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Latest journal articles

Updated 7 December 2021

MJA Podcasts 2021 Episode 49: Early treatment of COVID-19, with Adj A/Prof James Branley and A/Prof Lucy Morgan
Adjunct Associate Professor James Branley heads the Department of Microbiology and Infectious Diseases at Nepean Hospital. Associate Professor Lucy Morgan is a respiratory physician treating COVID-19 patients at Nepean and Concord Hospitals. They discuss how to save lives in the first few days of COVID-19 symptoms. MJA 7 December 2021

Care of older people and people requiring palliative care with COVID19: guidance from the Australian National COVID19 Clinical Evidence Taskforce
The practice points in the flow charts emphasise quality clinical care, with a focus on addressing the most important challenges when caring for older individuals and people with COVID19 requiring palliative care. The adult recommendations contain additional considerations for the care of older people and those requiring palliative care. MJA 6 December 2021

Reality of living with COVID-19 becoming clear
COVID-19 delivered shockwaves across the globe, disrupting economies and upending lives. That disruption and uncertainty were acutely felt by Australians through lockdowns, closed borders, severe illness and deaths, and fears about the pressure it would place on our health system. MJA insight 6 December 2021

COVID-19 landscape shifts: the good and bad news
Three months on from the release of OzSAGE’s initial advice document, the COVID-19 landscape has shifted significantly. There is both good and bad news to dissect. MJA insight 6 December 2021

What's new at this update

WHO classifies Omicron as variant of concern

  • The World Health Organization has designated the Omicron variant (B.1.1.529), first discovered in South Africa in November 2021, as a variant of concern.
  • Omicron is a highly divergent variant with a high number of mutations, and may be associated with immune escape potential, higher transmissibility, and an increased risk of reinfection compared with other variants of concern. However, there are still considerable uncertainties and there are a lack of laboratory and epidemiological data available.
  • See the Classification section under Aetiology for more information.

BMJ 3 December 2021

Immunogenicity of extended mRNA SARS-CoV-2 vaccine dosing intervals
Longer mRNA vaccine dosing intervals demonstrated improved immunogenicity, which was consistent when responses were measured based on timing of the first or second dose. These data suggest that extending dosing intervals may be particularly advantageous against the Delta variant. JAMA 3 December 2021

Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19
The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies. The Lancet respiratory medicine 3 December 2021

Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study
By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. The Lancet rheumatology 3 December 2021

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial
All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. The Lancet 2 December 2021

Maternal-fetal immunologic response to SARS-CoV-2 infection in a symptomatic vulnerable population: A prospective cohort
These results demonstrate the combined role of biologic, clinical and socioeconomic variables associated with maternal SARS-CoV-2 RBD-specific antibodies and supports early vaccination strategies for COVID-19 in socioeconomically vulnerable pregnant women. Journal of infectious diseases 2 December 2021

Transmission dynamics of the Delta variant of SARS-CoV-2 infections in South Korea
The author’s findings suggest that the Delta variant is highly transmissible in indoor settings and households. Rapid contact tracing, isolation of the asymptomatic contacts, strict adherence to public health measures, and increased uptake of COVID-19 vaccination including booster doses are needed to reduce the community transmission of the Delta variant. Journal of infectious diseases 2 December 2021

Covid 19: Why we need a global pandemic treaty
The world was not prepared for this pandemic. While countries affected by severe acute respiratory syndrome (SARS) in 2003 responded quickly and efficiently to the early warnings of covid-19, most stumbled at the first hurdle and are still not catching up. BMJ 2 December 2021

Audio interview: The Omicron variant of SARS-CoV-2
In this audio interview conducted on November 29, 2021, the editors are joined by South African researcher Salim Abdool Karim to discuss the omicron variant recently identified in southern Africa. NEJM 2 December 2021

Myocarditis after Covid-19 vaccination in a large health care organization
Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. NEJM 2 December 2021

Myocarditis after BNT162b2 mRNA vaccine against Covid-19 in Israel
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild. NEJM 2 December 2021

Role of asymptomatic and pre-symptomatic infections in covid-19 pandemic
Liming Li and colleagues highlight the importance of identifying people without symptoms to control outbreaks of covid-19 BMJ 1 December 2021

