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Monkeypox information
Updated 8 December 2022

Department of Health and Aged Care – health alert – Monkeypox (MPX) resources 

SA Health – health alert – Monkeypox

UpToDate – Monkeypox  if accessing outside of SA Health computer network use your library login

Monkeypox Resources for Health Professionals (Wolters Kluwer)

Monkeypox Resource Centre (JAMA)

World Health Organization Health alert

Journal articles

Breakthrough infections after postexposure vaccination against Mpox
During the current outbreak of monkeypox (recently renamed mpox), smallpox vaccination has been recommended to prevent mpox infection in persons who have had mpox exposure, but evidence to support this practice is limited.1,2 We conducted a study to evaluate potential breakthrough infections in participants who had received smallpox vaccine after high-risk exposure to mpox. In this study population, 4% of the participants who had received postexposure vaccination with a third-generation smallpox vaccine had a subsequent mpox infection during the first month after receipt of the first vaccination. NEJM 7 December 2022

Monkeypox – review article
The gradual decline in immunity to smallpox may partly explain an increase in the incidence of monkeypox in some regions where the disease is endemic. However, the current epidemic reminds us that viral emergence is a permanent phenomenon without boundaries and is often unpredictable in its nature, target, and magnitude. This outbreak illustrates how a disease affecting one region of the world can have a strong effect on areas where it is not endemic, with different target populations and new clinical presentations. NEJM 10 November 2022

Contact tracing and exposure investigation in response to the first case of Monkeypox Virus infection in the United States during the 2022 Global Monkeypox Outbreak
In a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified. Annals of infectious diseases 8 November 2022

Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study
Our data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response. These results might have implications on the expected immunogenicity of monkeypox vaccination, suggesting that it might not be necessary to vaccinate people who have already been infected. The Lancet infectious diseases 7 November 2022

Monkeypox virus and ophthalmology—A primer on the 2022 Monkeypox outbreak and Monkeypox-related ophthalmic disease
The ophthalmologist may play an important role in the diagnosis and management of monkeypox. MPXROD may be associated with severe ocular and visual morbidity. As the current outbreak evolves, up-to-date guidance from public health organizations and professional societies are critical. JAMA 3 November 2022

Ocular pox lesions in a male patient with Monkeypox treated with Tecovirimat
Monkeypox can be transmitted via bodily fluids, blood, infected lesions, or respiratory droplets. The infection is usually self-limited, lasting 2 to 4 weeks. Along with cutaneous and systemic findings, ocular manifestations include conjunctivitis, eyelid edema, keratitis, corneal scarring, and conjunctival lesions. Herein, the authors describe a case of ocular pox lesions in a male individual successfully treated with tecovirimat, an expanded-access investigational therapy, and conservative ocular management. JAMA 3 November 2022

Transmission dynamics of monkeypox in the United Kingdom: contact tracing study
Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods. BMJ 2 November 2022

Monkeypox : review article
The gradual decline in immunity to smallpox may partly explain an increase in the incidence of monkeypox in some regions where the disease is endemic. However, the current epidemic reminds us that viral emergence is a permanent phenomenon without boundaries and is often unpredictable in its nature, target, and magnitude. This outbreak illustrates how a disease affecting one region of the world can have a strong effect on areas where it is not endemic, with different target populations and new clinical presentations. NEJM 26 October 2022

Monkeypox: Challenging clinical questions
This article summarizes the ACP/Annals virtual forum held on 11 October 2022. Annals of internal medicine 14 October 2022

Neonatal Monkeypox virus infection
Reports of neonatal monkeypox virus infection are rare. This was a case of neonatal monkeypox virus infection after peripartum transmission within a family cluster; transplacental transmission could not be ruled out. Because this was a single case, it is not possible to attribute the clinical illness to either pathogen (monkeypox virus or adenovirus) directly, nor is it possible to attribute the improvement in the infant’s clinical condition to the use of tecovirimat or cidofovir. Monkeypox virus infection should be considered in the differential diagnosis of a neonatal vesicular rash. NEJM 12 October 2022

Development of an accessible and scalable qPCR assay for Monkeypox virus detection
During the 2022 monkeypox (MPX) outbreak, testing has been limited and results delayed, allowing ongoing transmission. Gold-standard qPCR diagnostics are difficult to obtain. This research adapted the June 2022 CDC MPX qPCR assay for broad implementation. Validated using MPX stocks in a matrix with multiple sample types, MPX was detected with Cq values of 17.46 to 35.59 and titer equivalents 8.01 × 106 to 2.45 × 100 PFU/mL. The detection limit was 3.59 PFU/mL. Sensitivity and specificity were both 100%. This qPCR assay can be quickly and broadly implemented in research and public health labs to increase diagnostic capacity amid the growing MPX outbreak. Journal of infectious diseases 12 October 2022

Air and surface sampling for monkeypox virus in a UK hospital: an observational study
These data show contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures. The Lancet microbe 7 October 2022

Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study
Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact. The Lancet infectious diseases 7 October 2022

Asymptomatic monkeypox infection: a call for greater control of infection and transmission
National surveillance programmes should be conducted, particularly among populations at high risk of infection, to detect asymptomatic cases. Such surveillance will require rapid diagnostic or home-based tests that could identify undiagnosed infections. Surveillance at a country's entry points (eg, airports) might be effective, particularly in non-endemic countries with little evidence of local transmission, similar to approaches previously suggested for asymptomatic COVID-19 transmission.9,  10 Health-care providers should also establish a proper differential diagnosis before excluding monkeypox, especially considering the increasing non-specific presentations of the disease. Finally, cases could be decreased and the processes of case identification and contact tracing could be facilitated by individuals limiting their numbers of sexual partners and by limitations on areas and gatherings where people commonly engage in anonymous sexual activities. The Lancet microbe 6 October 2022

Recognizing minimal cutaneous involvement or systemic symptoms in Monkeypox
In patients with umbilicated or ulcerated lesions, particularly localized to the anogenital region, clinicians should perform a thorough social history and maintain a high index of suspicion for monkeypox, even in those with mild constitutional symptoms, who report a new sexual partner in the preceding 2 weeks. Increased public awareness of risk factors, the ability to recognize subtle skin findings, as well the increased availability/dissemination of vaccines will be important in containing and preventing further outbreaks. JAMA 6 October 2022

Human Monkeypox virus infection in the immediate period after receiving modified Vaccinia Ankara vaccine
In this small study, the majority of postvaccination monkeypox infections occurred within 2 weeks of receiving the first dose of MVA-BN, before full effectiveness was likely to have been achieved, in line with published immunogenicity data. Because the incubation period for monkeypox is 3 to 17 days, some of the cases occurring between 1 and 14 days after vaccination may not represent true vaccine failure because patients may have sought vaccination after realizing they were exposed. Of concern is that at least 2 breakthrough infections were observed in individuals at least 3 weeks after a second dose. JAMA 30 September 2022

Intradermal vaccination for Monkeypox — Benefits for individual and public health
Despite limited clinical evidence, all available data suggest that intradermal administration of JYNNEOS will be as immunogenic as subcutaneous dosing for preventing monkeypox infection and illness, which leads the authors to favor intradermal use from both the individual and public health perspectives. The Centers for Disease Control and Prevention and the FDA are committed to performing the studies needed to assure that these expectations are borne out. In the meantime, they urge people who are at the highest risk for infection to receive both doses of the two-dose vaccine, and we encourage manufacturers to consider routinely testing intradermal dose administration in future clinical vaccine trials, in order to expand our understanding of this operationally attractive option. The currently available evidence suggests that shifting to intradermal dosing that requires less vaccine is not a lesser option. Rather, it is a rational, evidence-informed means of advancing access, equity, and our chances of controlling the monkeypox outbreak. NEJM 29 September 2022

Neurologic complications of Smallpox and Monkeypox: A review
Monkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness. JAMA 20 September 2022

Monkeypox prevention and treatment while nursing
Although no specific guidelines have appeared for monkeypox, individuals with smallpox are recommended not to breastfeed their infant because of the risk of passing variola virus to the infant through direct contact. Presumably, the same precautions apply with monkeypox. Providing pumped milk to the infant may be possible if no lesions are near the breast and adequate precautions are taken with respect to cleaning hands, breasts, breast pumps, and any other apparatuses used to provide milk to the infant. As the current monkeypox situation evolves, recommendations may change, so refer to the CDC website for the most up-to-date information Breastfeeding medicine 15 September 2022

