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COVID-19 wrap: antiviral drugs trial, mental health, asymptomatic infections and the role of GPs in long-term care

Victoria has continued to drive down its coronavirus second wave this week but worldwide coronavirus cases exceeded 40 million, amid record one-day increases in new infections.

The United States, India, and Brazil remain the worst affected countries in the world, but many countries in western Europe are battling surging second waves.

Reuters data shows the pace of the pandemic continues to pick up. It said it took just 32 days to go from 30 million global cases to 40 million, compared with 38 days to get from 20 to 30 million, 44 days between 10 and 20 million, and the three months it took to reach 10 million cases from when the first cases were reported in Wuhan in early January.

Ireland has moved back into lockdown, as well as Wales and other parts of the UK. France has imposed curfews while other European nations are closing schools and cancelling surgeries.

In the latest Croakey COVID-19 Wrap, public health researcher Alison Barrett looks at mental health impacts on older Australians early in the pandemic, a study on people who remain asymptomatic, the role of GPs in care, and early results from the WHO study on four anti-viral drugs, including remdesivir which was used to treat President Donald Trump.


Repurposed antiviral drugs, for COVID-19; interim WHO SOLIDARITY trial results

WHO Solidarity Trial Consortium, MedRxiv Preprint server, 15 October 2020

The World Health Organization has published yet to be peer-reviewed results from its Solidarity Therapeutics Trial, reporting that four anti-viral drugs — remdesivir, hydroxychloroquine, lopinavir and interferon — had little or no benefit on hospitalised COVID-19 patients.

The world’s largest randomised control trial on therapeutic drugs for COVID-19 evaluated the repurposing of the four anti-viral drugs for use in treating patients with the novel coronavirus. Between 22 March and 4 October, 11,266 patients were enrolled in the study from 405 hospitals across 30 countries and randomised into one of five drug groups or a control group, where no drug was provided.

Outcomes of the study were to assess the effect of the drugs on in-hospital mortality, ventilation and duration in hospital; the study found no benefit or harm of any of the drugs on these outcomes.

As  reported (10 June) in an earlier  COVID-19 Wrap and in The Health Wrap, throughout the pandemic, hydroxychloroquine has been much-touted as a potential treatment for those with COVID-19, prompting the United States to start stockpiling the drug and President Trump to start taking the medication as a preventive measure in May.

Similar to the results from the Solidarity trial, other studies have found that hydroxychloroquine provides no benefit to COVID-19 patients. One study published in August 2020 found that the drug did not prevent people becoming infected with the virus, and results from another recently published randomised controlled trial (RCT) found that COVID-19 patients who received hydroxychloroquine did not have a lower incidence of death compared to those in the trial who did not receive the drug.

Results from another recently published RCT found that lopinavir was not associated with reduced mortality, hospital stay or ventilation, with the authors concluding that the use of that drug was not supported to treat patients with COVID-19.

Contrary to the Solidarity trial results, another research group has found that remdesivir shortened patient’s recovery time, when compared to those who received a placebo.

Remdesivir was one of the drugs given to Trump as part of his treatment for COVID-19. The drug’s manufacturer Gilead rejected the findings of the trial, saying the findings of the study were “inconsistent with more robust evidence” and it was “concerned” that the results have yet to be reviewed.

While the Solidarity trial has many strengths and has been welcomed, it also prompted mixed responses about its design and rigour.

Without doing a rigorous analysis and systematic review of these trials, it is hard to compare the different studies; however, the mounting evidence indicates that the use of hydroxychloroquine, lopinavir and interferon provide little to no benefit to COVID-19 patients.

The conflicting results about the effectiveness of remdesivir indicate that more research is required; however, it is an expensive drug and the value of pursuing future trials of remdesivir needs to be considered.


The effect of COVID-19 on mental health and wellbeing in a representative sample of Australian adults  

Dawel, A et al, Frontiers in Psychiatry, 6 October 2020

An online survey conducted in the early stages of the pandemic in Australia has found that changes to work and social function due to COVID-19 resulted in higher levels of depression and anxiety in Australian adults.

The survey was conducted between 28-31 March, not long after coronavirus restrictions, were implemented, with 1,296 participants who were representative of the Australian community.

Questions were asked to determine levels of depression, anxiety, and general wellbeing in the two weeks prior to 28 March; and what, if any, direct exposure they had had to COVID-19 (for example, diagnosis of virus, or diagnosis of a close contact).

Thirty-six percent of participants reported having direct exposure to the virus; however, depression and anxiety were more related to disruptions to work and social activities than the amount of contact someone had with the virus.

