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

Higher level of advanced colorectal cancer diagnosed during COVID-19

The COVID-19 pandemic period was associated with a higher level of advanced colorectal cancer diagnoses compared to pre-pandemic levels.

Italian researchers have found that the COVID-19 pandemic was associated with the diagnosis of more advanced stage colorectal cancer in comparison to pre-pandemic levels.

The World Health Organization describes how globally, colorectal cancer is the third most common cancer with nearly two million cases and almost one million deaths in 2020.

Nevertheless, despite screening programs being widely available, emerging data from, for example, the US, clearly shows how after the national lockdowns imposed because of COVID-19, while stool testing increased by 7%, there was a 16% decrease in colonoscopy between 2018 and 2020.

Consequently, there have been concerns that the pandemic together with a reluctance of patients to seek medical attention, could be associated with a risk of more advanced colorectal cancer at diagnosis.

Moreover, one modelling study estimated 1,176,942 to 2,014,164 fewer colorectal cancer screenings, 8,346 to 12,894 fewer colorectal cancer diagnoses and 6,113 to 9,301 fewer early-stage colorectal cancer diagnoses between 2020 and 2023.

Nevertheless, there has been a lack of real-world evidence on the actual level of advanced colorectal diagnoses because of COVID-19.

In the present study, the Italian team set out to determine if the pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer.

The team undertook a retrospective, multicentre cohort study of all adult patients who underwent surgery for colorectal cancer from 1 March 2020, to 31 December 2021 (pandemic period) in comparison to 1 January 2018, to 29 February 2020 (the pre-pandemic period).

They considered any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections.

The primary outcome was advanced stage of colorectal cancer at diagnosis whereas secondary outcomes included distant metastasis and T4 stage.

Advanced colorectal cancer outcomes

A total of 17,938 patients with a mean age of 70.6 years (55.8% male) underwent surgery for colorectal cancer, 43.5% of whom had surgery during the pandemic period.

The proportion of patients with stage 1 disease was significantly lower during the pandemic period compared to the pre-pandemic phase (20.7% vs 23.3%, p < 0.001). In addition, there was a significantly higher proportion of stage 4 disease during the pandemic (15% vs 13.9%, p = 0.03).

Using regression analysis, the pandemic period was found to be significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio, OR = 1.07, 95% CI 1.01 – 1.13, p = 0.03), an aggressive biology (OR = 1.32, p < 0.01) and stenotic lesions (OR = 1.15, p = 0.03).

The authors concluded that the COVID-19 pandemic was significantly associated with a risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer. They added that these results may indicate a potential reduced survival for these patients.

Citation
Rottoli M et al. Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy. JAMA Netw Open 2022.

Nirmatrelvir and ritonavir safe in pregnancy

12th December 2022

The combination of nirmatrelvir and ritonavir appear to be safe and well tolerated when used in pregnancy among mothers infected with COVID-19.

The nirmatrelvir and ritonavir (Paxlovid) can be used safely in pregnant women infected with COVID-19 according to a case series study by researchers from Johns Hopkins University School of Medicine, Baltimore, US.

COVID-19 leads to a consistent and substantial increase in severe maternal morbidity and mortality and neonatal complications in pregnant women.

In fact, available data suggests that severe acute respiratory syndrome caused by COVID-19 during pregnancy leads to placental inflammation and a reduced antiviral antibody response, which could impact upon the efficacy of treatment in pregnancy.

The combination of nirmatrelvir and ritonavir has been authorised by the European Medicine’s Agency for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19.

However, the summary of product characteristics states that ‘there are no data from the use of paxlovid in pregnant women’ and that ‘paxlovid is not recommended during pregnancy.’

Despite the lack of human data, animal studies of nirmatrelvir and ritonavir reported no clinically relevant risks associated with administration during pregnancy or in males and females of reproductive age.

In the present study, the US researchers reported on a case series that included pregnant patients who were diagnosed with COVID-19 and who received nirmatrelvir and ritonavir. The team recorded the clinical characteristics and pregnancy outcomes through a manual review of medical records.

Nirmatrelvir and ritonavir and pregnancy outcomes

A total of 47 women with a median age of 34 years were included and who received the drugs during pregnancy, 57.4% during the third trimester and 34% during the second trimester.

In addition, 85.1% of women had received some level of COVID-19 vaccination, with 44.7% having received the initial series and one booster. Co-morbidities included a mental health disorder (44.7%), obesity (25.5%) and diabetes (10.6%).

A total of 53.2% of mothers delivered after treatment with nirmatrelvir and ritonavir and of whom, 12 (48%) underwent a caesarean delivery, although three quarters of these were scheduled. Only two patients discontinued the drugs due to adverse effects.

Based on these findings, the authors concluded that pregnant patients treated with nirmatrelvir and ritonavir tolerated the treatment although there was an unexpectedly high rate of caesarean deliveries.

