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While the virus is still circulating throughout the country with 610 clusters detected since 9 May 2020 according to the Directorate General for Health (DGS), fears of a “second wave” are growing. In order to better understand the epidemic dynamics, several indicators are taken into account by epidemiologists and health authorities.

One of them, the reproduction rate of the R virus, is particularly studied because it provides valuable information on an important aspect of the epidemic: the transmissibility of the virus.

However, it cannot be interpreted in isolation to predict a possible resurgence of the epidemic, and must be analysed carefully in the light of other indicators of the health situation and linked to available epidemiological data. A reproduction rate greater than 1 cannot by itself be a precursor of a second wave.

What is the reproduction rate R?

The reproduction rate is an estimate (over the last 7 days) of the average number of people that a carrier of the virus infects. It is calculated from three parameters: the probability of transmission of the virus during a risky contact, the number of risky contacts and the duration of the generation interval between two infections (which can be assimilated to the duration of the contagious period).

For example, in France, on 15 March 2020 (shortly before the epidemic peak), the R was estimated to be 2.8 (i.e. a carrier of the virus infected an average of 2.8 people). It then decreased during the lockdown period, mainly due to the reduction in the number of at-risk contacts between people. For example, on May 11, 2020, when deconfinement was implemented, it was 0.8. In other words, an infected person was infecting less than one other person. Based in particular on these figures, the epidemic was then considered to be on the decline in France.

For several weeks now, the reproduction rate has been increasing. On 24 July 2020, the national reproduction rate had thus reached 1.3. Nevertheless, significant regional variations were noted (the most affected region being currently Brittany with an R equal to 1.87).

These figures reflect a rebound in the epidemic, but the R remains a volatile indicator, particularly sensitive to variations in the number of cases, even when these are small. For example, in the context of massive testing campaigns, it can rapidly increase because a large number of cases is suddenly detected.

Get a more complete picture

To better understand the resurgence of the epidemic, it is also necessary to look at other indicators transmitted by the DGS which, beyond the transmissibility of the virus, also reflect the severity of the health situation and provide additional information on the risk of a second wave.

Among them, the positivity rate of RT-PCR tests carried out. As of 24 July, it was 1.2%, a slight increase over the past three weeks. To this indicator should be added the incidence rate, which is an estimate of the number of new cases of Covid-19 diagnosed by RT-PCR tests, in relation to the number of inhabitants in each department.

Equally important for estimating the threat of a “second wave” and proposing optimal management of the epidemic, it is also important to understand the risk to the hospital system. This is why, among the indicators of epidemic recovery, the health authorities are interested in hospital tensions on beds in intensive care units. A figure which today reaches 8.9% and which corresponds to the average occupancy rate of beds in intensive care units by Covid-19 patients compared to the initial capacity of intensive care beds by region.

To go further, other elements also remain under surveillance, for example the presence of clusters (127 under investigation as of 24 July), tensions on supplies (equipment, medicines, etc.), or particular situations impacting the epidemic at a local level (epidemic co-circulation, social climate, population displacements, etc.). The analysis of all these indicators must be carried out in collaboration with actors in the field who are familiar with the situation in their locality.

The idea is to understand the dynamics of the epidemic as accurately and comprehensively as possible. Always with one objective: to limit the circulation of the virus and the number of cases on the territory, to preserve the health system, and to offer the best possible care to all patients.

Text written with the support of Inserm researchers Vittoria Colizza and Dominique Costagliola (Pierre-Louis Institute of Epidemiology and Public Health).

The composition and quality of non-pharmaceutical remedies based on Artemisia vary greatly due in particular to differences in the composition of the plant materials used. © Krzysztof Ziarnek, Kenraiz / CC BY-SA

Native to Asia, the Artemisia plant has been used in traditional Chinese medicine for centuries. Nearly 400 species of the plant now grow around the world, including Artemisia annua (annual mugwort). It is from this species that artemisinin is extracted, the active ingredient contained in the main antimalarial treatments used to treat the disease today.

