Open Access
Focus on COVID-19

COVID-19 Summaries: a recap of recent research

Open Access
Focus on COVID-19

COVID-19 Summaries: a recap of recent research

Anne Chang, Richard T. Ellison III, Rajesh T. Gandhi, Andrew Henderson, Christine McDonald, Renae McNamara, Natasha Smallwood

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Professor Anne Chang am,* Respiratory Specialist, Head, Child Health Division, Menzies School of Health Research, Darwin, NT. Professor Richard T. Ellison III, MD, Professor of Medicine, Microbiology, and Physiological Systems, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, USA. Professor Rajesh T. Gandhi, MD, Professor of Medicine, Harvard Medical School; Director, HIV Clinical Services and Education, Massachusetts General Hospital, Boston, USA. Dr Andrew Henderson,* Infectious Diseases Specialist, Princess Alexandra Hospital, Brisbane, Qld. Professor Christine McDonald am,* Director, Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Vic; Department of Medicine, University of Melbourne, Melbourne, Vic. Dr Renae McNamara,* Clinical Specialist Physiotherapist, Pulmonary Rehabilitation Coordinator, Prince of Wales Hospital, Sydney, NSW. Associate Professor Natasha Smallwood, Clinical Associate Professor and Honorary Principal Fellow, Department of Medicine, University of Melbourne, and Respiratory Physician, Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, Vic. Acknowledgements We thank Dr Sebastian Le Feuvre, Thoracic and Sleep Physician, and Professor Ian Yang, Thoracic Physician, The Prince Charles Hospital and The University of Queensland, Brisbane, Qld, for reviewing the selection of research papers summarised in this article. We are also grateful for the assistance of members of Lung Foundation Australia’s COVID-19 Expert Working Group,* in compiling this article.

 

From NEJM Journal Watch Dexamethasone: first drug found to reduce mortality in people with COVID-19

The reduction in mortality was greatest in those on mechanical ventilation; people who were not on oxygen did not benefit and might have experienced harm.1

Because patients with severe COVID-19 often have evidence of excess inflammation, intense interest has centred on whether anti-inflammatory medications, such as glucocorticoids, have a role in treating COVID-19. In the RECOVERY trial, patients hospitalised with COVID-19 were randomised to receive dexamethasone (6 mg/day for up to 10 days; n=2104) or usual care (n=4321).

Mortality within 28 days was lower with dexamethasone than with usual care (22.9% vs 25.7%; age-adjusted rate ratio [RR], 0.83). Among patients receiving mechanical ventilation at enrolment, dexamethasone recipients had an age-adjusted 36% lower mortality than usual-care recipients (29.3% vs 41.4%; RR, 0.64). Those requiring supplemental oxygen (but not mechanical ventilation) had a smaller but still significant mortality difference between dexamethasone and usual care (23.3% vs 26.2%; RR, 0.82). Among patients not receiving supplemental oxygen, dexamethasone conferred no benefit over usual care; indeed, their results were consistent with potential harm (RR, 1.19).

Comment by Professor Rajesh Gandhi

This landmark trial was designed to evaluate the effect of treatment on major clinical outcomes, like death. It cannot address why dexamethasone worked, whether biomarkers can identify individuals most likely to benefit, and other questions.

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Moreover, the mortality in this trial was higher than what is being seen in the current stage of the pandemic, toxicity information is not presented, and the results pertain to only hospitalised patients; ambulatory patients should not receive dexamethasone. Nevertheless, the findings support an emerging paradigm for how different therapies affect COVID-19. The antiviral remdesivir is most beneficial in people with severe COVID-19 who are not yet critically ill, suggesting an important role for viral replication in this disease stage.2 By contrast, dexamethasone’s largest impact is in critically ill people, suggesting that excess inflammation drives much of the damage at this stage. Trials are underway to assess the combination of antiviral and anti-inflammatory therapies in people with severe COVID-19.

1. Horby P, et al. Dexamethasone in hospitalized patients with Covid-19 – Preliminary report. N Engl J Med 2020 Jul 17; doi.org/10.1056/NEJMoa2021436.
2. Beigel JH, et al. Remdesivir for the treatment of Covid-19 – Preliminary report. N Engl J Med 2020 May 22; doi.org/10.1056/NEJMoa2007764.

 

From NEJM Journal Watch What’s the duration of immunity to SARS-CoV-2?

Individuals with mild COVID-19 infection have a rapid decline in SARS-CoV-2 antibody levels.

One of the many still unanswered questions regarding COVID-19 is the duration of protective immunity following infection. A recent report from China indicated that individuals with asymptomatic COVID-19 had a less robust immune response to SARS-CoV-2.1 California investigators now report further longitudinal data on antibody levels after mild COVID-19.2

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Thirty-four individuals with mild COVID-19 (30 that were polymerase-chain-reaction assay confirmed) had serial anti–SARS-CoV-2 receptor binding domain IgG levels determined at a mean of 37 and 86 days after symptom onset. The estimated mean IgG half-life was 36 days.

Comment by Professor Richard Ellison III

The finding of a relatively short anti–SARS-CoV-2 IgG half-life in these two reports has received substantial coverage in the lay press and does raise concerns regarding the duration of protective immunity that is present both after infection and with a COVID-19 vaccine. Still, the present report did not directly assess neutralising antibodies, and neither this nor the report from China assessed either T-cell mediated immunity or the potential for an anamnestic response to this virus.

1. Long, Q, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020; 26: 1200–1204.
2. Ibarrondo FJ, et al. Rapid decay of anti–SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med 2020 Jul 21; org/10.1056/NEJMc2025179.