They added that the lack of serious adverse effects affecting pregnant patients or offspring suggests that the drug combination is suitable for the treatment of infected, pregnant women.

Citation
Garneau WM et al. Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection. JAMA Netw Open 2022.

Telmisartan fails to improve disease severity among patients hospitalised with COVID-19

5th December 2022

An RCT has found that the use of telmisartan failed to improve disease severity among patients hospitalised with COVID-19 compared to placebo

Telmisartan given to patients hospitalised due to COVID-19 but not requiring oxygen, provided no benefit (in terms of improvement in disease severity score) compared to placebo according to the findings of randomised, double-blind, placebo-controlled trial by Australian and Indian researchers.

The COVID-19 virus gains entry into cells via the angiotensin converting enzyme 2 (ACE2) receptor and makes use of the serine protease TMPRSS2 for protein priming. ACE2 is a key regulator of the renin-angiotensin system, responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory effect mediated through the angiotensin II type 1 receptor (ATR1). Consequently, it is possible that blockage of the ATR1) receptor with angiotensin receptor blockers (ARBs) such as telmisartan, may represent a safe, low-cost solution for reducing COVID-19 respiratory outcomes. In fact, a prospective study has already demonstrated that angiotensin converting enzyme inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. However, randomised trials with ARBs to date have been equivocal. For example, one trial using losartan concluded that initiation of the drug to hospitalised COVID-19 patients did not improve the arterial partial pressure of oxygen to fraction of inspired oxygen ratio at 7 days compared to placebo. Furthermore, use of losartan did not reduce hospitalisations among outpatients prescribed the drug. In contrast, a study using telmisartan 80 mg twice daily, among patients hospitalised with COVID-19, showed that the drug reduced C-reactive protein (CRP) plasma levels compared to placebo.

In order to provide more data on the value of ARBs, in the current trial researchers randomised patients hospitalised with COVID-19, 1:1 to either telmisartan 40 mg daily or matching placebo. The primary outcome was COVID-19 disease severity (based on the World Health Organisation (WHO) Clinical Progression Scale) assessed after 14 days. The WHO scale ranges from 1 to 7 with lower scores indicating less severe disease.

Telmisartan and COVID-19 disease severity outcome

A total of 788 participants with a mean age of 49 years (64 % male) were randomised to either telmisartan (393) or placebo. The baseline overall WHO scale score was 3, equating to hospitalised but not requiring oxygen.

At day 14, the WHO score had improved to 1 (i.e., not admitted to hospital and with no activity limitations) in 384 telmisartan patients with 382 assigned to placebo (Odds ratio, OR = 1.51, 95% CI 1.02 – 2.23, p = 0.98). There were also no significant differences when the primary outcome was examined in different subgroups based on gender, co-morbidities or hypertension. In fact, the trial was stopped when a pre-specified futility rule was met.

Based on these findings, the authors concluded that there was no evidence of benefit, based on disease severity score, from the use of telmisartan in hospitalised patients with COVID-19 and who had predominately mild disease.

Citation
Jardine MJ et al. Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. BMJ 2022

Post-COVID-19 condition persists for at least 2 years

24th November 2022

Post-COVID-19 condition symptoms are still present in both hospitalised and non-hospitalised patients two years after their acute infection

Research by a Spanish team has revealed how symptoms of post-COVID-19 condition (i.e., long covid) persist in both hospitalised and non-hospitalised patients for at least 2 years following their acute infection with the virus.

It has become increasingly recognised that approximately 10% – 20% of people infected with COVID-19 continue to experience a variety of mid- and long-term effects after they recover from their initial illness. The World Health Organisation uses the term ‘post-COVID-19 condition’ and which refers to the constellation of long-term symptoms that some people experience after they have been infected with COVID-19. A wide range of symptoms have been reported affecting various systems in the body, some of which leading to both cognitive and sensory impairment. In fact, a 2021 scoping review identified more than 100 symptoms and whose prevalence varied significantly and were not explained by data collection approaches, study design or other methodological approaches. To date several reviews have examined post-COVID-19 condition symptoms but have only been able to report on the prevalence up to 1 year following an acute infection. In the present study, the Spanish team set out to explore and compare the presence of symptoms in both hospitalised and non-hospitalised patients after a follow-up period of two years.

Hospitalised and non-hospitalised patient data was collected and a random sample from both cohorts who were infected during the first wave of the pandemic and had not been subsequently re-infected were included. Demographic and clinical data were collected from medical records and invited participants agreed to have a scheduled telephone interview 2 years after their infection and which enquired about the presence of a range of symptoms.

Post-COVID-19 condition symptoms after 2 years

A total of 360 hospitalised patients with a mean age of 60.7 years (45% female) and 308 non-hospitalised patients (mean age = 56.7, 59.4% female) were included in the study. The hospitalised and non-hospitalised groups were assessed after a mean of 23.8 and 23.4 months respectively.

