Coronavirus Research Tracking - 22 January
New vaccine trials, reinfection rates, asymptomatic transmission, mask effectiveness, and immune responses to viral variants
In this week’s Research Tracker results from vaccine clinical trials, assessing reinfection rates, frequencies of asymptomatic transmission, impacts of mask wearing, predicting disease progression, reports of long-ish lasting immunity, and testing the possibility of immune or vaccine avoidance by new variants.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Mixed results in Sinovac phase 3 trials
Sinovac reported results from its CoronaVac Brazilian trial through a press release. This is an inactivated SARS-CoV-2 vaccine, which does not need to be stored at cold temperatures. The trial, involving 9,200 healthcare workers, indicated an efficacy of 50.4%, which is much lower than the 90+ % for Moderna’s and Pfizer’s vaccines. The trial results are also lower than results from other trials of the vaccine but, as Nature reports, not surprising given the lower level of efficacy and smaller scale of the trials.
However, 50% efficacy is still a good level of protection for a vaccine, and CoronaVac is also being distributed in several countries.
Janssen/Johnson & Johnson vaccine phase 1/2 trial
Results of a Phase 1/2 trial for Janssen’s vaccine were published in the New England Journal of Medicine. This is an adenovirus-based vaccine containing the SARS-CoV-2 spike protein. The trial involved 805 participants, and adverse effects were relatively minor. The majority of people vaccinated developed CD4+ T cell responses within two weeks, indicating the vaccine stimulated an immune response.
Some participants received one dose, while others had two. Research is still underway to compare the effectiveness of single versus double doses.
Reinfection with SARS-CoV-2 is rare
Reinfection by Covid-19 is rare, based on two studies.
The SIREN study (not yet peer-reviewed) in England followed for five months over 6,000 healthcare workers who already had antibodies for SARS-Cov-19 or confirmed previous infections. It detected 44 (0.7%) possible or probable reinfections, compared to 318 infections in 14,173 participants (2.2%) who were not previously infected.
“Possible” reinfections were determined by showing two positive PCR tests at least 90 days apart, while “probable” reinfections required in addition more detailed serological data and/or genomic data from both infections to avoid confusing persistent viral genetic material with a new infection.
The authors calculated that those who had already been infected had a 83% lower risk of infection, and that the minimum median protective period following infection was five months.
Only about 30% of the people with possible re-infections reported any symptoms, compared with 78% of participants with first-time infections. A news item in Nature discusses this study.
A Qatari study (not peer-reviewed) monitored 43,000 infected people (based on the presence of antibodies against SARS-CoV-2) for up to 7 months. It found that over 90% did not become reinfected. The risk of reinfection was calculated to be 0.10%. Symptoms following re-infection were usually less severe than the original infection.
Asymptomatic people less likely to infect others
A review (not yet peer-reviewed) of 80 studies of transmission concluded that people with asymptomatic infections can infect others, but less frequently (with about 1% of cases infecting others) than those with symptoms (6%) or pre-symptomatic cases (7%).
The review found that most transmission events were associated with people living with the index case, or group activities such as sharing meals and playing board games.
A study published in The Lancet Infectious Diseases analysed transmission patterns in 27,000 households in Wuhan. It too found that asymptomatic individuals were much less likely to infect others, while pre-symptomatic cases were the most infectious. The authors calculated that asymptomatic individuals exhibited about 80% lower infectivity than pre-symptomatic individuals.
This study also found that people aged 60 years or older were at a higher risk of infection than other age groups, while children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older.
Infants (0–1 years old) were significantly more likely to be infected than older children, which may be due to their having a weaker innate immune system and closer contact with parents than older children.
Mask wearing is effective …
A review in the journal Med highlights several studies that demonstrate the effectiveness of mask wearing for reducing risks of Covid-19 infection. The authors recommend for basic protection a high-quality surgical mask or a fabric mask of at least two layers with high thread count.
A study in The Lancet Digital Health surveyed Americans about mask wearing. Of nearly 400,000 respondents the authors found that communities with high reported mask-wearing and physical distancing had the highest predicted probability of transmission control.
A commentary on this article notes that the evidence is clear that masks work. However, it also notes that mask wearing is a collective intervention and buy-in from society is necessary for success.
… but it’s not sufficient in reducing infection risks
A study in Vermont (which has a relatively low infection rate for the US) published in the JMIR Public Health Surveillance assessed infection risks by surveying nearly 1,700 people about their work and living situations, income, behavior, sociodemographic characteristics, and pre-pandemic health characteristics. This information was linked to 454 of the respondents who were tested for SARS-CoV-2.
The number of contacts with adults and older adults was the key factor influencing infection risk. Going out to work, living in an apartment (rather than a house), and regularly wearing a mask outside of work were associated with having more contacts. The authors speculate that mask wearing may provide a false sense of security that leads to people letting their guard down and so may make contact with more people.
