The coronavirus COVID-19 compendium - 10th April
In the past week, a much anticipated serology test for SARS-CoV-2 was developed, Ebselen was shown to inhibit the coronavirus protease, and modelling suggested that closing schools may do more harm than good by preventing healthcare workers from working
It feels like I have been writing about COVID-19 for at least a couple of years, but I only started this update two weeks ago. Back then, there were 1200 papers on the topic. There are now more than 3000.
In order to write this weekly update I have read the titles of 600 papers, of which 51 were worth writing up, below. Less than 10% of papers published on COVID-19 are original research, the remainder being fairly unoriginal commentaries and opinions, which I have to sift through to find the science. To read 51 research articles on a Friday morning (Good Friday indeed) is not the worst way to spend my time, but it has been difficult to avoid my sunny balcony.
I do not wish to wallow in self pity, for I consider it a privilege to help, and a service to the coronavirus community of virologists, many of whom I worked with when I was a virologist at Public Health England, the University of Reading, and Imperial College London. They are to be celebrated and honoured, and this summary is in some ways a weekly tribute to them. I hope it continues to be useful.
In a study the world has been waiting for, several serological diagnostic tests for SARS-CoV-2 antibodies were developed, including a plaque-reduction neutralisation and ELISAs against different antigens. They did not cross react with seasonal coronaviruses, although there was some reactivity with both SARS and MERS. Some commercial tests were included in the analysis, and were shown to be less sensitive.
Treatments and vaccines
A pioneering study in Nature used structure assisted drug design to identify existing drugs that may bind to and inhibit the coronavirus protease. Of these, Ebselen showed the strongest effect in vitro. A new pan-coronavirus anti-viral called N3, previously developed by the same group, was crystallised in complex with the viral protease, which allowed researchers to model drug interactions.
A new broad spectrum anti-viral is effective against the viruses that cause SARS, MERS, and COVID-19, as well as some bat coronaviruses. The ribonucleoside analog β-D-N4-hydroxycytidine leads to lethal mutagenesis of the viral genome.
Ivermectin, a widely prescribed anti-parasitic drug, kills SARS-CoV-2 in tissue culture, as do remdesivir, lopinavir, homorringtonine, and emetine, warranting further investigation of these FDA-approved drugs in human trials.
Convalescent plasma works
Convalescent plasma from recovered COVID-19 patients can be used to treat severe disease, according to a study of 10 patients who received transfusions. All tolerated the treatment, with symptoms disappearing with three days of treatment.
Vaccine for MERS
A vaccine for MERS coronavirus was developed, using parainfluenza virus 5 as a vector. It protected mice from a lethal infection and so may be modified as a COVID-19 vaccine.
Schools: to open or close?
Should schools close or stay open? 29% of US healthcare workers have childcare obligations and a new modelling study in The Lancet Public Health shows that closing schools could cause more harm than good, due to a potential 15% reduction in the healthcare workforce.
Modelling the outbreak
A massive study of more than 8000 cases of COVID-19 in China outside of Wuhan showed that the time from symptoms to hospital admission decreased from 4.4 days to 2.6 days from January to February. They also showed that after 8th February the epidemic was shrinking in China, with the reproductive number below 1, showing the power of social distancing and isolation.
Flu was really COVID-19
A re-analysis of swabs from suspected influenza-like illness in Wuhan, published in Nature Microbiology, found that 9 out of 640 were in fact due to SARS-CoV-2. This shows that there was community transmission of COVID-19 in Wuhan in early January.
Lack of transmission in hospital
A reassuring study from Hong Kong showed that a COVID-19 patient failed to infect any of the dozens of medical staff and patients who had contact with him in Queen Elizabeth Hospital. This shows that the virus does not spread through airborne transmission, and can be stopped by basic infection control measures, giving hope to hospital workers across the world.
Wuhan outbreak may have spread more quickly than thought
Less reassuring is a study that looked again at the spread of disease in Wuhan. Their modelling suggests that the outbreak doubled every 2-3 days, not every 6-7 days as previously thought. This would give the virus a reproductive number of 5.7, considerably higher than the generally assumed 2-3. Whether this number is relevant to the outbreak in other locations is unclear, but it will certainly focus minds.
COVID-19 in the USA
The first human-to-human transmission of SARS-CoV-2 in the USA, from a woman who visited China in January to her husband, is reported in The Lancet. None of their 75 contacts caught the virus. Similarly, a COVID-19 patient with mild disease in Arizona failed to infect any of their close contacts, all of whom were identified through contact tracing.
Outbreaks across the world
An epidemiological study of the COVID-19 outbreak in Huangshi showed that the case fatality rate was 3.7%, lower than in Wuhan, with 83% presenting with mild disease.