Overall, 59.7% of hospitalised and 67.5% of non-hospitalised patients reported having at least 1 post-COVID-19 condition symptom at their follow-up interview. Dyspnoea was more prevalent at the onset of illness among hospitalised compared to non-hospitalised patients (31.1% vs 11.7%, p < 0.001). In contrast, anosmia was more common among non-hospitalised individuals (21.4% vs 10.0%, p = .003).

Th most frequent condition in both cohorts was fatigue (44.7% vs 47.7%, hospitalised vs non-hospitalised), with a similar level of pain symptoms including headaches (35.8% vs 29.9%), memory loss (20% vs 15.9%) and dyspnoea at rest (3.9% both groups).

In multivariate regression analysis, among hospitalised patients, the number of pre-existing co-morbidities was significantly associated with fatigue (odds ratio, OR = 1.93, 95% CI 1.09 – 3.42, p = 0.02) and dyspnoea (OR = 1.91, 95% CI 1.04 – 3.48, p = 0.03). Among non-hospitalised patients, the number of pre-existing co-morbidities (OR = 3.75) and the number of symptoms at infection onset (OR = 3.84) were both associated with the presence of fatigue.

The authors concluded that their cross-sectional study suggested the presence of at least 1 post-COVID-19 symptom in a large proportion of infected patients and which appeared to be irrespective of disease severity.

Citation
Fernández-de-las-Peñas C et al. Post-COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients. JAMA New Open 2022

Review suggests serum vitamin D levels might protect against developing COVID-19

21st November 2022

Serum vitamin D levels may protect against the development of COVID-19 but appears to have little impact on other outcomes such as mortality

Serum vitamin D levels might offer some protection against infection from COVID-19 but there is a lack of positive evidence for other outcomes such as reducing disease severity or mortality, according to the conclusion of a systematic review (available as a preprint) by researchers from the Philadelphia College of Osteopathic Medicine, US.

Much has been made of the potential protective role of higher serum vitamin D levels and COVID-19. This arises from studies showing how vitamin D affects multiple immune system mechanisms including a dampening of the entry and replication of the virus, reducing concentrations of pro-inflammatory cytokines, raising levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activation of defensive cells such as macrophages. Much of the hope for the vitamin comes from a 2017 systematic review in which the vitamin was given as a supplement, concluding that it protected against acute respiratory tract infections and how those who had a deficiency of vitamin D or who did not receive bolus doses, experienced the most benefit. Moreover, throughout the COVID-19 pandemic, emerging data has demonstrated an association between deficiency of vitamin D and the severity of infection and subsequent post-infection mortality.

In the present review, the US researchers looked at studies assessing vitamin D levels and how this impacted on the level of infection, levels of inflammatory markers, disease severity and mortality. The team compared the effects of sufficient vitamin D (serum 25(OH) D levels > 30 ng/ml, insufficient (21 – 29 ng/ml) and deficient levels (< 20 ng/ml).

Serum vitamin D levels and COVID-19 outcomes

A total of 19 studies were included. Among those who tested positive for COVID-19, the median vitamin D levels were 27.08 nmol/L and 48.67 nmol/L in those who were negative. The authors termed this difference to be ‘near significant’ (p = 0.059).

In some of the included studies, elevated levels of C-Reactive Protein (which is a marker for inflammation) and therefore disease severity, were found to be significantly associated with low levels of vitamin D. In one such study, inpatients with a median serum vitamin D levels < 12 ng/ml had more severe disease compared to those with median values > 12 ng/ml (p = 0.004). However, this was not a consistent finding.

In relation to length of hospital stay (used as a measure of disease severity), studies were mixed, with some highlighting a significant association and others no difference. In fact, median vitamin D levels were 45.02 nmol/L in those categorised as having moderate severity disease and 38.08 nmol/L in those with severe disease and this difference was not significant (p = 0.22). Finally, the differences in serum levels between those who survived and died of COVID-19 were also not significantly different.

The authors concluded that there seemed to be a correlation between vitamin D deficiency and the likelihood of developing severe illness from COVID-19 when observing studies individually but that when comparing studies on a larger scale, the significant difference seemed to fade.

Citation
Kersh L et al. What is the Impact of Vitamin D Levels on COVID-19 Severity?: A Systematic Review. Research Square 2022

Review finds tixagevimab/cilgavimab effective for immunocompromised patients

17th November 2022

A systematic review of real-world evidence suggests that the combination tixagevimab/cilgavimab is effective for immunocompromised patients

A systematic review by UK researchers, which is currently available as a preprint, has concluded that the monoclonal antibody combination tixagevimab/cilgavimab is effective against COVID-19 breakthrough infections, hospitalisation, intensive care unit (ITU) admission and both all-cause and COVID-19 specific mortality.

