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 21/07/2021 and 27/07/2021]
Yet more evidence that vaccines work
According to latest data from England, protection against symptomatic infection after two doses is 88% for Pfizer/BioNTech and 67% for AstraZeneca/Oxford. Despite an apparent drop in protecting against infections, vaccine effectiveness against severe COVID-19 remains very high (around 90%).
A cohort study in the US with 3975 health care and frontline workers detected SARS-CoV-2 infection in 204 participants (5%), of whom 5 were fully vaccinated, 11 partially vaccinated, and 156 were unvaccinated. Viral loads were 40% lower in vaccinated as compared to unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower and the duration of illness was shorter.
A cluster of infections by the Gamma (P.1) variant among mine workers in French Guiana shows that half of the affected persons had been fully vaccinated with the Pfizer vaccine. However, all breakthrough infections were asymptomatic or mild.
Vaccination prevented around 75% of hospitalizations in England's Delta wave, as determined by modelling by the FT. Without vaccines, hospitalizations would already be above the winter peak.
A longer interval between doses of the Pfizer vaccine (around 8 weeks) could work even better in terms of antibody production, while virus-specific T cells are maintained, according to a study in the UK.
High probability of infection?
The successive emergence of more transmissible viral variants means that the vast majority of the global population is expected to get infected by the virus, maybe more than once over their lifetime, according to several experts. In fact, the latest serosurvey in India suggests that up to two thirds of its population may have been infected with SARS-CoV-2, up from less than 25% in January.
Another potential treatment?
A screen of over 1000 clinically safe drugs identified the oral drug masitinib, an anticancer treatment, as a broad antiviral that inhibits the main proteases of coronaviruses, and that effectively reduced SARSCoV2 replication in mice.
People in low and middle income countries are much more willing to take a COVID-19 vaccine (mean 80%) compared with the United States (mean 64.6%) and Russia (mean 30.4%), according to a survey. Thus, prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage.
Another pandemic side effect
More than 1.5 million children around the world have lost a parent, grandparent, or other caregiver to COVID-19, according to a estimates. Countries with the highest deaths of primary caregiver per 1000 children are Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0).
[Evidence published between 07/07/2021 and 20/07/2021]
New data from Vo
A study in the Italian town of Vo, one of the most studied in the pandemic, shows that 98.8% of people who were seropositive in the first wave still showed detectable levels of antibodies to at least one SARS-CoV-2 antigen 9 months later, regardless of whether they were symptomatic or not; and 18.6% of them even showed an increase of antibodies or neutralisation activity.
Viral loads in people infected with the Delta variant were up to 1000 times higher than infections by the original strain on the day when the virus was first detected, according to a study of a large transmission chain in China. These findings indicate this variant is more infectious in the pre-symptomatic phase.
Two doses for Delta
A study from France shows that sera from individuals having received one dose of Pfizer or AstraZeneca vaccines barely inhibited variant Delta, while administration of two doses generated a neutralizing response in 95% of individuals, even if titers were 3 to 5-fold lower against Delta than Alpha. Another study found that the majority of convalescent patients and all individuals vaccinated with two doses of mRNA vaccines had detectable neutralizing activity against both Alpha and Delta variants. Vaccine effectiveness against symptomatic disease by Delta is 80% after 2 doses, according to data from England.
Children and Long Covid
Long-term symptoms after COVID infection in children were found to be very uncommon and not significantly different than observed in the control group, according to a study in Switzerland. As Nature points out, estimates of Long Covid in children vary greatly between studies (somewhere between 1 and 10%), highlighting the need to clearly define the condition.
People with HIV
People living with HIV face a 13% higher risk of hospitalization and a 30% increased risk of death from COVID-19 regardless of age, gender, and comorbidities, according to a study presented at the IAS Conference on HIV. They should therefore be front of the line for vaccines.
More on treatments
Molecules called long-chain polyphosphates show strong antiviral and anti-inflammatory properties against SARSCoV2, according to experiments performed in the laboratory, and represent a potential drug against COVID-19.
A meta-analysis with hospitalised COVID-19 patients concludes that antibodies against the pro-inflammatory molecule IL6 reduced the risk of death (by 17%) and of mechanical ventilation (by 21%) compared with standard care alone. The WHO has endorsed the use of these rheumatoid arthritis drugs for treating COVID-19.
Instead, a single dose of azythromicin in non-hospitalised patients showed no benefit in a study with over 200 participants in US.
Results from Chile, which has immunised its population with Sinovac’s inactivated virus vaccine, shows an effectiveness of 64% against infections and 87% against hospitalizations and deaths.
Giving 25ug instead of 100ug for each dose of Moderna’s COVID-19 vaccine elicits durable antibody and T cell responses across all age groups, according to a small study. These findings suggest that ‘dose stretching’ could help to address the world’s acute vaccine shortage.
More on vaccine safety
Two doses of the Pfizer/BioNTech COVID-19 vaccine were safe and 78% effective in preventing infection in pregnant women in a real-world study in Israel.
Johnson and Johnson’s Covid-19 vaccine may trigger Guillain Barre Syndrome (GBS) in very rare cases, says the FDA. There have been about 100 preliminary reports of GBS, among 12.8 million doses administered in the US.