Annals on call - Diagnosis and treatment of Monkeypox Proctitis
In this episode of Annals On Call, Dr. Centor discusses the diagnosis and treatment of monkeypox proctitis with Drs. Jose Lucar and Tara Palmore. Annals of internal medicine 13 September 2022

Vaccinia-virus-based vaccines are expected to elicit highly cross-reactive immunity to the 2022 Monkeypox Virus
Beginning in May 2022, a novel cluster of monkeypox virus infections was detected in humans. This virus has spread rapidly to non-endemic countries, sparking global concern. Specific vaccines based on the vaccinia virus (VACV) have demonstrated high efficacy against monkeypox viruses in the past and are considered an important outbreak control measure. Viruses observed in the current outbreak carry distinct genetic variations that have the potential to affect vaccine-induced immune recognition. Here, by investigating genetic variation with respect to orthologous immunogenic vaccinia-virus proteins, we report data that anticipates immune responses induced by VACV-based vaccines, including the currently available MVA-BN and ACAM2000 vaccines, to remain highly cross-reactive against the newly observed monkeypox viruses. Viruses 3 September 2022

Reports of asymptomatic Monkeypox suggest that, at the very least, some infections go unnoticed
Two recent case reports from Europe have raised the possibility that some monkeypox virus infections may be asymptomatic. Whether or not these infections were truly symptom free, the studies suggest that clinicians and individuals at high risk should be aware that monkeypox can go unnoticed—possibly even when it’s transmissible. JAMA 31 August 2022

Monkeypox Virus infection in humans across 16 Countries — April–June 2022
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread. NEJM 25 August 2022

Compassionate use of Tecovirimat for the treatment of Monkeypox infection
The authors assessed adverse events and clinical resolution of systemic symptoms and lesions in an uncontrolled cohort study of patients with monkeypox who were treated with tecovirimat on a compassionate use basis. In this preliminary study, oral tecovirimat was well tolerated by all patients with monkeypox infection, with minimal adverse effects. However, adverse effects could not always be differentiated from symptoms related to the infection. No control group was included, limiting conclusions of antiviral efficacy pertaining to duration of symptoms or severity. Time from symptom onset to presentation was variable among patients, and conclusions related to antiviral use vs natural evolution of disease should be made with caution. Limited clinical data exist on the use of tecovirimat for monkeypox infection. In one case report, no new lesions followed 24 hours of therapy and no adverse effects occurred by treatment completion at 14 days. JAMA 22 August 2022

How does monkeypox spread? An epidemiologist explains why it isn’t an STI and what counts as close contact
The monkeypox virus typically spreads through direct contact with respiratory secretions, such as mucus or saliva, or skin lesions. Skin lesions traditionally appear soon after infection as a rash – small pimples or round papules on the face, hands or genitalia. These lesions may also appear inside the mouth, eyes and other parts of the body that produce mucus. They can last for several weeks and be a source of virus before they are fully healed. Other symptoms usually include fever, swollen lymph nodes, fatigue and headache. MJA Insight 22 August 2022

Audio interview: Responding to Monkeypox
In this audio interview conducted on August 16, 2022, the editors are joined by White House National Monkeypox Response Deputy Coordinator Demetre Daskalakis to discuss the new public health emergency and what HIV and Covid-19 have taught us. NEJM 18 August 2022

Update on the Monkeypox Outbreak
The current monkeypox outbreak illustrates why global health cannot be ignored. Despite monkeypox being endemic in Africa for decades, clinical trials on treatments and vaccines were not done. Now more than 3 months into the global monkeypox outbreak, there is much to learn. While test capacity has been increased, more is needed. Contact tracing is not happening, and data systems are not informing the response in rapid fashion. Many individuals at risk for monkeypox may not be engaged with the health care system, making diagnosis, containment, and prevention challenging. The demand for vaccines far exceeds availability. Although the supply of tecovirimat has increased, this drug must still be used under an IND protocol, which limits access. In addition, a decentralized and wholly underresourced public health infrastructure is even more strained as officials must now respond to both COVID-19 and monkeypox. JAMA 11 August 2022

The changing face of monkeypox
What should patients and clinicians look out for? BMJ 10 August 2022

Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study
In this cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. The Lancet 8 August 2022

Ophthalmic manifestation of monkeypox infection
Despite mucosal localisation of vesicles being not uncommon in monkeypox, the diagnosis might be overlooked. During the ongoing monkeypox outbreak, monkeypox should be included in the differential diagnosis of patients with vesicular and pustular eye lesions, especially in the presence of epidemiological links or risk factors. The Lancet infectious diseases 29 July 2022

Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series
These findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission. BMJ 28 July 2022

Monkeypox virus infection in humans across 16 countries — April–June 2022
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread. NEJM 21 July 2022

Is Australia ready for monkeypox?
Disease control efforts can draw on lessons from the past and prevent the epidemic from becoming established in Australia MJA 18 July 2022

Monkeypox emerges on a global scale: a historical review and dermatological primer
The current monkeypox outbreak reawakens the concern that poxviridae have high potential of zoonotic spillover and for causing pandemic.1 Much fieldwork and research has been done by healthcare and public health workers in Africa during previous human outbreaks, and their knowledge should inform our global response to the current outbreak. However, unusual clinical presentations now have potential implications in recognizing disease. Infections from poxviridae such as monkeypox have common cutaneous signs that occur early, may be related to periods of transmissibility, and can leave scarring. Therefore, dermatologists will play a key role in recognizing and diagnosing infections, and in educating and preparing front-line healthcare workers for early detection of new cases and clusters of monkeypox. Journal of the American Academy of Dermatology 8 July 2022

Efficacy of biocidal agents and disinfectants against the monkeypox virus and other orthopoxviruses
As orthopoxviruses may stay infectious on inanimate surfaces under laboratory conditions for up to 42 days, disinfection may be relevant in the surroundings of confirmed cases. The aim of this review was to evaluate published data on the antiviral efficacy of biocidal agents and disinfectants against the monkeypox virus and other orthopoxviruses. Journal of hospital infection 28 June 2022

The outbreak of monkeypox 2022: An overview
On May 6, 2022 an outbreak of monkeypox (MPX) was confirmed in the United Kingdom, originating from a British resident who had travelled to Nigeria. As of May 21, 2022, 92 cases have been confirmed worldwide, from 13 countries where monkeypox virus (MPXV) is not endemic. Reported cases thus far have mainly but not exclusively been identified among gay and bisexual men aged 20–50. MPXV is a viral zoonosis transmitted to humans via contacting or eating an infected animal, and direct connect with natural host’s blood and body fluids. In addition to contacting with a patient’s respiratory droplets, lesions, body fluids and polluted personal objects. Symptoms including shivers, headaches, fainting, backaches, and myodynia do not have any specific characteristics making it difficult to establish a proper diagnosis. Nevertheless, lymphatic hyperplasia, one of the most common symptoms of monkeypox, can be useful for diagnosing the disease. Clinical symptoms help establish the suspicion of monkeypox. However, in the absence of confirmed diagnostic tests it is very difficult to verify the disease and determine its cause based on clinical symptoms alone. There are numerous methods for detecting MPX, involving genetic, phenotypic, immunological methods, and electron microscopy. These tests require modern equipment and expert hands, which may not be available in developing countries where this disease is prevalent. Currently, there is no definite treatment for MPX. CDC recommends administering the smallpox vaccine within 4 days of exposure which may prevent the disease from happening, and within 2 weeks to reduce symptoms severity. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms. Annals of medicine and surgery 24 June 2022

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UpToDate

COVID-19 and asthma control in children 
Initial data suggested that COVID-19 did not increase asthma morbidity in children, contrary to that expected for a viral respiratory infection. However, asthma control may have improved during the early waves of the pandemic due to an overall decrease in viral respiratory infections. A comparison of nearly 62,000 children with asthma from 108 health care systems in the United States from March 2020 through February 2021 found that a SARS CoV-2 polymerase chain reaction-positive test was associated with increased rates of emergency department visits, hospitalizations, and use of short-acting beta agonist and oral glucocorticoids in the six months following the positive test compared with those who tested negative [17]. This reinforces the importance of patients continuing medications necessary to maintain optimal asthma control so as to better weather COVID-19 and other viral respiratory infections. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies", section on 'Advice related to Covid-19'.) 
 
