A new study published in The Lancet shows that sepsis was the most common complication in more than half of patients committed to the first Chinese medical centres that took in patients with Covid-19. In theory, this indicates that a future effective treatment against sepsis could potentially be positioned as a supportive treatment in order to decrease mortality as a consequence of viral infections such as Covid-19.
The retrospective cohort study published in The Lancet on 9th March was based on patient data from 191 patients who had been discharged from or died at two Chinese hospitals during the period between 29th December, 2019 and 31st January, 2020. The patients came from the disease’s epi centre in Wuhan, meaning that they correspond to the sub-group deemed ill enough to need continuous hospital care.
Of those patients, 62 per cent were men and 48 per cent suffered from underlying chronic conditions. The most common factor among them was high blood pressure (30 per cent), followed by diabetes (19 per cent) and coronary heart disease (8 per cent).
High median age among the deceased
The average age of all patients was 56 years, while it was 69 for those who later died, confirming reports that old age is a risk factor for Covid-19 mortality.
These data are supported by another recently published report from China Center for Disease Control. This report demonstrates that, based on 72,314 patients in China, the majority (87 per cent) were aged between 30 and 79. Only 8,1 per cent were in their 20s, 1,2 per cent were teenagers whilst 0,9 per cent were 9 years or younger. The report shows that 2,3 per cent of the confirmed cases died, but that mortality was as high as 14,8 per cent in individuals aged 80 or older and decreased dramatically with decreasing age. Of people in their 50s 1,3 per cent died. For individuals in their 40s the corresponding figure was 0,4 per cent whilst only 0,2 per cent aged 10 – 39 died.
A poorer treatment outcome in the elderly may partly be due to the weakening of the immune system that comes with increasing age and the fact that the risk for more prolonged inflammation increases. This can in turn cause permanent damage to the heart, brain and other organs.
Sepsis – a common complication in the most seriously affected patients
Another major difference between those who recovered from Covid-19, despite needing initial hospital care, and those who died as a result of the virus was their initial health status. Among the deceased, co-morbidity was significantly higher even before the factoring in the viral infection.
Among the disease complications due to the severe viral disease, sepsis was the most frequently observed, and it affected more than half of the patients. This was followed by respiratory insufficiency, acute respiratory distress syndrome (ARDS), heart failure and septic shock. Half of those who died contracted a secondary infection and / or hospital-acquired pneumonia.
Of the 191 observed patients, 112 developed sepsis and 54 of these later died while 58 recovered. The virus was measurable for between 8 and 37 days in the patients who survived and until the point of death in the 54 patients who died.
Virus infections and sepsis causes cytokine storms
Sepsis happens when the bloodstream is infected, and the body defends itself by initiating an inflammation and a massive release of immune boosting signals into the bloodstream. When the immune response becomes too powerful, it can lead to a so-called cytokine storm with septic shock and organ failure as a result.
Sepsis can occur in a few hours and people with impaired immune systems, elderly or those already sick, are extra vulnerable, which is in line with the patient group studied above. Sepsis is often caused by another infection such as seasonal flu or a coronavirus. Each year, 49 million are affected by the condition and of these, 11 million die.
One of the characteristics of severe viral infections such as SARS, MERS, avian influenza – and now, preliminarily, also of coronavirus – are cytokine storms that are also associated with sepsis.
Sepsis treatment being developed
Swedish Aptahem develops Apta-1, an emergency treatment for sepsis. Unlike today’s treatments, Apta-1 has anti-inflammatory, anticoagulant, anti-thrombotic and immune dysfunction-antagonising effects that address the complex interaction between coagulation and inflammation in sepsis. In animal models, Aptahem has been able to demonstrate significantly improved survival in sepsis and sepsis-like disease states.
In light of the findings from the population-limited Chinese study of hospitalised patients, there is a theoretical scope that an effective drug for sepsis could also be beneficial during major virus outbreaks, such as the ongoing Covid-19 pandemic. In such a situation, Apta-1 would be used to reduce the risk of organ dysfunction and multi-organ failure, and to reduce the mortality of, for example, seriously ill elderly patients. Apta-1 could thus potentially be used as a supportive therapy for complications associated with the virus outbreak, but not as a treatment for the virus itself.
So far, however, this line of reasoning is hypothetical and Aptahem’s drug candidate needs to undergo clinical development and be tested in humans to confirm the promising preclinical data shown in animal models of sepsis. Aptahem focuses on the course of sepsis itself, but this does not exclude future studies beyond this indication.
In a comment to BioStock, CEO Mikael Lindstam says:
»2COVID-19 has proven to be a formidable challenge for the global healthcare system, and today we do not know if and how the virus will mutate in the future. However, what we can see from this smaller cohort study and from the scientific literature is that sepsis is an underlying ’silent disease’ that kills many patients every day worldwide, in relation to several diseases. In this regard virus pandemics are no exception«
»Being able to quickly apply a treatment that has the properties that we have seen preliminary indications of Apta-1 could fill a medical vacuum in both emergency situations and in hospitals where sepsis tends to claim many victims. Aptahem is currently focusing on sepsis, but there is possibility for potentially expanding the indication. At present, no such decision has been made, but we are not ruling it out«
Also see: Aptahem on the potential for collaboration with the US military (4 March 2020)
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