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Take a look at a selection of our recent media coverage:

Long COVID symptoms exceed 35 weeks in the majority of cases

3rd August 2021

An online survey among those with long COVID has found that the over 90% continue to experience a wide range of symptoms for over 35 weeks.

While early in the COVID-19 pandemic, there was considerable focus on mortality, an emerging theme has been the presence of prolonged symptoms, even among those with mild disease and which has been termed long COVID. However, a precise definition of long COVID has remained elusive and a wide range of symptoms have been ascribed to the condition. In the US, the Centers for Disease Control and Prevention have preferred the term “post-COVID conditions”, as an umbrella term for the wide range of health consequences that are present four of more weeks after infection with the virus. In trying to more clearly define the patient experience and recovery process, a team from Sainsbury Wellcome Centre, University College London, UK, conducted an online survey among those who have suffered with long COVID symptoms. The aim was to better understand the lived experience with an emphasis on symptom trajectory and severity over time and the return to baseline. The research team worked closely with a patients who had themselves suffered with COVID-19 and who helped to create the survey. In addition, the researchers worked with a number of other patients to compile the list of symptoms and questions related to how long COVID symptoms impacted on daily life. The final survey included 257 questions that required over an hour to complete although respondents were permitted up to 30 days to complete it. Though created in English, the questionnaire was translated into several other languages including Spanish, French, Portuguese, Italian, Dutch and Russian. It was distributed via support groups e.g., Body Politic, Long COVID Support Group and social media, e.g., Twitter, Facebook and data collected between September 2020 and November 2020. The team quantified disease duration, severity and symptom prevalence and respondents were asked to indicate the number of days that each of a listed number of symptoms persisted.

Findings
There were 3,762 usable responses received from predominately women (78.9%), of white ethnicity (85.3%) with the highest proportion (31%) aged between 40 and 49 years. Overall, 91.9% of respondents answered the questions in English. For the complete cohort, 2454 individuals (65%) experienced symptoms which lasted for at least six months and the authors calculated the probability of symptoms lasting beyond 35 weeks as 91.8%. Symptoms affected 10 different organ systems and the most frequent still present after 6 months were fatigue (>95%), post-exertional malaise (approx. 90%) and cognitive dysfunction (88%). Moreover, 85.9% of respondents experienced a relapse of long COVID symptoms often triggered by exercise (70.7%), mental activities (46.2%) and stress (58.9%) and 45.2% had to reduce their work schedule because of symptoms.

Commenting on these findings, the authors reported on how long COVID symptoms appeared to be a heterogenous mix affecting many different organ systems. The authors also felt that the morbidity of COVID-19 has often been greatly overlooked and created a hugely negative impact upon sufferers’ quality of life, highlighting the need for multidisciplinary research to develop effective treatments.

Citation
Davis HE et al. Characterising long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine 2021.

More severe infection associated with variants in pregnant women

2nd August 2021

Infection with the Alpha and Delta COVID-19 variants was associated with severe infection and worse outcomes for pregnant women.

Women pregnant infected with COVID are more likely to be admitted to an intensive care unit (ICU) or need invasive ventilation. During the pandemic, two separate variants have emerged; alpha and delta, with the former becoming the dominant variant until May 2021, when it was superseded by the latter. While there is evidence that both the alpha and the delta are associated with a greater level of transmissibility and hospitalisations in the non-pregnant population, there is limited published comparative information of the impact of the original (wild-type) and the alpha and delta variants in pregnant women. The evidence that is available, would suggest that the delta variant lead to more admissions to an ICU.

In the absence of such comparative data, a team from the National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, UK, sought to examine the differences of these different variants on the severity of maternal infection over time. The study was part of the Obstetric Surveillance System which is a research platform that records information on specific pregnancy complications. The primary outcome measure was a composite indicating moderate to severe COVID-19 infection: oxygen saturation < 95% on admission, the need for oxygen therapy, evidence of pneumonia on imaging, admission to an ICU or maternal death. Although the individual patient-level data did not indicate the specific variant responsible for infection, the outcomes were collected for hospitalised pregnant women with confirmed COVID-19 infection or within two days of giving birth, across the periods of time in which the wild-type (original strain), the alpha and delta variant were dominant.