Drainage or splenectomy for splenic abscess
Splenic abscess is an uncommon infection that typically results from a hematogenous source such as endocarditis. Along with broad-spectrum antibiotics, a procedure is often needed to remove the fluid collection. A new systematic review of splenic abscess treatment in nearly 600 patients found that approximately half were treated with percutaneous drainage and half with splenectomy [25]. There were no statistically significant differences in mortality or complications. Drainage is less invasive and was associated with trends toward lower mortality and complication rates, but this may have reflected differences in patient populations or local expertise. The choice of procedure is individualized; percutaneous drainage may be preferable to some individuals if feasible. (See "Evaluation of splenomegaly and other splenic disorders in adults", section on 'Management (abscess/infarction)'.)

Palivizumab for prevention of hospitalization during the 2022-2023 RSV season
During the COVID-19 pandemic, interseasonal respiratory syncytial virus (RSV) activity increased in some regions, resulting in increased pediatric hospitalizations. In regions with interseasonal activity similar to that in a typical fall-winter season, expert groups supported administration of palivizumab to eligible children outside of the typically recommended schedule. If regional RSV activity persists at high levels through the fall and winter of the 2022-2023 RSV season, the American Academy of Pediatrics supports administration of more than five consecutive doses of palivizumab to eligible children who initiated palivizumab earlier than typically recommended [45]. Information about state-level RSV activity in the United States is available from the Centers for Disease Control and Prevention. We agree with this endorsement. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Increased interseasonal activity during COVID-19 pandemic'.)

Effect of SGLT2 inhibitors on kidney disease progression 
UpToDate recommends therapy with a sodium-glucose co-transporter 2 (SGLT2) inhibitor in both patients with diabetic kidney disease and those with proteinuric nondiabetic kidney disease. A meta-analysis of 13 trials and more than 90,000 participants with and without preexisting chronic kidney disease (including the CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials) examined the effect of SGLT2 inhibitors on kidney disease progression, which was defined as a sustained ≥50 percent decline in estimated glomerular filtration rate (eGFR), need for maintenance dialysis or kidney transplantation, a sustained decline in eGFR to <10 to 15 mL/min/1.73 m2, or death from kidney failure [1]. Compared with placebo, SGLT2 inhibitors reduced the rate of kidney disease progression regardless of whether the patient had diabetes. The data from this large meta-analysis support our current recommendations. (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.) 

Timing of preoperative hemodialysis and postoperative mortality in patients with end-stage kidney disease 
For patients on maintenance hemodialysis, a dialysis treatment is usually performed on the day before or the day of an elective surgical procedure. In a retrospective cohort study of approximately 350,000 patients with end-stage kidney disease on hemodialysis, day-long intervals between dialysis and surgery of zero (ie, dialysis on the same day of surgery), one, two, and three days were associated with 90-day postoperative mortality risks of 4.0, 4.2, 4.7, and 5.2 percent, respectively [6]. These data support the current practice of scheduling maintenance hemodialysis on the day before or the day of a surgical procedure when practical. (See "Medical management of the dialysis patient undergoing surgery", section on 'Routine dialysis prior to surgery'.) 

Long-term results of renal denervation in patients with resistant hypertension 
Renal denervation lowers blood pressure in patients with untreated and treated hypertension, although the usefulness of the procedure in patients with resistant hypertension was unclear. In the SYMPLICITY HTN-3 trial, renal denervation, compared with a sham-control procedure, did not significantly improve ambulatory blood pressure at six months. However, renal denervation produced a larger decrease in ambulatory systolic blood pressure at 12 months (-7.5 versus -0.1 mmHg) and 36 months (-15.6 versus -0.3 mmHg) [12]. These data suggest that renal denervation can effectively lower blood pressure in patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Renal denervation'.) 

Dose of LMW heparin for VTE prevention in pregnancy 
Low molecular weight (LMW) heparin is used for venous thromboembolism (VTE) prophylaxis during pregnancy and postpartum, but optimal dosing has been unclear. The Highlow trial evaluated dosing in 1110 pregnant individuals with a prior VTE receiving LMW heparin for VTE prophylaxis from the first trimester to six weeks postpartum [16]. Compared with weight-adjusted intermediate dosing, those assigned to daily fixed low-dose (60 mg) LMW heparin had a slightly higher rate of VTE (1 percent in both groups antepartum, 2 versus 1 percent postpartum); the difference did not reach statistical significance. Bleeding risk was 4 percent in each group. While we continue to perform an individualized risk assessment for each patient, this trial provides reassurance for the efficacy of fixed low-dose LMH heparin, especially antenatally. (See "Use of anticoagulants during pregnancy and postpartum", section on 'LMW heparin'.) 

CDC updates opioid prescribing guidelines 
The United States Centers for Disease Control and Prevention (CDC) has published a new guideline for prescribing opioids for acute, subacute, and chronic pain, updating their 2016 guideline (table 4). The guideline is intended for clinicians who prescribe opioids to outpatients ≥18 years of age and does not apply to pain related to sickle cell disease, cancer, palliative care, or end of life care [32]. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Opioid therapy in the context of the opioid epidemic'.) 

DHA supplementation for very low birth weight infants 
The long-term effect of enteral supplementation with docosahexaenoic acid (DHA) on cognitive outcomes in low birth weight premature infants has been inconsistent. In a continuation of an earlier trial in 480 premature infants <29 weeks gestation assigned to DHA (60 mg/kg per day) or placebo at the initiation of enteral feeding, scores for full-scale intelligence quotient (IQ) at five years of corrected age were higher for the DHA-supplemented group (mean difference 3.5 points [95% CI 0.4-6.5], a 4-point difference is clinically relevant) [13]. Based on these findings and benefits identified for other comorbidities of prematurity in other studies, we suggest that premature infants receiving human milk also receive supplementation with DHA. Our approach is to add a human milk fortifier that contains these nutrients to breast milk. (See "Long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants", section on 'Very low birth weight infants'.) 

Persistence of asthma control after stopping omalizumab therapy 
Omalizumab, an anti-IgE monoclonal antibody, is an effective add-on therapy for uncontrolled moderate-to-severe asthma but the optimal duration of therapy and the persistence of benefit after discontinuation are unclear. In an analysis of the French national healthcare database that included over 19,000 patients with asthma (over 2000 children) who received omalizumab for a median duration of approximately 4.5 years, rates of asthma hospitalizations were reduced by 75 percent and the need for oral corticosteroids by 30 percent after two years of treatment [1]. Among patients with asthma control during treatment, symptoms remained controlled in a significant percentage one, two, and three years after discontinuation (76, 44, and 33 percent in children and 70, 39, and 24 percent in adults, respectively). These findings indicate a lasting benefit after discontinuation of omalizumab in patients with controlled asthma and provide a basis for anticipatory guidance for those who discontinue treatment. (See "Anti-IgE therapy", section on 'Observations post-treatment'.) 

Insulin resistance in severe asthma 
Several studies have identified an increased prevalence of asthma and difficult-to-control asthma among obese individuals, although the exact reason for the association is not known. A recent study of patients with severe asthma included extensive metabolic phenotyping as well as long-term follow-up [2]. Patients with insulin resistance demonstrated more rapid decline in lung function and increased resistance to beta-agonist and oral glucocorticoid therapies compared with patients having normal insulin sensitivity. Whether targeting insulin resistance can impact these severe asthma features requires further investigation. (See "Severe asthma phenotypes", section on 'Asthma associated with obesity'.) 

Oral antihyperglycemics and prevention of COPD exacerbations 
Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT-2) inhibitors are antihyperglycemics increasingly used for the treatment of type 2 diabetes. In a recent study of patients with COPD and new initiation of an antihyperglycemic agent, patients who began GLP-1 receptor agonists or SGLT-2 inhibitors were less likely to be hospitalized for COPD exacerbations than similar patients receiving sulfonylureas [9]. Future trials are needed to determine whether use of GLP-1 receptor agonists or SGLT-2 inhibitors are preferable to other antihyperglycemic agents in patients with diabetes mellitus and risk for COPD exacerbations. (See "COPD exacerbations: Prognosis, discharge planning, and prevention", section on 'GLP-1 receptor agonists and SGLT-2 inhibitors, for diabetic patients'.) 

