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 26/06/2020 and 02/07/2020]
Lessons from the Italian town of Vo’
Vo’, in northern Italy, successfully managed to contain the epidemic by testing almost all of the 3,200 people living in the town for SARS-CoV-2 infection at two timepoints: at the start of the quarantine and fifteen days later. Findings reveal that 42.5% of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The study also found similar viral loads in symptomatic and asymptomatic individuals, suggesting they have a similar potential for transmission.
Infections in the USA: multiply by ten?
The number of coronavirus infections in many parts of the USA is more than 10 times higher than reported, according to data from antibody surveys released by the CDC. The survey includes people who had blood specimens taken between March and April for reasons unrelated to COVID-19, across 10 sites in different states.
The CDC also reported data collected through a telephone survey of 350 adults who tested positive for SARS-Cov-2 infection. Only half recalled having had contact with a COVID-19 case, and most contacts were a family member or a work colleague. About one third said they had not recovered their “normal” state of health three weeks after testing positive.
Neurological and neuropsychiatric complications
A UK study reports 125 COVID-19 cases with some kind of neurological or neuropsychiatric complication. The most common brain complication observed was stroke, which was reported in 77 patients. Almost one third of the patients showed signs of confusion or changes in behaviour.
Children: a large European study
Researchers looked at 582 children that tested positive for COVID-19, aged from three days to 18 years and across 25 European countries. A quarter had underlying health conditions. More than half of the children studied were admitted to hospital, and 8% needed treatment in intensive care. Children co-infected with other respiratory viruses were more likely to be admitted to intensive care. Of the four deaths during the study (0.69%), none were in children under 10, and two of those who died had pre-existing health conditions.
Immunity: higher than antibody tests suggest?
Researchers from the Karolinska Institute in Sweden systematically studied T cells (which orchestrate the immune response and antibody production) in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. SARS-CoV-2-specific T cells were detectable in individuals that developed no or mild COVID-19 symptoms, even in those who had no detectable antibodies. These results suggest that immunity to COVID-19 could be higher than antibody tests have shown.
In fact, seroconversion in asymptomatic patients might take longer, according to a South Korean study that found neutralizing antibodies in completely asymptomatic patients eight weeks after PCR diagnosis.
Discouraging results for an HIV drug
Lopinavir-ritonavir, an HIV drug, does not provide clinical benefit in hospitalised COVID-19 patients, according to a statement from the UK-led RECOVERY trial. There was no significant difference in the mortality or in the risk of progression to mechanical ventilation or length of hospital stay in the treated group as compared to the non-treated group.
The Recovery trial was launched in March to test the efficacy of: dexamethasone (a corticosteroid), lopinavir-ritonavir (an HIV drug), hydroxychloroquine (an antimalarial drug), azithromycin (an antibiotic), tocilizumab (an anti-inflammatory drug) and convalescent plasma (collected from COVID-19 recovered donors).
The trial has shown that dexamethasone reduces mortality in critically ill patients, while hydroxychloroquine and lopinavir-ritonavir provide no clinical benefit.
On another more positive note, a study from New York finds that people with HIV who contract Covid19 do not have worse outcomes than people without HIV.
China pushes ahead with its vaccines
China has approved CanSino’s adenovirus vaccine for military use for the next year, according to the New York Times coronavirus vaccine tracker, while the Sinopharm (inactivated virus) vaccine is starting phase III trials.
[Evidence published between 19/06/2020 and 25/06/2020]
How to avoid a second wave
A model developed to measure the relevance of non-pharmaceutical interventions (i.e. not involving vaccines or drugs) shows that deconfinement must be gradual and that individual behaviour (maintaining social distancing, use of face masks, hand hygiene) is key to avoiding future waves.
Miniature human organs to study viral infection
A study with cells and organoids derived from human stem cells shows that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection. Other cell types that also express the ACE2 receptor, such as endothelium, macrophages, and cortical neurons show low or no permissiveness to infection, suggesting there are other factors involved in viral entry (for example, the TMPRSS2 surface protein). The results obtained with pancreatic beta cells add to evidence suggesting the new coronavirus may trigger diabetes, although further studies are needed.
Detecting early transmission
Italian scientists have found traces of SARS-CoV-2 in wastewater collected from Milan and Turin in December 2019, suggesting the virus was already circulating in northern Italy before China reported the first cases. However, it does not automatically imply this was the source of the large epidemic in Italy, or if there were later introductions into the country. Along these lines, an analysis performed with samples from blood donors in Lodi, northern Italy, reveals that five samples from mid-February tested positive for SARS-CoV-2 antibodies, suggesting that the virus was already circulating a few weeks before the first patient was identified.
