Policy & Global Development

COVID-19: Scientific Updates

ISGlobal COVID-19 scientífic updates
Photo: Quinten Braem / Unsplash

The epidemic –now pandemic– of the new coronavirus is advancing at a staggering pace. 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 will regularly update, we will summarise the most relevant emerging information on SARS-CoV-2.

 

[Evidence published between 17/02/2020 and 23/02/2021]

The difference lies in the sugar

Recent evidence suggests that SARS-CoV-2 S protein has a higher binding affinity to the human ACE2 receptor than SARS-CoV-1. A study shows that this is because the SARS-CoV-2 receptor binding domain interacts with a sugar (or glycan) attached to an amino acid (asparagine in position 90) on ACE2. This interaction is absent in the SARS-CoV-1 virus. These results could help develop new strategies to block viral infection.

Viral mutations and monoclonal antibodies

One year after its emergence, the SARS-CoV-2 population has accumulated over 75 mutations, which could have implications not only for vaccines but also for monoclonal antibody-based therapies. In fact, a study mapped how mutations in the receptor binding domain (RBD) may escape recognition by monoclonal antibodies developed by REGENERON and Lilly. The results show that some mutations potentially capable of escaping these individual antibodies are already circulating in the human population.

Underreporting in Africa?

A study performed in a hospital in Zambia suggests that COVID-19 cases and deaths have been under-reported because testing was rarely done. SARS-CoV-2 was detected in 16% of 400 deceased people in whom postmortem nasopharyngeal swabs were analysed. Although the number of confirmed COVID-19 deaths in the African continent represents a small fraction of those reported globally, the death toll has been rising fast, reaching 100,000 confirmed deaths.

20 million years of life lost to COVID-19

Over 20.5 million years of life may have been lost due to COVID-19 globally, with an average of 16 years lost per death, according to a study across 81 countries. In heavily affected countries, this means 2-9 times the average seasonal influenza. Three quarters of the years of life lost result from deaths below 75. Men have lost 45% more life years than women.

Inhibition of interferon alpha signalling

Patients with severe COVID-19 produce antibodies that block a functional response to interferon alpha, one of our first lines of antiviral defence. The study compared gene expression in a wide variety of immune cells from patients with mild or severe COVID-19.

Long-lived memory B cells

Another study in patients recovered from mild to moderate COVID-19 supports long-lived immunity to SARS-CoV-2: although a decline in antibodies is observed over the first 4 months post-infection, virus-specific memory B cells consistently accumulate over time.

An intranasal lipopeptide

Intranasal administration of a lipopeptide that inhibits the fusion between the viral and cell membranes completely prevented viral transmission in ferrets. These lipopeptides are highly stable and may represent a safe and effective prophylaxis to reduce transmission of SARS-CoV-2.

More data on approved vaccines

Longer intervals between doses for Oxford vaccine

A pooled analysis of the Oxford vaccine shows that efficacy was higher among those with a longer interval between the two doses (81.3% with a 12-week interval versus 55% with an interval under 6 weeks). There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after 21 days of the first shot, versus 15 in the control group.

Protection after the first dose of the Pfizer vaccine

A study comparing vaccinated and unvaccinated health care workers in Israel shows that the rate of reduction of SARS-CoV-2 infections among the former was 30% (days 1-14) and 75% (days 15-28) after the first dose. However, it is not known how long protection lasts following one single dose.

Protection against hospitalisation

Preliminary results from Scotland suggest that both the Pfizer/BioNTech and the Oxford/AZ vaccines protect against severe infections. The showed that, by the fourth week after the initial dose, the risk of hospitalisation among people over 80 years of age was reduced between 85% and 94%. In total, there were just over 8,000 people who ended up in hospital, and only 58 were among the vaccinated group. These results have not yet been peer-reviewed. In turn, Israel announced that the Pfizer vaccine has an efficacy of 98.9% in preventing hospitalization and deaths by COVID-19.

 

[Evidence published between 10/02/2020 and 16/02/2021]

More on its origin

The emergence of SARS and SARS-CoV-2 could be the direct consequence of climate change that led to shifts in bat distribution in the Chinese Yunnan province and neighbouring regions, according to a study.

In fact, bats that harbour coronaviruses related to SARS-CoV-2 show an extended geographic distribution from Japan and China to Thailand, over a 4800-km range.

In turn, the WHO-led mission that recently visited China has concluded that the “jump” from bats to humans likely involved an intermediary host such as rabbits, ferrets or bamboo rats, which are susceptible to the virus and were sold at the Wuhan market.

