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Nirmatrelvir treatment reduces the risk of Post-COVID-19 condition

6th April 2023

Nirmatrelvir treatment for patients with COVID-19 has been found to also reduce the risk of developing most post-COVID-19 condition symptoms.

A study by US researchers from St Louis, Missouri has revealed that nirmatrelvir treatment during the acute phase of a COVID-19 infection, reduces the subsequent risk of developing post-COVID-19 condition or long covid.

Post-COVID-19 condition or long COVID is an often debilitating illness that occurs in at least 10% of those infected with the virus and is estimated to affect 65 million people worldwide.

In a clinical trial, nirmatrelvir treatment for symptomatic, unvaccinated, non-hospitalised adults at high risk for progression to severe COVID-19, reduced the risk of disease progression by 89% compared to placebo.

Given that to date, there are no approved treatments for post-COVID-19 condition, it is important to examine whether the use of the available anti-viral therapies are able to reduce the risk of developing the condition.

Thus far, the evidence suggests that COVID-19 vaccines might have protective and therapeutic effects on long COVID, though more robust data are required to confirm this effect.

In the current study, the US researchers examined whether nirmatrelvir (Paxlovid) treatment for COVID-19 was associated with a reduced risk of developing post-COVID-19 condition.

They used a US database to identify patients who had a positive COVID-19 test, who were not hospitalised, had at least one risk factor for progression to severe COVID-19 illness and received oral nirmatrelvir.

This group was then compared to one in which no COVID-19 anti-viral or antibody treatment had been given during the acute phase of their illness.

Nirmatrelvir treatment and the risk of post-COVID-19 condition

A total of 281,793 patients with a mean age of 61.9 years (86% male) were treated with the drug.

In comparison to the control group, anti-viral treatment was associated with a 24% reduced risk of developing post-COVID-19 condition (relative risk, RR = 0.74, 95% CI 0.72 – 0.77).

Drug therapy was also associated with reduced risk of post-acute death (Hazard ratio, HR = 0.53, 95% CI 0.46 – 0.61) and post-acute hospitalisation (HR = 0.76, 95% CI, 0.73 – 0.80). Nirmatrelvir treatment was associated with reduced risk of post-COVID-19 condition, in those who were unvaccinated, vaccinated and vaccine boosted, as well as individuals who had a re-infection.

The authors concluded that nirmatrelvir treatment was associated with reduced risk of post-COVID-19 condition regardless of vaccination status and history of prior infection.

Citation
Xie Y et al. Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition. JAMA Intern Med 2023.

EMA refuses lagevrio marketing authorisation for treatment of COVID

28th February 2023

Lagevrio was refused a marketing authorisation by the European Medicines Agency on the 23rd February 2023, for the treatment of adults with COVID-19. However, the manufacturer, Merck Sharp & Dohme B.V., may ask the EMA to re-examine its opinion within 15 days.

Data on lagevrio had initially revealed how treatment with the drug treatment led to a reduction in the risk of hospitalisation or death among unvaccinated individuals with at least one risk factor for more severe disease. However, with the introduction of widespread COVID-19 vaccination, the question of whether the drug would still offer benefit to at-risk and vaccinated patients, remained unanswered. Nevertheless, while there was some preliminary data which suggested that the drug retained anti-viral activity against several COVID-19 variants, even among those who had been vaccinated, more definitive data were required.

The PANORAMIC trial was designed to examine if the addition of lagevrio to usual care could reduce hospital admission and COVID-10-related mortality among patients who had been vaccinated against the virus. PANORAMIC was a huge, randomised trial, recruiting over 26,000 patients and assigning nearly 13,000 to lagevrio. The results clearly showed that lagevrio failed to reduce the frequency of COVID associated hospitalisations or deaths in high-risk, vaccinated individuals. In fact, the authors of the PANORAMIC trial went as far as to say that the observed avoidance of both hospitalisation and mortality due to COVID-19 were largely as a result of extensive vaccination.

In a letter explaining the decision, the EMA noted that after an evaluation of the data provided by the manufacturer, it was concluded that clinical benefits of the drug among patients who are not receiving supplemental oxygen but still at risk of developing severe COVID-19, could not be demonstrated. In fact, the EMA stated that ‘based on the totality of the data, it was not possible to conclude that Lagevrio can reduce the risk. of hospitalisation or death or shorten the duration of illness or time to recovery in adults at risk of severe disease.’ Adding that ‘it was not possible to identify a specific group of patients in whom a clinically relevant benefit of Lagevrio could be demonstrated.’