In the United States, a spike in Influenza like illness (ILI) suggests that there were over 8.7 million new undiagnosed SARS-CoV-2 infections between March 8 - 28, 2020.
Asymptomatic and mild infections: high percentage, less antibodies?
An analysis of 5,484 contacts of SARS-CoV-2 cases in Lombardy, Italy, reveals that roughly half of the contacts became infected. However, 73.9% of all infected individuals aged less than 60 years did not develop symptoms. The risk of symptoms increased with age - 6.6% of infected subjects older than 60 years had critical disease.
The blood donor study mentioned above also revealed that 28% of blood donors recruited between 18 March and 6 April, had been infected by the virus, but most did not develop symptoms or developed only mild symptoms. They also had lower levels of SARS-CoV-2 specific antibodies as compared to convalescent patients, a finding that is confirmed in several other studies:
A Chinese team studied 37 individuals who were diagnosed by RT–PCR for SARS-CoV-2 infection but without any relevant clinical symptoms. Compared to age and sex-matched patients with mild symptoms, the asymptomatic group had lower antibody levels in the acute phase of the infection. Two months after leaving the hospital, antibody levels decreased in both groups and 40% of asymptomatic individuals became seronegative for IgG antibodies.
Another study with 149 convalescent PCR-confirmed patients (most with mild symptoms) shows that most did not have high levels of neutralizing antibodies. Nevertheless, rare but recurring antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
T cells: a better indicator of viral exposure?
Detecting T cells specific for the virus may be a more sensitive indicator of SARS-Co-V-2 exposure than antibodies, according to a study. The researchers investigated humoral (antibodies) and cellular (T cells) immune responses against SARS-CoV-2 in seven households with at least 1 known positive Covid-19 case. Six of eight household contacts had blood samples with measurable T-cell responses, but no measurable antibodies.
Treatment with convalescent plasma
A study with 20,000 hospitalized patients that received COVID-19 convalescent plasma provides evidence that it is safe, and shows some effectiveness in reducing mortality, although it was not a clinical trial.
Indirect impact on cancer mortality
The COVID-19 crisis could cause 10,000 excess deaths from colorectal and breast cancer in the United States due to interruptions in diagnosis and treatment.
[Evidence published between 12/06/2020 and 18/06/2020]
The epicentre is in Latin America
Brazil and Mexico, along with the rest of Latin America is now accounting for half of global COVID-19 deaths (and likely more than that). Brazil’s total death toll has surpassed Britain to become the 2nd worst-affected country by COVID-19 in the world after the USA.
The importance of keeping distances…
A modelling study with data from over 40,000 participants in UK, shows that moderate physical distancing can reduce the proportion of cases that would need to self-isolate and of contacts that would need to be traced, in order to control SARS-CoV-2 transmission.
… and using face masks
An analysis of transmission clusters in Japan identified 22 probable primary case-patients for the clusters: most were 20–39 years of age and presymptomatic or asymptomatic at virus transmission.
Airborne transmission represents the dominant route to spread the disease, and the use of face masks shaped pandemic trends in Wuhan, Italy and New York City, according to a study .
Global population at risk
About one in five individuals worldwide could be at increased risk of severe COVID-19 disease if they become infected, due to underlying health conditions. This risk however varies considerably by age. These estimates do not include socioeconomic factors, but they do provide a starting point for considering the number of individuals that might need to be protected or vaccinated worldwide.
Children: less susceptible to infection?
According to age-based transmission models, people under 20 years of age are at half the risk of SARS-CoV-2 infection than those over 20. Only 21% of those aged between 10 and 19 are likely to show symptoms, compared with 69% of people over 70 years of age. The author’s modelling also found that school closures had little effect on stopping viral spread. Similarly, a seroprevalence study in Geneva shows that antibody prevalence was significantly lower in children under 10 years of age or adults over 64 years of age.
On the other hand, the Kids Corona study by Hospital Sant Joan de Déu reveals that children have a prevalence of SARS-CoV-2 antibodies similar to that in adults, but most develop very mild symptoms. The study followed 724 children with a COVID-19 positive parent.
In any case, there is mounting evidence that healthy blood vessels protect children from serious effects of COVID-19, such as stroke.
A cheap corticosteroid to reduce mortality?