Another risk factor?

Low birth-weight has been identified as an independent risk factor for severe COVID-19 in adults under 70 years of age, according to the follow-up of almost 400 patients at the Hospital Clinic in Barcelona.

No cross-protection by common colds?

Many people possessed cross-reactive SARS-Cov-2 antibodies before the pandemic as a result of infections by human cold coronaviruses. A study shows that although these antibodies are boosted upon SARS-CoV-2 infection, they are not protective.

Breastfeeding and COVID-19

A study that analysed milk samples from women diagnosed with COVID-19 shows that none of the milk samples contained the virus, but 80% contained anti-SARS-CoV-2 IgA and/or IgG antibodies. In addition, 62% of milk samples were able to neutralise the virus in the laboratory. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19.

Repurposed drugs

A rheumatoid arthritis drug

The RECOVERY trial in UK has presented data showing that the tocilizumab (an antibody that blocks the inflammatory IL6 cytokine) significantly reduces the risk of death when given to hospitalised patients with severe COVID-19: 29% of the patients treated with tocilizumab and dexamethasone died within 28 days, compared with 33% of those treated with dexamethasone alone. Tocilizumab also shortened the time until patients were successfully discharged from hospital and reduced the need for a mechanical ventilator.

Blood thinners

The analysis of a nationwide cohort of COVID-19 patients in the US shows that early initiation of blood thinners among patients admitted to hospital with COVID-19 was associated with a decreased risk of mortality after 30 days and no increased risk of serious bleeding events.

Engineered nanobodies

Camel-derived antibodies (or nanobodies) are smaller than human antibodies and therefore easier to produce and administer. Researchers have engineered nanobodies that simultaneously target distinct epitopes of the SARS-CoV-2 spike protein. These multivalent nanobodies are much more potent in neutralising the virus and could work against different viral variants.

In fact, it should be possible to develop antibodies and pan-virus vaccines, capable of recognising a large variety of coronaviruses, say several experts.

Anaphylaxis related to mRNA vaccines

To date, 66 cases of anaphylaxis have been reported in the US, out of 18 million vaccinations with mRNA vaccines (0.0003%). All but 1 occurred within the first 11 minutes, and there were no deaths.

Good signs from Israel

In Israel, 90% of adults over 60 years-old have received one or two doses of the Pfizer vaccine, and the results are starting to show.

The country has seen a 94% drop in symptomatic COVID-19 infections among 600,000 people who received two doses of the Pfizer mRNA vaccine. The same group was 92% less likely to develop severe illness.

Furthermore, preliminary results show a significant decrease in viral load among people over 60 years of age, one month after the vaccination rollout started in this age group. This suggests that vaccination may also impact on transmission.

 

[Evidence published between 03/02/2020 and 09/02/2021]

Latest news on variants

Vaccine efficacy

A further analysis of the AstraZeneca/Oxford vaccine trial indicates that, although vaccine-induced antibodies were less effective in neutralising the B1.1.7 variant in the laboratory, vaccine efficacy against symptomatic infections caused by the variant was only slightly lower (75% vs 84%).

However, a small trial with 2,000 people in South Africa shows that the same vaccine offered almost no protection against mild and moderate disease caused by the B1.3.5 variant. Experts still hope it will protect against hospitalisation and death, but authorities have decided to stop rolling out the AstraZeneca vaccine and roll out the Johnson and Johnson vaccine instead, until more data are available.

Convergent evolution

Scientists in the UK reported that a small number of B1.1.7 variants have developed the E484K mutation, which is also found in variants in Brazil and South Africa and may help SARS-CoV-2 partly evade immunity.

Transmission: getting a grip on the who, when, and how

An analysis performed in the US concludes that at least 65% of SARS-CoV-2 infections originated from individuals aged 20-49.

Another analysis of 282 COVID-19 clusters in Catalonia shows that the viral load was a leading driver of SARS-CoV-2 transmission. People with low viral load infected 12% of their contacts, while people with high viral load infected 24% of their contacts.

A study that followed 655 hospitalised patients in France concludes that the peak in viral load occurs in average one day before symptom onset and that the decline in viral load is slower in older patients. It also confirms that the dynamics of viral load after hospital admission is a predictor of the risk of death.

Another follow-up study with over 200 patients shows that around 5% were persistently PCR-positive after 90 days. However, transmission to close contacts was not observed, indicating that these individuals are not contagious at the post-symptomatic stage of the infection.

It is now clear that SARS-CoV-2 is transmitted predominantly through the air, by people talking and breathing out large droplets and aerosols. In contrast, catching the virus by touching infected surfaces seems to be rare.

