Covid-19 report 3: Promising new tests, but disappointing hydroxychloroquine results

This is the third issue of the Covid-19 coronavirus report. We point you to the latest quality science on the pandemic. If you come across unfamiliar terms, there is a glossary at the bottom of the article.

Promising new tests

Broadly, there are three types of tests for an infection such as Covid-19:

• Polymerase chain reaction (PCR) tests, which check for the genetic material of the virus. In South Africa, when you get tested for Covid-19, this is currently what’s used.

The advantages are that the tests are reliable and tell if you’re currently infected, although only a few days after being exposed.

The disadvantages are that these types of tests are mostly time-consuming and expensive.

• Antigen tests, which detect viral protein fragments. The Food and Drug Administration (FDA) in the US has given emergency authorisation use – which is not the same as approval – to the first such test, made by Quidel Corporation.

The advantages are that testing is cheap, about $5 (R91), according to one source; the test gives results in 15 minutes, but as far as we can tell it has to be done in a lab (we’re not sure); and Quidel can quickly start producing millions of them. If you test positive, you’re almost certainly currently infected.

The disadvantage is that the test has a high false-negative rate. In other words, you may be infected but the test may say you’re not.

• Antibody tests, on the other hand, detect if you have previously been infected with Covid-19. These tests give a positive result even after you’ve recovered. They’re usually less expensive to make and usually give results quicker than PCR tests. This is vital for surveillance to see what percentage of the population has been infected. From this we can learn how fast the virus spreads and how much immunity people have against reinfection. However, they don’t tell you if you’re currently infected.

Up until now, the accuracy of antibody tests has been low and this has resulted in some poor quality surveillance studies that have received wide media coverage.

A study published in scientific journal Nature found that every person infected with Sars-CoV-2, the virus that causes Covid-19, develops a type of antibody called Immunoglobulin G within 19 days of developing symptoms. The antibodies appear to be specific to this virus, so in theory we should be able to get close to perfect accuracy antibody tests.

Swiss-based pharmaceutical company Roche claims that it has developed a test that detects Sars-CoV-2 antibodies with 100% accuracy if you have them, meaning no false negatives, and with more than 99.8% accuracy detects when you don’t have them, meaning few false positives, with the condition that it is at least 14 days since a PCR test would have shown that you are infected.

It also claims to be able to produce more than 10 million tests from this month.

The FDA has granted Roche’s test emergency use authorisation. Whether Roche has hyped its claims or made a breakthrough remains to be seen.

Another modest drug trial result

Last week we reported on the modest findings about the drug remdesivir. Now the medical journal The Lancet has published the results of a clinical trial in Hong Kong, China, comparing two drug regimens: interferon beta-1b, ribavirin and the anti-HIV drug lopinavir/ritonavir versus lopinavir-ritonavir alone.

The study compared the time it took for the patients on each regimen, all with mild to moderate Covid-19 symptoms, to test negative from when they started treatment – in other words, be officially recovered. It took on average seven days for patients on the more intensive regimen, versus 12 days for the lopinavir-ritonavir alone. None of the 127 trial participants died.

As one South African pharmacologist has pointed out, this trial had no placebo arm nor a standard-of-care arm (lopinavir/ritonavir is not known to treat Covid-19, though see below).

Also the end point was virological (PCR test result) rather than clinical (how well the patients were doing).

On the same day the outcome of a trial of lopinavir/ritonavir was published in The New England Journal of Medicine (NEJM) and found no benefit (or harm). Here the end point was clinical rather than virological improvement.

Taken together, these two studies suggest a modest benefit to the three drug regimen. Whether there’s sufficient benefit for this regimen (or remdesivir) to become part of standard practice remains to be seen. We’re not convinced.

Setback for hydroxychloroquine?

A published NEJM analysis of 1 446 Covid-19 patients at a New York medical centre, 811 of whom received hydroxychloroquine, showed no benefit to using the drug.

It’s not a clinical trial – only an observational study – and this doesn’t necessarily mean that it’s the end of the road for hydroxychloroquine and Covid-19.

Also, the patients who were given the drug tended to be sicker. But it suggests that if hydroxychloroquine does help, its benefits will be modest.

A well-run clinical trial that provides more definitive information on the drug’s safety and efficacy is still needed. That trial may now have been done.

A not yet peer-reviewed study of 150 patients in China found no difference in time to testing negative for people with mild and moderate Covid-19 taking hydroxychloroquine compared to not taking it. There were more adverse events in the hydroxychloroquine patients. It’s a small number of patients, and the paper needs more scrutiny, but it’s not looking promising for hydroxychloroquine.

Coronaviruses and the common cold

A single paragraph from an article in the latest issue of academic journal Science is packed with useful information:

“The coronaviruses are single-stranded RNA viruses that infect vertebrates and move between different host species. With the emergence of Sars-CoV-2, there are now seven coronaviruses that are known to infect humans.

Four of them (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) are responsible for approximately 30% of cases of the common cold in humans. Two of them caused recent epidemics that had considerable associated mortality: Sars-CoV-1, which emerged in 2002 to 2003 and caused approximately 10% mortality, and the Middle East Respiratory Syndrome coronavirus (Mers-CoV), which emerged in 2012 and is still active, and causes approximately 35% mortality.

Both epidemics affected a relatively small number of patients compared with Covid-19, which is more transmissible for several reasons, including asymptomatic carriers, a long latency period and high infectivity.

Before Covid-19, only Sars-CoV-1 and Mers-CoV caused severe disease. Therefore, coronaviral drug discovery has been a small effort relative to that for other viral diseases such as influenza.”

The SA Medical Research Council’s weekly update shows that the number of registered deaths (7 135) for the latest week for which there is data, April 22 to 28, is lower than the expected deaths (7 319 to 8 494). Natural deaths are as expected, but deaths owing to homicides and vehicle accidents are down.

The National Institute For Communicable Diseases (NICD) has published a good article on who should get an influenza vaccine this year: “Pregnant women, children aged between six months and five years, people older than 65 years, those with chronic medical conditions such as HIV and heart or lung problems, and healthcare workers.”

The jab doesn’t protect against Covid-19 at all. But it does reduce the risk of getting both Covid-19 and flu. If people get vaccinated, it will reduce the pressure on the health system.

The NICD has also published the second issue of its useful Covid-19 weekly epidemiology brief. One of the many interesting tidbits in it is that in terms of tests per 100 000 people, the Western Cape (788) is still well ahead of Gauteng (560), KwaZulu-Natal (407) and the Eastern Cape (369).

A letter in the SA Medical Journal by several clinicians from Tygerberg Hospital in Cape Town describes how they are treating severely ill Covid-19 patients.

The first six patients to the intensive care unit were put on ventilators; they all died.

“Following international reports of improved survival rates with non-invasive ventilation, the Covid-19 intensive care unit at Tygerberg ... changed its standard operating procedure in mid-April 2020 from the initially promoted ‘early intubation and mechanical ventilation’ to ‘high-flow nasal cannula oxygen therapy’ to avoid intubation.”

One out of seven such patients died.

This was a tiny number of patients and this wasn’t a clinical trial or study, but the results were promising. Another letter in the journal warns that placing people who live on the street in temporary shelters as part of the lockdown increases the risk of overdose among people who are dependent on heroin.

This article was produced by Spotlight, an online publication monitoring South Africa’s response to TB and HIV

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