Dexamethasone, an anti-inflammatory corticosteroid, seems to reduce COVID-19 mortality in critically ill patients, according to an announcement by the UK Recovery trial. For patients on ventilators, it cut the risk of death from 40% to 28%. For patients needing oxygen, it cut the risk of death from 25% to 20%. However, the data have not been published.
Other news on treatments
Regeneron has launched clinical trials of an antibody cocktail for treating COVID-19. It will be tested as a therapeutic agent for COVID-19 patients and as a preventive therapy in high-exposure-risk groups.
Meanwhile, the US Food and Drug Administration has withdrawn an emergency approval for use of hydroxychloroquine as Covid-19 treatment .
Sleep during confinement
An online survey in Switzerland, Germany, and Austria and a survey with university students in the USA reveal that, overall, during the lockdown people had healthier sleeping routines, although the quality of their sleep was lower. Exposure to daylight and exercising may help increase sleep quality in these situations.
Mice for testing treatments and vaccines
Mice that express the human ACE2 receptor develop pneumonia when exposed to SARS-CoV-2 and provide a good model to evaluate therapies and vaccines against COVID-19.
[Evidence published between 05/06/2020 and 11/06/2020]
Restrictions including shelter orders and business closures prevented around 285 million cases in China and 60 million in the US, according to researchers at the University of California, Berkeley. Another study from Imperial College London estimated that strict shutdowns may have saved 3 million lives across 11 European countries.
Residual waters: an early alert
A retrospective analysis of residual waters of Barcelona shows that by January 15 there were detectable levels of the virus in the samples – 40 days before the first case was reported, according to University of Barcelona researchers.
Diagnosis by dogs?
The sweat odour of COVID-19-infected persons is different and can be detected by dogs, according to a study that has not yet been peer-reviewed.
Male hormones and COVID-19
All the epidemiological data confirm that COVID-19 mortality is higher in men than in women. There are several possible reasons for this, but an article in Science points to androgens as a major suspect. In the prostate, androgens induce expression of TMPRSS2, one of the molecules used by the virus to infect human cells. It is still not clear if this also happens in the lung, but a study in Italy showed that patients on androgen-deprivation therapy (ADT) were less to be hospitalized and to die. Another couple of studies associated baldness with severe disease in men, and the analysis of data from hundreds of male COVID-19 patients in UK showed a correlation between androgen levels in blood and severity of disease. Several veteran hospitals have started clinical trials with an androgen-suppressing drug in COVID-19 patients.
A study with macaques indicates that early initiation of remdesivir treatment in COVID-19 patients can prevent progression to pneumonia.
BTK is a protein (tyrosine kinase) involved in the activation of macrophages, which are part of our first line of immune defence. A study with a small number of patients with severe COVID-19 shows that treatment with a BTK inhibitor (acalabrutinib) can be beneficial in these patients. These results need to be confirmed with larger, controlled trials.
Three big trials, no efficacy in COVID-19 treatment or prevention.
Recovery, the largest trial yet, showed that treatment with hydroxychloroquine had no benefit for patients hospitalized with Covid-19. Mortality rates were similar among the over 1,500 patients who received hydroxychloroquine and the more than 3,100 patients who did not (25.7% and 23.5%, respectively).
Two other trials show that hydroxychloroquine is not effective in preventing the disease either. The first study, performed in USA and Canada, sent drug or placebo by mail to over 800 close contacts of confirmed cases. Twelve per cent of those that took the drug developed the disease, versus 14% of those who took the placebo.
The second study was performed in Barcelona’s Germans Trias i Pujol Hospital with more than 2300 people exposed to the virus. There was no significant difference between the number of people in each group who developed COVID-19, according to an announcement of trial leader Oriol Mitjà to Science .
A first controlled trial with convalescent plasma as therapy for COVID-19 showed no clinical benefit, although the number of patients was small.
The Imperial College is starting clinical trials for its “self-amplifying” mRNA vaccine in June, with 300 volunteers. If safe, it will conduct a 6,000-participant phase in October to test the vaccine’s effectiveness. This vaccine would require smaller doses than Moderna’s mRNA vaccine and less costly manufacturing facilities. The institute is creating an enterprise called VacEquity Global Health to make its vaccine available at the lowest possible cost in Britain, as well as in low- and middle-income countries.
The Oxford group has said it will start testing its vaccine in Brazil, in collaboration with Sao Paulo’s University. They will first test it in 1,000 highly-exposed volunteers.
The World Health Organisation has published a draft landscape on COVID-19 vaccines. There are currently 133 vaccines in development. Ten leading vaccines are already in human trials.