So what are the phases of Covid-19 infection? What is this about “long covid” and “longer covid” I heard on the BBC news yesterday? Well this is how I am looking at Covid-19 based on my clinical experience within a district general hospital in the UK, and from talking and listening to other infection specialists - I think we are all seeing the same patterns or phases. But this is most definitely NOT about Tiers… which is an entirely different discussion best had between politicians…!
Phase 1: The incubation period
After being exposed to any infectious organism there is a period of time before symptoms begin; this is the incubation period. The incubation period for Covid-19 is on average 4-5 days, although the range is from 3-14 days in some studies. This is not the same as the time from exposure to be being able to infect other people which can be shorter, and it is thought that infected people can be contagious up to 48 hours before they develop symptoms.
Some people do not develop any symptoms with Covid-19, about 13% in some studies, and this is thought to be more common in children and young adults than in older people.
Phase 2: The viral phase
The earliest symptoms of Covid-19 are non-specific and are due to the presence of virus within the upper and lower respiratory tracts as well as probably throughout the body. It is the virus and the body’s initial response to the virus that causes the symptoms.
Symptoms include fever, non-productive cough, muscle aches, tiredness, chills, headache, sore throat, loss of appetite, and loss of the sense of smell. Loss of sense of smell is pretty specific for Covid-19 and occurs in 30-85% of patients depending upon which study you read.
Importantly nasal congestion is not a symptom of Covid-19, and not the reason for the loss of sense of smell (which is due to viral damage of cells involved in smelling). This lack of nasal congestion will hopefully help us differentiate some of the normal winter coughs and colds from Covid-19.
Patients in this phase need to self-isolate for 14 days although most are not that unwell and the vast majority will clear the infection themselves without any need for specific treatment. This causes us doctors a bit of a dilemma. This is the phase where some of our new medications will probably have their best effect, including Remdesivir and experimental monoclonal antibodies such as those produced by Regeneron (and given to President Trump), but these drugs are unlicensed, expensive and may themselves have side-effects we don’t yet know about. The most recent publication from the World Health Organisation (WHO) states that Remdesivir’s effects on Covid-19 are modest at best… it does reduce duration of illness significantly (decreasing from 15 days to 10 days) but has little effect on mortality. Just so you know Remdesivir costs nearly £2,000 for a 5-day course and is still in relatively short supply!
The current UK recommendation is to start Remdesivir in patients with a confirmed Covid-19 result, who are admitted to hospital, and who require oxygen therapy. Therefore it’s often not started in Primary Care or A&E but rather after the patient has been in for a little while. However based on the fact that Remdesivir acts on viral replication it has been suggested it is given as early as possible to prevent the virus getting established and causing any damage. But who in Primary Care is going to afford/recommend £2,000 per patient to their CCGs on the off chance that that patient will develop severe Covid-19 rather than a mild illness? Unfortunately we aren’t yet able to predict which of our patients will go on to develop severe Covid-19 infections and therefore in whom we should be intervening early and using this drug.
Regeneron’s monoclonal antibodies are even more at the experimental stage of development, even though President Trump was used as a guinea pig, but these would also probably be most effective early on as they would be expected to neutralise the virus before any damage has occurred. I bet these are expensive as well.
So most patients in this viral phase get better but some go on to get really sick as their own immune system goes in to over drive, and these are the ones we see most often in hospital.
Phase 3: the immune phase
Those patients ending up in hospital with really severe Covid-19 tend to be those in whom their own immune system is starting to go out of control. The immune system itself starts to attack the lungs and other body organs causing damage. This usually occurs after about a week of the viral phase.
The term that has been adopted for this phase of Covid-19 is the rather dramatic “cytokine storm”. Cytokines are inflammation controllers and if you produce them in an uncontrolled way and at high levels they kick the immune system into overdrive which then causes damage.
This group of patients often have severe hypoxia (low oxygen), liver and kidney dysfunction, very high inflammatory markers such as C-reactive protein, Interleukin-6 and Procalcitonin, and high neutrophil to lymphocyte ratios. They often require organ support, especially mechanical ventilation, and the prognosis is guarded.
This is the group though that do much better if they are given steroids. It doesn’t seem to matter whether this is Dexamethasone or Hydrocortisone, as long as the immune system is dampened down to allow the body time to recover. Even before the RECOVERY trial was reported many of us saw dramatic responses in some of our sickest Covid-19 patients when they were given steroids. Clinical trials, and meta-analyses of these trials, show that steroids appear to reduce mortality in these patients by up to a third. Fortunately steroids are licensed, available and cheap!
The other drug that is being studied in this patient group is Tocilizumab, an Interleukin-6 blocking agent, which is also suspected to be able to damp down the cytokine storm. There are ongoing clinical trials to assess the benefit of Tocilizumab and whether its prolonged effect on the immune system (up to 3 months) may actually be harmful in the long term. Watch this space!
Phase 4: the clotting phase
About 2 weeks after the onset of symptoms people with Covid-19 start to be at risk of spontaneous clot formation, and they don’t have to have been that unwell initially. This can cause deep venous thrombosis (DVT) in the legs, but also clots in other blood vessels. If these clots either block major blood vessels or break off and fly into major arteries (e.g. pulmonary embolus or embolic stroke) then patients can die.
It is now standard practice to give hospitalised Covid-19 patients prophylactic low molecular weight heparin anticoagulation to try and prevent these clots from forming. A balance has to be struck between the risk of clot formation and the risk of spontaneous bleeding, and an individual patient-by-patient risk assessment should be done by the admitting clinical team.
Phase 5: Recovery phase
Okay, so some patients get better quickly and have few ongoing symptoms, but many patients who have had Covid-19 have ongoing issues with symptoms such as severe tiredness, malaise, muscle and joint pains, cough, shortness of breath, relapsing fevers and sleep disturbance. This has been shown in a recently published study by King’s College London and has been termed “long covid”. The study has shown that 1 in 7 patients have ongoing symptoms at 1 month, 1 in 20 at 2 months, and 1 in 45 at 3 months. The researchers found older people, women, a history of asthma and those with a greater number of different symptoms (>5) in the first week of their illness were more likely to develop “long covid”.
Covid-19 is not a trivial illness; many patients are severely debilitated by on-going and relapsing symptoms. Although there is nothing specific we can do as healthcare professionals to cure these problems we can help provide symptomatic relief with drugs like Paracetamol for fevers, Non-Steroidal Anti-Inflammatory drugs for severe joint pains, and some would advocate using other drugs like n-acetyl-cysteine for the ongoing chest symptoms and melatonin or antihistamines for the sleep disturbance. I think it is important to at least consider the options available for managing these symptoms but more importantly we as healthcare providers (and also peoples employers) should recognise and acknowledge that “long covid” or this prolonged recovery phase of the illness does exist and needs support, kindness and managing carefully.
The final big question is how long are recovering patients infectious for? Well essentially this depends on whether the patient has had a mild or severe illness and whether they are immunosuppressed or not. Based on what we currently know the figures are:
- Mild or not admitted to hospital – 10 days
- Severe, admitted to hospital or immunosuppressed – up to 20 days (this is still a bit of a controversial area and likely to change)
So this is MY experience with Covid-19 based on my clinical experience and a lot of reading and listening to new evidence. It’s what I have seen in terms of how patients present and what the course of a Covid-19 infection can look like and when the different treatments are likely to be of benefit. What’s your experience? What have you seen and do you also recognise these phases of the illness?
Do let us know what you want for future blogs… “Yes more on Covid-19” or “No way something different please”!?
I for one vote “No way”! Maybe a non-covid topic again next time then….