Findings
There were 3371 women admitted to hospital across the three time periods and the majority of admissions occurred during the period for which the alpha variant was dominant. From 2521 admissions during this period, just under half (45%) were due to COVID-19. Overall, the proportion of COVID-19 related admissions increased across the variants from 41.1% (wild-type), 45.9% (Alpha) and 54.2% (Delta). The proportion of women hospitalised with at least one marker of moderate to severe disease increased from 25% (wild-type) to 35.8% (Alpha) and 45% (Selta). Women admitted during the alpha period were significantly more likely to require admission to ICU than during the wild-type period (odd ratio, OR = 1.61, 95% CI 1.24–2.10) and while there was a slightly higher rate of admission during the Delta vs Alpha period, this difference was not significant. Fortunately, the majority of babies were live born with no differences in the proportion of stillbirths across the different time periods.

In their discussion, the authors commented on how the delta variant caused the biggest increase in symptomatic pregnant women and appeared to experience more severe disease though the difference was not statistically significant. They concluded that pregnant women appear to be at an increased risk of more severe infection and admission to ICU and should be considered as a priority group for vaccination.

Citation
Vousden N et al. Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort. MedRxiv 2021

Are mental health disorders associated with increased COVID-19 mortality?

29th July 2021

A review has identified that after adjusting for known risk factors, mental health disorders are associated with increased COVID-19 mortality.

Patients with mental health problems might be at a greater risk of worse outcomes when infected with COVID-19, especially as such patients often have other co-morbidities, some of which have been identified as risk factors. In addition, mental health problems are associated with low socioeconomic status and which has been linked to a greater risk of critical care admission among those infected with COVID-19. In fact, data collected from several countries has already revealed how severe mental illnesses such as schizophrenia, are a risk factor for greater COVID-19 mortality although other work has concluded that a diagnosis of mental illness was not associated with an increased likelihood of testing positive for COVID-19. While a recent meta-analysis has suggested a pre-diagnosis of mental disorders worsens the prognosis of COVID-19, the analysis had methodological issues and did not examine the effect for individual diagnoses. This led a team from the CEReSS-Health Service Research and Quality of Life Centre, Marseille, France, to undertake a systematic review and meta-analysis of the accumulating evidence on mental health disorders and COVID-19. Their primary objective was simple to determine whether patients with mental health disorders were at an increased risk of COVID-19 mortality compared to those without such problems. A secondary objective was to explore if the presence of a mental health disorder increased the risk of intensive care admission and if there were any mental health conditions that specifically increased the risk of COVID-19 mortality. The team searched for articles which included participants with a diagnosis of a mental health disorder and a clinical diagnosis of COVID-19 and where intensive care unit and mortality data were included. Adjustments were made for the presence of other known risk factors for COVID-19, i.e., co-morbidities, age etc.

Findings
A total of 16 population-based cohort studies across seven countries with 19,086 patients were included in the meta-analysis. Overall, the present of mental health disorders was associated with an increased risk of COVID-19 mortality (odds ratio, OR = 1.38, 95% CI 1.15–1.65). In studies where only severe mental illness such as schizophrenia or bipolar disorder were included, the mortality risk was higher (OR = 1.67, 95% CI 1.02–2.73). There was no apparent association between any specific mental health disorder and COVID-19 mortality and there was insufficient data to determine whether mental health disorders were associated with intensive care admission.

Commenting on these findings, the authors suggested that individuals with mental health disorders should be targeted as a high-risk population for severe COVID-19, requiring enhanced disease management strategies. They concluded by calling for future studies to examine the risks associated with individual mental health disorders and to confirm their findings of the link between severe mental health and increased COVID-19 mortality.

Citation
Fond G et al. Association Between Mental Health Disorders and Mortality Among Patients With COVID-19 in 7 Countries. A Systematic Review and Meta-analysis. JAMA Psychiatry 2021

Study assesses response to a third COVID vaccination in kidney transplant patients

Even after a third COVID-19 vaccine dose, only half of kidney transplant patients developed a sufficient antibody response to vaccination.