Practical recommendations on quantifying and interpreting treatment effects in the presence of terminal competing risks: A review
This article enhances the understanding of each method’s advantages and shortcomings and assists practitioners in choosing appropriate methods for handling competing risk problems in practice. JAMA 1 December 2021

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial
Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. The Lancet respiratory medicine 1 December 2021

Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England
SARS-CoV-2 reinfections were rare in older residents and younger staff. Protection from SARS-CoV-2 was sustained for longer than 9 months, including against the alpha variant. Reinfection was associated with no or low neutralising antibody before reinfection, but significant boosting occurred on reinfection. The Lancet healthy longevity 1 December 2021

Comparative effectiveness of BNT162b2 and mRNA-1273 vaccines in U.S. veterans
The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance. NEJM 1 December 2021

Rituximab infusion timing, cumulative dose, and hospitalization for COVID-19 in persons with Multiple Sclerosis in Sweden
Among 172 Swedish persons with multiple sclerosis who received rituximab before contracting COVID-19, the authors found no statistically significant association between the timing of rituximab infusion or cumulative lifetime rituximab dose and the odds of hospitalization for COVID-19, although the study power was limited. JAMA 1 December 2021

SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern
The unprecedented SARS-CoV-2 pandemic has called for substantial investigations into the capacity of the human immune system to protect against reinfection and keep pace with the evolution SARS-CoV-2. We evaluated the magnitude and durability of the SARS-CoV-2 specific antibody responses against parental WA1 SARS-CoV-2 receptor binding domain (RBD) and a representative variant of concern (VoC) RBD using antibodies from two antibody compartments: long-lived plasma cell-derived plasma antibodies and antibodies encoded by SARS-CoV-2 specific memory B-cells. Thirty-five subjects naturally infected with SARS-CoV-2 were evaluated: While only 25/35 subjects had VoC RBD reactive plasma antibodies, 34/35 (97%) subjects had VoC-RBD-reactive memory B-cell derived antibodies. The author’s finding that 97% of previously infected individuals have MBCs specific for variant RBDs provides reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to elicit immunity with the capacity to limit disease severity and transmission of VoCs as they to arise and circulate. Journal of infectious diseases 1 December 2021

Risk of COVID-19 hospital admission among children aged 5–17 years with asthma in Scotland: a national incident cohort study
School-aged children with asthma with previous recent hospital admission or two or more courses of oral corticosteroids are at markedly increased risk of COVID-19 hospital admission and should be considered a priority for vaccinations. This would translate into 9124 children across Scotland and an estimated 109 448 children across the UK. The Lancet respiratory medicine 30 November 2021

Odds of testing positive for SARS-CoV-2 following receipt of 3 vs 2 doses of the BNT162b2 mRNA vaccine
Previous studies have demonstrated that vaccine-derived protection against SARS-CoV-2 wanes over time. In this case-control analysis, we showed an association between receipt of the booster dose and a reduction in the odds of testing positive for SARS-CoV-2, potentially counteracting waning immunity in the short term. Further monitoring of data from this population is needed to determine the duration of immunity following the booster. JAMA 30 November 2021

Gene expression risk scores for COVID-19 illness severity
These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity Journal of infectious diseases 30 November 2021

Early Immunogenicity and safety of the third dose of BNT162b2 mRNA Covid-19 vaccine among adults older than 60 years; real world experience
The authors demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals>60 years. Journal of infectious diseases 29 November 2021

Vaccines, therapeutics, and diagnostics for covid-19: redesigning systems to improve pandemic response
Rohit Ramchandani and colleagues propose a framework to ensure essential public health tools are fairly distributed in future pandemics. BMJ 29 November 2021

From response to transformation: how countries can strengthen national pandemic preparedness and response systems
Victoria Haldane and colleagues delve into the characteristics of national responses to covid-19. They suggest actionable steps at a national level that can guide states to achieve the independent panel’s recommendations for making this the last pandemic. BMJ 29 November 2021

From dichotomisation towards intersectionality in addressing covid-19
Anne-Sophie Jung and colleagues argue that understanding mechanisms of response to the covid-19 pandemic as trade-offs reinforces false dichotomies and hamstrings attempts to create stronger and more equitable health systems BMJ 29 November 2021

