS, and SARS-CoV-2 variants.

Another vaccine for COVAX

The WHO has granted emergency use listing to Covaxin (the inactivated virus vaccine developed by Bharat Biotech). The vaccine was shown to have an efficacy of 77.8% against symptomatic COVID-19 and 93% against severe infection, according to the results of the phase 3 clinical trial.

Next generation vaccines

Australian researchers developed a patch that delivers to the Spike protein directly into the skin and elicits virus-specific T cells and antibodies. A single dose provided complete protection in mice. 

Researchers at Boston Children’s Hosptial developed a vaccine consisting of the SARS-CoV-2 Spike receptor-binding domain fused to a nanobody (a single-chain antibody) that targets antigen presenting cells. The vaccine elicits robust immunity in mice, is stable for at least 7 days at room temperature, and can be lyophilised.

A self-amplifying mRNA vaccine protected macaques against SARS-CoV-2 infection when given either as a homologous 2-dose regimen or as a boost following a first dose with a chimpanzee adenoviral vector. Both regimens are being evaluated in phase 1 clinical trials.

Deer too

30% of white-tailed deer sampled in Iowa tested positive for SARS-CoV-2 RNA, likely resulting from multiple human to deer transmission events, together with sustained transmission among deer.

Measles time bomb

The number of infants missing their first measles vaccination jumped by 3 million last year—the largest increase in 20 years, according to a WHO/US CDC report.

 

 

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[Evidence published between 20/10/2021 and 02/11/2021]

The world has reached 5M official deaths by COVID-19, and almost 250M cases. Real numbers are likely much higher.

Flying under the radar

Community transmission of SARS-CoV-2 was happening in several areas of Europe and the US by January 2020 and, by early March, only 1 to 3 in 100 SARS-CoV-2 infections were detected by surveillance systems, according to a study.

A seasonal infection?

Climate played a strong role in modulating viral transmission during the first pandemic waves in both hemispheres, shows a modelling study. The findings predict that COVID-19 will behave as a seasonal infection and highlight the role of airborne transmission.

In the inner ear

SARS-CoV2 can directly infect cells of the inner ear tissue, which co-express the ACE2 and TMPRSS2 receptors, shows a study. This would explain problems with hearing and balance in some patients.

Good news from the treatment front

A controlled clinical trial in Brazil shows that early treatment with a cheap antidepressant (fluvoxamine) among high-risk patients with confirmed COVID-19 reduced the need for hospitalisation by 32% (from 16% to 11%) as compared to placebo. Fluvoxamine has an anti-inflammatory effect.

Merck has signed a deal with the Medicines Patent Pool that will allow the 105 poorest countries to produce its antiviral drug molnupiravir for as little as $20 per treatment (a 5-day course), compared to the $712 per course in the U.S.

Vaccine beats infection

Unvaccinated adults with a previous SARS-CoV2 infection were 5.5-times more likely to contract COVID-19 as compared to fully vaccinated adults who had not been infected, concludes a study from the CDC in the US. Without the vaccine, people may get reinfected after 5-12 months, according to another study. 

More estimates of vaccine effectiveness

A study from Scotland estimates the overall vaccine effectiveness against death from Delta infections was 90% for Pfizer-BioNTech and 91% for AstraZeneca-Oxford (and 87% and 90%, respectively, for people over 60 year of age). Another study from Israel shows 93% effectiveness against Delta infections in over 100,000 adolescents (which had not been previously infected). And data from Israel also show that a booster dose further reduces the risk of severe disease, but this risk was already very low in people with two doses and no comorbidities (3 per 100,000).

Transmission in households

A study evaluating community transmission in the UK shows that fully vaccinated individuals that get infected can transmit the virus in household settings, including to fully vaccinated contacts. However, vaccination reduces the risk of delta variant infection and accelerates viral clearance.

On the benefits of mixing

A dose of the AstraZeneca-Oxford vaccine followed by a dose of the Pfizer-BioNTech vaccine confers better protection against SARS-CoV-2 infection than two doses of the Pfizer vaccine, according to a French study in healthcare workers. And Spain has just recommended that all people vaccinated with the one-dose J&J vaccine (around 2M people) receive an mRNA booster shot.

The dark side of boosters

Rich countries have given out more boosters in 3 months than poor countries have given total doses in the whole year, according to a Financial Times analysis. Only 261M (14%) of the 1.8 billion doses pledged by wealthy nations have arrived in low-income countries.

 

 

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[Evidence published between 06/10/2021 and 19/10/2021]

Reducing the risk of blood clots

A randomized clinical trial shows that heparin at therapeutic doses reduced the incidence of major thromboembolism (28.7 vs 42%) in high-risk patients with COVID-19.

More on long Covid

A review of 57 studies comprising more than 250,000 survivors of COVID-19 concludes that more than half of COVID-19 survivors experienced sequelae 6 months after recovery, mostly mental health, pulmonary, and neurologic disorders. Another study shows that being female, middle aged, having 2 or more comorbidities, and having had more severe disease were related to not recovering 6 months after being discharged from the hospital.