Promising treatments?

Interferon lambda-1 is a small molecule involved in the innate response against respiratory pathogens. A small trial with non-hospitalised COVID-19 patients shows that a subcutaneous injection of this molecule resulted in lower viral loads in treated patients as compared with the placebo group.

Researchers used messenger RNA (mRNA) to code for Cas13, an enzyme that is known to target RNA viruses. In hamsters, delivery of this Cas13a mRNA through a nebuliser reduced SARS-CoV-2 replication and reduced symptoms.

More on vaccines

A further analysis of the trials for the Oxford /AZ vaccine provides some additional information: there were no hospitalisations in the vaccine group after the initial 21-day exclusion period, as compared to 15 in the control group; vaccine efficacy after one dose of vaccine from day 22 to day 90 post vaccination was 76%; and, in the group that received two full doses, efficacy was higher with a longer interval between doses: 82% for a 12 week interval versus 55% for an interval of 6 weeks or less. PCRs made on swab samples obtained from vaccinated individuals also suggest the vaccine could help reduce viral transmission.

Indirect effects

Many countries saw cancer diagnostics and treatment partially or completely disrupted during the pandemic (in Spain, for example, the number of cancer diagnosis fell by 20% in 2020). This means that cancer’s death toll will surely increase in the coming years.

 

[Evidence published between 27/01/2020 and 02/02/2021]

One year ago (Jan 30, 2019), the WHO declared the outbreak of COVID-19 a Public Health Emergency of International Concern, with around 8,500 confirmed cases globally. Today we stand at 103 million cases.

Infectious time-window

A study in South Korea confirms that, in average, infected people are no longer contagious 7 days after symptom onset, even if they can remain positive by PCR for more than 30 days. The study performed viral culture and PCRs from patients hospitalized with COVID-19.

Another risk factor

Schizophrenia may be a risk factor for mortality in patients with COVID-19, according to a retrospective cohort study with 7348 adult patients in New York.

A broad diversity of T cells

Patient-derived T cells recognise a broad range of SARS-CoV-2 protein fragments (or epitopes) – at least 30 to 4o epitopes in each donor. These T cell epitopes hardly overlap with epitopes recognised by antibodies, making it less likely that the new variants can also escape T cell immunity.

Worrying signs from Manaus

In Manaus, Brazil, a study of blood donors indicated that around 76% of the population had been infected with SARS-CoV-2 by October, 2020, which would be above the theoretical herd immunity threshold. However, there has been an abrupt increase in COVID-19 hospitalisations during January 2021. Possible explanations include the higher transmissibility of the P1 variant and/or its potential capacity to escape from immunity.

Only one dose for some people?

Results from two studies (not yet peer-reviewed) suggest that, in people who have already been infected by SARS-CoV-2, one single vaccine dose (Pfizer or Moderna) induces antibody titers equal to or higher than those found in “naïve” (non-infected) individuals after two doses.

Efficacy data for two more vaccine candidates

Novavax announced its protein-based vaccine showed an 89.3% efficacy in its trial in the UK, with over 15,000 participants between 18 and 84 years of age. Of 62 symptomatic cases, 56 (1 of them severe) were in the placebo and 6 in the vaccine group. Over 50% of cases were infected with the B1.1.7 variant, indicating that the vaccine also works against this variant. However, the efficacy dropped to 60% in a smaller trial (4,400 participants) in South Africa, where the B1.3.5 variant is circulating. The efficacy was lower (49.3%) when including HIV-positive people.

Johnson & Johnson also announced efficacy data for its adenoviral-vectored vaccine. One single dose protected from symptoms although efficacy depended on the location: from 72% in the US to 66% in Mexico and 57% in South Africa. Importantly, the trial had enough cases to conclude that, by 28 days after the shot, the vaccine provided an 85% protection against severe cases and complete protection against hospitalisation and death, even in South Africa.

The Gamaleya Institute published the interim results for the phase 3 trial of its vaccine candidate (Sputnik V), based on two adenoviral vectors. The results show the vaccine was safe and had an efficacy of 91.6%, even in people older than 60. 

Companies are already planning how to update their vaccines against the new variants, if necessary.

The European Medicines Agency has approved the use of AstraZeneca’s vaccine for people from 18 years of age. Although there are not enough efficacy data in participants over 55, the EMA considered the vaccine can be used in this population.

COVAX starts to deliver

The COVAX platform expects to deliver 35.3m doses of AstraZeneca’s COVID-19 vaccine to 36 Caribbean and Latin American countries from mid-February to the end of June, PAHO announced.

