Coronavirus disease (COVID-19) literally needs no introduction. It arrived in China as an unwelcome New Year’s Eve present and although it may have taken a few weeks for many to become aware of it, it has become an ever-present in our lives since. It is, as we write, creating an epidemic across the world and is now sweeping across Europe. It is impacting everyday life in many ways and this impact is likely to become much more marked in the coming months.
The single-strand RNA virus was named novel coronavirus 2019 (2019-nCoV), but due to its pulmonary consequences has been renamed as severe acute respiratory syndrome corona virus type 2 (SARS-CoV-2). It arises from mutation of a virus an animal reservoir, and origins from laboratory sources has been ruled out. It is related to the common cold virus and that causing severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Vaccines against these viruses are complex to develop, as illustrated by the fact we currently have no vaccine against the cold, SARS or MERS. The disease caused by SARs-CoV-2 is termed corona virus disease-19 (COVID-19) because the World Health Organization (WHO) was first notified of the localised surge in cases of pneumonia of unknown cause in Wuhan, China on 31 December 2019.
|Incubation||Up to 14 days|
|Most infective time||1–14 days|
The R0 describes the number of patients that a single patient will infect, in an uncontrolled setting. In the early stages of the epidemic it is believed that this figure may have been much higher, and R0s tend to reduce during the evolution of an epidemic. Control measures such as isolation and quarantine reduce R0. If these measures are effective, R0 may be reduced to below 1 and if this is sustained the epidemic will eventually wane and stop. As long as the R0 is >1, the epidemic will continue and there will be a geometric rise in cases. The impact of R0 is important. Influenza has an R0 of approximately 1.3: after 10 infective cycles this would lead to 14 infected patients from a single source. For SARS-CoV-2 after 10 infective cycles 59,000 patients would be infected. By comparison Ebola has an R0 of around 2, SARS of approximately 3 and MERS ranged from 1 to 5.7 until finally it reduced to <1.
Combined with this high R0 is a high virulence, so while many cases cause mild disease the mortality rate is many fold higher than that of even pandemic influenza. Various figures for mortality have been quoted, but each is dependent on the numerator and denominator chosen. Of the first 100,000 confirmed cases approximately 3,400 died: thus, the case fatality rate (CFR) is 3.4%. However, it is likely that many cases, mostly because they cause asymptomatic or mild symptoms, are not detected. If this ‘ascertainment rate’ is only 10% this means 90% of cases are missed and the infected mortality risk (IFR) is 0.34%. But these figures only consider those who are infected, and the burden of disease in the population is also dependent on the proportion of the population who are infected (attack rate): many estimates are around 30%, but some as high as 60% or even 80%. If the attack rate is 30% and the IFR 0.34% the overall mortality rate would be close to 0.1% (1 in 1000 of the population). Lead-time bias (the fact that many patients will undergo several weeks of treatment before dying) complicates factors further and currently means that the initial 3.4% CFR is likely to be an underestimate.
However, illness and mortality are not spread evenly across the population. A remarkable epidemiological report from the Chinese Centre for Disease Control (CDC), published only a few days after data collection finished reported differential mortality rates by sex, age, comorbidity.
|Baseline characteristics||Confirmed cases; n (%)||Deaths; n (%)||Case fatality rate, %|
|10–19||549 (1.2%)||1 (0.1%)||0.2%|
|20–29||3,619 (8.1%)||7 (0.7%)||0.2%|
|30–39||7,600 (17.0%)||18 (1.8%)||0.2%|
|40–49||8,571 (19.2%)||38 (3.7%)||0.4%|
|50–59||10,008 (22.4%)||130 (12.7%)||1.3%|
|60–69||8,583 (19.2%)||309 (30.2%)||3.6%|
|70–79||3,918 (8.8%)||312 (30.5%)||8.0%|
|≥80||1,408 (3.2%)||208 (20.3%)||14.8%|
|Male||22,981 (51.4%)||653 (63.8%)||2.8%|
|Female||21,691 (48.6%)||370 (36.2%)||1.7%|
|Hypertension||2,683 (12.8%)||161 (39.7%)||6.0%|
|Diabetes||1,102 (5.3%)||80 (19.7%)||7.3%|
|Cardiovascular disease||873 (4.2%)||92 (22.7%)||10.5%|
|Chronic respiratory disease||511 (2.4%)||32 (7.9%)||6.3%|
|Cancer (any)||107 (0.5%)||6 (1.5%)||5.6%|
|None||15,536 (74.0%)||133 (32.8%)||0.9%|
|Missing||23,690 (53.0%)||617 (60.3%)||2.6%|
|Critical||2,087 (4.7%)||1,023 (100%)||49.0%|
|Period (by date of onset)|
|Before Dec 31, 2019||104 (0.2%)||15 (1.5%)||14.4%|
|Jan 1–10, 2020||653 (1.5%)||102 (10.0%)||15.6%|
|Jan 11–20, 2020||5,417 (12.1%)||310 (30.3%)||5.7%|
|Jan 21–31, 2020||26,468 (59.2%)||494 (48.3%)||1.9%|
|After Feb 1, 2020||12,030 (26.9%)||102 (10.0%)||0.8%|
Mortality is higher in males and particularly in those aged over 70 and with cardiovascular disease. This is most notably a disease that kills the elderly: patients aged over 70 represented fewer than 1 in 8 of those infected, but more than half of those who died. Deaths in those under 40 years-of-age account for < 3%. Early evidence outside of China is not reassuring and epidemiological patterns and mortality rates seem to be broadly in line with those from China.