A closer look at the immune response

Virus-specific T and B cell memory cells are present in bone marrow, spleen, lung, and multiple lymph nodes for up to 6 months after SARS-CoV-2 infection, according to a study. Virus-specific germinal centers (where B cells are selected to produce high-affinity antibodies) were detected in lung-associated lymph nodes, indicating site-specific coordination of immune responses for protection against future infections.

Longer intervals

A study with healthcare workers in UK shows that a longer interval (6-14 weeks) between Pfizer COVID-19 vaccine doses induces higher levels of neutralizing antibodies and CD4+T cells as compared to shorter intervals (3-4weeks).

Mixing vaccines

A Swedish study finds that giving a first dose of the AstraZeneca vaccine followed by a mRNA dose was more effective in preventing symptomatic infection than two AstraZeneca doses: 67% effectiveness for AZ/Pfizer, 79% for AZ/Moderna and 50% for AZ/AZ. This is one of the first studies to report vaccine effectiveness by heterologous vaccine combinations. 

Vaccine protection against severe disease

A French study comparing a cohort of 11M vaccinated or non-vaccinated people confirms vaccines are >90% effective in protecting against severe disease in people aged 50 or older, even for the Delta variant (84% effective in people over 75, 92% in people between 50 and 74). And an ongoing review of EU-licensed COVID-19 vaccines shows a vaccine effectiveness of: 63% against asymptomatic infection, 76% against symptomatic infection, and 91% against hospitalisation. With Delta, effectiveness against mild disease was reduced by 10–20%, but fully maintained against severe COVID19.

A  study that followed almost 5,000 vaccinated participants shows that, although total anti-Spike IgG levels declined over the 6 months following the second dose, the decline in neutralising antibodies was much slower. This was confirmed by another study which in addition showed robust cellular immunity (memory B and T cells) to SARS-Cov-2 and variants (including Delta) for at least 6 months after mRNA vaccination. In fact, SARS-CoV-2 specific memory B cells increased between 3 and 6 months after mRNA vaccination, even as antibody levels declined. These data suggest that although booster shots may provide a temporary increase in antibodies, they will have little impact on already durable memory cells.

However, protection by China’s inactivated virus vaccines seems to wane faster. This week, WHO’s advisory group recommended that people over 60 who received CoronaVac or Sinopharm vaccines should receive a third dose of the same or another vaccine to ensure sufficient protection. These vaccines account for almost half of the 7.3 billion COVID-19 vaccine doses delivered globally.

And against transmission

A cohort study in Sweden suggests that vaccines play a key role in reducing transmission within households: family members without immunity had a 45-97% lower risk of contracting COVID-19 as the number of vaccinated family members increased.

Pandemic side effects

The COVID-19 pandemic was associated with an increase in depression (27.6%) and anxiety (25.6%) cases globally, with women and younger people the most affected, according to a systematic review.

Deaths from tuberculosis increased for the first time in a decade, according to WHO’s latest Global TB report. Fewer people were diagnosed and treated due to the COVID pandemic. The increase in deaths was mainly concentrated in 30 nations including Angola, Indonesia, Pakistan, the Philippines, and Zambia.

 

[Evidence published between 22/09/2021 and 05/10/2021]

Multiple introductions

In the early phase of the pandemic, the virus was introduced in Spain at least 500 times from multiple international sources, concludes a Spanish team that sequenced 2,170 SARS-CoV-2 samples, mostly before lockdown measures. The analysis shows that lockdown measures were effective in controlling virus spread.

Bacteria that protect against COVID-19?

Our risk of developing severe COVID-19 may partly depend on the type of bacteria that normally inhabit our respiratory tract (i.e. the microbiome), according to an analysis on 142 patients. Poor clinical outcome was associated with lower levels of an oral commensal bacterium called Mycoplasma salivarium. 

Estimating the probability of reinfection

A study analysed available data on antibody duration for the six other coronaviruses known to infect humans. The authors estimate that, under endemic conditions, reinfection by SARS-CoV-2 will likely occur between 3 months and 5 years after peak antibody response, with a median of 16 months. These findings highlight the importance of vaccinating everyone with prior COVID-19.

Good news on the treatment front

Merck announced that its antiviral drug molnupiravir, given as an oral pill, reduces the risk of hospitalization and death compared to placebo when given early as a five-day course. In the placebo group, 53 patients (14%) were hospitalized or died. In the treated group, 28 (7%) were hospitalized and none had died by day 29. The drug targets viral replication, meaning it should be effective as the Spike protein continues to mutate.

Taking anticoagulants before contracting COVID-19 is associated with a 43% lower risk for hospital admission, and receiving anticoagulants while in the hospital is tied to a lower death rate, according to a retrospective analysis in the US. However, to date there are no controlled trials to determine the type, dosage or duration of the anticoagulant therapy.