COVID-19 vaccine effectiveness highlights possible need to continue preventative measures

15th February 2023

With COVID-19 vaccine effectiveness reducing over time it is likely that preventative measures such face-masks might still be needed

According to the findings of a systematic review in the Lancet, COVID-19 vaccine effectiveness wanes over time, even following booster doses, indicating that in the longer-term, it may be necessary to continue with preventative measures such as face-mask wearing and physical distancing to help manage the pandemic.

While the introduction of COVID-19 vaccines had an enormous impact on hospitalisations and mortality due to infection with the virus, it has been recognised that induced antibody levels reduce over time. A previous systematic review in 2022 observed that while vaccine efficacy against severe disease only dropped by 10% from one to six months, it reduced by approximately 21% against infection after 6 months and by nearly 25% against symptomatic illness. However, the analysis did not consider the impact of COVID-19 booster doses. As a result, in the current study, researchers examined the effectiveness of vaccination against infection, hospitalisation and death among those who had received a booster dose.

The team examined studies that provided data on vaccine effectiveness for at least 112 days after the primary series of vaccinations or at least 84 days after receipt of a booster dose. They set the primary outcomes of interest as effectiveness against COVID-19 infection, hospitalisation and mortality.

Vaccine effectiveness against COVID-19 outcomes

A total of 68 studies were included in the final analysis.

Overall effectiveness against any strain of COVID-19 reduced from 83% after a primary series of vaccinations to 62% by 112 to 139 days. Similarly, baseline effectiveness against hospitalisation was initially high at 92% but dropped to 79% after 168 – 195 days, as did effectiveness against mortality (91% to 86%) over the same period of time.

Among those who had received booster doses and for which most studies included the omicron variant, vaccine effectiveness against infection was initially 70% but reduced to 43% after 112 days. Similarly, boosted doses against hospitalisation reduced from a baseline of 89% to 71% over the same period of time. The authors reported that there was insufficient data to assess the impact on mortality.

Commenting on their findings, the authors suggested that maintaining COVID-19 prevention behaviours including the wearing of face-masks and physical distancing as well as vaccination may be necessary to reduce transmission of the virus, given how immunity wanes over time. They called for future studies to investigate the effectiveness of simultaneously using multiple approaches such as vaccination and face-masks as transmission preventative strategies.

Citation
Wu N et al. Long-term effectiveness of COVID-19 vaccines against infections, hospitalisations, and mortality in adults: findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022. Lancet Respir Med 2023

Is heart failure risk increased following COVID-19 infection?

18th January 2023

Incident heart failure risk is significantly increased after an acute COVID-19 infection and directly influenced by age and prior hypertension

Heart failure risk has been found to be significantly elevated within 9 months of an acute COVID-19 infection and directly related to both age and a previous history of hypertension, according to a systematic review and meta-analysis by Italian researchers.

Although COVID-19 is primarily a respiratory infection, myocardial injury is a significant pathogenic feature and associated with worse in-hospital outcomes. In fact, it has become recognised that in addition to acute COVID-19-related cardiac complications such as myocarditis or pericarditis, follow-up studies also suggest an increased incidence of arrhythmia, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension and diabetes mellitus. One condition which has not fully explored, although identified as a potential adverse sequelae following infection with COVID-19, is incident heart failure (HF) risk. In the present study, the Italian team undertook a systematic review and meta-analysis of all studies, either retrospective or prospective, published at any time up to September 1, 2022 and which reported on the mid/long-term risk (defined as > 4 months) of incident HF in COVID-19 recovered patients. The researchers set the pooled incidence of HF in recovered patients as the primary outcome and the secondary outcome was the risk of incident HF compared to contemporary control group patients, i.e., those without COVID-19 infection.

Heart failure risk following COVID-19 infection

The analysis identified only 5 relevant and retrospective studies. These studies involved 21,463,173 patients with mean age 54.5 years (58.7% males), of whom, 1,628,424 had confirmed COVID-19 infection while the remaining 19,834,749 represented the controls.

A random effect model revealed a pooled incidence of post COVID-19 HF in 1.1% of cases (95% CI 0.7 – 1.6). After a mean follow-up of 9.2 months, recovered COVID-19 patients had a significantly elevated incident heart failure risk (Hazard ratio, HR = 1.90, 95% CI 1.54 –3.24, p < 0.0001) in comparison to non-infected controls.