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Cochrane library

Pre‐emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer
For people with cancer who are at high‐risk of febrile neutropenia, pre‐emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over‐all and IFD‐related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain. Cochrane Database of Systematic Reviews – Intervention 28 November 2022

Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Cochrane Database of Systematic Reviews – Intervention 25 November 2022

Antipsychotic dose reduction compared to dose continuation for people with schizophrenia
This review synthesised the latest evidence on the reduction of antipsychotic doses for stable individuals with schizophrenia. There was no difference between dose reduction and continuation groups in quality of life, functioning, and number of participants with at least one adverse effect. However, there was a higher risk for relapse and dropouts, and potentially for rehospitalisations, with dose reduction. Of note, the majority of the trials focused on relapse prevention rather potential beneficial outcomes on quality of life, functioning, and adverse effects, and in some studies there was rapid and substantial reduction of doses. Further well‐designed RCTs are therefore needed to provide more definitive answers. Cochrane Database of Systematic Reviews – Intervention 24 November 2022

High versus low blood pressure targets for cardiac surgery while on cardiopulmonary bypass
A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide confidence interval (Cis), further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with cardiopulmonary bypass (CPB). Cochrane Database of Systematic Reviews – Intervention 30 November 2022

Cervical pessary for preventing preterm birth in singleton pregnancies
In women with a singleton pregnancy, cervical pessary compared with no treatment or vaginal progesterone may reduce the risk of delivery before 34 weeks or 37 weeks, although these results should be viewed with caution due to uncertainty around the effect estimates. Cochrane Database of Systematic Reviews – Intervention 1 December 2022

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Cochrane clinical answers

For adults hospitalized with acute or suspected COVID‐19, what are the benefits and harms of systemic corticosteroids?
Compared with no corticosteroids, moderate‐certainty evidence shows that for adults hospitalized with acute or suspected COVID‐19 (disease severity from 4 to 9 on the World Health Organization Clinical Progression Scale), systemic corticosteroids probably reduce overall mortality (246 vs 274 per 1000 people; all results on average); one trial with 1535 participants and some concerns in the overall risk of bias reported a higher mortality rate with corticosteroids for a subgroup of people not receiving oxygen (178 vs 140 per 1000 people). Cochrane clinical answers 21 November 2022

How does pharmacological treatment compare with placebo for people with coronary artery disease and comorbid depression?
For adults with coronary artery disease and depression, pharmacological treatment may be beneficial for reducing depression symptoms and increasing depression remission; however, the evidence is sparse due to the low number of trials and heterogeneity of the examined populations and interventions. Cochrane clinical answers 28 November 2022

What are the benefits and harms of mobility training for older community‐dwelling people with frailty?
In older adults living in the community with frailty, mobility training (including gait, balance and functional exercises, strength or resistance training, endurance training, or a combination of these) resulted in improved mobility and better function when compared with usual care, based on high‐ to moderate‐certainty evidence. Cochrane clinical answers 28 November 2022

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Evidently Cochrane

Giving information after stroke: what’s helpful
James Garrard (Specialist Registrar in Stroke and Geriatric medicine) and Annette Dancer (stroke survivor and research advisor) give their reflections on giving information to people after stroke, and look at the evidence on what might be helpful for stroke survivors and their carers. Evidently Cochrane 1 December 2022

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MJA

Twelve‐month mortality outcomes for Indigenous and non‐Indigenous people admitted to intensive care units in Australia: a registry‐based data linkage study
Twelve‐month mortality outcomes are poorer for people admitted to ICUs in Australia than for the general population. Further, after adjusting for age and other factors, survival outcomes are poorer for Indigenous than non‐Indigenous people admitted to ICUs. Critical illness may therefore contribute to shorter life expectancy among Indigenous Australians. MJA 21 November 2022

Precision medicine in Australia: now is the time to get it right
Implementation science based health care research is urgently needed for genomic and precision medicine in Australia. MJA 28 November 2022

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BMJ

Understanding and neutralising covid-19 misinformation and disinformation
Key messages

  • Research on the political and commercial determinants of health points to the importance of understanding how evidence is generated and promulgated
  • During the covid-19 pandemic, several groups have been active in opposing evidence based public health measures
  • A rapid rise in misinformation and disinformation in digital and physical environments over a short period is called an “infodemic”
  • Active management of infodemics must form part of a comprehensive pandemic response
  • Further investigations into the social and public health effects of misinformation groups are needed to inform policy

BMJ 23 November 2022

Endometriosis
What you need to know

  • Consider endometriosis when women of reproductive age present with abdomino-pelvic pain associated with menstruation, sexual intercourse, urination, defecation, and/or infertility 
  • Consider gynaecology referral if three months of simple analgesia (with or without combined oral contraceptive pill) is ineffective for suspected endometriosis
  • A normal pelvic exam and/or pelvic ultrasound does not exclude endometriosis

BMJ 28 November 2022

Assessment of suspected motor neuron disease
What you need to know

  • Amyotrophic lateral sclerosis (ALS, a form of motor neuron disease) was previously considered rare, but incidence is expected to increase by 30% by 2040
  • ALS is a multisystem disease that commonly causes cognitive and behavioural changes; up to one quarter of patients meet the criteria for dementia
  • Diagnostic delay may reduce access to treatment and support that could improve survival and quality of life; refer urgently for expert assessment patients with asymmetrical painless progressive weakness or unexplained changes to swallowing

BMJ 23 November 2022

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial
Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. BMJ 23 November 2022

Advances in diagnosis and treatment of testicular cancer
This review summarizes recent advances and discusses relevant issues in the biology and management of testicular cancer. BMJ 23 November 2022

Oxygen administration during surgery and postoperative organ injury: observational cohort study
Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded. BMJ 30 November 2022

Association between grass, tree and weed pollen and asthma health outcomes in Adelaide, South Australia: a time series regression analysis
Monthly risk assessment indicated that most pollen-related asthma health outcomes in children occur in the colder part of the year, while adults are affected in the warm season. The findings indicate a need for year-round pollen monitoring and related health campaigns to provide effective public health prevention BMJ 22 November 2022

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JAMA

Effect of regular, low-dose, extended-release Morphine on chronic breathlessness in chronic obstructive pulmonary disease : The BEAMS randomized clinical trial
Extended-release morphine compared with placebo did not significantly reduce the intensity of worst breathlessness in people with COPD. JAMA 29 November 2022

Risk factors associated with first and second primary melanomas in a high-incidence population
Findings of this cohort study suggest that within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanomas. JAMA 23 November 2022

Effect of irrigation fluid temperature on recurrence in the evacuation of chronic subdural hematoma : A randomized clinical trial
In this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with chronic subdural hematoma (cSDH). When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care. JAMA 21 November 2022

Effect of a virtual reality environment using a domed ceiling screen on procedural pain during intravenous placement in young children: A randomized clinical trial
The findings of this trial indicate that displaying VR using a domed ceiling screen may be an effective distraction method that reduces distress in young children undergoing IV placement. JAMA 21 November 2022

Association between hemorrhage control interventions and mortality in US trauma patients with hemodynamically unstable pelvic fractures
This study found that among patients with pelvic fracture who received early transfusions and at least 1 invasive pelvic hemorrhage control intervention, more than 1 in 3 died, despite the availability of advanced hemorrhage control interventions. Only pelvic AE was associated with a reduction in mortality. JAMA 30 November 2022

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Other journals

Understanding patient preferences for emergency care for lower triage acuity presentations during GP hours: a qualitative study in Australia
Multiple factors led patients to seek ED care for low acuity presentations during GP hours. Some of these factors could be addressed to meet patient needs in the community, however this is currently not the case. Addressing these factors to improve access to GP clinics and the availability of services outside the hospital setting could reduce ED presentations and likely improve patient experience. BMC health services research 29 November 2022

Associations of extended work, higher workloads and emotional work demands with sleep disturbance among night-shift workers
Extended work, higher workload, and emotional work demands were significant factors for sleep disturbance among night-shift workers. These findings highlight the importance of adjusting work demands and mitigating extended work to reduce sleep disturbance in night-shift workers. BMC public health 21 November 2022

A roadmap to reduce information inequities in disability with digital health and natural language processing
As medical successes have increased lifespans and improved health outcomes around the world, global ageing and more frequent occurrence of chronic diseases are contributing to a corresponding increase in the impact of disability worldwide. People with disabilities often experience injustices and ableism in healthcare, and as the prevalence and impacts of disability continue to grow, there is a clear need for more disability-focused and disability-aware practices in healthcare. Here, the authors present a roadmap towards bringing better information on the concrete impacts and lived experience of disability into healthcare practice, as a key step towards addressing this need. Plos digital health 17 November 2022