Among immunocompromised individuals such as kidney transplant patients, a single COVID-19 vaccine dose has been found to elicit a sufficient response in only 17% of individuals. Furthermore, after a second dose, the response only increased to 54%. With evidence of a lower immune response to vaccination, the French National Authority for Health issued a recommendation in April 2021, that immunosuppressed, recent bone marrow transplant, those on dialysis, and patients with autoimmune diseases who did not respond after two doses of a COVID-19 vaccine, should be offered a third dose.

Given the evidence that even among kidney transplant patients who are fully vaccinated, severe COVID-19 can develop, a team from the Department of Nephrology and Transplantation, Strasbourg University Hospital, France, set out to assess the response to a third vaccination among kidney transplant patients who had an inadequate response to a second vaccination dose. The team examined the effect of the mRNA-1273 (Moderna) vaccine and included all kidney transplant patients who had no prior history of infection with COVID-19 and had anti-spike IgG antibody levels less than 50 arbitrary units, one month after administration of the second vaccination dose. They set a minimum antibody titre level of 50 units, so that any responses above this level could be considered as positive.

Findings
A total of 159 kidney transplant recipients with a median age of 57.6 years (61.6% male) and a median time from transplantation of 5.3 years were included in the analysis. After the second dose of vaccine, 59.7% (95) of patients had not generated an antibody response and the remaining patients showed a response below the positivity limit (6.8–49.9 units). The third vaccine dose was administered a median of 51 days after the second dose and the antibody response was then measured approximately 28 days after this third injection. However, at this time-point, only 49% of patients had antibody levels above 50 units. In addition, a response to the third vaccination was much more likely among those who had developed a response to the second dose (81.3% vs 27.4%, p = 0.01, second dose responders vs non-responders). The results also showed how kidney transplant patients prescribed a combination of tacrolimus, mycophenolate and steroids, were much less likely develop a response than those treated with other regimes (35% vs 63%, p = 0.006). No other factors such as sex, years since transplantation, or serum creatinine levels, had an effect on the development of an antibody response.

The authors reported on how despite three vaccination doses, 51% of kidney transplant patients failed to generate a positive antibody response and that this was more likely among those prescribed a triple therapy regime and concluded that kidney transplant patients should be offered a third vaccination dose.

Citation
Benotmane I et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients with Minimal Serologic Response to 2 Doses. JAMA 2021

Echocardiographic parameters identify mortality risk in COVID-19

27th July 2021

In an analysis of suspected cardiac complications in COVID-19, echocardiographic parameters were independently associated with mortality.

Patients hospitalised with COVID-19 experience a wide range of organ system complications including cardiac problems such as arrhythmias and myocarditis. Due to its widespread availability and potential for bedside use, echocardiographic information captured through transthoracic echocardiography (TTE), has become recognised as the preferred first-line imaging modality for patients with either known or suspected cardiac problems. Nevertheless, advice from the European Association of Cardiovascular Imaging (EACVI) is that cardiac imaging should only be performed where appropriate and only if it is likely to substantially change patient management or be lifesaving. Whether echocardiographic data can help with risk stratification in patients hospitalised with COVID-19 has been poorly explored. Thus, a team from the Department of Medicine and Surgery, University of Salerno, Italy, sought to determine whether echocardiographic parameters were associated with in-hospital mortality among those with COVID-19. They undertook a retrospective observational study among consecutive patients admitted to hospital with confirmed COVID-19 infection at seven Italian centres between March and April 2020. All patients underwent TTE within 48 hours of admission and the need for TTE was confirmed as being clinically appropriate by a consultant cardiologist. All patient demographics (age, gender, weight and height) clinical (i.e., co-morbidities, current therapies), laboratory and echocardiographic data were collected and stored electronically. Echocardiographic data included an evaluation of left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV). Left ventricular function was assessed by determination of left ventricular ejection fraction (LVEF) and the parameter used to assess global right ventricular function was tricuspid annular plane systolic excursion (TAPSE). The clinical course of patients was also recorded including the proportion who developed acute respiratory distress syndrome (ARDS).