In addition, a meta-regression analysis showed a significant and direct relationship for the risk of incident HF using age (p  =  0.001) and a previous history of hypertension (p  =  0.02) as moderators. Interestingly, there was an indirect association observed when the follow-up length was adopted as moderating variable (p = 0.01), suggesting that this risk was higher in the early post-acute phase of the infection.

The authors concluded that COVID-19 survivors had an additional 90% risk of developing HF following infection, especially in the early post-acute phase of the infection.

Citation
Zuin M et al. Risk of incident heart failure after COVID-19 recovery: a systematic review and meta-analysis. Heart Fail Rev 2022

Remdesivir treatment improves biomarkers associated with severe COVID-19

16th January 2023

Remdesivir treatment accelerates the improvement of multiple biomarkers of COVID-19 disease severity associated with better clinical outcomes

Remdesivir treatment has been shown to produce an improvement in the level of several COVID-19 severity biomarkers which are associated with better clinical outcomes according to an analysis of trial data by researchers at Gilead Sciences.

Laboratory biomarkers act as indicators of the underlying pathogenic process responsible for disease progression and can inform on the risk of disease progression. In COVID-19, several biomarkers have been identified including lymphocyte and neutrophil count, C-reactive protein (CRP), interleukin (IL)-6 and D-dimer as well as angiopoietin-2, which is a relevant predictor for intensive care unit admission. However, what is less clear, is how levels of these biomarkers change in response to treatment. In an attempt to understand the impact of COVID-19 therapy on these biomarkers, researchers focused on the effect of remdesivir treatment. Remdesivir is an anti-viral agent and in a recent study (PINETREE) of symptomatic, non-hospitalised patients with COVID-19, at a high risk for disease progression, a 3-day course of the drug resulted in an 87% lower risk of hospitalisation or death than placebo. The primary outcome of the trial was COVID-19-related hospitalisation or death at day 28. Using data from patients in the PINETREE trial, researchers obtained plasma samples of biomarkers at baseline, day 3 (on-treatment) and day 14 (post-treatment). The biomarkers analysed included soluble angiopoietin 2 (sAng2), interleukin (IL)-6, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), prothrombin time and lymphocyte counts.

Remdesivir treatment and biomarker changes

The PINETREE trial included 312 patients with a mean age of 52 years (47% female) who were randomised 1:1 to remdesivir treatment (168) or placebo and who consented to longitudinal biomarker assessments. Overall, only 6 participants (two given remdesivir and four placebo) met the primary endpoint.

Biomarker values at baseline were compared between patients who either met or did not meet, the primary endpoint. The results show that six of these markers, sAng2, CRP, IL-6, ferritin, LDH and PCT, were significantly elevated (p < 0.05) in those who met the primary endpoint.

Among all of the biomarkers measured, there were no significant difference in values between the two treatment arms at baseline. However, by day 14, there was a significant decrease in biomarker values in remdesivir treated patients compared to placebo for sAng2, ferritin, LDH, D-dimer, the international normalised ratio and prothrombin time. The most prominent difference between the treatment arms was for D-dimer at day 14 (compared to baseline) and which continued to increase in placebo-treated patients but quickly returned to baseline levels in those given remdesivir.

The authors concluded that their findings suggested that remdesivir treatment may accelerate the improvement of multiple biomarkers of COVID-19 severity, leading to better clinical outcomes.

Citation Pan DZ et al. Remdesivir improves biomarkers associated with disease severity in COVID-19 patients treated in an outpatient setting. Commun Med 2023

Screening-based predictive tools for COVID-19 in ED inferior to PCR test

13th January 2023

Three screening-based predictive tools for COVID-19 infection used in an emergency department were far less sensitive compared to a PCR test

Three screening-based predictive tools for COVID-19 used within an emergency department (ED) have been shown to be inferior to a polymerase chain reaction (PCR) test according to the results of a study by US researchers.

During the early phase of the COVID-19 pandemic, diagnostic testing was not always readily available. Consequently, there was a need for clinical decision-making methods to identify patients most likely to be infected with the virus. Some such methods were developed and one study using a risk score for COVID-19 diagnosis, achieved an area under the receiver operating characteristic curve of 0.85 in a validation dataset, prompting the authors to suggest that it could be used as a supplemental tool to assist in the clinical decision to quarantine patients admitted to hospital from the emergency room. Nevertheless, while there are several available methods, no studies have compared the performance of different methods to predict the likelihood that a patient presenting to an ED has COVID-19.