An outbreak of COVID-19 in a care home in Washington State showed the importance of asymptomatic and presymptomatic individuals in viral spread, as did a study of the early outbreak in Vietnam, and another study in Zhejiang. Droplet transmission of the virus was responsible for an outbreak in an air-conditioned restaurant in Guangzhou.
14.5% of COVID-19 patients discharged from a Chinese hospital, who had tested negative for the virus, subsequently tested positive again. The return of viral RNA, and some symptoms, late after infection, presents a challenge to discharge policies.
SARS-CoV-2 RNA was detected in blood from four blood donors in Wuhan, who had donated in January and had no symptoms. Thankfully, no samples from February tested positive, suggesting that control measures were effective. Viral RNA was detected in the stool of an asymptomatic child, showing that this could be useful for diagnostics, but also potentially have a role in spread (although live virus has so far not been detected).
No vertical transmission
A pregnant woman did not pass on SARS-CoV-2 to her child, either in utero, or during delivery, showing that vertical transmission is unlikely.
Ferrets as a model
Ferrets can be infected with SARS-CoV-2 and seem to show similar disease to humans, allowing this to be used as an animal model to test new antivirals and vaccines.
A paper from Ian Wilson's group, published in Science, provides the crystal structure of a neutralising antibody from a SARS patient in complex with the SARS-CoV-2 receptor, revealing a highly conserved cryptic epitope. Antibodies against SARS conveniently bind to both SARS-CoV and SARS-CoV-2, the cause of COVID-19. Further understanding of this cross-reactive epitope may allow the development of a universal coronavirus vaccine, although that is likely some way off.
SARS‐CoV‐2 enters human cells via ACE2, with a potential role for another molecule called TMPRSS2. A study of human lung tissue found that ACE2 and TMPRSS2 are mainly expressed in bronchial transient secretory cells.
Surveys and social media
Lifestyle changes due to COVID-19
An online survey shared on social media received more than 9000 responses describing how life had changed for people in the USA. The most common lifestyle changes were handwashing, avoiding social gatherings, and stockpiling food. 19% were in social isolation.
Misinformation is rife
A rapid online survey given to 3000 people in the UK and 3000 in the USA found that there were common misconceptions about how COVID-19 spread and who was most at risk. Misinformation about COVID-19 is rife on social media, according to a study from Iran.
Face masks cause skin reactions
As well as causing headaches, face masks also cause skin problems, with 75% of doctors and nurses who responded to a survey reporting adverse skin reactions, much higher than under normal working conditions.
Why do COVID-19 patients lose their sense of smell?
A detailed case study of a COVID-19 patient with loss of smell showed that this was due to inflammatory obstruction of the olfactory clefts (not nasal obstruction), preventing odorants from reaching the olfactory epithelium. They recommend that corticosteroids are not used. Similarly, a study of 417 mild and moderate COVID-19 patients found that more than 85% had olfactory and gustatory dysfunctions.
Risk factors for severe disease
A large study of more than 1500 intensive care unit patients in Italy showed that the majority had at least one comorbidity, and most were older men. 99% required respiratory support and 11% needed ventilation. A similar study in China found that hypertension, diabetes, and coronary heart disease were the most common comorbidities with fatal cases of COVID-19. Another study described exacerbation of psoriasis in a COVID-19 patient, most likely due to treatment with hydroxychloroquine.
Coagulopathy, conjunctivitis, and co-infections
A patient with Covid-19 and coagulopathy, antiphospholipid antibodies, and multiple infarcts was described. Another case of COVID-19 conjunctivitis was described, showing again how the eye can become infected. A possible case of COVID-19 meningitis showed detection of viral RNA in cerebrospinal fluid.
Mass screening of children in hospitals in Madrid found 41 children with COVID-19 disease in March 2020, again mostly mild, representing 0.8% of cases in the Madrid region. No children died, and two had co-infections with influenza B virus. Clinical findings of 11 patients in Thailand also found that two had co-infections: one with adenovirus, another with influenza A virus.
What are the most commons symptoms?
The most common symptoms of COVID-19 in non-critically ill patients were fever (75%) and cough (52%), according to a study of more than 1000 people in a Fangcang hospital. In South Korea the most common symptoms of COVID-19 were cough (29%) and sore throat (29%), followed by fever (25%). Diarrhoea was not common (11%), but not rare either. Two mild COVID-19 cases from a Japanese cruise ship were described, as well as CT scans from the first Brazilian patient that I have seen published.
The clinical course of 344 intensive care patients in China was described, as were the clinical features of 102 patients in Wuhan, 9 children with mild disease, and a study of 25 fatal cases in Wuhan.
These body parts are not affected
It's always nice to end this briefing with some negative results, which are often harder to publish, but just as important as positive findings. Our first negative study of the week showed that liver impairment is not a prominent feature of COVID-19. The second showed that SARS-CoV-2 was not found in the vaginal fluid of women with severe COVID-19 disease. This will, I'm sure, be a relief to many.