Pandemic side effects
Around 118 million more people were facing hunger in 2020 than in 2019, according to the latest report by FAO, IFAD, UNICEF, WFP and WHO.
And the number of children who did not receive any vaccination went up from 13.6 million in 2019 to 17.1 million in 2020, says a report by WHO and UNICEF.
[Evidence published between 23/06/2021 and 06/07/2021]
Going back in time
A new analysis suggests that the first COVID-19 case arose around mid-November, 2019 in China, and that the first case outside of China occurred in Japan on January 3, 2020, the first case in Europe occurred in Spain on January 12, 2020, and the first case in North America occurred in the US on January 16, 2020.
COVID and the brain
Molecular expression of brain samples from people who died from COVID shows no evidence of SARS-CoV-2 in the brain, but reveal signs of inflammation and impaired brain circuits, similar to what is observed in neurodegenerative diseases.
Ivermectin shows no effect
A new ‘meta-analysis’ of 10 controlled studies shows ivermectin is not an effective treatment for COVID-19. The analysis included 1173 patients in total, and looked for ivermectin’s effect on mortality, length of hospital stay, and viral clearance compared to standard of care.
Two years lost
Overall, life expectancy in the US dropped almost 2 years due to the pandemic, with a disproportionate effect on minorities, according to two studies. Life expectancy in Brazil, which accounts for 28% of all COVID-19 deaths globally, has also fallen two years in 2021, with a steeper decline for men than for women.
Impact of Long-covid
A study in Norway reveals that 52% of young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%), fatigue (21%), shortness in breath (13%), impaired concentration (13%) and memory problems (11%). In UK, over 2 million adults are estimated to have experienced coronavirus symptoms over 12 weeks, according to the REACT-2 study. And in a follow-up study with non-hospitalised patients, 39% of them reported residual symptoms 7-9 months after diagnosis, including fatigue, loss of taste or smell, shortness of breath and headache.
Results of a study in Spain and a trial in UK provide evidence that giving one first dose of AstraZeneca followed by a second dose of Pfizer (heterologous vaccination) results in a robust immune response that is equal to or even superior to giving two doses of the same vaccine. The studies, however, were not designed to measure efficacy against infection or disease.
Two studies published in Science confirm that natural immunity to SARS-CoV-2 is substantially increased by one mRNA vaccine dose, to an extent that a single vaccine dose is likely to protect against more aggressive variants.
COVID deaths are now preventable
Almost all of the people who are dying from COVID-19 now are unvaccinated. In the US, only about 150 of the more than 18 000 COVID-19 deaths in May were in fully vaccinated people, or less than 1%.
A study by the CDC in US, which performed regular swabs in almost 4000 healthcare workers, shows that the mRNA vaccines (two doses) are 91% effective in preventing infection. Among those infected despite vaccination, the vaccines greatly reduced the viral RNA load, the risk of febrile symptoms, and the duration of illness
Vaccines versus Delta
Johnson and Johnson announced that its single COVID-19 shot protects against the Delta variant. An analysis showed that immune responses elicited by the vaccine against Delta were higher than against the Beta variant (B1.351), and that these responses lasted for at least 8 months. Moderna also announced that its vaccine produced neutralising titers against Delta and other circulating variants. And a population study in Canada suggests that even a single dose of Pfizer, Moderna or AstraZeneca provide good protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern, and that 2 doses are likely to provide even higher protection.
Towards a pan-coronavirus vaccine
A study identifies four antibodies from three patients early in the outbreak, with potent neutralizing activity against 23 variants including the Alpha, Beta and Gamma variants. Two of these antibodies are ultrapotent and could help guide the design of universal coronavirus vaccines. And a chimeric spike mRNA vaccine, encoding different regions of the Spike protein, represents showed protection against different SARS-like coronaviruses in aged mice.
[Evidence published between 16/06/2021 and 22/06/2021]
A study using health care data of 2.9 million households in the US during the first 10 months of 2020 shows that small and informal social gatherings, such as birthdays, and in particular, children’s birthdays, were potentially an important source of SARS-CoV-2 transmission.
Immunity to Delta
Antibodies from convalescent patients or vaccinated individuals have reduced neutralising activity against the Delta variant's sublineages (B.1.617.1 and B.1.617.2) but there is no evidence of widespread antibody escape, as seen with the Beta variant (B.1.351). The study results however suggest that individuals previously infected with Beta or Gamma (P.1) may be more susceptible to reinfection by Delta.
The latest report on the Delta variant in the UK has some good news: while Delta has clearly led to an increase in hospitalizations, their length is decreasing, likely due to younger patients. Two doses of vaccine (AstraZeneca or Pfizer) remain highly effective against hospitalisations, and no increase in reinfections with Delta has been observed to date.
Low rates of reinfection
Reinfection was identified in 0.7% of 9,119 patients that were followed up after SARS-CoV-2 infection. The mean period between two positive tests was 116 days. Asthma and nicotine dependence/tobacco use were associated with re-infection.