In the current study, the US team retrospectively assessed three screening-based methods to determine which was better at detecting those who ultimately tested positive for COVID-19. The three methods were a nursing triage screen (NTS), an ED review of systems (ROS) performed by physicians and physician assistants and a standardised COVID-19 probability assessment (PA) by an ED attending (i.e., consultant) physician. The study included all patients aged 18 years or older who were admitted to hospital from the ED and who had a PCR confirmed positive COVID-19 infection. The NTS for example, involved asking about the presence of symptoms including fever, chills, weakness, severe headache, anosmia, dysgeusia, conjunctival injection, sore throat, cough, shortness of breath (SOB), abdominal pain, vomiting, diarrhoea, bruising or bleeding, myalgia, arthralgia and rash. Similarly, the ED review of ROS asked about symptoms, whereas after the initial ROS (but before the COVID-19 test result was available), the attending physician would classify the patient as high, moderate, low or no probability of having COVID-19. The sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method. and regression analysis used to assessed each tool’s performance.

Screening-based prediction and COVID-19 positivity

A total of 748 patients with mean age of 57.5 years (56.8% male) were included in the analysis. Overall, 21.3% of patients tested positive for COVID-19 following a PCR test.

The attending physician had the highest sensitivity (0.62, 95% CI 0.53 – 0.71), followed by the ED ROS (0.53, 95% CI 0.43 – 0.62) and the least sensitive was the NTS (0.46, 95% CI 0.37 – 0.56). Specificity values were also highest for the attending physician (0.76) though this was similar to the NTS (0.71) and lowest for the ED ROS (0.62). Nevertheless, all three methods had a low positive predictive value, ranging from 26% (ED ROS) to 40% (attending physician).

The authors concluded that none of the three screening-based tools was accurate enough to replace a COVID-19 PCR test, adding that hospitals should not rely symptom screening to identify infected patients and recommended universal COVID-19 testing prior to all admissions.

Citation
Dilorenzo MA et al. Performance of three screening tools to predict COVID-19 positivity in emergency department patients. Emerg Med J 2023

Molnupiravir treatment fails to reduce adverse outcomes among high-risk vaccinated patients

11th January 2023

Molnupiravir treatment in vaccinated, high-risk patients infected with COVID-19, failed to reduce both the rate of hospitalisation and death compared to usual care according to the results of a large, randomised trial by members of the PANORAMIC Trial collaborative group.

It is possible that the early treatment of COVID-19 infected patients with anti-viral agents, might prevent deterioration, speed up recovery and reduce the need for hospital admission. One such anti-viral is molnupiravir (EIDD-2801) and which was originally shown to be a potentially effective clinical candidate with high potential for monotherapy of seasonal and pandemic influenza virus infections.

Nevertheless, early molnupiravir treatment in patients infected with COVID-19 and at least one risk factor for severe illness, was subsequently shown to reduce the risk of hospitalisation or death in unvaccinated adults. But with millions of individuals now vaccinated against COVID-19, it remains uncertain whether molnupiravir treatment is still an effective option in such patients.

There is some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this is not conclusive. As a result, in the present study, researchers set out to establish the effectiveness of molnupiravir in vaccinated, high-risk, community patients at reducing hospital admission or death.

The study included community (i.e., non-hospitalised) patients aged 50 years and older, or 18 years and older with relevant comorbidities and who had COVID-19 symptoms within the previous 5 days, together with a positive PCR or rapid antigen test within the past 7 days. Eligible participants were randomly assigned (1:1) to receive molnupiravir 800 mg twice daily for 5 days plus usual care or usual care alone. The primary outcome was set as all-cause hospitalisation or death within 28 days of randomisation.

Molnupiravir treatment and adverse COVID-19 outcomes

A total of 25,783 individuals with a mean age of 56·6 years (58.5% female) were randomised to molnupiravir (12, 821) or usual care. Additionally, 69% of the whole cohort had comorbidities and 94% had received at least three doses of a COVID-19 vaccine.

Hospitalisations or deaths were recorded in 1% of both groups (adjusted odds ratio, aOR = 1·06, 95% CI 0·81 – 1·41, p = 0.33). Moreover, in subgroup analyses, there were no significant differences when assessed on several factors including the presence/absence of co-morbidities, age (< 65 vs > 65), or among those who were immunocompromised.

Despite no difference in the primary outcome, molnupiravir treatment was associated with a reduction in the median time from randomisation to first recovery (hazard ratio, HR = 1·36, 95% CI 1·32 – 1·40).