 

 

[Evidence published between 20/01/2020 and 26/01/2021]

More on viral variants

Good news

Moderna has announced that its vaccine retains neutralising activity against the variants first identified in the UK (B1.1.7) and South Africa (B1.351). Although a six-fold reduction in virus neutralisation was observed with the B1.351 variant, the titers of neutralising antibodies after two doses of the vaccine remain above those needed for protection. The company is nevertheless preparing a shot against this variant, in case it becomes necessary.

Not so good news?

According to a report by an advisory group in the UK, new analyses show there may be an increase in disease severity in patients infected with the B1.1.7 variant. However, more data are needed to draw firm conclusions.

The virtues of contact tracing

An analysis of COVID-19 fatality rates in 139 countries shows, quite unsurprisingly, that comprehensive contact tracing is instrumental not only for slowing transmission but also for reducing cases fatality rates.

Estimating asymptomatic infections

Data collected from numerous studies and reports indicate that at least one third of total SARS-CoV-2 infections are truly asymptomatic (i.e. they never develop symptoms).

“Bad” kind of antibodies

Increasing evidence suggests that antibodies directed against our own proteins or tissues (called autoantibodies) could be driving severe disease upon SARS-CoV-2 infection. Autoantibodies recognising a variety of targets - including interferon, B cells and other components of the immune system as well as components of the cell membrane such as phospholipids and more recently Annexin A2 - have been detected in patients with severe COVID-19. This could explain the long-lasting damage to certain organs observed in some of these patients.

More on treatments

Blood thinners

A series of large clinical trials conducted worldwide show that treatment of moderately ill patients with a full dose of heparin (an anticoagulant) reduced the need for ventilation.

Monoclonal antibodies

A combination of two monoclonal antibodies developed by Eli Lilly significantly lowered viral loads in mild to moderately ill patients by day 11, as compared to those who received placebo.

In addition, the company announced that one of those antibodies (bamlanivimab) reduced the risk of developing COVID-19 symptoms by up to 80% among nursing home residents treated preventively with the drug. Although the antibody does not substitute the vaccine, it could be used to prevent outbreaks when it is too late to vaccinate.

Another study engineered a human monoclonal antibody that can recognise and neutralise a broad range of SARS-like viruses.

A drug from the sea

Plitidepsin, an anticancer drug derived from a marine invertebrate, was shown to be much more potent than remdesivir against SARS-CoV-2 in cell lines and reduce viral replication in mice infected with the virus. The drug, developed by the Pharmamar company under the name of aplidin, now needs to be tested in patients with COVID-19.

More on vaccines

Preclinical studies with mice and/or baboons show promising results for Novavax’s vaccine candidate (comprising nanopoarticles of the Spike protein) and for a vaccinia virus-based candidate (MVA-CoV2-S) developed by a Spanish team.

In contrast, Merck announced it will stop developing its both vaccine candidates, following phase 1 results which showed that, although well tolerated, the immune response to the shot was lower than that observed upon natural infection.

Anaphylactic reactions

Out of 1.9 million doses of the Pfizer vaccine administered in the US between December 14 and 30, 2020, 21 cases of anaphylaxis were reported, corresponding to an estimated rate of 11 cases per million doses administered. No deaths were reported.

Vaccination impact

In Israel, 75% of the older population has been vaccinated and this is starting to show: there has been a 60% drop in hospitalisations among vaccinated older people, according to recent data. Assessing the impact of vaccination on transmission at the population level will need more time.

Pandemic inequalities

For the world’s top billionaires, it only took nine months to recover their pre-pandemic fortune. For the world’s poorest, it may take more than a decade, according to Oxfam’s report The Inequality Virus. The pandemic has the potential to increase economic inequality in almost every country at once - the first time this happens since records began.

 

[Evidence published between 13/01/2020 and 19/01/2021]

A precursor of the B1.1.7 variant?

Genome sequencing of virus isolated from an Italian patient with persistent infection suggests that SARS-CoV-2 variants with a mutation at position 501 of the Spike protein might have circulated even before September 2020. The virus evolved within the same patient, accumulating three additional mutations in less than three months.

Combined effect

Experts agree that, when analysing the possible effect of SARS-CoV-2 mutations in this and other variants, it is important to look beyond one single point mutation and consider the interactions between the different mutations. This involves integrating genomic data with clinical evidence and laboratory studies.

