Coronavirus Research Tracking - 1 October - Non-vaccine edition

Long Covid, Covid mortality rates, viral origins

This week’s non-vaccine studies include the prevalence of long Covid, the high rates of Covid-19-related deaths, understanding what happens in the lungs in severe cases, more research into viral origins, and a correlation between authoritarian views and infection rates.

The tracker is shared with the COVID-19 Vaccine Media Hub.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Non-vaccine-related papers

Long Covid is not uncommon

A study involving 273,000 Covid-19 cases in the US found 57% had at least one of nine symptoms in the six months after diagnosis, with 36% reporting symptoms three to six months after Covid-19. Some symptoms (such as abnormal breathing) were more commonly seen in the first 90 days, and others (anxiety/depression) in the subsequent 3 months. 

Nearly 43% of patients who had recovered from influenza reported at least one long Covid symptom within the next six months. However, the nine symptoms were more common in Covid-19 cases than in people who had had the flu, so the results do not appear to be related to viral infections in general. The authors note, though, that they can’t exclude the possibility of people being more likely to report longer lasting symptoms after Covid than after the flu.

The risks of long Covid were higher for those who had more severe Covid-19, the elderly and females. However, cases were also reported by young adults who had had relatively mild Covid-19. 

The results are based on those who sought healthcare for longer lasting symptoms, so are not representative of all people who had Covid-19. The paper was published in PLOS Medicine.

A study from China found that 45% of 2,400 participants reported one of more Covid symptoms one year after discharge from hospital. The most common symptoms were fatigue, sweating, chest tightness, anxiety, and myalgia. More severe Covid-19 was associated with having more symptoms and a higher score on a chronic obstructive pulmonary disease assessment (indicating greater respiratory problems) one year later. The paper was published in JAMA Network Open.

Covid-19 mortality rates in an historical context

Covid-19 increased mortality rates to levels not seen since World War 2 in many European countries. This conclusion is based on life table calculations for 29 countries. Life expectancy at birth declined by more than 6 months in 27 out of 29 countries. Declines for males in the USA (2.2 years) and Lithuania (1.7 years) were the largest. 

Most of the decline is due to increased deaths of people over 60. However, in the US there was a significant increase in mortality for working age males. The paper notes that social disadvantage and inequalities in access to health care contribute to higher mortality within some groups in the US, which can be obscured by national statistics.

The authors note that some other data indicate that mortality rates in lower and middle-income countries are larger than the countries included in this study. The paper was published in the International Journal of Epidemiology.

Microbial differences in the lungs of patients with severe Covid-19

A lot of what we know about Covid-19 comes from studies of the upper respiratory tract and immune responses in the peripheral blood system. In cases of severe Covid-19 this can miss important changes and responses deeper in the body. But studying the lungs is harder.

A News and Views article Nature Microbiology makes this point when summarising a detailed study of microbial and immune responses in Covid-19 patients requiring mechanical ventilation.

The study, published in the same issue of Nature Microbiology, found that the number, diversity and metabolic activity of microbes in the lungs were associated with clinical severity and death. Greater diversity and activity correlated with patients who later died.  In contrast, SARS-CoV-2 and other microbial levels in the upper respiratory tract were not correlated with patient deaths. 

The result possibly reflects a weak immune response in the lungs of patients with severe Covid-19, rather than lung damage being due to an overactive immune response. SARS-CoV-2 levels in the lower respiratory tract correlated with mortality and lower IgG antibody levels.

The study involved 142 patients on mechanical ventilation. It used DNA and RNA sequencing to identify microbes and the genes being transcribed, rather than traditional microbe culturing methods. The authors highlight the need for further research into the interactions between microbes and host tissues to improve understanding of diseases such as Covid-19.

Susceptibility and individual variation in innate immunity

Differences in SARS-CoV-2 susceptibility may be partly due to individual variation in interferon-stimulated genes. People who expressed a membrane-bound version of one of these genes were 1.6 times less likely to require intensive care, or to die, than those where the alternate version of the protein was not bound. The authors note that there is considerable complexity in this group of genes and their expression, so a lot more research is required. The paper was published in Science.

Nanobodies show efficacy in animal trials

A nanobody from llamas is effective at neutralising SARS-CoV-2 in Syrian hamsters. Treated animals showed less weight loss, reduced lung damage, and reduced viral shedding compared to those which did not receive the nanobody.

The nanobody can be administered by nasal spray or injection. Only 6 hamsters were used for each treatment. Further trials are underway. Nanobodies are cheaper to produce and easier to administer than normal antibodies. The paper was published in Nature Communications.

Ivermectin study flaws

A letter published in Nature Medicine discusses flaws in studies of the effect of Ivermectin on Covid-19. The authors suggest that summary statistics from studies shouldn’t be used in meta-analyses. Instead all the data from the studies should be used, and individual patient data made available to others to examine.

Modelling protein structures improves understanding of mutational impacts

Structural modeling of antibody binding sites in the spike protein has identified how they may be disrupted by mutations. The results can help predict and understand the effects of new mutations, and help drug developments and treatments. The paper was published in Science.

Going from pandemic to endemic

The transition from a pandemic to an endemic disease is described in a paper published in Immunity. The authors note that several coronaviruses have previously become endemic in human populations. These show that after a period of immunity, people can be reinfected. 

Progress is finding SARS-CoV-2 closest bat virus ancestor

There has been speculation that SARS-CoV-2 evolved from bats via an intermediate host (such as pangolins). This is because the receptor binding domain in the closest known bat coronavirus is quite different. Evidence for a pangolin or other intermediate host however has been weak. Now a study of bats in North Laos has found coronaviruses with receptor bindings domain very similar to the one in SARS-CoV-2. 

Experiments demonstrated that this domain is able to bind as strongly to the human ACE2 receptor as SARS-CoV-2. This supports the hypothesis of recombinations between coronaviruses in bats living in limestone caves in southeast Asia leading to SARS-CoV-2. 

However, the results don’t solve all the origin questions. The distinctive furin cleavage site is not present in the bat viruses, and how the virus(es) may have reached Wuhan is not known. Further research is required to determine if people close to these caves have been infected with such viruses. The paper has not yet been peer reviewed

The paper is also discussed in a Nature News & Views article. 

Genomic analyses to predict future zoonoses

Genome analysis may help identify potential zoonotic viruses. The method involves machine learning and uses phylogenetic analysis along with training with evidence of previous zoonotic incidents or potential human infectivity. 

The method identified the risk of SARS-CoV-2 and related genomes without them being used in training the algorithm. The approach may help better target surveillance of potential zoonotic risks, although the authors note that large numbers of viruses are flagged as high risk. The paper was published in PLOS Biology

Authoritarian attitudes correlate with infectious disease levels

Higher regional infectious disease rates often correlate with more authoritarian attitudes. This relationship was seen for human to human infections but not for animal to human (zoonotic) infections. It supports the “Parasite Stress Theory of Sociality”, which proposes that at high infection rates people will avoid dissimilar others and show preferences for obedience and conformity.

The study was undertaken before the pandemic. The results come largely from short questionnaires in 47 countries. Longer surveys may lead to different conclusions. In addition, the authors note, “authoritarianism” is a spectrum rather than a clear exclusive state. The paper was published in the Journal of Social and Political Psychology.

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