The WHO has classified the Lambda COVID-19 variant (C.37) as global 'variant of interest' due to its elevated presence in Peru and rest of South America. Lambda carries mutations that might increase its transmissibility or help it evade immunity, but the evidence remains very limited.
More on treatments
Preliminary results from the RECOVERY trial in UK shows a clinical benefit for Regeneron’s cocktail of monoclonal antibodies in hospitalised patients who did not produce virus-specific antibodies: the drug reduced mortality by 20% in seronegative patients, as compared with usual care alone.
Inhaled nanovesicles containing the ACE2 receptor prevented COVID-19 in macaques challenged with SARS-CoV-2. These ACE2 ‘nanodecoys’ derived from human lung cells can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection.
Not all mRNA vaccines are equal
An interim analysis of CureVac’s mRNA vaccine showed a disappointing 47% efficacy against symptomatic infections. The Phase 3 trial enrolled approximately 40,000 participants in ten countries in Latin America and Europe. Although the reasons are not yet known, the lower efficacy could be related to the fact that, in contrast to Pfizer-BioNTech and Moderna, the company did not modify the chemical composition of the mRNA.
Novavax publishes a first study that demonstrates the safety, immunogenicity, and efficacy profile of its COVID-19 vaccine when co-administered with seasonal influenza vaccines.
2.7 billion doses have been administered globally. Less than 1% of people in low-income countries have received at least one dose. In an interview with Science, WHO Director General Dr. Tedros talks about his exasperation at this vaccine inequity, which is leading to a two-track pandemic. South America is COVID-19’s global hot spot, with 8 times the world’s death rate, but cases are rising at an alarming pace in many African countries.
[Evidence published between 09/06/2021 and 15/06/2021]
Looking for bat viruses
Researchers in the Chinese province of Yunnan province discovered 24 new coronaviruses in bats, including what could be a very close relative to SARS-CoV-2
More on Delta
Data from England and from Scotland indicate that Delta (B1617.2) is 40-60% more transmissible than Alpha (B1117) and the risk of hospitalization with is 2x higher in those with the Delta variant as compared to Alpha. Two doses of the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines were highly effective (96% and 92%, respectively) in reducing the risk of SARS-CoV-2 hospitalisation in people infected with the Delta variant. No rise in reinfections is observed for the moment.
According to sources from England, the Delta variant may be associated with different symptoms than the original variant. The most frequent symptom now is headache, followed by sore throat, runny nose, and fever (more like a “bad cold” in young people).
Senescent cells become hyperinflammatory in response to pathogens, and aged mice were more disposed to severe inflammation and death from infection with a coronavirus related to SARS-CoV-2. These findings would help to explain why elderly and chronically ill patients are especially vulnerable to COVID19.
Two more studies point to a robust and long-lasting immunity after infection. One study found long-lasting plasma cells (which produce anti-Spike antibodies) in the bone marrow of patients 7-8 months after infection, even in those who experienced mild symptoms. Another study found that virus-specific B cells remain relatively stable 6 to 12 months after infection, and that one single vaccine dose can induce high levels of neutralising antibodies effective against all circulating variants.
Anticoagulants and COVID-19
Aspirin doesn't improve chances of survival for patients hospitalized with COVID-19, according to the RECOVERY trial. However, anticoagulants given as prophylaxis may increase survival of patients hospitalized with COVID-19.
More on vaccines
Another highly effective vaccine
Novavax announced Phase 3 results for its protein subunit vaccine: 93% efficacy against moderate or severe disease caused by circulating variants of concern, and 91% efficacy in high-risk populations (over 65 or with comorbidities). The study enrolled 29,960 participants in the U.S. and Mexico. A total of 77 cases were observed: 63 in the placebo group (of which 10 moderate and four severe) and 14 in the vaccine group.
Lower risk of infection
COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the Pfizer and AstraZeneca vaccines, according to a study in the UK.
Another study in Israel with over 6,000 individuals estimated Pfizer’s vaccine reduced the risk of infection by 61% two weeks after the first dose and 89% two weeks after two vaccine doses.
T cells and variants
A study of antibody and T cell responses from individuals vaccinated with Johnson & Johnson’s vaccine shows reduced neutralizing antibody activity against P.1 (Gamma) and B1.351 (Beta) variants, but T cell responses against all variants were similar.
[Evidence published between 02/06/2021 and 08/06/2021]
How dangerous is Delta?
Preliminary data from the UK suggests that infections with the B1617.2 (Delta) variant could be more likely to require hospitalization, but more data are needed to confirm this. The positive news is that its transmissibility is not as high as initially thought (40-50% higher than Alpha instead of 75% higher). Plus, full vaccination remains effective against disease caused by this variant. Only 3.7% of Delta cases occurred in fully vaccinated people. The Delta variant in England now accounts for 73% of sequenced cases.
Beware this summer
A study in collaboration with the SeqCOVID-SPAIN consortium shows that a variant (EU1) that emerged in Spain in early summer of 2020 quickly spread across Europe. This was not due to increased transmissibility but to more travel and less screening and containment.