Findings
A total of 1401 patients were hospitalised with COVID-19 and of whom, 226 (16.1%) underwent echocardiographic testing with TTE. Among this smaller cohort, the mean age was 68.9 years (62.4% male) and the majority (61.1%) had hypertension. In addition, 36 and 13 patients had previously undergone percutaneous coronary interventions and coronary artery bypass grafting respectively. Overall, 68 patients within this cohort died in hospital among whom, ARDS was more common (83.3% vs 31%, p <0.001). In those who died in hospital, there was a lower mean LVEF (47.6% vs 55.5%, death vs survivors, p < 0.001) and a lower TAPSE (17.5 vs 21.7, p < 0.001). Using regression analysis and after adjustment for various factors, amongst patients who experienced in-hospital mortality, reduced LVEF was independently associated with in-hospital mortality (relative risk, RR = 0.93, 95% CI 0.89–0.97, p < 0.001), as was reduced TAPSE (RR = 0.80, 95% CI 0.72–0.88) and the development of ARDS (RR = 3.05).

In discussing these findings, the authors highlighted how the risk of mortality was increased among patients with ARDS and the echocardiographic parameters TAPSE < 17 and an LVEF <50%. They suggested that TTE was useful for risk stratification in COVID-19 patients but recognised the limitation of not having TTE data prior to hospitalisation. The authors concluded that while their study has suggested an important relationship between echocardiographic parameters and in-hospital mortality, further studies were necessary to confirm these findings.

Citation
Silverio A et al. Clinical conditions and echocardiographic parameters associated with mortality in COVID-19. Eur J Clin Invest 2021

Survey shows high mental health burden among critical care staff during pandemic

23rd July 2021

Healthcare staff experienced a high mental health burden during COVID-19 but less is known about the effect on intensive care staff.

Healthcare workers are three times more likely to become infected with COVID-19 compared to community individuals. Nevertheless, during viral epidemic outbreaks, an additional burden to healthcare staff is the impact on their mental wellbeing that accompanies the associated increased workload, leading to stress and anxiety. With thousands of patients across the globe developing more severe infection, there has been much focus on management within intensive care units. Such units are a highly demanding environment with staff continually exposed to traumatic and stressful events and a study from 2007, revealed a higher incidence of post-traumatic stress disorder (PTSD) among intensive care nursing staff. Given the high levels of 28-day mortality among patients with COVID-19, this undoubtedly further increases the mental health burden of intensive care staff. However, there is a lack of data specifically examining the mental wellbeing of intensive care staff.

Using an online survey, a team from the Department of Surgery and Cancer, Imperial College Healthcare NHS Trust, Imperial College, London, UK, sought to gain a better understanding of the mental health burden experienced by intensive care staff. The overall aim was to establish the prevalence of indices of depression, insomnia, and PTSD, which the authors suspected would be high among intensive care staff. The survey was conducted among all healthcare professionals working within the intensive care environment and distributed across the UK, France, Italy, Belgium, Egypt, Taiwan and Mainland China.

For the survey, three previously validated questionnaires were included: the two-item patient health questionnaire (PHQ-2) which sought to grade depression severity, an 8-item Athens Insomnia scale (AIS-8) and the 10-item trauma screening questionnaire (TSQ). The corresponding cut-off values for these questionnaires are 3 (PHQ-2), 8 (AIS-8) and 6 (TSQ). As well as these questionnaires, the authors included a series of general questions on wellbeing.

Findings
The final cohort included 515 responses from seven different countries and the majority of respondents were female (73%), of white ethnicity (73%) and aged 31–40 years (43.3%). Interestingly, 5.8% of respondents reported a pre-existing mental health condition. Just over half (52.4%) were nurses, with the remainder being senior (13.8%), residents/fellows (8.9%) and junior (6.4%) doctors, physiotherapists and others. Furthermore, nearly two-thirds (60.2%) had been re-deployed from another specialty and only a third (33.8%) were normally based within an intensive care ward.