Assessing the role of qualitative factors in pandemic responses
Melisa Tan and colleagues argue that assessments of national pandemic preparedness and response capacities should be extended to include social factors, leadership, and use of evidence. BMJ 29 November 2021

Aggressive containment, suppression, and mitigation of covid-19: lessons learnt from eight countries
Shishi Wu and colleagues examine three distinct response strategies for covid-19 in eight countries and argue that aggressive containment is the optimal approach to limiting loss of lives and livelihoods and achievable in the absence of vaccines and effective therapies. BMJ 28 November 2021

Strengthening the basics: public health responses to prevent the next pandemic
Victoria Haldane and colleagues argue that to make covid-19 the last pandemic, public health responses to outbreaks must be strengthened, starting with their most basic functions. BMJ 28 November 2021

Investing in trust and community resilience: lessons from the early months of the first digital pandemic
Salma M Abdalla and colleagues examine how an atmosphere of misinformation, disinformation, and erosion of trust shaped the early response to covid-19 on both global and national levels. BMJ 28 November 2021

Resetting international systems for pandemic preparedness and response
Sudhvir Singh and colleagues summarise the recommendations of the Independent Panel for Pandemic Preparedness and Response to try to prevent future pandemics. BMJ 28 November 2021

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study
The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. The Lancet regional health Europe 28 November 2021

Population level physical activity before and during the first national COVID-19 lockdown: A nationally representative repeat cross-sectional study of 5 years of Active Lives data in England
Restrictions introduced in Spring 2020 likely reduced physical activity levels in England. The magnitude of the declines were not uniform by demographic groups or by activity type, which future policies should consider. The Lancet regional health Europe 28 November 2021

Effect of High-Titer Convalescent Plasma on progression to severe respiratory failure or death in hospitalized patients with COVID-19 pneumonia : A randomized clinical trial
In patients with moderate to severe COVID-19 pneumonia, high-titer anti–SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. JAMA 29 November 2021

Most cases of Thrombosis and Thrombocytopenia Syndrome (TTS) post ChAdOx-1 nCov-19 are Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT)
Understanding the true incidence and mortality of VITT is dependant on robust and consistent diagnostic criteria such as those used in the UK. The studies by Thiele and Pavord showed that not all cases included in the TTS diagnostic category are confirmed as VITT and not all cases of VITT are included as TTS. The Lancet regional health Europe 28 November 2021

Surface and air contamination with SARS-CoV-2 from hospitalized COVID-19 patients in Toronto, Canada, March-May 2020
The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited. Journal of infectious diseases 27 November 2021

Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms
The study presented here demonstrates the usefulness of “next generation plasma protein profiling” to identify molecular signatures of importance for disease progression and to allow monitoring of disease during recovery from the infection. The results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus. EBioMedicine 26 November 2021

Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study
This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. The Lancet respiratory medicine 26 November 2021

Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial
Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2–transmission risk, provided a comprehensive preventive intervention was implemented. The Lancet infectious diseases 26 November 2021

Prevention and management of thrombosis in hospitalised patients with COVID-19 pneumonia
In this Viewpoint, the authors provide a summary of the pathophysiology of thrombosis and associated laboratory and clinical findings, and highlight key considerations in the management of coagulopathy in hospitalised patients with severe COVID-19, including coagulation assessment, identification of thromboembolic complications, and use of antithrombotic prophylaxis and therapeutic anticoagulation. We await the results of trials that are underway to establish the safety and benefits of prolonged thromboprophylaxis after hospital discharge. The Lancet respiratory medicine 25 November 2021

Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses
The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity. The Lancet infectious diseases 25 November 2021

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France
In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated. The Lancet regional health Europe 25 November 2021

Preventing pandemics in the world’s most vulnerable settings
A global framework convention must include the needs of fragile and conflict affected settings. BMJ 25 November 2021

Headlines play down the gravity of covid-19 in children
Media coverage has been criticised for minimising the effect of covid-19 on children, implying that the lives of those with underlying health conditions are somehow less important than the lives of healthy individuals BMJ 25 November 2021

Immune responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines and to natural COVID-19 infections over a three-month period
Antibody responses after the 2nd dose of BNT162b2 are higher than after the 2nd dose of ChAdOx1 and like those occurring after natural infection. T cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees. Journal of infectious diseases 25 November 2021