SARS-CoV-2 can infect the brain

SARS-CoV-2 can infect neurons in the brain cortex and alter their metabolism, according to a study that used three independent approaches to confirm this: human brain organoids in a dish, mice expressing the human ACE2 receptor, and autopsies from deceased COVID-19 patients.

Impact of the COVID-19 pandemic in Brazil

A study of the first 250,000 patients hospitalised with COVID-19 in Brazil shows that almost half were under 60 years-old and two of every five patients died. In-hospital mortality was higher in areas with fragile health systems.

More good news regarding duration of immunity

Memory B cells to SARS-CoV-2 persist for more than 6 months and produce antibodies that are more potent and likely more resistant to mutations in the Spike protein than those produced one month after infection, according to a study by the Rockefeller University.

A UK study that followed 20,000 healthcare workers shows that people that have had COVID-19 are likely to be protected from disease for several months, although some may still become infected in nose and throat and transmit the virus.

From pandemic to endemic

A model predicts that, once SARS-CoV-2 becomes endemic, exposure during early childhood will cause no more than a common cold but will be enough to induce long-lasting immunity that protects from severe disease later in life.

Results for more vaccine candidates

Phase 1/2 results for another viral vector vaccine candidate

The safety and immunogenicity results for Janssen’s Ad26-based COVID-19 vaccine candidate show that neutralizing antibodies were detected in all participants between 30 and 60 days after one single shot. Antibody and T cell responses were lower in adults aged over 65 years, raising the question whether one single shot will be enough to protect this population. In fact, those participants who received a second dose showed a further increase in antibody levels. A phase 3 trial with one versus two doses of the vaccine is currently underway.

Final efficacy results for Sinovac’s vaccine?

Brazilian researchers announced the efficacy of Sinovac’s inactivated virus vaccine was around 50% (after having announced an efficacy of 78% last week). Of the 9200 health workers who participated in the trial, 167 cases were recorded in the placebo group and 85 in the vaccinated group. None of the vaccinated cases had to be hospitalized. A Sinovac spokesman said that the vaccine efficacy was higher (around 70%) if the dosing interval was longer (three weeks instead of two). Turkey and Indonesia, who also performed clinical trials with the vaccine, have authorised its use.

Vaccination: a very unequal start

Over 39 million vaccine doses have been administered in 49 high-income countries. Only 25 doses have been given in one low-income country. “The world is on the brink of a catastrophic moral failure”, said WHO’s director, Dr. Tedros Ghebreyesus.

 

[Evidence published between 06/01/2020 and 12/01/2021]

One year ago, the first death from COVID-19 was reported. Today, the world has reached almost 2 million deaths.

More on viral variants

Transmissibility?

An updated analysis by Public Health England indicates that 15% of the contacts of people infected with the B.1.1.7 variant went on to test positive themselves, compared with 11% of contacts of those infected with other variants. Increased transmission is observed across all age groups, arguing against a special effect in children.

Immune escape?

Preliminary experimental data suggest that the mutations of the B1.1.7 lineage do not affect recognition by antibodies resulting from natural immunity or from immunisation with the Pfizer vaccine. However, the E484 mutation – present on a strain that is rapidly spreading in South Africa and another one in Brazil – could potentially reduce the effect of neutralising antibodies, according to another study.

Estimating the percentage of infected people

A study using data of reported cases and seroprevalence surveys estimates that by mid-November 14,3% of the population in the US had been infected with SARS-CoV-2. This is 3 times higher the number of reported cases at the time but still far from reaching herd immunity.

According to recent estimates based on the number of COVID-19 deaths and the infection fatality rate, one in five people (22%) in England may have been infected.

And two studies in Africa suggest that the virus may be more widespread than thought: Analysis of antibodies among blood donors in Kenya shows an average seroprevalence of 4.3%, while another study with over 700 health volunteers in the Congo shows that 15% had antibodies against the virus.

Long Covid

A follow-up study in China with over 1,700 COVID-19 patients shows that 6 months after the onset of symptoms, around 75% of survivors still had at least one symptom (mostly fatigue, muscle weakness, sleep difficulties and anxiety or depression). A considerable percentage of those who were severely ill still had abnormal lung function, underlining the need of providing post-recovery care for these patients.

On the importance of IgA antibodies

Two studies this week underline the role of IgA antibodies in viral clearance. One study shows that IgG, IgM and IgA antibodies are produced early in the disease, but that IgAs may be better at neutralising virus and controlling the infection. IgA antibodies decreased in blood after one month, but remained detectable in saliva up to 73 days after symptoms. Another study shows that dimers of IgA (which are the dominant form in the nasal and throat mucosae) are much more potent in neutralising SARS-CoV-2 than monomers (which are found in blood).