The median scores were 2, 10 and 3 for PHQ-2, AIS-8 and TSQ respectively. Overall, 37.3%, 78.6% and 27.7% of participants had scores for PHQ-2, AIS-8 and TSQ respectively, that were above the thresholds for each condition. Across the different countries, 16–44% of respondents exceeded the threshold for depression, 60–80% for insomnia and 17–35% for PTSD.

The authors concluded that the COVID-19 pandemic had created a significant mental health burden for intensive care staff and recommended that all such staff have access to mental wellbeing resources, especially given the possibility of further surges in the rates of infection in the future.

Citation

Ezzat A. The global mental health burden of COVID-19 on critical care staff. Br J Nurs 2021

Procalcitonin levels predictive of severe disease in COVID-19

Measurement of procalcitonin levels was found to be most discriminatory for severe disease course among patients hospitalised with COVID-19.

Knowledge about COVID-19 has advanced at rapid pace over the last 15 months and with a large number of patients being admitted to hospital, it is of upmost importance to be able to assess which patients are at the highest risk of disease progression. Based on earlier observational studies, it has become clear that older patients and those with co-morbidities are more likely to develop severe disease and several biomarkers including C-reactive protein and procalcitonin, have been shown to be associated with severe disease. A further potential complication of COVID-19 is bacterial co-infection though in an analysis of 24 studies including 3338 patients, the presence of bacterial co-infection in COVID-19 was found to be very low at 6.9%. Nevertheless, whether the use of biomarkers such as procalcitonin could be used to identify bacterial co-infection among patients with COVID-19 has been suggested as a potentially valid strategy, but there is a lack of evidence to support this approach.

This absence of evidence prompted a team from the Department of Internal Medicine, Haga Teaching Hospital, Den Haag, The Netherlands, to retrospectively evaluate the association between multiple biomarkers, including procalcitonin and the clinical and microbiological outcomes in patients hospitalised with COVID-19. The team used data from the PredictED study, a single centre, prospective observational study, designed to evaluate procalcitonin as a marker for bacteraemia in patients who present to the emergency department. While the original study was designed to examine all patients admitted to the emergency department, the authors turned to a subset of patients with PCR-confirmed COVID-19. A number of tests were undertaken, including blood cultures, C-reactive protein and procalcitonin although the results of this latter test were not immediately available to the treating clinician. The primary outcome of the study was the incidence of bacterial co-infection at the initial emergency department presentation and its association with procalcitonin.

Findings
The subset of COVID-19 patients testing positive for the virus was 142 with a mean age of 61 years (66% male). More than half of these patients had co-morbidities including diabetes (25%) and cardiovascular disease (24%) and from the complete cohort, 41 developed severe COVID-19, all of whom were hospitalised and 24 (17%) subsequently died within 30 days. Procalcitonin levels were significantly associated with the development of severe disease (odds ratio, OR = 1.8, 95% CL 1.3 – 2.2), as were higher levels of the biomarker. In addition, C reactive protein levels were also significantly associated with more severe disease (OR = 1.8, 95% CI 1.3–2.6). Using the area under the receiver operating curve for procalcitonin, the predictive value was 0.76.

Commenting on their results, the authors noted that procalcitonin demonstrated the highest discriminatory power between severe and non-severe COVID-19. Although only a small number of COVID-19 patients (1.4%) had a bacterial co-infection, the authors concluded that measurement of procalcitonin levels appeared to be a promising approach to help clinicians recognise patients a higher risk of more severe COVID-19 infection.

Citation
Kaal A et al. Diagnostic yield of bacteriological tests and predictors of severe outcome in adult patients with COVID-19 presenting to the emergency department. Emerg Med J 2021

Diagnostic accuracy of lateral flow tests comparable to PCR in same COVID patient cohort

20th July 2021

Lateral flow tests provide a quick alternative to PCR tests for COVID-19, offering an effective prevention/ control strategy for the virus.