The authors concluded that in a highly vaccinated population at high risk of complications from COVID-19, the avoidance of hospitalisation and death was primarily achieved via extensive vaccination. They added that the benefits of molnupiravir in terms of a faster recovery time need to be considered in the context of several other relevant factors including the prevailing disease, burden on health-care services, drug-acquisition cost, social circumstances, cost-effectiveness, and opportunity costs.

Citation
Butler CC et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2022.

Favipiravir shortens recovery time only for younger hospitalised COVID-19 patients

10th January 2023

Favipiravir reduces the recovery time from infection among patients hospitalised with COVID-19 but only in those under 60 years of age

The anti-viral agent favipiravir reduces the recovery time in hospitalised patients with COVID-19 but only for those under 60 years of age, according to the findings of a randomised, controlled trial by the PIONEER group.

Intravenous remdesivir was the first effective antiviral agent in adults hospitalised with COVID-19 and shown to be superior to placebo in shortening the time to recovery in adults. Moreover, other anti-viral agents such as oral molnupiravir and nirmatrelvir plus ritonavir have all been shown to be effective at reducing COVID-19 disease progression.

Favipiravir is another anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase of RNA viruses and has demonstrated in vitro activity against COVID-19. In addition, favipiravir has demonstrated an antiviral effect against COVID-19 in a small animal model study though the authors suggested that clinical studies were needed to assess the efficacy in humans.

Consequently, in the present study, researchers conducted an open-label, randomised, phase 3 controlled study of favipiravir plus standard care versus standard care alone.

The PIONEER Trial recruited adults admitted to hospital for suspected or confirmed COVID-19 and then randomised participants 1:1 to receive oral favipiravir (1800 mg twice daily orally on day 1, followed by 800 mg twice daily from day 2 to day 10) and standard care or standard care alone. In the trial, standard care evolved as per local guidelines, with systemic corticosteroids, remdesivir, and tocilizumab used by the clinical teams as necessary. Individuals were followed for 28 days and assessed on a seven category ordinal scale, ranging from 1 (not hospitalised with resumption of normal activities) through to 7 (death). The primary outcome was the time from randomisation to recovery which was censored at 28 days.

Favipiravir and COVID-19 outcomes

A total of 502 patients with a mean age of 58.9 years (61% male) were randomised to favipiravir (251) or standard care alone.

Overall, there was no significant difference between those assigned to favipiravir and standard care, relative to those who received standard care alone in the time to recovery (Hazard ratio, HR = 1.06, 95% CI 0.89 – 1.27, p = 0.52). However, in a post-hoc analysis, it was found that patients younger than 60 years who received favipiravir, showed a faster rate of recovery compared to standard care alone (HR = 1·35, 95% CI 1.06 – 1.72, p = 0.01). Despite this age-related benefit on recovery time, the researchers found that there were no aged-related mortality effects.

There were also no significant between-group difference with respect to serious adverse events (p = 0·87).

The authors concluded that whilst there was no overall benefit from favipiravir, there was a benefit in terms of the time to recovery, in patients younger than 60 years. They added that the indiscriminate use of favipiravir globally should be cautioned and called fir further studies of antiviral agents in COVID-19.

Citation
Shah PL et al. Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care. Lancet Resp Med 2022

Vaccination found to reduce risk of post-COVID-19 condition

5th January 2023

Vaccination against COVID-19 appears to provide a small but significant protection against the development of post-COVID-19 condition

Receiving a COVID-19 vaccination has been found to reduce the risk of subsequently developing post-COVID-19 condition (or long covid) although the vaccine effectiveness is low according to the findings of a meta-analysis by US researchers.

Vaccine effectiveness is a measure of how well vaccination protects individuals against a condition but differs from the efficacy measured in a trial, because efficacy cannot predict exactly just how effective a vaccine might be in a larger and more variable population. Nevertheless, real-world evidence suggests that some vaccines, such as BNT162b2, have an effectiveness comparable to that reported in phase III clinical trials. Although in practice, many patients make a full recovery after an acute COVID-19 infection, for a minority, there is the continuation or development of other symptoms. The World Health Organisation has described this as ‘Post COVID-19 condition’ and which occurs in individuals with a history of probable or confirmed COVID-19 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.