For several years now, a debate has been raging in the scientific community about the efficacy of various non-pharmaceutical products based on Artemisia, such as infusions or herbal products. While some believe that these plant-based treatments have a role to play in the fight against malaria, particularly in endemic and remote areas, most researchers point to the lack of solid efficacy data.

The issue has not finished being discussed, especially since in the context of the Covid-19 pandemic, Artemisia is once again in the spotlight after the Malagasy president announced that a drink based on extracts from the plant, called Covid-Organics, could be a cure for the new coronavirus SARS-CoV-2.

Other African countries have already followed suit, including the Democratic Republic of the Congo, which wants to launch a clinical trial to measure the effectiveness of Artemisia annua herbal tea in the treatment of Covid-19. Canal Détox is taking stock of the situation in order to cut short the preconceived ideas about this plant described by some as “miraculous”.

Treating malaria and avoiding resistance

The treatment of malaria recommended by WHO is now based on artemisinin-based combination therapies (ACTs). The idea is to combine an artemisinin derivative, which acts quickly and effectively to eliminate parasites, with a drug to prevent their recurrence. The aim of this therapeutic combination is therefore to achieve a cure for the patient by completely eliminating the parasite from the blood to prevent it from evolving into a serious and potentially fatal form. It should be noted that artemisinin derivatives are no longer used alone as monotherapies since 2017 to prevent the emergence of resistant strains of the Plasmodium falciparum parasite.

In some malaria-endemic areas of the world, however, access to ACTs may be limited or too costly for patients. For this reason, the use of the whole plant containing artemisinin, particularly in the form of herbal tea, has been promoted by various actors. This natural treatment would work because of the presence of artemisinin and other compounds in the plant, interacting together to reduce the number of parasites in the blood. To eliminate all infectious agents in the blood, a sufficiently high dose of herbal tea would have to be taken, at the risk of a new malaria crisis.

Problem: the composition and quality of non-pharmaceutical remedies based on Artemisia vary greatly due in particular to differences in the composition of the plant materials used, which can be influenced by various genetic and environmental factors (temperature, time and place of harvest, etc.). Similarly, the method of preparation of herbal teas and the dose of active ingredient contained in them are not standardized, and may also vary from one product to another. If these treatments can therefore improve the symptoms of certain patients, uncontrolled and often insufficient doses can lead to therapeutic failure: not all parasites are eliminated, the disease may reappear.

Furthermore, artemisinin resistance also has a greater likelihood of developing and spreading when a parasites population is exposed to too low levels of this active ingredient. Finally, the potential toxicity of herbal tea has not been accurately assessed in all populations and safety data are still patchy.

Conducting clinical trials

Some believe that the use of the whole plant would have an added value compared to ACTs because compounds other than artemisinin could have activity against the parasite, or could act in synergy with it, improving its efficacy and bioavailability, for a more powerful anti-malarial effect. The administration of the plant would thus not be similar to a monotherapy containing only one active principle against the parasite, but to a therapy containing several active principles acting in concert. This would reduce the risk of parasites developing resistance.

Several studies, mainly in vitro, have been conducted on the subject. The results are still contradictory and difficult to apply to humans, but on the whole, they suggest that the activity of other plant components against P. falciparum, such as flavonoids, is negligible compared to that of artemisinin. Finally, while some compounds do indeed appear to work in synergy with artemisinin, the risk is that they are rapidly degraded in the herbal tea.

To test the efficacy and safety of these non-pharmaceutical therapies, rigorous clinical trials are necessary. The main studies of the in vivo efficacy of Artemisia extracts have mainly been carried out using animal models of malaria. The results are of definite interest and advance research, but they cannot be applied as they stand to humans.

Clinical studies that have been conducted, while they appear to rule out the risk of adverse effects at this time, have often been conducted on a small sample of patients, with many methodological biases and/or too short a follow-up period, thus compromising the significance of the efficacy results.