The use of mitigation strategies for COVID-19 such as social distancing and the wearing of face-masks have helped to minimise the spread of the virus. In addition, the use of an effective Test-Trace-Isolate (TTI) strategy, involving the testing of symptomatic cases and tracing their contacts, is crucial for the detection of the virus. The current gold standard test is the polymerase chain reaction (PCR) although this testing modality can only be undertaken within a hospital laboratory and is therefore expensive for population-wide testing. While the testing process itself takes several hours, there are additional time constraints and which slow the overall process, e.g., transporting of samples to the laboratory testing site, presence of a sufficient number of trained staff and high sample volumes. An alternative is the use of lateral flow tests and these have been recognised as being able to increase testing capacity.

Lateral flow tests are are much cheaper than PCR tests and can be produced in large quantities and deliver results on site and within 15 to 30 minutes. Whereas PCR tests involve amplification of the nucleic acid sample, lateral flow tests rely on the detection of a viral antigen in the patient’s sample and are therefore deemed to be of lower sensitivity. However, there have been no comparative studies of outcomes associated with the use of PCR and antigen testing in the same patient cohort and this led a team from the Centre for Primary Care, Wolfson Institute of Population Health, Queen Mary University, London, to assess the diagnostic accuracy of both methods in the same patients. The study was undertaken among a network of general practitioners in Austria and included patients who self-reported mild to moderate flu-like illness (e.g., cough, fever, runny nose etc). Such individuals received a same-day appointment and given an antigen test and also given a PCR test.

Findings
Based on lateral flow tests for 2562 patients, 1027 who tested positive, were also given a PCR test and of whom, 826 (79.7%) tested positive. From this cohort of 826, 788 had also tested positive on the antigen test. The authors then calculated that overall sensitivity of the lateral flow tests to be 95.4%, with a specificity of 89.1%. In addition, positive lateral flow and PCR tests were correlated (r = 0.968).

The authors discussed how these findings indicated that using antigen tests for patients with mild to moderate symptoms, allows for a reliable and accurate detection of COVID-19 and which is comparable to PCR. They concluded that implementation of lateral flow tests should be accompanied by standardised training for operators, quality assurance of testing and a coordinated approach to services.

Citation
Leber W et al. Comparing the diagnostic accuracy of point-of-care lateral flow antigen testing for SARS-CoV-2 with RT-PCR in primary care (REAP-2). EClinicalMedicine 2021

Olfactory dysfunction test enables identification of COVID-19 infection

19th July 2021

Olfactory dysfunction is common in those with COVID-19 and a smell test can be used for the identification of infected individuals.

Olfactory dysfunction has been defined as the best predictor of infection with COVID-19. Moreover, in a study of 60 patients, 59 exhibited some dysfunction during a smell identification test. The study also revealed how only 58% of those tested had anosmia indicating in imperfect relationship between olfactory dysfunction and anosmia. It is possible therefore that the use of an inexpensive, rapid and sensitive method, based on olfactory dysfunction would be of potential value in identifying those with COVID-19. Based on this assumption, a team from the Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, US, sought to evaluate the prognostic value of a smell test for identifying those with COVID-19. The team enrolled healthy adults (18 years and over) from a single university campus screening site. Each of the participants were tested for olfactory dysfunction using a novel scent card (SAFER Diagnostics) and immediately followed up with a PCR test for COVID-19. The card itself contained several different scents under a scratch-off and sniff label and participants had eight options: grape, floral, blueberry, banana, mint, unsure or no scent. Using a QR code, the answers were processed electronically and an incorrect choice was labelled as olfactory dysfunction. The team collected participant demographics, medical history, any COVID-19 symptoms and a subjective smell test on a binary (yes/no) and a 10-point visual analogue scale, where 0 indicated no sense of smell and 10 was a normal sense of smell. Using regression analysis, the team assessed the association between the SAFER card and PCR test results, controlling for the presence of any other COVID-19-related symptoms such as fever, fatigue and cough.