Immune memory: at least 8 months

Science has published the results of a study that analysed the different compartments of immune memory to SARS-CoV-2. IgG antibodies to Spike were relatively stable over more than 6 months, Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptoms, and the estimated half-life of virus-specific T cells was of 3-5 months.

More solid results for two treatments

Convalescent plasma: yes, if given early?

A controlled clinical trial in Argentina showed that convalescent plasma can reduce COVID-19 progression in older adult patients if given within the first 72 hours after the onset of symptoms and if the plasma is screened for high titers of SARS-CoV-2 antibodies.

Anti-inflammatory drugs

A trial in the UK shows that in critically ill COVID-19 patients, treatment with the IL6 antagonists tocilizumab and sarilumab (normally used for rheumatoid arthritis) can improve disease outcome and increase survival. The results have not yet been peer-reviewed.

More on vaccines

Indonesia has approved the inactivated virus vaccine developed by the Chinese company Sinovac, after an interim analysis of phase 3 results showed an efficacy of 65%. The same vaccine was reported to have a 78% efficacy in Brazil. Detailed data for these vaccine trials have not yet been published.

Gorillas get it too

Several gorillas at San Diego Zoo have tested positive for SARS-CoV-2 and are showing some mild symptoms. Wildlife experts are concerned about the virus infecting gorillas and other endangered apes.

 

[Evidence published between 23/12/2020 and 05/01/2021]

More on viral variants

A report published by the Imperial College, based on genetic and epidemiological data, indicates that a larger share of people under 20 are being infected with the UK variant (named B1.1.7). For now, all data indicate that this variant is indeed more transmissible. Although the precise reasons are still not known, B1.1.7 presents three mutations in the spike protein that may have biological effects:

  • Mutation N501Y is within the domain that binds to the ACE2 receptor, and may increase the affinity with which the virus binds to such receptor. This mutation has been identified in a South African variant (named 501.V2), which also seems to be spreading faster.
  • A deletion of two amino acids (69,70 del) may help evade the effect of certain antibodies. This deletion was also described in a variant isolated from a mink farm in Denmark.
  • Mutation P681H is next to a site (called furin cleavage site) that enhances viral infectivity. This same mutation has been found in a separate variant identified in Nigeria.

One hypothesis is that this variant may have risen in an immunocompromised patient, where a weakened immune system gives an opportunity for the virus to evolve. In fact, a study shows that patients with profound immunosuppression may remain infected with SARS-CoV-2 for at least two months.

Modelling estimates suggest that, with the new variant, reducing the Rt to less than 1 will require stricter lockdown measures.    

The emergence of this and other potentially worrying variants further underlines the urgent need to curb viral spread and vaccinate as rapidly as possible.

Need for more efficient testing

An analysis in France found that 9 out of 10 cases were not detected in the first seven weeks following lockdown from May 11 to June 28 2020, even if the test positivity rate did not exceed WHO recommendations (5%). Only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. More aggressive and targeted testing with easier access is required to fight the pandemic.

Further data on antibody duration

A follow-up study of 12,541 health care workers in UK shows that the presence of IgG antibodies against the spike or nucleocapsid proteins of SARS-CoV-2 was associated with a substantially reduced risk of SARS-CoV-2 infection in the following 6 months. Only two seropositive individuals had a positive PCR test during the 31 weeks of follow-up, and both infections were asymptomatic.

Along the same line, a South Korean study detected virus-specific antibodies up to 8 months after asymptomatic or mild infection with SARS-CoV-2 by using four different tests.

More vaccines approved

The UK approved AstraZeneca-Oxford’s vaccine on December 30 and has started to roll out the vaccine, of which it has ordered 100M doses. The UK plans to stretch the interval between the two doses required to allow more people to get the first dose sooner. However, experts have raised concerns that this could favour the generation of vaccine-resistant strains by building a cohort of partially immunised individuals. The European Medicine Agency has advised against spacing the two shots of the Pfizer vaccine more than 42 days.

India has formally approved the emergency use of 2 COVID vaccines: The one developed by AstraZeneca /Oxford University (known as Covishield and produced locally by the Serum Institute of India), and one based on inactivated virus developed by Bharat Biotech (named Covaxin), for which no efficacy data have been published.

 

 

 

[Evidence published between 16/12/2020 and 22/12/2020]

A new viral variant - reason for concern but not for panic

A new variant that has rapidly spread in the UK (named B1.1.7) has accumulated 17 mutations all at once, of which 9 are in the Spike protein. The impact of these combined mutations is still not clear, but three questions arise:

Is it more transmissible?