The main feature of severe COVID-19 disease is a viral pneumonia. This presents as fever, cough and dyspnoea progressing to hypoxaemia and respiratory failure and ARDS. Importantly it often presents at least a week after symptoms start. Cardiovascular co-morbidity as a risk for mortality and evidence of hypertroponinaemia, myocarditis and sudden cardiovascular death are notable but incompletely characterised. Acute kidney injury affects up to a third of patients.
Approximately 1 in 12 patients identified with the disease are hospitalised and 1 in 6 of these are critically ill. Of the critically ill approximately half require mechanical ventilation with more than half of these patients dying in most series.
What about the UK?
It is likely the epidemic will provide a daunting challenge to healthcare services for a period of approximately three months, a period we are just entering and which is likely to last until at least the end of May. The Chief Medical Officer estimates that 95% of cases will emerge over an 9-week period and 50% of cases in a 3-week period.
The UK’s critical care capacity, which is one of the lowest in Europe, may need to be expanded at many-fold during this surge in demand. This will seriously challenge provision of the 4-Ss of surge capacity in critical care: space; staff; systems; and stuff (equipment). Expansion of critical care capacity requires planning on a massive scale. Critical care provision for COVID-19 patients will likely displace all elective surgical work as critical care units are expanded in many hospitals into operating theatres and anaesthetists and theatre staff become the first staff to augment the insufficient numbers of critical care staff. Emergency surgery will still be required as will provision of critical care for non-COVID-19 illnesses.
Central to care of these patients is staff safety. In the early stages, patients will need to be isolated from other patients and as the epidemic progresses, they will need to be cohorted away from non-infected patients. Staff protection will require a system that includes, but is not restricted to, strict use of personal protective equipment (PPE). Donning and doffing PPE, using a buddy system to ensure this is optimised and engaging in low patient contact methods will need to become second nature for all healthcare workers. Anaesthetists and intensivists are highly invested in this topic because airway management, including tracheal intubation, is associated with some of the highest risks of transmission of infection. PPE is likely to be effective, so too are simple methods of decontamination of surfaces, equipment and ourselves with soap and alcohol-based cleaning processes.
PPE is an emotive and important subject. In China, healthcare workers experienced high rates of infection in the early period of the epidemic, when PPE use may not have been optimal. Over time this rate of infection has reduced but it remains significant, and there is soft evidence from both China and Italy that healthcare workers who are infected have a higher rate of severe and critical illness than the normal population, plausibly because of exposure to a higher viral load. There are likely to be limited PPE stocks and appropriate use of it is essential to maintain stocks throughout the epidemic.
What can we do?
If not already done, it is time to plan and time to act. Every hospital needs to plan its response to admission of its first patients with COVID-19 (phase 1 and 2), its first critically ill patient, and cohort of patients (phase 3). There is a pressing need for anaesthetists and intensivists to talk to each other, join forces and work together to organise and test the best response they are able. Collaboration in planning and delivery of critical care services in the predicted epidemic offers the greatest chance of weathering the storm. Given that the UK has half of the critical care beds per 100,000 capita of population than in Italy who have branched into the operating theatres already, there is a clear risk that our current resources will not suffice . There will also be great strain on PPE supplies and medical, nursing and other workforces.
The numbers do however provide some hope. The spread of the disease beyond Hubei province in China is wide geographically but the number of cases and deaths is rapidly diminishing. The considerable efforts made by the Chinese government and people to control the epidemic appear to have worked and R0 is now less than 1. On 8th March there were no new cases reported in China outside Hubei. Drug trials are underway and will be reported soon, there may be therapies that reduce the severity of illness or help manage critically ill patients.
In the meantime, it is going to be a very difficult period for frontline clinicians and all those we work with. Information and guidance changes often and rapidly. For anaesthetists and intensivists in the UK, a central source of information is likely to be a joint hub page run by all the key organisations who have joined together at this time for simplicity and clarity.
We encourage all readers to take stock at this time, get fit mask tests as a priority, familiarise themselves with their institutional PPE policies, practice and train for the management of COVID-19 patients, and agree robust local procedures for the likely epidemic to come.
Professor Tim Cook and Dr Kariem El-Boghdadly