When the authors compared depression and anxiety scores for participants in this study with scores from other previously collected community samples, they found that moderate to high levels of depression and anxiety were more prevalent in this study cohort. Sixteen percent of the group scored moderate to high levels of depression, compared to 5.6 percent in other communities, and 20.3 percent scored high levels of anxiety compared to five percent in other communities. However, it should be noted the comparison data that the authors report comes from general population samples in United States (depression) and Germany (anxiety).

The authors also found that having a pre-existing mental health condition, being younger age or identifying as female increased the risk of poor mental health.

Some limitations of the study include its self-report nature and that it may be biased towards people with higher internet literacy and greater access to the internet. The authors highlight that another limitation is that these results are only based on one time-point early in the pandemic, and difficult to determine the exact cause for the higher levels of anxiety and depression. They intend to report on further survey results as they become available.

While limitations in the study exist, the findings of increased anxiety and depression resulting from COVID-19 are consistent with studies recently published in the US and United Kingdom.

The authors wrote:

The current study provides a snapshot of the acute phase impact of COVID-19 on the mental health of the Australian adult community. The findings are concerning, suggesting markedly elevated rates of depression and anxiety, even among individuals with no current diagnosis.”

Interventions to alleviate the social and financial impacts brought on by COVID-19, especially in those identified at higher risk, would be beneficial for the mental health of the adult community in Australia.


Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis

Buitrago-Garcia, D et al, Plos Medicine, 22 September 2020

A systematic review has found that 20 percent of people infected with SARS-CoV-2 remain asymptomatic (without symptoms) throughout the duration of their infection.

Previous studies about the proportion of asymptomatic patients reported the proportion to be anywhere between six and 96 percent. However, these studies were based on patient’s symptom status at one time-point, without a follow-up to determine if symptoms developed at a later stage during their infection.

The authors of this systematic review searched academic databases and preprint servers between 25 March and 10 June for studies of people diagnosed with SARS-CoV-2 that reported on patient’s symptom status at the beginning and end of follow-up.

While the available data was too varied to statistically determine the proportion of patients who were pre-symptomatic (diagnosed with the virus, had no symptoms at the beginning, but developed during their infection), the authors were able to estimate that 20 percent of patients with SARS-CoV-2 remained asymptomatic.

They were also able to estimate that the risk of acquiring an infection from an asymptomatic patient seems to be lower than from a symptomatic person, however the variation in available studies meant their estimation is not very precise and further studies are required.

The main limitation in the review is that included studies were too varied in design and definitions of asymptomatic/pre-symptomatic for the authors to determine the proportion of pre-symptomatic infections, which is a more precise estimate for asymptomatic infections and risk of infection from both asymptomatic and pre-symptomatic when compared to symptomatic patients.

However, the systematic review was very thorough, used rigorous methods to minimise bias and only included studies that reported symptom status at the beginning and end of follow-up.

In summary, this review provides important information for preventing the transmission of SARS-CoV-2. While the findings indicate that most people who are infected with the virus will not remain asymptomatic, the combination of asymptomatic and pre-symptomatic infections mean that preventive measures, such as physical distancing, hand washing hygiene, testing and contact tracing, are still the best measures to prevent ongoing infections.


GPs vital in long-term care of COVID-19 patients

Royal Australian College of General Practitioners (RACGP), 15 October 2020

In a 15 October media release, the RACGP advocated the need for better resources in supporting patients with long-term symptoms from COVID-19.

While some COVID-19 patients fully recover from the virus, evidence indicates that many are left with long-term symptoms, including post-viral fatigue, brain fog and lung scarring.

RACGP Acting President Associate Professor Ayman Shenouda said:

These long-term effects are likely to be particularly severe for older people, those with chronic disease and those who experienced severe acute COVID-19. GPs will be crucial in managing the health and wellbeing of these patients in the years ahead.”

GPs need the government’s support to care for the long-term physical and mental health impacts from COVID-19.

The RACGP have prepared a guide for GPs, Caring for adult patients with post-COVID-19 conditions, that includes information on infection-control, identification and management of post-COVID-19 symptoms, collaboration with the patient in developing an individualised plan for their recovery, care for older patients and people with disability.


Alison Barrett is a Masters by Research candidate and research assistant at University of South Australia, with interests in public health, rural health and health inequities. Follow on Twitter: @AlisonSBarrett. Croakey thanks her for providing this column as a probono service to our readers.

See previous editions of the COVID wrap.

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