Further research efforts are needed to resolve this debate. As a first step, it would be crucial to conduct better quality studies to test the hypothesis that the plant, when administered as a herbal tea and in sufficient quantity, contains several active ingredients against the parasite, acting or not acting synergistically. It is also clear that the debate cannot be resolved without new therapeutic trials based on more robust methodology and good clinical practice, including populations particularly at risk for malaria, such as pregnant women and children.

What about Covid-19?

While it is mainly another anti-malarial drug, hydroxychloroquine, that has been the talk of the town in the midst of the Covid-19 pandemic, the debate on the efficacy of Artemisia annua against Covid has also been launched following the announcement by several African governments expressing interest in the Malagasy remedy Covid-Organics and in general in this plant in the treatment of the disease.

This interest in Artemisia in the context of coronavirus epidemics is not new. Already during the SARS epidemic in China in the early 2000s, studies had highlighted the antiviral properties of the plant’s extracts. Clinical trials on the effects of traditional Chinese medicine (including the use of Artemisia) had been conducted. Positive effects had been reported on some patients, although their methodological rigour had been criticized.

The idea was recently echoed in an editorial published in the journal Nature Plants in March, suggesting that some herbal treatments could be interesting complementary therapies to drug treatments. However, this hypothesis should be rigorously tested to ensure that plants do not interact with drug treatments given to patients.

In Germany, scientists have initiated in vitro studies to test the efficacy of plant extracts against SARS-CoV-2. The team evaluated its activity against SARS-CoV-2 in a monkey lung cell model, and suggested that Artemisia herbal teas would have an antiviral effect. The hypothesis of an anti-inflammatory effect of the plant has been put forward, but no clinical data have been provided to date to support it. These results should therefore be taken with caution, especially since no figures on the extent of the antiviral effect have been shared and nothing has yet been published, either in preprint or in a peer-reviewed journal.

The plant therefore opens up interesting avenues of research, but in the absence of robust data or longer-term studies with controlled doses of Artemisia annua extracts, it does not currently constitute a treatment against Covid-19. Very rigorous clinical trials, conducted in a multidisciplinary manner with a solid methodology are therefore more than ever necessary to reach a conclusion in this thorny debate.

Deconfinement is now well under way. At the heart of the system is a promise: massive testing of the population to isolate people contaminated by Covid-19 and stop the epidemic. But these tests, what exactly are they? Are they reliable? Will everyone be entitled to them? And will they tell us if we’re immune once and for all? Canal Detox cuts off false information.

Our knowledge of SARS-Cov-2 remains for the moment too fragmentary to affirm with certainty its seasonality, but every publication insists on the importance of preventive measures. © chuttersnap sur Unsplash

Will SARS-CoV-2 die out with the arrival of summer? With the current lifting of lockdown restrictions, some are hoping that the warm weather will herald a decrease in the R0, as is the case with other viruses whose transmission is better documented, such as those of seasonal influenza.

The issue of viral seasonality has long been studied by scientists, but many questions remain. Some viruses are linked to epidemic peaks at certain specific periods of the year: not just influenza but also poliovirus which, in the absence of vaccination, leads to an increase in the number of cases of polio, particularly in summer and autumn. The rubella virus is associated with an increased number of infections during the months of April and May. Generally speaking – and as shown by a study published in The Lancet Infectious Diseases  in 2004 following the SARS epidemic in China – seasonality can be observed with most well-established respiratory viruses, appearing in the population in a cyclical manner. Given the lack of necessary data, this trend is a little less clear when it comes to emergent viruses such as SARS-CoV-2.

The seasonality of the coronaviruses

Research published on the other human coronaviruses nevertheless makes it possible to pinpoint useful avenues for understanding how the spread of SARS-CoV-2 could evolve during the summer. A study published at the beginning of April in The Journal of Infectious Diseases looked at four of the seven types of coronavirus that are known to infect humans and which are responsible for mild respiratory diseases. The authors identified 993 infections with these viruses in the USA between 2010 and 2018 – infections which had all been observed between December and May, with a peak in January and February.  This research echoes a study published in 2018 that looked at MERS-CoV infections in the Middle East between 2012 and 2017, showing that a certain seasonality of the virus can again be observed, with a peak between April and June.