Predictor of death
The presence of SARS-CoV-2 RNA in blood was identified as the most important predictor of mortality in patients with severe COVID-19.
Repeated testing of IgM, IgG, anti-RBD IgG, and NAb titers in 215 COVID-19 patients during 10 months shows a very small decline after 10 months (except for IgM), regardless of age or severity of illness.
Latest on treatments
Up the nose
A single intranasal dose of an engineered IgM neutralising antibody conferred prophylactic and therapeutic efficacy against COVID-19 in mice, even when infected with P.1 or B1.351 variants. The engineered IgM is >200-fold more potent than its parental IgG in neutralizing SARS-CoV-2 and all major variants, in vitro.
Under the skin
The FDA authorised the subcutaneous delivery of Regeneron’s antibody cocktail (REGEN-COV) in non-hospitalized patients, which showed it reduced of hospitalisation or death by 70% in high-risk patients.
The cocktail retains neutralization potency against all current SARS-CoV-2 Variants of Concern (VOC) and of Interest (VOI), according to a study published this week.
And on vaccines
Also under the skin
An Australian team developed a high-density microarray patch that delivers SARS-CoV-2 spike proteins directly to the skin. One single dose of the patch induced good cellular and antibody responses in mice, even against circulating variants, and protected them against disease, according to a study that has not yet been peer-reviewed.
Four studies (not yet peer reviewed) posted this week show that a first dose of the AstraZeneca vaccine followed by a second dose of the Pfizer vaccine is well tolerated and induces potent humoral and cellular responses. Three of the studies (one from Spain, and two from Germany) did not include a comparison group vaccinated with two doses of AstraZeneca, but a fourth small study (also in Germany) did. This study showed that heterologous vaccination led to a significant 11.5-fold increase in anti-Spike IgG, as compared to the 2.9-fold increase after homologous AZ/AZ vaccination. It also induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, higher titers of neutralizing antibodies against the B.1.351 (beta) and the P.1 (gamma) variants of concern.
Some cases of myocarditis and pericarditis in young adults have been reported after vaccination with mRNA vaccines, more frequently after the second dose. In most cases, the symptoms improve rapidly after medications and rest.
More than 2 billion doses of vaccines have been administered worldwide. Poorer countries have received less than 1%.
[Evidence published between 26/05/2021 and 01/06/2021]
Not only deaths
A rough first estimate suggests that as much as 30% of the COVID-19 health burden could be due to COVID-induced disability, not death. Using the right indicators of disability and disease will help evaluate cost-effective strategies in different countries.
New variant names
The WHO announced a simpler naming system for SARS-CoV-2 variants. Each variant of concern or of interest will receive a name from the Greek alphabet. B.1.1.7, the variant first identified in Britain, will be known as Alpha and B.1.351, (first seen in South Africa), will be Beta. P.1, (first seen in Brazil) will be Gamma and B.1.671.2, the so-called Indian variant, is Delta.
Unequal viral loads
A German team analysed PCR samples of more than 25,000 cases with different symptom severities. They found that the youngest had a lower viral load than older subjects, and individuals who required hospitalization had higher viral loads over the entire time course. 8% of subjects had very high viral loads in the throat, and one third of them were pre-symptomatic, asymptomatic or mildly symptomatic.
A study finds that over 90% of critically ill COVID-19 patients had IgM antibodies reactive against 260 self-antigens expressed by different organs. These autoantibodies may be involved in the pathogenesis of severe COVID-19.
Two studies (not yet peer reviewed) show that vaccinated individuals provide indirect protection to their household members. A study in Finland with vaccinated healthcare workers shows that mRNA-based vaccines not only prevented infections among vaccinated individuals but also (although to a lesser degree) among unvaccinated household members (43% of indirect protection by 10 weeks after the first dose). Another study in Scotland shows that household members of vaccinated HCWs had a lower risk of contracting COVID-19 compared to those of unvaccinated HCWs.
The force of T cells
An analysis of humoral (antibody) and cellular immune responses in healthcare workers vaccinated with mRNA vaccines shows that, despite a decrease in neutralizing capacity of antibodies against the B1.351 variant, no differences in CD4+ T-cell activation were observed. These results indicate that the mutations in B.1.1.7 and B.1.351 Spike do not evade T-cell-mediated immunity induced by vaccination with the original S protein.
A clinical trial with Pfizer’s mRNA vaccine in 12-to-15-year-old recipients showed a good safety profile and high efficacy against COVID-19. The study included 2,260 adolescents. 16 cases occurred in placebo group and none in vaccinated group. The vaccine has been cleared by EMA for its use in children ages 12-15.
Moderna will also seek authorization to EMA after announcing similar results.
However, many health experts have been question ing the ethics- and the logic- of vaccinating teenagers in rich countries when vulnerable people in low- and middle-income countries have not been vaccinated. In this sense, Science identifies 4 actions to fight vaccine inequality, and how long this may take: i) donating doses through COVAX (weeks to months), ii) expanding production (months), iii) sharing knowledge (months to years), and iv) building plants worldwide (years).
[Evidence published between 19/05/2021 and 25/05/2021]
Vaccines versus variants
COVID-19 vaccines currently deployed in Europe are effective against variants circulating in the region, says WHO-Europe.