Associations between data-driven lifestyle profiles and cognitive function in the AusDiab study
In this population of community-dwelling Australian adults, a sub-group characterised by moderate activity levels and higher rates of non-smoking had better cognitive function compared to two other identified sub-groups. This study demonstrates how LPA can be used to highlight sub-groups of a population that may be at increased risk of dementia and benefit most from lifestyle-based multidomain intervention strategies. BMC public health 29 November 2022

Television-viewing time and bodily pain in Australian adults with and without type 2 diabetes: 12-year prospective relationships
Bodily pain severity increased with age in middle-aged and older Australian adults over a 12-year period, and increments in TV time predicted increased bodily pain severity at any given period, which was more pronounced in those with T2D. While increasing physical activity is a mainstay of the prevention and management of chronic health problems, these new findings highlight the potential of reducing sedentary behaviours in this context. BMC public health 29 November 2022

A case-control study on the effects of incomplete, one, and more than one dexamethasone course on acute respiratory problems in preterm neonates born between 280 and 366 weeks of gestation
Preterm singleton newborns whose mothers were given multiple courses of dexamethasone had an increased incidence of RDS and other adverse outcomes than those of mothers receiving a full course. However, very preterm newborns whose mothers were administered 1 full dexamethasone course had a significantly lower incidence of RDS than those whose mothers were given partial courses. BMC pregnancy and childbirth 28 November 2022

The association between endometriosis and risk of endometrial cancer and breast cancer: a meta-analysis
Endometriosis can increase the risk of endometrial cancer and breast cancer, and women with endometriosis are recommended to receive routine screening in long-term management. BMC women’s health 18 November 2022

Temperature control after cardiac arrest
Most of the patients who die after cardiac arrest do so because of hypoxic-ischemic brain injury (HIBI). Experimental evidence shows that temperature control targeted at hypothermia mitigates HIBI. Critical care 24 November 2022

Association between exclusive breastfeeding and postpartum post-traumatic stress disorder
Exclusive breastfeeding up to 42 days after childbirth was associated with reduced risk of postpartum PTSD. While the potential for reverse causation cannot be ruled out, strategies to improve rates of exclusive breastfeeding through teaching, counselling, and support may benefit mothers and their infants by reducing the risk of postpartum PTSD. International breastfeeding journal 23 November 2022

Increased CO2 levels in the operating room correlate with the number of healthcare workers present: an imperative for intentional crowd control
The air in an operating room becomes more contaminated as the occupancy of the room increases. Individuals residing in a room can potentially emit infectious agents. In order to inhibit and better understand the epidemiology of surgical site infections, it is important to develop procedures to track room occupancy level and respiration. Patient safety in surgery 17 November 2022

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Access medicine

Recent e-books added to the catalogue – you will need your library login

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AIHW

Health expenditure Australia 2020-21
Regular reporting of national health expenditure is vital to understanding the health system and its relationship to the economy as a whole.

  • Total health spending was $220.9 billion, equating to $8,617 per person.
  • Health spending increased by 7.1% in real terms, which was higher than the average growth rate of the decade (3.4% per year).
  • Government health spending increased by 7.3% while non-government spending rebounded from low growth in the previous year to increase by 6.4% in 2020–21.

AIHW 23 November 2022

Injury in Australia
Injury is a major cause of hospitalisation and death in Australia. This web report explores injury hospitalisations in 2020-21 and injury deaths in 2019-20. It describes the main causes of injury and their impact on specific populations. AIHW 25 November 2022

Australia's mothers and babies
The health of both mothers and babies can have important ongoing implications. In 2020, there were 295,976 babies born to 291,712 mothers in Australia. Explore the characteristics and health of mothers and their babies through interactive data visualisations, and in-depth information and trends on the antenatal period, labour and birth, and outcomes for babies at birth. This web report also provides information on stillbirths, neonatal and maternal deaths, including causes, maternal characteristics, timing and investigations. AIHW 29 November 2022

National Perinatal Data Collection data availability resource
The AIHW’s National Perinatal Data Collection (NPDC) is a national population-based cross-sectional collection of data on pregnancy and childbirth in Australia. The NPDC data availability resource is an interactive (data visualisation) information resource detailing all the data held in the NPDC. It includes timely information on data availability at the national and state/territory level, detailed information on the history of data elements (including data development), and practical information for users of the data. AIHW 30 November 2022

National Cervical Screening Program monitoring report 2022
This is the fourth report to monitor the National Cervical Screening Program since it introduced 5-yearly HPV tests in December 2017. In 2018–2021, more than 4.2 million people aged 25–74 participated, and in 2021, 11% of screening HPV tests performed were positive for HPV types that cause cervical cancer. Cervical cancer incidence and mortality remained low at 11 new cases and 2 deaths per 100,000 women, respectively. AIHW 1 December 2022

Disease expenditure in Australia 2019–20
2019–20 data is presented using Australian Burden of Disease Study (ABDS) conditions including COVID–19, with spending reported by health care sector, type of condition, age group, and sex. Information is presented on the web pages using interactive visualisations, and a downloadable Microsoft Excel workbook. AIHW 1 December 2022

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Updated 9 December 2022

Seeing blue dots after COVID-19 infection
To the author’s knowledge, 16 cases of acute macular neuroretinopathy (AMN) in patients with COVID-19 have been reported, all in adults aged 21 to 71 years (mean age, 26 years). The median time from onset of symptoms to diagnosis was 17 days, ranging from 4 to 35 days. To their knowledge, no cases of SARS-CoV-2 associated with AMN have been reported in a child (younger than 18 years). The association of symptomatic SARS-CoV2 with new onset of AMN findings could be consistent with a causal link. JAMA 8 December 2022

Evaluation of publication of COVID-19–related articles initially presented as preprints
Researchers are able to communicate their findings immediately by posting papers on preprint servers, which has become even more important during the COVID-19 pandemic. In this cross-sectional study, we observed that slightly more than half of the preprints related to COVID-19 posted on medRxiv in 2020 were later published in peer-reviewed journals as of October 2022. This publication rate is only slightly greater than that observed 7 months earlier in March 2022, which suggests that a substantial change in the proportion of papers subsequently published in peer-reviewed journals is not expected in the future. Another notable finding of this study is the high quality of the journals in which these articles were subsequently published, as nearly half of the preprints were published in quartile 1 journals. JAMA 8 December 2022

Efficacy of antiviral agents against Omicron subvariants BQ.1.1 and XBB
This data suggests that the omicron sublineages BQ.1.1 and XBB have immune-evasion capabilities that are greater than those of earlier omicron variants, including BA.5 and BA.2. The continued evolution of omicron variants reinforces the need for new therapeutic monoclonal antibodies for Covid-19. NEJM 8 December 2022

Neutralization of Omicron subvariant BA.2.75 after Bivalent vaccination
These data further support the cross-neutralization ability of the omicron-containing bivalent booster vaccine against emerging omicron subvariants that are not contained in the vaccine. Real-world data on the effectiveness of booster vaccines are needed to evaluate whether the potent and broad neutralizing antibody responses elicited by bivalent vaccines confer enhanced protection against Covid-19.  NEJM 8 December 2022

Audio interview: Covid-19 and health equity
In this audio interview conducted on December 6, 2022, the editors are joined infectious disease physician Matifadza Hlatshwayo Davis, Director of the St. Louis Department of Health, to discuss the challenges of bringing equity to health care and the critical need to invest in public health. NEJM 8 December 2022

Effectiveness of BNT162b2 COVID-19 vaccination in prevention of hospitalisations and severe disease in adults with SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant between June 2021 and July 2022: A prospective test negative case–control study
BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease. The Lancet regional health - Europe 7 December 2022

Awake prone positioning and covid-19
In clinical trials with selected populations and increased monitoring, awake prone positioning was found to be safe, with infrequent dislodgement of vascular catheters (2.5%) and skin breakdown or ulcers (0.7%). Given that the definitive reductions were in endotracheal intubation and not mortality, it is worth noting that participants and clinicians could not be masked and this could bias decisions about intubation. Whether due to bias or physiological effects, high quality evidence now shows that awake prone positioning can safely reduce endotracheal intubation in patients with covid-19 related hypoxaemia without increasing the risk of mortality. BMJ 7 December 2022

Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB
This data suggest that the omicron sublineages BQ.1.1 and XBB effectively evade current humoral immunity induced by mRNA vaccines or natural infection. A previous study using pseudotyped viruses reported that BQ.1.1 and XBB were less well recognised than BA.2 and BA.4/5 by plasma from convalescent individuals and mRNA vaccinees.3 These findings show that BQ.1.1 and XBB clinical isolates have higher immune evasion abilities than earlier omicron variants, including BA.5 and BA.2. The Lancet infectious diseases 7 December 2022

