COVID-19 and the ‘second week deterioration’


COVID-19 and the ‘second week deterioration’

As we manage patients with COVID-19 remotely and try to avoid face to face clinical contact unless essential, understanding the natural course of the infection and the potential complications is vital to give appropriate safety netting advice. With the lack of central ‘top down’ guidance, GPs and primary care teams are doing an amazing job in working out largely for themselves how to manage COVID-19.

A key paper in the Lancet 2020 has already taught us that patients typically have a mild, viral illness for a week and then may clinically deteriorate with respiratory distress syndrome and sepsis in the second week of the illness. This was based on data from hospitalised patients in Wuhan. Respiratory failure from ARDS is the most common cause of ICU admission and death. We therefore need to carefully safety net our patients in primary care for a possible ‘second week deterioration’, with a special emphasis on dyspnoea.

Clinical experience from GPs here in the UK, anecdotally from us and widely shared by GPs across social media, is that high fever, cough and respiratory symptoms are commonly encountered in the second and sometimes third week of the illness. This has thrown up a common question: is this all viral COVID-19 or should patients be given antibiotics to cover possible secondary bacterial pneumonia?

These patients might fulfil NICE clinical criteria for community acquired pneumonia but of course this cannot be extrapolated to COVID-19 and we just have no published evidence to help us. However, our clinical experience and that of other GPs is that some patients with fever and cough into the second week can respond quickly to antibiotics and the persistent fever is driven by secondary bacterial infection. Some local guidelines such as Barnet Primary Care Guide COVID-19 recommend antibiotic cover (amoxicillin + clarithromycin, or doxycycline) for patients with moderate symptoms. Other local guidelines are not recommending this approach, highlighting the uncertainty. However, what is clear is that we don’t want to miss treatable illness and once people end up in hospital most are getting antibiotics for that reason. I have got some local expert ID advice here in Oxford which supports this ‘low threshold for antibiotics’ approach.

New knowledge for some of us is that there is accumulating evidence Lancet 2020 that a subgroup of patients with severe COVID-19 may deteriorate rapidly in the second week with a ‘cytokine storm’. This is cytokine release syndrome, a systemic response to the virus when the immune system trips into over-drive with a systemic hyper-inflammatory response leading to a flood of immune cells and inflammatory proteins into the lungs and other organs leading to respiratory distress syndrome and multiple organ failure. Crucially cytokine storm can occur rapidly, like sepsis, leading to a rapid clinical deterioration and death. It is thought that some of the younger, fitter people who become very unwell and die from COVID-19 may have a genetic ‘host’ factor that puts them at greater risk of a cytokine storm. The sooner this syndrome is recognised, the better the prognosis.

So, whilst there is still a lot of COVID-19 uncertainty, useful leaning points for us are that:

  • Whilst the vast majority of patients in the community will have a mild illness with COVID-19, we need to be aware of the risk of the ‘second week deterioration’ and safety net appropriately
  • In patients with on-going fever and respiratory symptoms and signs, it is not possible to clinically distinguish between viral and secondary bacterial pneumonia so have a low threshold for antibiotic cover
  • Patients may deteriorate rapidly due to either sepsis or the cytokine storm syndrome, requiring urgent admission, and this needs appropriate safety netting


Dr Simon Curtis
2nd April 2020

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