In effect, preliminary data released by Public Health England shows that vaccines remain highly effective (around 80%) against symptomatic disease caused by the B1617.2 (“Indian”) variant, but two doses are necessary to achieve protection. A slight drop in vaccine efficacy was observed for both vaccines: from 94% to 88% for Pfizer from 66% to 60% for AstraZeneca. The difference between vaccines may be due to the fact that the second dose of the AZ vaccine is given later and takes more time to reach maximum protection.
A little help from Apps
The number of cases averted by the NHS COVID-19 app was estimated to be between 284,000 and 594,000. The app was used by 16.5 million users (28% of the population) in England and Wales.
More on disease pathology
One stud shows that SARS-CoV-2 can directly infect and kill insulin-producing pancreatic cells, which could explain why some patients develop type 1 diabetes after COVID-19.
The other one shows a dramatic increase in autoantibodies targeting components of the immune system in severe COVID-19 patients, as compared to uninfected individuals. These autoantibodies could exacerbate disease severity, as observed in a mouse model of SARS-CoV-2 infection.
Some antibodies found in convalescent patients may actually enhance viral infectivity, according to a study. These antibodies, which target the N-terminal region of the Spike protein, were found at higher levels in severe patients.
Further evidence supporting long-lived immunity
Two studies published this week suggest the immunological memory after natural infection is long-lived. One showed a slow rate of decline of anti-spike antibodies as time progressed. The other found that even after mild infections, a robust antibody response is induced and plasma cells (which produce antibodies) are detected in the bone marrow 7 to 8 months after infection.
A Swedish study with a cohort of individuals who suffered mild COVID-19 shows that 26% of them presented at least 1 moderate to severe symptom lasting for 2 months or more, and 15% for at least 8 months. For around 10% of these individuals, these symptoms disrupted work, social, and/or home life.
Good news in children
A follow-up of paediatric patients who developed inflammatory syndrome associated with COVID-19 (MIS-C) shows that few sequelae were observed after 6 months, despite severe initial illness.
Queensland researchers have developed two peptide-based drugs that could prevent COVID-19 infection and disease. One peptide reduces viral entry by inhibiting viral interaction with the ACE2 receptor. The other one reduces viral replication by inhibiting viral interaction with a host protein. The researchers hope to start testing them in humans in a few months.
Another vaccine candidate
A vaccine that consists of virus-like particles and is produced in plants has given promising phase 1 and phase 2 results. The vaccine was well tolerated and induced good titers of neutralising antibodies (up to 10-fold higher than those in convalescent patients).
13,000 deaths avoided
according to estimates from Public Health England, vaccines have prevented 13,000 deaths in people over 60 years of age in England, up to May 9, 2021. Vaccine effectiveness against symptomatic disease was very similar for both Pfizer and AstraZeneca vaccines (55-70% after one dose and 85-90% after two doses).
[Evidence published between 12/05/2021 and 18/05/2021]
The sequencing gap
Researchers point out that there are not enough viral samples being sequenced globally to keep track of emerging variants. Wealthy nations are doing most of the sequencing, while variants are likely circulating unnoticed in many countries with high viral transmission. “It would be much more interesting to sequence the last 1,000 cases in the Central African Republic than the next 100,000 cases in Germany,” says one of the experts interviewed.
Markers that predict severe COVID-19 disease
Certain markers associated with the activation of the complement cascade (a part of the immune system that helps clear microbes and damaged cells) are elevated in patients with severe COVID-19, as compared to other non-COVID patients with respiratory failure, according to a study by Yale and Washington University.
Also, asymptomatic or mild disease was found to be associated with an early and strong response of CD8+ T cells and plasmablasts (that differentiate into antibody-secreting cells), and the absence of systemic inflammation, according to a study that analysed serial samples from 200 infected individuals with a range of disease severities. In contrast, hospitalized patients had systemic inflammation that was already evident after developing the first symptoms.
New vaccine candidates enter Phase 3
Inovio published safety and immunogenicity results of the Phase 2 trial (4oo participants) for its DNA vaccine against SARS-CoV-2. The vaccine was well-tolerated and induced good humoral and cellular responses.
Sanofi and GSK also announced positive results for the phase 2 clinical trial of their COVID-19 vaccine, based on recombinant Spike proteins. They said one single dose generated strong levels of neutralizing antibodies in recipients across all ages, but results have not yet been published. They will test two formulations in their Phase 3 trial - one targeting the original Wuhan strain and the other targeting the B.1.351 variant).
Preliminary data from the Com-CoV study in the UK, which is testing the benefits of combining doses of different COVID-19 vaccines, suggests that mixing AstraZeneca and Pfizer vaccine doses causes more moderate side effects (such as fever or headaches) than using the same vaccine for both doses. The adverse reactions however were temporary and there were no other safety concerns.
The ISCIII in Spain announced preliminary results for its CombivacS study, showing that a second dose of Pfizer 8-12 weeks after a first dose of AstraZeneca is safe and induces good levels of anti-Spike antibodies.