Promising vaccines for middle and low-income countries

A phase 1 trial in Thailand (not yet peer-reviewed) shows a good safety profile and potent immunogenicity for NDV-HXP-S, a vaccine based on an inactivated virus (Newcastle virus) expressing the SARS-CoV-2 spike. This vaccine can be produced at low cost using the same technology that is used for influenza virus vaccines, and is being produced locally in Thailand, Brazil, Vietnam and Mexico.

China’s Clover pharmaceuticals announced that two doses of its vaccine, based on a modified SARS-CoV-2 protein with a CpG/Alum adjuvant, offered 100% protection against severe COVID-19 and 79% against symptomatic disease. The trial enrolled over 30,000 adult and elderly participants across 4 continents. CEPI has committed up to $328 million to support its development and COVAX has an agreement to purchase up to 414 million doses.

Vaccines reduce transmission

Using data from more than 50,000 COVID19 contacts, Oxford researchers show that, despite similar CT counts (amount of viral ARN) between vaccinated and unvaccinated people, vaccination reduces transmission of Delta, although by less than for Alpha. The impact of vaccination on transmission decreased over time since second vaccination. Data also show that children are less susceptible to infection and less infectious. The study has not yet been peer reviewed.

Two-dose data for J&J

Johnson&Johnson announced that a two-dose regimen of its vaccine was 100% effective against severe disease and that a six-month interval seems to work better than 2 months. The company also released further data from the study of the one-dose vaccines, showing that efficacy against hospitalization remained high, at 76%.

Sharing for self-interest

Using models of SARS-CoV-2 dynamics that take vaccine access into account (high vs low), a study demonstrates that sharing vaccines equitably is a high-return strategy. It would lower disease burdens in countries with less access, reduce the cost of having to be constantly vigilant for case imports, and minimize virus evolution.

Reminder: 97.7% of people living in low-income countries have not received one single vaccine dose.

 

[Evidence published between 08/09/2021 and 21/09/2021]

Narrowing down on its origin

A team at Institut Pasteur found a couple of bat coronaviruses in Laos that differ in only one or two aminoacids from the SARS-CoV-2 receptor binding domain. These bat coronaviruses bind efficiently to the human receptor (hACE2) and mediate cell entry, although they do not harbour a furin cleavage site. These findings indicate that horseshoe bats in the Indochinese peninsula harbour SARS-CoV-2-like viruses that are potentially infectious for humans.

Another study analysing viral genomes taken from people infected early during the pandemic (late 2019) suggests that SARS-CoV-2 could have spilled from animals to people multiple times. The earliest viral sequences can be split into 2 lineages with key genetic differences. Lineage B became the dominant lineage globally and includes samples taken from people who visited the Huanan market. Lineage A is linked to other markets in Wuhan.

In fact, an average of 400,000 people could be infected with SARS-related coronaviruses every year, in spillovers (i.e. jumps from animal reservoirs to humans) that never grow into detectable outbreaks, according to an assessment that has not yet been peer-reviewed.

Why Africa must not be left behind

Ongoing viral transmission and increasing mobility in Africa led to the emergence and spread of many variants of concern and interest, shows a study, highlighting the need to increase vaccine coverage in the continent. In the first half of 2021, the whole of Africa administered about the same number of COVID-19 vaccines as California, despite having 30 times more population.

Long Covid in children – very rare

Data from UK show that the rates of common symptoms after COVID-19 at 12 weeks are extremely low for children 12-16 (3%) and even lower for children 2-11 compared to a control group (3% vs 1.3% and 3.6 vs 4.1%, respectively). The percentage of children suffering of continuous symptoms was also very low (3% vs 0.5% in controls).

Autoantibodies in COVID-19 patients

A significant proportion of hospitalised COVID-19 patients (around 50%) develop de novo a subset of IgG autoantibodies that recognise self-antigens or cytokines and that go hand-in-hand with immune responses to SARS-CoV-2 proteins.

No benefit for remdesivir

A clinical trial conducted in 48 sites across Europe with 857 participants shows no clinical benefit from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and/or required oxygen support.

More real-world data on vaccine effectiveness

A study of 969 COVID-19 patients admitted to hospital in New Haven, US, shows that only 54 of them (5%) were fully vaccinated. Of these, 14 had severe disease and three died. The median age of these patients was 80 years.

Among almost 4,000 US adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization (March–August, 2021) was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%).

The latest report by Public Health England shows that, by 20 weeks, protection against infection has declined but remains high against hospitalization (>90% for Pfizer, 75-90% for AstraZeneca) and death (>90% for both). There is some suggestion of greater waning in the oldest age groups and in high clinical risk groups, which may benefit from a booster dose. Data also suggest that very short intervals (3 weeks) between Pfizer doses seem to produce lower protection than longer intervals.

A group of experts concludes that the currently available evidence does not support the need for booster doses in the population that has received an effective primary vaccination regimen. Vaccine efficacy against severe COVID19 regardless of the variant remains high enough so that booster doses are not appropriate at this stage in the pandemic. They point out that the gain obtained by boosting will not outweigh the benefits of providing initial protection to the unvaccinated.

 

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