It is therefore possible to imagine that the SARS-CoV-2 epidemic will also progress in a differentiated manner according to the seasons. A study published in Science is also suggestive of this. Based on data available on the seasonality of coronaviruses OC43 and HKU1, which are associated with common colds and in some cases pneumonia, the researchers modelled the possible spread of SARS-CoV-2.

The results suggest that this virus is capable of causing epidemics at any time of the year in the absence of social distancing measures or lasting immunity, but that the autumn and winter seasons are more conducive to a major resurgence in the number of cases.

Environmental and behavioral factors

What are the factors that explain the seasonality of certain viruses? This is a key question if we are to better understand the spread of infectious diseases and predict epidemic peaks over the course of the year. To learn more about the seasonality of SARS-CoV-2, it is necessary to examine various environmental and biological factors influencing the epidemic flows, climate, population behaviors, individual immune system fluctuations over time, and look at how these factors combine to promote transmission of the virus.

Several studies on the seasonality of viruses suggest that the climate and weather conditions could play a role. In temperate environments, a cold, dry winter climate is thought to be linked to the increased transmission of certain viruses.

Concerning SARS-COV-2, a Chinese study published in Science of the Total Environment at the end of April, based on data collected in 166 countries suggests that temperature and humidity are factors to consider in the spread of the epidemic. A 1°C increase in temperature was associated with a 1.5% to 4.6% reduction in the number of daily new cases, and a 0.44% to 1.95% reduction in daily new deaths. Furthermore, a 1% increase in humidity was associated with a 0.51% to 1.19% reduction in the number of daily new cases.

According to the researchers, it must be noted that relying on the weather to improve the health situation is untenable: taking steps to prevent and control the sources of infection remains essential.

Added to these environmental factors are behavioral factors. The epidemic peaks observed in autumn and winter in the temperate climates can also be linked to the fact that people tend to spend more time in groups in confined environments during this period, thereby promoting contacts and exposure to viruses.

Some studies have also focused on the role of the immune system and how it varies with the seasons, whether or not it promotes infections. A weakening of the immune system in winter has been reported. A study by the University of Surrey (UK) in collaboration with Columbia University (US) has recently been launched in order to explore immune system changes according to the time of day and the seasons. Its objective is to open up new avenues in understanding the seasonality of viruses – including SARS-CoV-2 – and to identify whether administering vaccines at certain times of the day is more conducive to increased efficacy.

Our knowledge of SARS-CoV-2 is still too piecemeal to express with certainty whether or not it is seasonal, but what we can take away from the various studies is the importance of prevention measures. In the absence of certitude concerning collective immunity and without an effective vaccine, barrier measures, testing, and measures to control the epidemic continue to remain necessary.

Injection d’un vaccin avec une seringue pré-remplie. © Inserm/Depardieu, Michel

There has been a lot of talk over the past few days that the BCG tuberculosis virus is a promising ally in the war against COVID-19. But is this actually the case?

Interestingly, epidemiological studies have shown a correlation between rates of BCG vaccination and rates of COVID-19 morbidity and mortality. While most of these studies point in the same direction, a causal relationship cannot be concluded because major biases remain, particularly in terms of differences in living standards and healthcare policies between countries with high and low vaccination rates.

However, BCG had in the past been found in children to demonstrate a non-specific protective effect against infections, particularly respiratory infections. Live vaccines, such the BCG, measles and oral polio vaccines, are thought to have non-specific beneficial effects on some infections. Therefore it is possible that BCG could reduce the intensity of SARS-CoV-2 infection by stimulating the memory of innate immunity, the first line of immunity in the face of infection, and thereby inducing “trained innate immunity”.

With over 3 billion people vaccinated worldwide, BCG is very well known; a lot of data is available and its few contraindications (notably immunodeficiency) have been well characterized. It is also one of the most inexpensive vaccines in the world.

The researchers remain cautious: while BCG represents a very interesting prospect, it still needs to be explored within the framework of rigorous clinical trials. At present, there are no data recommending this vaccine as a means of protection against COVID-19.