Findings
A total of 163 participants were enrolled with a mean age of 31.6 years (56.3% male) with the majority (62.5%) of white ethnicity. There were 16 participants who tested positive for COVID-19 and 7 (4.8%) who tested negative. From the 16 who were PCR positive, 12 (75%) also failed the olfactory dysfunction test. A failed scent card screen was found to be the greatest predictor for COVID-19 positivity (odds ratio, OR = 80.24, 95% CI 14.77–435.90). The authors calculated that the smell test had a sensitivity for detecting COVID-19 of 75% and a specificity of 95.2%. When adding the presence of fatigue as an associated symptom, the sensitivity of the olfactory dysfunction test increased to 93.8% and the specificity to 89.8%. However, when either fever or cough were included, there was no increase in sensitivity. Interestingly, only 6 of the 16 who tested positive for COVID-19 presented with subjective anosmia.

In a discussion of their findings, the authors noted how their rapid olfactory dysfunction test was a valuable screening tool for COVID-19. Nevertheless, they recognised that not all patients experience olfactory dysfunction but that in the presence of fatigue, the test became more sensitive. The authors concluded by calling for future studies to include a larger participant cohort to better account for other olfactory dysfunction risk factors.

Citation
Said M et al. A Rapid Olfactory Test as a Potential Screening Tool for COVID-19. JAMA Otolaryngol Head Neck Surg.

Modest reduction in COVID-19 infection among vaccinated cirrhosis patients

Vaccinated patients with cirrhosis had a delayed and reduced protection against COVID-19 infection but avoided hospitalisation and death.

Cirrhosis patients are immunocompromised and thus susceptible to infections. In fact, bacterial infections occur in up to 34% of those with cirrhosis admitted to hospital. Furthermore, data have shown that cirrhosis patients have a reduced response to pneumococcal vaccination. Although recent consensus guidelines advocate the use of COVID-19 vaccines for patients with liver diseases such as cirrhosis, this is based on expert opinion rather than facts. In recognition of this lack of evidence, a team from the Division of Hepatology, Bruce W Carter Medical Centre, Miami, US, undertook a retrospective cohort study of patients with cirrhosis who had received at least one dose of a COVID-19 vaccine. Eligible participants were those with cirrhosis aged 18 years and older and who received either the BNT162b (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccines. The team propensity matched these individuals based on 5 categories: sex, ethnicity, duration of follow-up, co-morbidities, alcohol-associated liver disease and finally, the severity of their liver disease. The team defined the index date, as the date of vaccination and each participant was matched to a control. The primary outcome of interest was PCR-defined COVID-19 infection, 28 days after the first dose of either vaccine. The team used this cut-off because it was anticipated that the benefits of either vaccine should be apparent after this period of time. Secondary outcomes included hospitalisation because of COVID-19 or death, again within 28 days of the first vaccine dose.

Findings
The team propensity-matched 20,037 cirrhosis patients with an equal number of controls. Among the cirrhosis group, the mean age was 69.2 years (96.8% male) and the majority (59.5%) were of white ethnicity, with 58.4% having alcohol-associated cirrhosis. Following the first dose of either vaccine, a total of 83 cirrhosis patients and 105 in the control group developed COVID-19 infection. After the first 28 days, receipt of a single dose of either vaccine was associated with a 64.8% reduction in COVID-19 infections. In addition, 28 cirrhosis patients (versus 29 in the matched control group), developed COVID-19-related hospitalisation. However, after 28 days, none of those with cirrhosis were hospitalised compared to 3 in the control group.

Seven days after the second vaccination dose, there were only 3 cases of COVID-19 infection among cirrhosis patients but 15 in the control group. The authors calculated that full vaccination was associated with a 78.6% reduction in COVID-19 infections and none of the cirrhosis patients were subsequently hospitalised because of COVID-19. Comparing decompensated and compensated cirrhosis patients, there was a 50.3% and 66.8% respectively, reduction in COVID-19 infections. Equally, none of either patient group (i.e., decompensated or compensated cirrhosis) were hospitalised because of COVID-19.

The authors noted that while individuals with cirrhosis, especially those with decompensated disease are known to be hypo-responsive to several commonly used vaccines, the current data indicated that while a single vaccination was not associated with a reduction in COVID-19 infections, fully vaccinated individuals experienced a significant reduction in infection. In other words, the response among those with cirrhosis was delayed and reduced, indicating a lower benefit among this patient cohort.

Citation

John BV et al. Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalisation Among Patients With Cirrhosis. JAMA Intern Med 2021