Alex Nowbar reviews the latest research from the top medical journals.
Annals of Internal Medicine
Twelve covid-19 autopsies
Venous thromboembolism has been recognised as a major part of covid-19 pathology. Wichmann et al’s cohort study of the first 12 consecutive covid-19-positive patients who died in Hamburg, Germany confirms this. Full autopsies were conducted including post-mortem CT. The cause of death in four cases was massive pulmonary embolism with deep venous thromboses in the lower limbs. A further three cases had deep vein thromboses that had not been suspected before death. Eleven cases had pre-existing heart disease. This points towards an important role for coagulopathy in this condition and gives some credence to a strategy of anticoagulation. As for the lungs, the histopathology showed diffuse alveolar damage which is consistent with difficulties ventilating.
Dude, where’s my immunity passport?
Actually, I don’t really want the UK to adopt this approach. It’s discriminatory. Why should only immune people get to travel/ work/ go about their business? It even penalises those who have been adhering to strict social distancing. Hall et al point out many of the issues in their letter. For example, they explain that understanding of immunity from the virus is “fairly rudimentary”. That’s an understatement. Not knowing the duration or level of immunity that comes with a positive IgG result is fairly critical for an immunity “passport” system. The authors also discuss the challenge of providing access to reliable tests on which to base such a system. In summary, while some parts of the world may end up using such a system to varying extents, particularly for healthcare workers, it doesn’t seem to have legs. If I had to speak in favour of this system, I would say that at least it could mean less restriction than full lockdown.
Meeting in the muddle
Hung et al randomised 127 patients with mild to moderate covid-19 in Hong Kong in an open-label trial. Both groups received lopinavir and ritonavir. One group also got interferon beta-1b and ribavirin. The aim was to reduce the time to a negative SARS-CoV-2 PCR on a nasopharyngeal swab. There was convincing and statistically significant evidence that the treatment group had a shorter time to a negative swab (a median of 7 days versus 12 days). It’s a bit weird that both groups got some background anti-virals that aren’t backed up with randomised evidence. Perhaps this was a pragmatic decision because clinicians are susceptible to “something is better than nothing” fallacy and therefore would not be happy to randomise people to a control group that gets no treatment. We humans can be so illogical sometimes. We fear that depriving patients of a treatment that might help is worse than not giving that treatment even if the treatment has no evidence base and could in fact do harm. And this fear spreads through us like a herd overriding our desire for the rigour of randomised trials. Nevertheless, this study was randomised and therefore has some value in supporting the use of triple antiviral therapy and interferon over lopinavir and ritonavir alone. This may be challenging to translate into clinical practice because lopinavir-ritonavir isn’t necessarily standard of care.
Hydroxychloroquine was the hottest potential covid-19 treatment a few months ago. While people clamoured for randomised controlled trials, it was dished out liberally to patients the world over. Geleris et al’s observational study in New York City is still not the evidence that can really be acted upon. However it is interesting that in 1446 consecutive patients hospitalised with covid-19, those who received the drug died or were intubated no less frequently than those who did not receive the drug. As with all observational data, it is important to caution that confounders can explain the relationship or lack of relationship between an intervention and an outcome. For example, patients who received hydroxychloroquine were more likely to be sicker and therefore do badly which could have reduced the chance of demonstrating that hydroxychloroquine has a benefit if indeed there is one. I can’t help but agree with the authors’ comments: “Given the observational design and the relatively wide confidence interval, the study should not be taken to rule out either benefit or harm of hydroxychloroquine treatment. However, our findings do not support the use of hydroxychloroquine at present, outside randomized clinical trials testing its efficacy.”
Dead person devices
Providing some not-so-light relief from covid-19, Khairy et al present their registry of 1051 patients who received implantable cardiac devices obtained from patients post mortem between 2003 and 2017 in underserved countries e.g Mexico and the Dominican Republic. The rate of infection was 2%. This was higher than matched controls who received a new device in Canada (1.2%) but the difference was not statistically significant. This wasn’t a randomised trial so the difference between the groups cannot be attributed to the device type alone. For example, patient and operator characteristics vary significantly between countries. However these data do support the use of reused devices in resource-limited countries where the alternative is potentially not getting a device inserted at all.
Alex Nowbar is a clinical research fellow at Imperial College London
Competing interests: None declared