Prevalence and severity of symptoms 3 months after infection with SARS-CoV-2 compared to test-negative and population controls in the Netherlands
Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which is higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65. Journal of infectious diseases 7 December 2022

Infections, hospitalizations, and deaths among US nursing home residents with vs without a SARS-CoV-2 vaccine booster
In this study, during a period in which both the Delta and Omicron variants were circulating, SARS-CoV-2 booster vaccination was associated with significant reductions in SARS-CoV-2 infections, hospitalizations, and the combined end point of hospitalization or death among residents of 2 US nursing home systems. These findings suggest that administration of vaccine boosters to nursing home residents may have an important role in preventing COVID-19–associated morbidity and mortality. JAMA 7 December 2022

What will happen to the orphans of covid-19?
At least 10.5 million children have been orphaned by covid-19. BMJ 7 December 2022

Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study
Lessons learned from leveraging an existing neighbourhood-level WBE reporting dashboard include: (1) community buy-in is key, (2) public data sharing is effective, and (3) sub-ZIP-code (postal code) data can help to pinpoint populations at risk, track intervention success in real time, and reveal the effect of local clinical testing capacity on WBE's early warning capability. This successful demonstration of transitioning WBE efforts from opioids to COVID-19 encourages an expansion of WBE to tackle newly emerging and re-emerging threats (eg, mpox and polio). The Lancet microbe 6 December 2022

Omicron sublineage recombinant XBB evades neutralising antibodies in recipients of BNT162b2 or CoronaVac vaccines
The data showed that both XBB.1 and XBB.3 were much more immunoevasive than ancestral strain and BA.5.2. This immunoevasion is consistently seen in patients with different history of vaccination or infection. Since patients infected with BA.5.2 might not elicit neutralising antibody against XBB sublineage, patients who have been infected with BA.5 or those with bivalent vaccine might have a higher risk of reinfection or vaccine breakthrough infection from XBB sublineage than previous sublineages. The Lancet microbe 6 December 2022

Incidence of viral rebound after treatment with Nirmatrelvir-Ritonavir and Molnupiravir
In this study, viral rebound was uncommon in adults with COVID-19 after treatment with nirmatrelvir-ritonavir and molnupiravir, suggesting that these novel oral antivirals should be prescribed to more patients with COVID-19 in the early phase of the infection. JAMA 6 December 2022

Association of glucose-lowering drugs with outcomes in patients with Diabetes before hospitalization for COVID-19: A systematic review and network meta-analysis
These findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19–related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes. JAMA 6 December 2022

Effect of hybrid immunity and bivalent booster vaccination on omicron sublineage neutralisation
Collectively, our results show that the emerging omicron sublineages BQ.1.1 and particularly BA.2.75.2 efficiently evade neutralisation independent of the immunisation history. Although monovalent and bivalent vaccine boosters both induce high neutralising activity and increase neutralisation breadth, BA.2.75.2-specific and BQ.1.1-specific neutralisation activity remained relatively low. This finding is in keeping with the concept of immune imprinting by initial immunisation with vaccines targeting the ancestral SARS-CoV-2 B.1 lineage. The Lancet infectious diseases 5 December 2022

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study
These findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies. The Lancet gastroenterology and hepatology 5 December 2022

Efficacy and safety of Pacritinib vs placebo for patients with severe COVID-19: A phase 2 randomized clinical trial
Pacritinib did not demonstrate a significant benefit over placebo in patients with severe COVID-19. JAMA 5 December 2022

Myopericarditis after COVID-19 mRNA vaccination among adolescents and young adults: A systematic review and meta-analysis
This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations. These findings are reassuring but continued follow-up is warranted. JAMA 5 December 2022

Characterizing SARS-CoV-2 transcription of subgenomic and genomic RNAs during early human infection using multiplexed droplet digital PCR
Ct values from qPCR correlate with active viral replication. More work is needed to understand why some cultures are negative despite presence of sgRNA. Journal of infectious diseases 5 December 2022

Sex, racial, and ethnic representation in COVID-19 clinical trials: A systematic review and meta-analysis
In this systematic review and meta-analysis, aggregate differences in representation for several demographic groups in COVID-19 prevention and treatment trials in the US were found. Strategies to better ensure diverse representation in COVID-19 studies are needed, especially for prevention trials. JAMA 5 December 2022

Social determinants of health associated with COVID-19 severity during pregnancy: a multinational cohort study (in the International Registry of Coronavirus Exposure in Pregnancy)
Findings suggest that employment setting and economic status have strong associations with COVID-19 severity, which warrants considering social determinants of health in the context of assessing risk factors of more severe COVID-19 during pregnancy. BMC public health 3 December 2022

Oxidative DNA damage by N4-hydroxycytidine, a metabolite of the SARS-CoV-2 antiviral molnupiravir
Molnupiravir is an antiviral agent recently used for treating COVID-19. Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases including COVID-19. Journal of infectious diseases 3 December 2022

Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants
While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children. The Lancet regional health - Americas 1 December 2022

The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis
This work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. eClinicalMedicine 1 December 2022

Effect of wearing glasses on risk of infection with SARS-CoV-2 in the community
In this randomized clinical trial, wearing glasses in the community was not protective regarding the primary outcome of a reported positive COVID-19 test. However, results were limited by a small sample size and other issues. Glasses may be worth considering as one component in infection control, pending further studies. JAMA 1 December 2022

A Randomized Clinical TrialAssociation of initial SARS-CoV-2 test positivity with patient-reported well-being 3 months after a symptomatic illness
In this study, participants in both the COVID-19–positive and COVID-19–negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19. JAMA 1 December 2022

Association of Remdesivir treatment with mortality among hospitalized adults with COVID-19 in the United States
In this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset. JAMA 1 December 2022

Audio interview: Five disease outbreaks beyond Covid-19
In this audio interview conducted on November 29, 2022, the editors discuss ongoing outbreaks of influenza, RSV, mpox, Ebola, and cholera in the context of our response to Covid-19. NEJM 1 December 2022

Mask wars (video)
This documentary video explores the controversies surrounding masks and mask mandates throughout the centuries. The changing perceptions of masking leading up to the Covid-19 pandemic are discussed. NEJM 1 December 2022

Six-month follow-up after a fourth BNT162b2 vaccine dose
In this prospective cohort study, a third dose of the BNT162b2 vaccine led to an improved and sustained immunologic response as compared with two doses, but the additional immunologic advantage of the fourth dose was much smaller and had waned completely by 13 weeks after vaccination. This finding correlated with waning vaccine effectiveness among recipients of a fourth dose, which culminated in no substantial additional effectiveness over a third dose at 15 to 26 weeks after vaccination. These results suggest that the fourth dose, and possibly future boosters, should be timed wisely to coincide with disease waves or to be available seasonally, similar to the influenza vaccine. Whether multivalent booster doses will result in longer durability remains to be seen. NEJM 1 December 2022

Effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines against infection and mortality in children in Argentina, during predominance of delta and omicron covid-19 variants: test negative, case-control study
Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time. BMJ 30 November 2022

Mental health outcomes following COVID-19 infection: impacts of post-COVID impairments and fatigue on depression, anxiety, and insomnia — a web survey in Sweden
These findings highlight that individuals infected with COVID-19, especially those who still have experienced post-COVID impairments, are more likely to suffer from mental ill-health and may be more vulnerable for poor mental health outcomes. Therefore, more effective actions are needed to take in order to promote and protect mental health of individuals with a history of COVID-19 infection. BMC psychiatry 29 September 2022

Effectiveness of early warning systems in the detection of infectious diseases outbreaks: a systematic review
Our study was able to evaluate the effectiveness of Early Warning Systems in different contexts and resource settings based on the EWSs’ method of data collection. There is consistent evidence that EWSs compiling pre-diagnosis data are more proactive to detect outbreaks. However, the fact that Syndromic Surveillance Systems (SSS) are more proactive than diagnostic disease surveillance should not be taken as an effective clue for outbreaks detection. BMC public health 29 November 2022

Analysis of clinical outcomes of pregnant patients treated with Nirmatrelvir and Ritonavir for acute SARS-CoV-2 infection
Results of this study suggest that pregnant patients with SARS-CoV-2 infection can be safely treated with nirmatrelvir and ritonavir. JAMA 29 November 2022

