I am on call at the Royal London Hospital and sitting in my office digesting some of my daily COVID-19 reading. However, something has just hit me between the eyes and I have to say wow aloud!
The paper and editorial below show you just how infective SARS-CoV-2 really is and why we are not going to win this battle for our vulnerable people without an effective anti-viral and/or vaccine. It also tells me that if we don’t get a vaccine things will not normalise for a very long time.
Who said the R0 (R-zero) for this virus was less than 3 and therefore we would get herd immunity at about a 60% seroprevalence rate? Not me!
R-zero or the basic reproduction number for SARS-CoV-2 is the expected number of cases infected by one case in a population where all individuals are susceptible to infection. The original calculations were based on symptomatic index cases and symptomatic contacts with positive swabs. The fact that a large number of people (possibly up to 50%) have now been shown to get asymptomatic infections and that the test for the virus is not 100% specific. This means that approximately 25% of cases with COVID-19 defined by clinical definition have negative nasopharyngeal (nose & throat) swabs; i.e. 25% of infected people who may be shedding are not detected with the swab test. Based on these assumptions I have estimated that in normal life (no social distancing) that the R-zero is likely to be somewhere between 6 and 7. This means that to get herd immunity, a point when natural transmission in the population stops, you need somewhere between 80% and 86% of the population to have immunity.
However, the study below just published in the New England Journal of Medicine makes me think this may even be an underestimate. In a well done ‘classic’ epidemiology study in a nursing home in Seatle, 23 days after the first positive test result in a resident, 64% tested positive for SARS-CoV-2; more than half (56%) of the residents were asymptomatic at the time of testing. Only half of these residents then went on to develop symptoms a few days later. A quarter of shedders never became symptomatic and most of these ‘asymptomatic shedders’ were shown to shedding viable virus. Tragically of the 57 residents who were shown to be infected with SARS-CoV-2 infection 15 died; a mortality rate of 26%.
Why is this so important? In short, a high or very high R-zero means that the government policy of relying on herd immunity to protect the vulnerable is not going to work.
Let me explain. Whilst we are socially distancing we reduce the R-zero of SARS-CoV-2 to less than 1 and hence the number of new cases falls and we flatten the curve. This is what is happening in the UK and many other countries at present. However, as soon as we stop the lockdown and allow social interaction the R-zero will rise above one and we will get more cases. But because this virus is so infectious we may need herd immunity to be well above 80% (possibly 90%) for the epidemic to peter out. At which time point the government is hoping to let vulnerable people remerge from self-isolation and feel confident that they will not be susceptible to being infected and dying from severe COVID-19.
The bad news is that 15.2% of the UK population is over 70 years of age (data from Age Concern) the government definition of the vulnerable population based on age. This is not taking into account all the other vulnerable groups who are less than 70 years of age, i.e. those who are obese and/or have diabetes, cardiovascular, respiratory diseases. This means that by the time we get herd immunity many more people will die from COVID-19. This is why the scientific community needs to push for anti-virals and an effective vaccine. But herein lies a problem.
To develop and test an effective vaccine we really need an epidemic to be in full swing, i.e. on the upside of the curve and not on the tail. A vaccine trial is like a drug trial; subjects are randomised to an active or SARS-CoV-2 vaccine arm or a comparator arm (placebo or another vaccine) and then you see whether or not there are fewer cases of COVID-19 on the active arm compared to the comparator arm. However, if there are too few cases developing COVID-19 because of social distancing, using face masks, hygiene measures, etc. it will take too long to get enough events or trial subjects getting COVID-19, to show the vaccine is working. This is why we the rich-world may need to go to parts of the world where social distancing etc. is not feasible and the R-zero remains high, i.e. the squatter camps, shantytowns, favelas or slums of the low and middle-income countries of the world.
We, the rich world, may have no choice but to take this low/middle-income route for the sake of the world. But if ‘we’ do take this route to develop an effective vaccine we have to make it ethical. We will have to offer these countries priority access to the vaccine. If we don’t it will be a travesty. I can imagine the headlines in the press if we don’t. ‘Vaccine Imperialism: How the Rich World Exploited The Poor!’
What are the implications for you if you have multiple sclerosis. If you are vulnerable you need to be prepared to self-isolate/shield for a very long time. If you are not vulnerable then you really need to prepare yourself for becoming infected with SARS-CoV-2 and getting COVID-19. I have a section on MS-Selfie that addresses this issue. I will be updating this section over the weekend as there are additional things you can do as an individual and as a family to help derisk your chances further.
I am sorry for bringing you bad news at the beginning of the weekend, but as always I feel it is important, to be honest, and frank.
The information in this post is quite complex so if you have any questions please feel free to ask.
Gandhi et al. Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19. NEJM April 24, 2020 DOI: 10.1056/NEJMe2009758
Arons et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. NEJM April 24, 2020 DOI: 10.1056/NEJMoa2008457
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.
METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.
RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide.
CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
CoI: none for this post