The EMA has said that Pfizer’s mRNA vaccine can be stored up to one month at 2-8 C (instead of only five days), which will facilitate the vaccine’s handling and roll-out in Europe and beyond.
[Evidence published between 05/05/2021 and 11/05/2021]
Counting the dead
A new analysis by the Institute for Health Metrics at the University of Washington suggests 6.9 million people worldwide have died from COVID-19, more than twice as officially reported. In certain countries such as India, Mexico, or Russia, the number of deaths has been dramatically undercounted. The analysis also estimates that roughly 2.5 million more people will die of COVID-19 in the next six months.
From interest to concern
Public Health England has decided to “upgrade” one of the three types of the Indian variant (B.1.617.2) from variant of interest to variant of concern, due to the observation that it may be spreading faster than the others, and as fast as the B117 variant. This B.1.617.2 variant does not harbour the E484 mutation associated with enhanced immune escape.
Few people carry high viral loads
Only 2% of infected individuals carry 90% of virions circulating in the community at a given time, according to a study that analysed saliva from SARS-CoV-2 positive individuals that were asymptomatic or presymptomatic. The study does not allow to determine whether everyone passes through a short time period of extremely high viral load. In any case, it suggests that at a given time, some people may be more infectious than others.
The secret lies in the speed
An analysis of humoral (antibody) immune responses in patients with COVID-19 with varying disease severities reveals that mortality does not correlate with the levels of anti-SARS-CoV-2 antibodies, but rather with the speed at which they are produced. Higher mortality correlated with slower seroconversion.
Beyond the receptor binding domain
A careful analysis of the antibody repertoire to the Spike protein in convalescent subjects shows that a high percentage of antibodies are directed against protein sequences (epitopes) outside the domain that binds to the ACE2 receptor. One of these epitopes (in the so-called N-terminal domain) is often mutated among emerging viral variants, suggesting these mutations have important implications for immune protection.
Vaccines work against variants
A single booster dose with of Moderna’s mRNA vaccine containing the sequence of the B.1.351 (“South African”) variant in previously vaccinated individuals increased titers of neutralising antibodies against this and the P.1 (“Brazil”) variant, according to the company.
However, updated vaccines may not even be necessary to fight these variants, according to real-world data from Qatar, where nearly all cases are due to B.1.1.7 or B.1.351. Two doses of the Pfizer /BioNTech vaccine was 90% effective against B.1.1.7 and 75% effective against B.1.351, for both asymptomatic and symptomatic infections. It was 97% effective against severe, critical, or fatal illness, for both variants. One dose provided much lower protection, particularly against the B.1.351 variant.
Furthermore, a study (not yet peer-reviewed) that followed convalescent individuals during 12 months indicates that immunity in these individuals will be long-lasting and that vaccination with the available mRNA vaccines should confer protection against circulating variants.
Expanding global access to vaccines
The WHO also approved China’s Sinopharm inactivated virus vaccine for emergency use. This approval will expand vaccine options for low- and middle-income countries. The vaccine’s efficacy for symptomatic and hospitalized disease was estimated to be 79%, all age groups combined.
A first step towards a pancoronavirus vaccine?
A vaccine consisting of nanoparticles composed of many receptor binding multimeric receptor binding domains of SARS-CoV-2 induced antibody responses in macaques, capable of cross-neutralizing bat coronaviruses, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. The study also shows that the current mRNA vaccines may provide some protection against future outbreaks of other related coronaviruses.
[Evidence published between 28/04/2021 and 04/05/2021]
An extensive review of more than 30 studies suggests that saliva is as sensitive as nasopharyngeal swabs for PCR-mediated SARS-CoV-2 detection, and much less costly. Thus, saliva samples could replace nasal swabs in most populations being tested.
A study in England shows that regular testing of a random population within the community can quickly detect SARS-CoV-2 outbreaks even if the number of infections is low. This surveillance at the community level could speed up public health responses.
Zooming in on COVID pathology
Several studies published this week look at the single cell level to get a better overall picture of the damage caused by SARS-CoV-2 infection. One study found profound alterations in different cell types obtained from the lung of people who died from COVID-19. Another study analysed single cells beyond the lung (kidney, liver, and heart and found similar results, while experiments with “intestines in a dish” showed that SARS-Cov-2 infection interfered with the immune response in the gut. Another single-cell study focusing on cerebral spine fluid identified SARS-CoV-2 antibodies that can also target neural antigens, suggesting that the neurologic sequalae of COVID-19 may have an autoimmune origin.
Behind the loss of smell
The loss of smell in many patients may be the results of virus that infects and persists in the human olfactory epithelium, which may in turn lead to prolonged inflammation, according to a study.
Obesity: risk confirmed
A study in the US found that, at a body mass index (BMI) above 23, there is a linear increase in COVID-19 hospitalisation and death. The risk was particularly notable in people younger than 40 years and in people of Black ethnicity. Another study with over 70,000 patients in Mexico shows that obesity alone increased almost three-fold the risk of dying of COVID-19. Having other diseases such as diabetes increased the risk even further.
