Coronavirus cases are mounting but deaths remain stable. Why?

Something rather odd is happening in the two Europeans nations worst hit by Covid-19. The UK and Italy have a rising number of cases but a stable and very low number of deaths, even weeks after the cases started rising again.

At the time of writing, the UK records 1750 new cases daily and one death in a population of 67 million. With a roughly similar population and an average of 602 cases a day, Italy has had just over four deaths a day over the last month. The ratio of cases to deaths is nowhere near what it was at the height of the pandemic. The other notable feature is a shift of cases to a younger population. There can be several explanations for this trend. First, the viral agent may have mutated to a less virulent form. Although there are some published studies showing minor mutations, these are what you would expect from an RNA virus which is inherently unstable (think of the influenza viruses, which perpetually change their suits).

Second, we may have got better at dealing with Covid-19. Apart from dexamethasone in the small population admitted to intensive care units, there are no specific treatments for the disease, and as we are not observing a substantial increase in admissions or severity of the disease, this seems also an unlikely explanation.

Third, our preventive measures may have worked, only allowing new cases when lapses have occurred. If this were the case we would expect effectiveness against all forms of acute respiratory infections, like the winter illnesses. This has indeed happened in the Southern hemisphere, but the age shift does not fit with this theory.

A fourth possible and much more complex explanation is what we call the 'reality problem'. There is rapidly accumulating evidence that the tests used worldwide to identify cases in a binary mode 'Yes or No' are being used in a simplistic and uncoordinated way. We have already explained the limits of polymerase chain reaction (PCR) to carry out mass testing.

PCR is a very sensitive test, which means that it detects the smallest fragments of the virus it is looking for by amplifying the sample millions of times. However, a fragment is not a whole virus, capable of replication and of infecting other human beings. It is a small part of the viral structure that the PCR primer is looking for, not the whole microorganism. Only whole viruses can infect us.

In addition, the number of amplification cycles necessary to reach a 'positive test' is rarely reported. We now know that his is a vital piece of information in interpreting results. A very high number of cycles may detect fragments and give a positive result but a lower number of cycles is far more likely to identify infected and infectious individuals requiring quarantine.

You would expect all of this to be reported in a PCR results but it is not routinely done. There is worse news to come. A very sensitive test is vulnerable to contamination with extraneous genetic material (hence the need for suiting up operators). The rapid expansion of testing capacity may have degraded our capacity for sterility by increasing throughput and straining lab staff training. We also have come across studies looking at the different performance of PCR kits on the same sample and the results are not encouraging, with wide variation in cycle thresholds for the same positive results indicating the absolute requirement to standardised tests worldwide continuously comparing procedures and performance of testing against the only real gold standard for gauging a person’s contagiousness: viral culture.

Evidence is mounting that a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with. Those whose immunity is more active are exactly in the age group of observed 'positives' and least likely to end with severe disease.

So, we appear to have the reality of viral circulation, probably waning fast and the perceived reality of a misused and simply interpreted genial test which can be used to great effect when viral circulation is far higher (making it more likely a positive test correctly identifies the virus) or in finding traces of bugs which are good at hiding in our bodies, or their fragments in waste waters indicating their presence at some time in the past.

To avoid this dual reality and the dangers of isolating non-infectious people or whole communities we need an international effort to standardise testing, periodic calibration against culture or other recognised measures of infectiousness and strict laboratory protocols and procedures probably with a central licensing authority. A lot more work needs to be done to correlate cycle thresholds, patients’ characteristics and intelligence on virus circulation. Medicine and public health are about people, not printouts.