While the effectiveness of vaccination against COVID-19 is widely accepted, what is uncertain, is whether vaccination reduces the risk of post–COVID-19 condition. This was the subject of the current study by the US researchers who reviewed the literature on the effectiveness of COVID-19 vaccines for post–COVID-19 condition and pooled the results of published studies to allow for a more precise estimate of effectiveness. The team looked for studies that: involved vaccinated and unvaccinated individuals and evaluated the long-term effectiveness of the COVID-19 vaccine. Post–COVID-19 conditions were defined as a wide range of health symptoms that were present 3 or more weeks after having COVID-19. Any studies without a comparison between vaccinated and unvaccinated individuals (or other vaccinated control group) were excluded. The team calculated the pooled diagnostic odds ratio (DORs) for post–COVID-19 conditions between vaccinated (i.e., those who received at least 1 dose of a COVID-19 vaccine) and unvaccinated individuals.

Vaccination and effectiveness against post-COVID-19 condition

A total of 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post–COVID-19 conditions and of which 6, were included in the meta-analysis. The pooled prevalence of post–COVID-19 conditions was 39.1% among those who were unvaccinated and 37.6% among those who received at least 1 dose.

The pooled DOR for post–COVID-19 conditions among individuals who received at least 1 dose was 0.708 (95% CI 0.69 – 0.73), giving an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%–30.8%).

However, vaccine effectiveness varied depending on whether an individual received the vaccine before or after being infected with COVID-19. For example, effectiveness was 35.3% (95% CI 32.3% – 38.1%) among those who received the COVID-19 vaccine before having COVID-19 but 27.4% (95% CI 25.4% – 29.3%) among those who received it after being infected.

The authors concluded that COVID-19 vaccination before and after having COVID-19 provided a low but statistically significant decrease in post–COVID-19 conditions for the variants circulating during the study period. They added that a more standardised definition of post–COVID-19 conditions was also needed both for research and clinical purposes.

Citation
Marra AR et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Health Epidemiol 2022

Higher liver stiffness persists several months after COVID-19 infection

19th December 2022

Greater liver stiffness which might reflect lasting injury to the organ was seen in patients undergoing ultrasound shear wave elastography

A retrospective study presented at the Radiological Society of North America (RSNA) 2022, of patients with a history of COVID-19 infection found that several weeks after an acute infection with the virus, there was a statistically significant higher level of liver stiffness compared to non-infected control patients.

Liver stiffness (LS) is closely associated with hepatic fibrosis in patients with chronic liver disease but is also increased in patients with acute hepatitis, acute liver failure and cholestasis. In fact, LS (which is expressed in kilopascals, kPa) is a rapid and excellent screening test for liver cirrhosis and which can be measured non-invasively with shear wave elastography. Previous work has shown that the presence of LS ≥ 9.6 kPa, is associated with more severe COVID‐19 disease hence liver stiffness can be used as a marker of fibrosis. However, whether LS persists over time and leads to liver damage is uncertain.

In the study presented at the RSNA, researchers from Massachusetts General Hospital in Boston, used ultrasound shear wave elastography (SWE) to compare LS in patients with and without COVID-19 infection. The researchers created three patient cohorts: the first cohort were COVID-19 patients, with a confirmed and positive PCR test result at least 12 weeks before their SWE; the second cohort was a pandemic, random control group who underwent elastography during the COVID-19 pandemic but with no history of COVID-19; the final group comprised a random sample of pre-pandemic patients. The team set the primary endpoint as the average difference in median Young’s modulus between post-COVID-19 patients and controls after adjusting for age, sex and time period in a linear regression model.

Liver stiffness differences between the groups

There were 131 patients with a mean age of 55.5 years (51.1 % female) included in the study, 31 of whom had tested positive for COVID-19 and scans were undertaken an average 44 weeks after participant’s infection with the virus.

After statically adjusting for age, sex, and time period, COVID-19 infection was associated with an average increase in median Young’s modulus of 1.71 kPa (95% CI 0.67 – 2.75, p = 0.002). In addition, COVID-19 participants had higher median liver stiffness compared to contemporaneous controls (median = 7.68 vs 5.99 kPa, p <0.001). However and somewhat unexpectedly, pre-pandemic controls had higher median stiffness compared to post-pandemic controls (median = 7.01 kPa, p = 0.56).

The researchers concluded that COVID-19 infection is associated with increased liver stiffness which may reflect lasting liver injury following infection.

However, in a press release from the conference, one of the researchers, Dr Firouzeh Heidari said that ‘we don’t yet know if elevated liver stiffness observed after COVID-19 infection will lead to adverse patient outcomes‘ adding that ‘we are currently investigating whether the severity of acute COVID-related symptoms is predictive of long-term liver injury severity.’

Citation
Heidari F et al. Lasting Liver Injury Following COVID-19 Infection Measured by Ultrasound Shear Wave Elastography. RSNA Conference 2022

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