Audio interview: What’s gone right in our battle against Covid-19
In this audio interview conducted on November 23, 2021, the editors discuss a string of successes against Covid-19, as well as a new study of the immunity provided by previous SARS-CoV-2 infection. NEJM 25 November 2021

Effectiveness of BNT162b2 vaccine against Delta variant in adolescents
A study involving more than 94,000 vaccinated and unvaccinated adolescents between the ages of 12 and 18 years in Israel showed increasing levels of protection against Covid-19 during the first month after receipt of two vaccine doses. The estimated vaccine efficacy at 7 to 21 days after receipt of two doses was 90% against infections and 93% against symptomatic disease NEJM 25 November 2021

COVID-19 hospital activity and in-hospital mortality during the first and second waves of the pandemic in England: an observational study
here was a substantial decline in adjusted mortality rates during the early part of the first wave which was largely maintained during the second wave. The underlying reasons for consistently higher mortality risk in some ethnic groups merits further study. Thorax 24 November 2021

A retrospective analysis of COVID-19-infected patients with acute hepatitis who develop acute liver failure in a safety net hospital
Findings from this study suggest that there is a significant association between mortality and the presence of ALF in patients infected with COVID-19. Further investigation into patients with COVID-19 and ALF can lead to enhanced treatment regimens and risk stratification tools, which can ultimately improve mortality rates during these arduous times. BMJ open gastroenterology 22 November 2021

Three-month and six-month outcomes of patients with COVID-19 associated hyperinflammation treated with short-term immunosuppressive therapy: follow-up of the CHIC study
No differences in medium-term outcomes are demonstrated in survivors of COVID-19-associated hyperinflammation treated or not treated with methylprednisolone with or without tocilizumab during the acute phase. Short-term benefits of this therapy, as showed in the baseline CHIC study analysis, are thus not hampered by medium-term adverse events. RMD Open 24 November 2021

Time-dependent COVID-19 mortality in patients with cancer: an updated analysis of the OnCovid Registry
The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time. JAMA 24 November 2021

mRNA vaccines: hope beneath the hype
mRNA vaccines have proven themselves as the most effective covid-19 vaccines, and their makers are now seeking to help conditions from cancer to HIV. Andy Extance investigates their promise and limitations. BMJ 24 November 2021

A possible role for Anti-idiotype Antibodies in SARS-CoV-2 infection and vaccination
The authors hypothesise that anti-idiotype immune responses may contribute to rare adverse events, such as myocarditis, after SARS-CoV-2 vaccination, as well as to sequelae of Covid-19 that persist after the resolution of infection NEJM 24 November 2021

Severity of SARS-CoV-2 reinfections as compared with primary infections
In this report from Qatar, the severity of SARS-CoV-2 second infections was investigated. The severity of illness associated with second infections was much lower that that associated with initial infections. NEJM 24 November 2021

Infants younger than 6 months old infected by SARS-CoV-2 show the highest respiratory viral loads
There is a paucity of reports on the characteristics of SARS-CoV-2 infection in infants, since most studies have grouped infants with older children. The authors analyzed the viral loads of 45,318 SARS-CoV-2-positive nasopharyngeal swab samples obtained in Buenos Aires, Argentina. Infants younger than 6 months old presented higher viral loads than any other age group. Children older than 6 months showed significantly lower viral loads, similar to those founds in adults. This observation raises new questions regarding the role of infants in the spreading of SARS-CoV-2 infection. Journal of infectious diseases 24 November 2021

Assessment of 4 Doses of SARS-CoV-2 Messenger RNA–based vaccine in recipients of a solid organ transplant
In this case series study, the author’s findings were similar to those of a prior study, in which a fourth dose of SARS-CoV-2 vaccine was associated with slightly improved humoral response among patients with a weak response after 3 doses and with no improvement among those with no response after 3 doses. JAMA 24 November 2021

COVID-19 infection among women in Iran exposed vs unexposed to children who received attenuated poliovirus used in oral polio vaccine
In this cohort study, indirect exposure to live attenuated poliovirus was associated with decreased symptomatic infection with COVID-19. Further study of the potential protective effect of OPV should be conducted, especially in nations where OPV is already in use for polio prevention and specific COVID-19 vaccines are delayed, less affordable, or fail to meet demand. JAMA 24 November 2021