A select group of superneutralisers
A study in convalescent individuals shows a large variation in the capacity of their antibodies to neutralise the SARS-CoV-2 virus. Around 3% were “superneutralisers”, 21% were high neutralizers, 45% were average, 10% were low and 20% were non-neutralisers.
One dose, two doses
An analysis by the US CDC shows that one vaccine dose decreased hospitalisation of adults above 65 years by 64%, while both doses (full vaccination) decreased it by 94%.
A study with healthcare workers shows that individuals who were previously infected produce neutralizing antibodies that are effective against B.1.1.7 (“British”) and B.1.351 (“South African”) variants after one vaccine dose. In contrast, healthcare workers without history of infection showed reduced immunity against these variants after one single dose, confirming the need for two doses in these individuals.
According to a modelling study, one-dose strategies may reduce infections in the short term but may increase the potential for viral evolution if the immune responses are suboptimal and the virus continues to replicate in some vaccinated people.
Vaccines and transmission: much-awaited results
A study in England shows that one single dose of the Pfizer or AstraZeneca vaccines can cut household transmission by 50%. The study was the first to follow household contacts of infected individuals who were previously vaccinated or not.
[Evidence published between 22/04/2021 and 27/04/2021]
Transmission and children
A study of household transmission in Wuhan suggests that children and adolescents are less susceptible to SARS-CoV-2 infection but more infectious than older individuals. The findings also indicate that people are most infectious before developing symptoms (presymptomatic), but those who do not develop symptoms (asymptomatic) are less infectious than those who do.
In the absence of vaccines for children, the rapid identification of silent infections among kids will be key to breaking transmission chains, according to a modelling study with simulations.
The largest study to date, with over 70,000 hospitalised and 13,000 non-hospitalised COVID-19 patients, shows these patients suffer from several sequalae beyond the first 30 days of illness. These include respiratory, neurocognitive, gastrointestinal, cardiovascular, and mental health disorders, as well as fatigue, muscle pain and anemia. The risk of post-covid sequelae was highest among those with severe disease.
T cells lead the way
A study (not yet peer-reviewed) shows that T cell responses almost reach their maximal level already after the first vaccine dose, while antibodies need two doses to reach maximal levels. In fact, the magnitude of the CD4 T cell response after the first dose predicted the levels of CD8 T cells and neutralizing antibodies after the second dose.
A super antibody?
The analysis of a large number of B cells (which produce antibodies) from COVID-19 patients identified a series of potently neutralizing antibodies targeting the Spike protein. One of these antibodies was capable of fully neutralising the original SARS-CoV-2, the B.1.1.7 and B.1.351 variants, and even SARS-CoV. These antibodies could help design future treatments and vaccines with broad effect against coronaviruses.
One dose for previously-infected people
Yet another study shows that one vaccine dose is enough for previously-infected individuals. Naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. In recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose and did not increase after the second dose.
Vaccines and pregnancy
Preliminary findings of a study with 35,691 pregnant participants do not show any safety signals among pregnant persons who received mRNA Covid-19 vaccines.
More clues on the rare cases of thrombosis
The German team that first studied the thrombosis cases associated to the AstraZeneca vaccine provides further evidence on the possible mechanisms. Certain non-viral vaccine components related to the vaccine fabrication process may be favouring the production of antibodies that activate the platelets and trigger the thrombotic events. The paper has not yet been peer-reviewed.
1 billion doses and a stark gap
Only 15 months after the pandemic started, more than 1 billion (1000, 000, 000) vaccine doses have been administered worldwide. However, almost 9 out of 10 have been administered in high and upper middle-income countries. Only 0.2% of these doses have reached the poorest countries.
[Evidence published between 14/04/2021 and 21/04/2021]
This week, the world surpassed 3 million COVID-19 deaths.
Innocent until proven guilty
Another variant first identified in India (B.1.617) has raised some alarm because it presents two mutations in Spike (E484Q and L452R) that have shown evidence of antibody escape in the laboratory. But there is no evidence yet that the variant is more transmissible or can escape immunity. This variant deserves close monitoring but is not cause for concern, experts say.
Antibodies obtained from a convalescent COVID-19 patient were found to neutralise multiple SARS-CoV2 variants of concern and SARS. A team from Scripps Institute identifies the binding sites that facilitate cross-reactivity of these antibodies. These findings provide valuable information for designing vaccines and therapeutic antibodies against current and future SARS-related viruses
Lower risk of reinfection
A study with young, healthy US Marine recruits shows that seropositive individuals (i.e. with antibodies to SARS-CoV-2) had about one fifth the risk of subsequent infection as compared with seronegative individuals (10% vs 48%). Furthermore, infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants, meaning they are less likely to transmit.
More on vaccines
Data from Chile
Chile has announced that Sinovac’s vaccine is 80% effective against death and 67% effective against COVID-19 symptoms. Protection after one single dose was much lower. Almost 34% of the country’s population has been fully vaccinated, 93% of which have received the CoronaVac vaccine.
Responses in older people
Single doses of either the Pfizer of the Oxford / AstraZeneca vaccine in older people induce humoral immunity (antibodies) in most donors and are greatly enhanced in those who had a previous infection, according to a study (not yet peer-reviewed) in the UK. Cellular responses (T cells) are weaker but overall better with the AstraZeneca jab.