Medical masks versus N95 respirators for preventing COVID-19 among health care workers : A randomised trial
Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of reverse transcriptase polymerase chain reaction (RT-PCR)–confirmed COVID-19 for medical masks when compared with hazard ratio (HRs) of RT-PCR–confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity. Annals of internal medicine 29 November 2022

Temporal improvements in COVID-19 outcomes for hospitalized adults: A post hoc observational study of Remdesivir group participants in the adaptive COVID-19 treatment trial
Changes in patient composition explained improved outcomes from Adaptive COVID-19 Treatment Trial (ACTT-1) to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved standard of care (SOC). These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. Annals of internal medicine 29 November 2022

Major update 2: Antibody response and risk for reinfection after SARS-CoV-2 infection—Final update of a living, rapid review
Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. Annals of internal medicine 29 November 2022

Outpatient treatment of confirmed COVID-19: A living, rapid review for the American College of Physicians
Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited. Annals of internal medicine 29 November 2022

Analysis of failure rates for COVID-19 entrance screening at a US academic medical center
The authors found limited benefit in maintaining hospital entrance screening for COVID-19 symptoms, exposures, or travel. Of the nearly 1 million persons screened, less than 0.1% had a failed screening. The failure rate was substantially higher in the beginning of the pandemic, possibly because of greater adherence to screening protocols and enhanced symptom and exposure vigilance. It is also possible that patient education and increased communication may have meant patients and visitors stayed home with exposures or symptoms or that people were not truthful on subsequent visits. They do not know whether having an entrance screener served as a deterrent, keeping sick persons from attempting to enter the hospital. JAMA 28 November 2022

Associations between COVID‐19 and hospitalisation with respiratory and non‐respiratory conditions: a record linkage study
SARS‐CoV‐2 infection is associated with higher incidence of hospitalisation with several respiratory and non‐respiratory conditions. Our findings reinforce the value of COVID‐19 mitigation measures such as vaccination, and awareness of these associations should assist the clinical management of people with histories of SARS‐CoV‐2 infection. MJA 28 November 2022

More proof COVID is a multi-system cluster bomb
Rowe and colleagues analysed population-wide surveillance and administrative data for all laboratory-confirmed COVID-19 cases notified to the Victorian Department of Health from 23 January 2020 to 31 May 2021 – prior to the vaccination rollout and the appearance of the Omicron variant – and linked hospital admissions data (admission dates to 30 September 2021). “A total of 20 594 COVID-19 cases were notified, and 2992 people (14.5%) were hospitalised with COVID-19,” Rowe and colleagues reported in the MJA. “The incidence of hospitalisation within 89 days of onset of COVID-19 was higher than during the baseline period for several conditions, including myocarditis and pericarditis (IRR, 14.8; 95% CI, 3.2–68.3), thrombocytopenia (IRR, 7.4; 95% CI, 4.4–12.5), pulmonary embolism (IRR, 6.4; 95% CI, 3.6–11.4), acute myocardial infarction (IRR, 3.9; 95% CI, 2.6–5.8), and cerebral infarction (IRR, 2.3; 95% CI, 1.4–3.9).” In other words, says Ms Rowe, “there are considerable risks associated with SARS-CoV-2 infection” beyond the initial COVID-19 illness. MJA insight 28 November 2022

SARS-CoV-2 Vaccine strain selection: Guidance from influenza
When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time. Journal of infectious diseases 25 November 2022

Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021–March, 2022: a national, observational, test-negative, case-control study
Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection. Journal of infectious diseases 24 November 2022

Audio interview: Making choices about Covid-19
In this audio interview conducted on November 22, 2022, the editors discuss both evolving choices about Covid vaccines and treatments as local conditions change and the current uptick in other respiratory infections. NEJM 24 November 2022

Lifting universal masking in schools — Covid-19 incidence among students and staff
Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded. NEJM 24 November 2022

Understanding and neutralising covid-19 misinformation and disinformation
Key messages

  • Research on the political and commercial determinants of health points to the importance of understanding how evidence is generated and promulgated
  • During the covid-19 pandemic, several groups have been active in opposing evidence based public health measures
  • A rapid rise in misinformation and disinformation in digital and physical environments over a short period is called an “infodemic”
  • Active management of infodemics must form part of a comprehensive pandemic response
  • Further investigations into the social and public health effects of misinformation groups are needed to inform policy

BMJ 23 November 2022

Audio interview: Making choices about Covid-19
In this audio interview conducted on November 22, 2022, the editors discuss both evolving choices about Covid vaccines and treatments as local conditions change and the current uptick in other respiratory infections. NEJM 24 November 2022

Lifting universal masking in schools — Covid-19 incidence among students and staff
Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded. NEJM 24 November 2022

Neutralization of Omicron Subvariant BA.2.75 after bivalent vaccination
These data in this study further support the cross-neutralization ability of the omicron-containing bivalent booster vaccine against emerging omicron subvariants that are not contained in the vaccine. Real-world data on the effectiveness of booster vaccines are needed to evaluate whether the potent and broad neutralizing antibody responses elicited by bivalent vaccines confer enhanced protection against Covid-19. NEJM 23 November 2022

Trends in clinician burnout with associated mitigating and aggravating factors during the COVID-19 Pandemic
Results of this survey study show that in 2020 through 2021, burnout and intent to leave gradually increased, rose sharply in late 2021, and varied by chaos, work control, teamwork, and feeling valued. Monitoring these variables could provide mechanisms for worker protection. JAMA 23 November 2022

Impact of vaccination, prior infection and therapy on Omicron infection and mortality
Booster vaccination and prior SARS-CoV-2 infection provide strong protection against ICU admission and death from omicron infection. Monoclonal antibody therapy is also beneficial. Journal of infectious diseases 23 November 2022

Protection of 2 and 3 mRNA vaccine doses against severe outcomes among adults hospitalized with COVID-19 – VISION Network, August 2021 – March 2022
COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated. Journal of infectious diseases 23 November 2022

Implementing mandatory COVID‐19 vaccination for Australian aged care workers
Despite concerns about the risk of workforce attrition and absenteeism affecting service delivery capability, mandatory vaccination was successfully implemented in the nation's aged care sector, demonstrating the commitment of Australia's aged care workforce to the safety of residents. While the imminent mandate was an important policy driver, the iterative and layered nature of the road to implementation was equally important. Vaccination mandates were subsequently recommended for disability workers and in‐home aged care workers, and for health care workers in some states and territories. MJA 21 November 2022

Primary care is the ideal setting to promote COVID‐19 vaccination for children
Primary care has an important role in supporting childhood COVID‐19 vaccine acceptance and access. General practice is a key setting in which trusted relationships with patients, families and the community can be leveraged to increase and sustain COVID‐19 vaccine acceptance and uptake among Australian children. MJA 21 November 2022 

Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity on decreasing COVID-19 vaccine effectiveness
Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While VE estimates against calendar-period-classified infections mirrored those against WGS-classified infections, the author’s analysis highlights the need for whole-genome-sequencing (WGS) when variants are co-circulating and misclassification is likely. Journal of infectious diseases 21 November 2022

Factors associated with vaccine-induced T cell immune responses against SARS-CoV-2 in kidney transplant recipients
Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs. Journal of infectious diseases 21 November 2022

Human cytomegalovirus infection of epithelial cells increases SARS-CoV-2 superinfection by upregulating the ACE2 receptor
SARS-CoV-2, the causative agent of COVID-19, has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40-100% of the population which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socio-economic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2. Journal of infectious diseases 21 November 2022

Return on investment of the COVID-19 vaccination campaign in New York City
Results of this modeling study showed an association of the New York City COVID-19 vaccination campaign with reduction in severe outcomes and avoidance of substantial economic losses. This significant ROI supports continued investment in improving vaccine uptake during the ongoing pandemic. JAMA 21 November 2022

Primary care is the ideal setting to promote COVID‐19 vaccination for children
Primary care has an important role in supporting childhood COVID‐19 vaccine acceptance and access. General practice is a key setting in which trusted relationships with patients, families and the community can be leveraged to increase and sustain COVID‐19 vaccine acceptance and uptake among Australian children. MJA 21 November 2022

Implementing mandatory COVID‐19 vaccination for Australian aged care workers
Despite concerns about the risk of workforce attrition and absenteeism affecting service delivery capability, mandatory vaccination was successfully implemented in the nation's aged care sector, demonstrating the commitment of Australia's aged care workforce to the safety of residents. While the imminent mandate was an important policy driver, the iterative and layered nature of the road to implementation was equally important. Vaccination mandates were subsequently recommended for disability workers and in‐home aged care workers,32,33 and for health care workers in some states and territories. MJA 21 November 2022