A conclusion from this research is to improve public health communication to emphasise that wearing a mask in an outbreak is essential, but by itself not sufficient to prevent infection.
Course of Covid-19 appears to be determined soon after infection
A UK study (not yet peer-reviewed) monitored immune cell responses in 207 people with a range of Covid-19 severities over 12 weeks from symptom onset. Forty five healthy people were used as controls. It found that asymptomatic or mild disease was characterized by an early robust immune response, without systemic inflammation. Those with more severe symptoms had delayed adaptive immune responses, and systemic inflammation appeared soon after symptom onset.
The pathway to severe Covid-19 conditions appears to be determined very early in the infection course, with Tumor Necrosis Factor-alpha and Interleukin-6 being important drivers of the immune responses associated with severe Covid-19. Profound changes in immune cell types persisted for weeks or months after infection.
Viral load (based on nasopharyngeal swabs) did not correlate with disease development, but it did influence later severity.
Viral loads in saliva are a good predictor of Covid-19 outcome
A study from the US (not yet peer-reviewed) reports that the viral load in saliva is an accurate predictor of Covid-19 severity and death, and disease progression. Viral loads from nasopharyngeal swabs were a less accurate predictor. High saliva viral loads correlated with high levels of pro-inflammatory molecules. High levels of specific IgG antibodies correlated with lower viral loads, indicating a good humoral immune response.
Higher viral loads were associated with older age, male patients, heart problems, cancer and some forms of immunosuppression. The authors suggest that viral levels in saliva may indicate infection of the lower respiratory tract, and so be a better reflection of infection progress.
Saliva tests are as accurate as nasopharyngeal ones
Research published in JAMA Internal Medicine found that nucleic acid tests for the virus in samples from saliva were as sensitive and specific as similar tests for nasopharyngeal samples.
Reasons for sex differences in Covid-19 outcomes
A perspective article in Science discusses the potential physiological and genetic factors that may explain why males tend to be more adversely affected by SARS-CoV-2. Other infectious diseases also show a similar bias in impacts.
Long lasting and evolving immunity to SARS-CoV-2
Research published in Nature finds that while antibody levels and neutralizing activity generally decline over six months following SARS-CoV-2 infection, levels of receptor-binding domain-specific memory B cells remain constant. This indicates that the immune system is able to rapidly and effectively respond to re-infection for at least six months.
The memory B cells also evolved, enabling the production of more potent and broader acting neutralizing antibodies. This evolution requires exposure to viral antigens and the paper also found that viral RNA and protein was detectable in tissues of the gastrointestinal tract months after infection.
New Zealand study shows some antibodies persist for up to 8 months
A New Zealand study (not yet peer-reviewed) found that 99% of tested sera had anti-RBD IgG antibodies and 96% had anti-Spike protein IgG antibodies above baseline levels for 4 to 8 months after infection. Neutralising antibodies were also found in 90% of samples, with anti-RBD antibodies strongly correlated with neutralisation.
The authors suggest that anti-RBD antibodies could be measured from finger prick samples to monitor vaccine immune responses.
Effectiveness of vaccines against new variants
Following on from Monday’s Tracker, several more studies have examined whether the new viral variants are likely to be as well controlled by natural and vaccine-induced immune responses as earlier variants.
One pre-print paper reports that the B.1.1.7 variant was neutralised by sera from 16 people who were vaccinated with the Pfizer/BioNTech vaccine.
However, another study (also not yet-peer reviewed) found that antibody and memory B cells in sera from people who had been vaccinated with either the Moderna or Pfizer vaccines had reduced activity against viral variants with E484K or N501Y or the K417N:E484K:N501Y combination mutations. The authors suggest that the mRNA vaccines may need to be periodically updated (like flu vaccines) to remain effective.
A third paper (not peer-reviewed) tested whether the South Africant variant (501Y.V2 or B.1.351) is as effectively neutralised by convalescent plasma as other variants. It found that neutralising antibodies were less effective, and that the K417N mutation appears to have a significant role in this resistance. However, non-neutralising antibodies were found to remain active against the variant.
It is not yet clear how effective this variant is at evading immune responses.
A summary on Twitter about this paper’s results suggests that a reduction in neutralising activity may not have as large an impact for highly effective vaccines, such as Moderna’s and Pfizer, compared to vaccines with lower efficacy. However, the author also notes that planning for updating vaccines to respond to new variants would be prudent.
The main focus of research has been on antibodies that target the spike protein, but another study (not yet peer-reviewed) reports that antibodies that target the N-terminal domain part of the virus were also potent blockers of infection, and at least one of these antibodies can protect Syrian hamsters from infection.
The new variants also have mutations in this part of the virus, but the authors suggest that a cocktail of monoclonal antibodies that target different regions of the virus may provide broad protection.
See also the news item in the current issue of Science.
No studies have yet been published that examine whether the new viral variants affect T cell responses. This is an important area of research to understand the impacts on immunity. See some of the research highlighted in the 3 July and 20 November editions of the Tracker.