Probably. Preliminary analyses suggest that this new variant may be up to 70% more transmissible than other circulating variants. This observation is supported by experimental data, which show that one of the mutations (N501Y) may increase viral binding to the human ACE2 receptor. This mutation is also present on a separate lineage in South Africa that has been rapidly spreading.

Is it more virulent?

No evidence for the moment. One of the mutations (involving the deletion of two amino acids) has been observed in other lineages, and one study suggests it could make the virus less susceptible to neutralising antibodies. However, at this time there is no evidence that the variant causes more severe disease.

Can it escape from natural or vaccine-induced immunity?

Unlikely, experts say. Even if one fragment of Spike changes, antibodies and T cells can recognise many different fragments of the protein.

Meanwhile, the ECDC has given a series of recommendations, which include reinforcing measures to stop viral spread and increasing the analysis and sequencing of virus isolates, particularly in people coming from affected areas, in suspected cases of reinfection, and in vaccinated individuals who develop the disease.

Transmission by asymptomatic individuals

A study in Singapore suggests that people with asymptomatic SARS-CoV-2 infection might be less infectious than symptomatic cases: the incidence of COVID-19 among close contacts of a symptomatic index case was 3·85 times higher than for close contacts of an asymptomatic case.

Seroprevalence studies

At least 10% of the Spanish population (over 4.5M people) has been exposed to SARS-CoV-2, according to results from the fourth phase of the national seroprevalence study (ENE-COVID). Seroprevalence was highest in healthcare workers (17%), women carers (16.3%), women cleaners (13.9%), women in socio-sanitary jobs (13.1%) and migrants (13%).

Another seroprevalence study in Geneva shows that 22% of its residents has virus-specific antibodies. The study shows a higher than expected prevalence of infection among children over 6 (23%). The less exposed were children under 6 (15%) and adults over 65 (10-14%). The most exposed were those aged 18 to 35 (27-28%).

Leading cause of mortality in the US

By October, COVID-19 became the third cause of death in the USA for persons aged 45 and older. Between November and December, it has become the first cause of death, surpassing daily mortality rates for heart disease and cancer. The USA, which constitutes 4% of the globe's population, has contributed to 19% of the global total of deaths (as of 14 Dec 2020).

More on vaccines

Codagenix and the Serum Institute of India announced they will start Phase 1 trials for COVI-VAC, an intranasal vaccine based on live attenuated virus developed using synthetic biology. The trial will be conducted in London.

The US FDA has granted emergency use authorisation to Moderna’s vaccine for use in adults aged 18 or older. Vaccine efficacy was 94.1% - 11 COVID-19 cases in the vaccine group and 185 cases in the placebo group. All severe cases (30) occurred in the placebo group.

And the European Medicines Agency (EMA) authorised Pfizer/BioNTech’s vaccine for use in the bloc’s 27 states. The EU has ordered 300 M doses but only a limited number will be available immediately.

 

[Evidence published between 10/12/2020 and 15/12/2020]

Evidence of early circulation?

An Italian team found SARS-CoV-2 RNA in a throat swab collected from a child in early December 2019, around 3 months before the first identified coronavirus disease case in Italy. The child had not travelled, so this finding raises the possibility that the virus was circulating outside China earlier than thought.

Impact on male fertility?

A small study on testis biopsies from COVID-19 patients reveals the virus can infect germ cells and affect the production of spermatozoids. These findings raise the possibility that the virus may affect male fertility.

A mortality risk calculator

A Johns Hopkins University team generated an online risk calculator for COVID-19 mortality based on sociodemographic factors and pre-existing health conditions for the US population. The model can identify relatively small fractions of the population that might experience a disproportionately large number of deaths, and could help set priorities for allocating early COVID-19 vaccines.

High-risk occupations

In the period between March and July, UK health care workers had a seven-fold higher risk of becoming severely sick from COVID-19 than non-essential workers, and this risk was even higher (8-fold) if they were non-white. Social and education workers were also at higher risk (1-8-fold) as compared to non-essential workers, according to the analysis.

More on treatment

No benefit for an antibiotic

The UK RECOVERY trial found no benefit from azithromycin in patients hospitalised with COVID-19. The preliminary analysis shows no significant difference in mortality, disease progression or length of hospital stay between treated and control groups.