Detecting early signs of SARS-CoV-2 infection using heart rate data
Although no comprehensive review studies exist for SARS-CoV-2 infection detection using smartwatches, application of these devices to detect atrial fibrillation indicates specificity and sensitivity exceeding 90%. A recent article analysing the same data presented here has shown a low specificity of around 40% but a reasonable sensitivity of around 85%. Clearly, more research needs to done before this technology can be used more generally in clinical practice as a source of specific information for the treating team. Despite this reservation, smartwatch data may suggest a decline in health as COVID-19 progresses from an initial diagnosis to the possibility of longer term complications, loosely defined as long COVID. The time course of such complications can be traced using commercial smartwatches that many people already own. MJA insight 21 November 2022

Immunogenicity of an additional mRNA-1273 SARS-CoV-2 vaccination in people with HIV with hyporesponse after primary vaccination
An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Journal of infectious diseases 19 November 2022

Safety of the fourth COVID-19 BNT162b2 mRNA (second booster) vaccine: a prospective and retrospective cohort study
Both the retrospective and prospective analyses support the safety of the second booster, with our findings reflecting physicians' diagnoses, patients' objective physiological measures, and patients' subjective reactions. We believe this study provides safety assurances to the global population who are eligible to receive an additional COVID-19 booster inoculation. These assurances can help increase the number of high-risk individuals who opt to receive this booster vaccine and thereby prevent severe outcomes associated with COVID-19. The Lancet respiratory medicine 18 November 2022

Omicron sublineage BQ.1.1 resistance to monoclonal antibodies
This data reveal that emerging omicron sublineages are resistant to most (ie, BA.4.6, BA.2.75.2, and BJ.1) or all (BQ.1.1) clinically used mAbs. As a consequence, in patients at high risk, treatment with mAbs alone might not provide a therapeutic benefit in regions of the globe in which BQ.1.1 is spreading, suggesting that additional treatment options (eg, paxlovid or molnupiravir) should be considered. Furthermore, novel, broadly active mAbs are urgently needed for prophylactic or therapeutic treatment, or both, in patients at high risk. The Lancet infectious diseases 18 November 2022

Association of National Football League fan attendance with county-level COVID-19 incidence in the 2020-2021 season
In this cross-sectional study of the presence of fans at NFL home games during the 2020-2021 season, results indicated that fan attendance was associated with increased levels of COVID-19 in the counties in which the venues are nested within, as well as in surrounding counties. The spikes in COVID-19 for crowds of over 20 000 people suggest that large events should be handled with extreme caution during public health event(s) where vaccines, on-site testing, and various countermeasures are not readily available to the public. JAMA 18 November 2022

COVID-19 and excess all-cause mortality in the US and 20 comparison countries, June 2021-March 2022
The US continued to experience significantly higher COVID-19 and excess all-cause mortality compared with peer countries during 2021 and early 2022, a difference accounting for 150 000 to 470 000 deaths. This difference was muted in the 10 states with highest vaccination coverage; remaining gaps may be explained by greater vaccination uptake in peer countries, better vaccination targeting to older age groups, and differences in health and social infrastructure. JAMA 18 November 2022

Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform
In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir. BMJ 17 November 2022

Human rights and the COVID-19 pandemic: a retrospective and prospective analysis
The authors propose embedding human rights and equity within a transformed global health architecture as the necessary response to COVID-19's rights violations. This means vastly more funding from high-income countries to support low-income and middle-income countries in rights-based recoveries, plus implementing measures to ensure equitable distribution of COVID-19 medical technologies. They also emphasise structured approaches to funding and equitable distribution going forward, which includes embedding human rights into a new pandemic treaty. Above all, new legal instruments and mechanisms, from a right to health treaty to a fund for civil society right to health advocacy, are required so that the narratives of future health emergencies—and people's daily lives—are ones of equality and human rights. The Lancet 17 November 2022

Neutralization escape by SARS-CoV-2 Omicron Subvariant BA.4.6
This data show that the BA.4.6 omicron subvariant markedly escaped neutralizing antibodies induced by infection or vaccination, with values that were lower than BA.5 titers by a factor of 2 to 2.7, which suggests continued evolution of SARS-CoV-2. These findings provide immunologic context for the increasing prevalence of BA.4.6 in populations in which BA.5 is currently dominant. Moreover, the R346T mutation had also recently been observed in other omicron subvariants, including BA.2.75 and BA.5, which suggests the biologic relevance of this mutation. The potential effect of the emergence of the BA.4.6 subvariant on vaccine boosters containing BA.5 immunogens or on infection with BA.5 remains to be determined. NEJM 17 November 2022 

Covid-19 vaccine protection among children and adolescents in Qatar
Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. NEJM 17 November 2022

Audio interview: The FDA and Covid-19 vaccines
In this audio interview conducted on November 15, 2022, the editors are joined by Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, to discuss the ongoing role of the agency in authorizing new vaccines. NEJM 17 November 2022

NICE recommends 3 treatments for COVID-19 in draft guidance
The recommended treatments are:

  • Nirmatrelvir plus ritonavir (also called Paxlovid and made by Pfizer).
  • Tocilizumab (also called RoActemra and made by Roche).
  • Baricitinib (also called Olumiant and made by Eli Lilly and company, subject to it receiving a marketing authorisation in Great Britain for treating COVID-19).

NICE 16 November 2022

In vitro efficacy of antiviral agents against Omicron subvariant BA.4.6
This data suggest that remdesivir, molnupiravir, and nirmatrelvir and the monoclonal antibodies bebtelovimab and imdevimab retain effectiveness against BA.4.6 in vitro. These findings also indicate that monoclonal antibodies casirivimab, sotrovimab, tixagevimab, and cilgavimab may not be effective against BA.4.6. NEJM 16 November 2022

Analysis of COVID-19 vaccination status among parents of hospitalized children younger than 5 years with SARS-CoV-2 infection during the Delta and Omicron waves
During both the Delta and Omicron periods, parents’ vaccination status was associated with a reduced risk of hospital admission for SARS-CoV-2 in children younger than 5 years. A study performed before the Omicron wave showed an association of parent vaccination with a reduced risk of SARS-CoV-2 infection in children, with lower odds ratios likely due to older children in the sample.4 The association between parent vaccination and reduced risk of admission for SARS-CoV-2 in children younger than 5 years suggests that parents played a major role in transmitting SARS-CoV-2 to their young children during both waves, but the association between protection and vaccination seemed lower in the Omicron vs Delta period. The Omicron variant has been shown to be more transmissible, and the vaccine effectiveness against infection seems lower. JAMA 16 November 2022

Assessment of Herpes Zoster risk among recipients of COVID-19 vaccine
In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians. JAMA 16 November 2022

Post–COVID-19 symptoms 2 years after SARS-CoV-2 infection among hospitalized vs non-hospitalized patients
This cross-sectional study suggested the presence of at least 1 post–COVID-19 symptom in 59.7% of hospitalized patients and 67.5% of nonhospitalized patients 2 years after infection. Small differences in symptoms at onset of COVID-19 were identified between hospitalized and nonhospitalized patients. Post–COVID-19 symptoms were similar between hospitalized and nonhospitalized patients; however, lack of inclusion of uninfected controls limits the ability to assess the association of SARS-CoV-2 infection with overall and specific post–COVID-19 symptoms 2 years after acute infection. Future studies should include uninfected control populations. JAMA 15 November 2022

Prevalence of contraindications to Nirmatrelvir-Ritonavir among hospitalized patients with COVID-19 at risk for progression to severe disease
In this study, contradictions to nirmatrelvir-ritonavir were prevalent in individuals hospitalized with COVID-19, as previously suggested. These findings also alert researchers to the risk of confounding by contraindication in observational studies focused on nirmatrelvir-ritonavir, which may overestimate treatment efficacy if not excluding patients with contraindications to this treatment. In addition, some of the contraindicated medications listed here could be temporarily held in the context of using nirmatrelvir-ritonavir. JAMA 15 November 2022

Monoclonal antibodies for treatment of SARS-CoV-2 infection during pregnancy
In pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment among persons who delivered. There was no difference in 28-day COVID-19–associated outcomes and non-COVID-19–related hospital admissions for mAb treatment compared with no mAb treatment in a propensity score–matched cohort. Annals of internal medicine 15 November 2022