Yes, vaccines work!
The US CDC has identified some 5,800 cases of SARS-Cov-2 infection among more than 66 million fully vaccinated Americans. These “breakthrough” cases, which are defined as positive PCR results at least two weeks after patients the second dose, represent 0.008% of the fully vaccinated population. 7% of these infections (i.e. 0.00056%) needed hospitalization and only 7 fully vaccinated people died (0.00001%).
Meanwhile, a study on the effects of vaccination among nursing home residents, staff and healthcare workers in Catalonia shows an 85%-96% reduction in SARS-CoV-2 infection in all three cohorts, and even bigger reductions (>95%) in hospitalisations and mortality amongst nursing home residents for up to two months.
A pan-coronavirus vaccine?
Developing a vaccine capable of protecting against known and unknown coronaviruses (at least those pertaining to the beta coronavirus family) is possible, and has suddenly become a top priority. Many teams are currently using different strategies to achieve this goal.
Rare thrombosis cases
EMA’s safety committee concluded that the unusual thrombosis cases linked to the Johnson & Johnson vaccine were very similar to those observed with the AstraZeneca vaccine and that unusual blood clots with low blood platelets should be listed as very rare side effect of the vaccine. The agency emphasised that the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.
The first study to examine suicides in the context of the COVID-19 pandemic in several countries found that, in high and upper middle-income countries, suicide numbers remained largely unchanged or declined in the early months of the pandemic. The situation however may change as economic effects are felt.
[Evidence published between 07/04/2021 and 13/04/2021]
Neurological and psychological sequelae
A retrospective study with almost 250,000 COVID-19 survivors shows that 33% of them had a neurological or psychiatric diagnosis in the following 6 months, particularly those who had severe COVID-19. However, almost 90% of these patients had already received a neurological or psychological diagnosis before COVID-19, and the reported symptoms ranged from dementia and stroke to anxiety and insomnia.
Protection by natural immunity
A follow-up study with over 25,000 health care workers in England shows that those with a previous history of SARS-CoV-2 infection had an 84% lower risk of infection and a 93% reduction in symptomatic infections for at least 7 months.
Protection against variants
Yet another study shows that sera from convalescent individuals collected up to 9 months after symptoms effectively neutralized the dominant (D614G) and the B.1.1.7 variants, but had reduced or no activity against B.1.351. Similar results were observed with sera from vaccinated individuals. These results indicate that B.1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
Good news on treatments
Avoiding COVID-19 with antibody cocktails
Regeneron announced that its monoclonal antibody cocktail reduced by 81% the risk of developing COVID-19 after exposure. The study enrolled 1,500 healthy volunteers, each of whom shared a home with someone who tested positive for SARS-CoV-2. The mAb cocktail was given subcutaneously (instead of intravenously). In those who did develop the disease despite treatment, the symptoms resolved after one week, compared to three weeks for those on placebo.
Early treatment with an asthma drug
In a small controlled trial in the UK, patients were given budesonide (an inhaled corticosteroid commonly used for asthma) within 7 days of developing mild symptoms. Treated patients showed a significant reduction of clinical deterioration and reduced time to recovery as compared to the placebo group. In another, larger, clinical trial which involved more than 1,700 people at high risk (above 50 or 60 years of age), two daily inhalations of the drug also helped people at home recover more quickly from COVID-19. The results have not yet been peer-reviewed.
More on vaccines
The French pharmaceutical company Valneva reported positive phase 2 data for its COVID-19 vaccine candidate based on inactivated virus particles: it was well tolerated and induced neutralising antibody titres at or above levels seen in convalescent sera, as well as broad T cell responses. It plans to launch a phase 3 trial by end of April.
A study in Israel (not yet peer-reviewed) shows that the few infections observed in fully vaccinated people (two doses) were mostly due to the B.1.351 variant (first identified in South Africa), while those infected between the first and second dose were mostly infected by B1.1.7. These results confirm that two doses of the vaccine effectively protect against B1.1.7, and that B1.351 poses more of a risk but its spread can be curbed if mass-vaccination is coupled with non-pharmaceutical interventions.
Sinovac’s inactivated virus vaccine (CoronaVac) shows a 50% efficacy in preventing symptomatic disease but a 100% protection against severe disease, according to data from the clinical trial performed in Brazil. Another study (not yet peer-reviewed) confirms that at least one dose of the vaccine showed 50% effectiveness against symptomatic infection and 35% effectiveness against all infections, in a context where the P1 variant is widely circulating.
Two studies (one in Germany and one in Norway) provide a possible explanation for the rare thrombotic events associated with the AstraZeneca vaccine. In all the cases studied, researchers found antibodies that bind to and activate platelets. The mechanisms leading to the production or the activation of these antibodies are being investigated. Researchers will closely monitor this type of events with the other COVID-19 vaccines based on adenoviral vectors. In fact, the EMA is supporting studies to identify cases, look for potential causes or risk factors, and evaluate whether the risk can be cut by reducing the amount of vaccine administered in each dose.