More on vaccines

Pfizer /BioNTech

The final Phase 3 results for the Pfizer-BioNTech vaccine were published this week. The two doses, given 21 days apart, were safe and 95% effective against COVID-19. Similar vaccine efficacy was observed in groups of different age, sex, ethnicity, body mass index or underlying health conditions. Ten cases of severe COVID-19 occurred after the first dose, 9 of them in placebo recipients and one in a vaccine recipient. Short-term side effects including pain at the injection site, fatigue, and headache were frequent. The incidence of serious adverse events was very low and similar in both groups. Safety monitoring of participants will continue for 2 years.

Mixing vaccines?

A trial may start soon to find out whether mixing COVID vaccines gives better protection than 2 doses of the same one. AstraZeneca will test combining one shot of its vaccine with a second shot of Pfizer’s vaccine. This heterologous prime-boost approach seeks to induce stronger cellular and humoral responses than with one single type of vaccine. It will also explore combining its vaccine with Gamaleya’s Sputnik V vaccine (which uses different adenoviral vectors).

Bad news for two vaccine candidates

Sanofi has suffered a setback in the development of their recombinant protein-based vaccine it is developing with GSK, after detecting a lower response in older adults due to a dosing problem in their formulation. This means that, if approved, it will not be deployed before the second-half of 2021.

The University of Queensland has decided to end the development of its recombinant protein vaccine after finding that vaccinated volunteers developed antibodies that could give false HIV-positive results. This is because the vaccine included a small “molecular clamp”, derived from a protein of HIV, to stabilise the SARS-CoV-2 Spike protein.

 

 

[Evidence published between 2/12/2020 and 9/12/2020]

Rapid nucleic tests without amplification

Two studies have described rapid tests capable of detecting SARS-CoV-2 ARN without having to amplify it. One test uses DNA probes that bind to specific regions in the viral genome, followed by fluorescent antibodies that detect these DNA-RNA hybrids. The assay achieved sensitivities of 100% and specificities of 99% for both saliva and nasopharyngeal swabs and gives results in less than one hour. The other test uses the CRISPR-Cas13a system to directly detect SARS-CoV-2 RNA in nasal swabs. Binding of Cas13a to specific viral sequences leads to the activation of fluorescent DNA probes. The results can be read in 30 minutes using a mobile phone reader device.

More on the dynamics of transmission

A global analysis to understand where SARS-CoV-2 transmission takes place, shows that the highest transmission rates are seen in households (a 21.1% probability of infection). The report from the Imperial College London also reveals that the chance of a symptomatic infected person infecting a close contact was 12.8%, which was four-times higher than if he or she was asymptomatic (3.5%).

Another study (not yet peer-reviewed) that performed regular PCRs on 68 basketball players shows that, on average, viral RNA concentrations peaked rapidly after the first detection (within 2.7 days), regardless of symptoms. However, asymptomatic individuals cleared the virus more rapidly (6.7 days) than symptomatic individuals (10.5 days). These studies raise hopes that, by reducing symptomatic infections, vaccines may also help reduce viral transmission.

A German study concludes that 20 days after becoming mandatory, face masks reduced the number of new infections by around 45%.

"Untuned" immune responses

Normally, type I and III interferons (IFN) are produced as a first line of antiviral defence, and precede the production of inflammatory cytokines. However, in COVID-19 patients with pneumonia, the production of pro-inflammatory cytokines (TNF, IL6, IL8) was shown to precede that of IFN type I and III, which were diminished and delayed.

Another potential treatment

A ribonucleoside analogue (which disrupts viral RNA) was repurposed for use against SARS-CoV-2. Therapeutic treatment of infected ferrets twice a day significantly reduced the SARS-CoV-2 load in the upper respiratory tract and completely suppressed spread to untreated contact animals. The drug, which can be given orally, is currently in Phase 2/3 clinical trials.

Ethical issues regarding vaccine trials

Now that some vaccines have shown to be effective, one question starts to emerge: should the vaccine be offered to the volunteers who got a placebo shot at the risk of losing valuable long-term information? This week, two groups of experts defend the need to continue having placebo-controlled trials. As long as vaccine supplies are limited, one group argues, it is ethical to continue the follow-up of placebo recipients in existing trials and to launch new trials with placebo groups. This would increase the probability of developing multiple vaccines with favourable benefit /risk profiles. The other group says that any plans to conduct placebo-controlled trials remain ethically appropriate given current evidence, and proposes to guarantee that individuals in the placebo arm will receive an efficacious vaccine once their participation in the study is completed. An article in the New York Times includes an interesting proposal: after several months, continue the blinded study giving placebo to the vaccine group and vaccine to the placebo group, and compare duration of immunity between both groups.