JACK WATERFORD. Digesting the cases being missed

May 13, 2020

As we cautiously begin to lift the lockdown, if we don’t know who the silent carriers are, how can they play an active role in keeping the community safe?

One reason that the public health authorities are reasonably bullish about a very severe dent on incidence and prevalence of Covid-19  is that there are now relatively few new cases, considerably fewer than at the peak weeks ago. If we assume say that five per cent of the infected end up being hospital cases then the number of fresh cases suggests that not many new people are being infected.

Against that is the fact that transmission in the community is creating an ever-increasing pool of cases, only a tiny proportion of whom have obvious symptoms or any at all. By now these may have been in the community long enough for many generations of transmissions. One study in the American Journal of Gastroenterology published on April 15 suggests that mild cases are likely to be out in the community, shedding and spreading the virus, for up to a week longer than those whose case becomes severe. Likewise, those with digestive tract symptoms only may be carrying the highest viral load, and appear to be infectious for significantly longer than cases with digestive and respiratory symptoms, and those with respiratory symptoms only.

For all of this set of patients, all of whom were hospitalised and later followed up, the mean interval between the first onset of symptoms and viral clearance (demonstrated by two negative tests at least 24 hours apart) was 38 days. But those with digestive symptoms only had an average interval of 41 days, compared with 33 days for respiratory cases.

To me, this suggests that the exiting screening in the community might be the wrong way about. We can expect that almost all serious cases will get through screens regardless. If the focus of screening is to isolate virus carriers, it would be better to spend as much time looking for digestive tract symptoms as respiratory ones.  The failure to do this over recent weeks, as well as the strict insistence on respiratory symptoms, may well mean that an ill-judged policy has prevented the finding of carriers.

The authors do note that digestive tract symptoms are not uncommon and that most cases of new-onset diarrhoea, nausea or vomiting are not from Covid19. Nevertheless, doctors should consider the possibility in the course of the pandemic.

“Failure to recognise these patients early may often lead to the unwitting spread of the disease among outpatients with mild illness who remain undiagnosed and unaware of their potential to infect others,” it concludes.

When the public was being persuaded of the virtues of isolation and distancing policies, it was said that an asymptomatic person could spread Covid-19 to more than 9500 people in 40 days (that with a Ro of 2.5 and 10 generations). If a high proportion of them have no symptoms, the impetus on them to conform to strict rules, or to stay on course, is much lower.  As Andy Slavitt pointed out in Medium the higher the proportion of asymptomatic or mild cases, the lower the case fatality rate. But that can make it more deadly, given that one’s guard is lower in the presence of those who appear uninfected.

The lockdown rules would have dramatically cut these numbers. But they are unlikely to have reduced it all together. Given that government seems to intend to bar air travel (except possibly to New Zealand) and maintain barriers to entry for non-Australians, it seems likely that it will be from this group in the population — whose numbers are unknown given the failure to conduct surveys — that second and third waves of the disease will come. With Spanish flu a century ago — which involved a fair measure of social distancing — the second wave killed many times more than the first wave. Those who had not had the virus were not in the least immune, and the only way in which they benefited from the earlier phases was that treatment was more organised. On the other hand, one might expect that certain fatigue with social distancing, and unwillingness to revert to it once the controls have been loosened, may mean that compliance is weaker.

It’s all very well to say that the longer the lockdown, the more damage is being done to the economy, and the longer it will take for it to revive. But premature re-opening, followed by an emergency lurch back into quarantine if the epidemic flares up again — will make those costs, and those delays, seem like a picnic.

The argument of the government health advisers against random mass screening — or selective random screening among vulnerable groups, such as Aborigines, aged-care institutions, the disabled, people with diabetes, or primary and secondary school-children, is, they say, both the problem of small numbers and low prevalence rates and the damnable problems of false positives and false negatives. The overwhelming proportion of the population does not have, yet at least, the virus.  Even if the true rate of infection is somewhat higher than expected, it is still only a small percentage of the population. If the whole population is screened, then the fact that some of the testing machines are unreliable may mean that many people are identified as having (or having had) the virus when, as further testing will show, they have not been exposed. Others will be said not to have the virus when they are in fact positive.

That seems to be a lazy excuse, particularly given the increasing sophistication of the testing equipment and given that the call on resources to for a medical (as opposed to social) fight against the virus is only a fraction of what was planned or expected. Nor should there be any great problem of doing double, or triple tests, say, directly for presence of the virus, and a serology test for antibody response. Perhaps a faecal sample — probably the most reliable. Increasingly there is equipment of high specificity and sensitivity, with far fewer wrong calls.

Australian public health authorities routinely screen large populations for conditions of lower prevalence than coronavirus, and in situations in which accurate diagnosis is far more difficult than with coronavirus. An example might be with PSA tests for prostate disease, of the most doubtful efficacy. Even PAP smears suffer from major problems of false positive and negatives, often leading to unnecessary further medical interventions.

What’s important to remember is that we not simply looking for cases who should be put immediately in an ambulance for treatment, or should be told to return to lockdown. While random mass testing should involve giving results to patients as promptly as possible,  a result for epidemiological purposes is not as urgent as one for clinical screening, allowing for examinations to be conducted centrally. We are trying to get a picture of disease in the community.

In the US there are plans to have two or three major random mass screenings, each involving about 50,000 people, and each involving the collection of blood samples. With most of the US not yet at its peak incidence, analysis of the data, but not the data collection itself,  may be delayed.

Modern epidemiology began in the 1950s, with doctors such as Archie Cochrane, firmly committed not only to mass surveys and providing service as much as research. Cochrane is now commemorated by the Cochrane Collection — a data base of international case studies, closely analysed for weaknesses of design and conclusions drawn.

I am beginning to suspect that newer technology, and the computer, has tended to make the typical epidemiologist of today more office-focused, and more statistically-oriented. Something like econometrics. Perhaps for shy doctors and bureaucrats with a fear of coming into contact with actual patients or real people. Cochrane used to stress that the very word epidemiology meant the study of disease — or epidemics — in one’s community, among one’s people. Like many non-bureaucratic epidemiologists, here and abroad, he would be scathing of the low priority given by bureaucratic advisers to government to the need for surveys.

As we cautiously begin to lift the lockdown, if we don’t know who the silent carriers are, how can they play an active role in keeping the community safe?

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