Tixagevimab/cilgavimab (Evusheld) is licensed as a pre-exposure prophylaxis of COVID-19 in adults who are not currently infected with COVID-19, without a known recent exposure to an infected individual infected as well as those who are unlikely to mount an adequate immune response to the vaccination against the virus and finally in those where vaccination is not recommended. Both monoclonal antibodies simultaneously bind to distinct, non-overlapping epitopes of the COVID-19 spike-protein receptor-binding domain to potently neutralise the virus. Trial data in those who were at an increased risk of an inadequate response to vaccination showed that COVID-19 occurred in only 0.2% of those given tixagevimab/cilgavimab compared to 1% of patients receiving placebo.  Furthermore, combination treatment has also been found to be effective in protection against progression to severe COVID-19 or death compared to placebo in unvaccinated individuals with mild to moderate disease.

Despite these positive findings, there is limited evidence from a real-world setting and against COVID-19 variants such as Omicron. Moreover, while Evusheld has been approved for use in many countries, the UK government recently took the decision that there is insufficient evidence available to support procurement and deployment of Evusheld through emergency procedures. In an attempt to provide more data on the effectiveness of tixagevimab/cilgavimab in those who are immunocompromised, in the present study the UK researchers sought to assess the efficacy against breakthrough infections, hospitalisation, ITU admission and mortality.

They searched for randomised, controlled trials, observational or cohort studies where the combination was used as prophylaxis and in studies where breakthrough infections were reported. Secondary outcomes reported upon were hospitalisations, ITU admissions and death.

Tixagevimab/cilgavimab outcomes among immunocompromised patients

A total of 17 studies with 24,773 immunocompromised participants of whom, 10,775 had received the combination therapy were included in the analysis.

Overall, the clinical effectiveness of the combination against breakthrough infections compared to control patients was 40.47% (95% CI 29.82 – 49.67, p < 0.0001). The combination was also significantly more effective than control against hospital admissions (69.23%, 95% CI 50.78 – 81.64, p < 0.00001). Moreover, the effectiveness against ITU admission was also very high at 87.89% (95% CI 47.12 – 98.66, p = 0.0008).

In relation to both all-cause and COVID-19-related mortality, tixagevimab/cilgavimab was also very effective with overall values of 81.29% (p < 0.0001) and 86.36% (p = 0.035) respectively.

The authors concluded that their study, based on real-world evidence showed that tixagevimab/cilgavimab proved to be highly effective, particularly during the Omicron wave and called for future trials to evaluate the on-going certain of this benefit.

Citation
Suribhatla R et al. Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients. MedRxiv 2022.

Omicron BA.2 sub-variant associated with less severe disease

8th November 2022

A study has suggested that COVID-19 variants may be weakening with Omicron BA.2 giving rise to less severe infections that other variants

With Omicron BA.2 (OBA2) giving rise to less severe infections, it is possible, suggests US researchers, that the COVID-19 virus is mutating to become milder.

In a study covering the period from October to December 2021 in South African, researchers concluded that infection with the Omicron COVID-19 variant led to a significantly reduced odds of hospitalisation. In fact, this was not an isolated finding and a Canadian study with 9,087 cases of Omicron, also found that infection with the variant was less severe. But as the virus mutated, an assessment of the severity of infections with one variant, OBA2, has produced conflicting results. For instance, one study found that all the Omicron variants investigated (including Omicron BA.2) led to a less severe infection compared to the Delta variant. In contrast, a French study showed that patients infected with the OBA2 variant were significantly more likely to be hospitalised and that the BA.2 variant was an independent risk factor for hospitalisation.

This led the US researchers to undertake a large, retrospective analysis of the severity of infection with the Omicron BA.2 lineage. They used data held within both inpatient and outpatient systems in New England and identified individuals infected with the Delta, Omicron B.1.1.529 and the Omicron BA.2 variants. Though genomic sequencing was not performed, infections were categorised as either Delta, Omicron or Omicron sub-variants according to the timing of the onset of disease detection. For example, infections between June and December 2021 were classed as Delta and cases between March and May 2022 as the Omicron BA.2 variant. The researchers included vaccination status, ethnicity and co-morbidities as covariates in their analysis and set the primary outcome as in-hospital death within 30 days of a positive COVID-19 test result. They also considered the need for invasive ventilation and intensive care unit admission as secondary outcomes.

Omicron BA.2 and COVID-19 outcomes

A total of 102,315 confirmed COVID-19 infections in patients with a mean age of 44.2 years (62% female) were included and of whom, 28,940 were classed as OBA2 and 65.9% of these individuals had been fully vaccinated and had a booster, compared to only 2.6% of those infected with the Delta variant.

The mortality rates were 0.7%, 0.4% and 0.3% for the Delta, Omicron and OB2 variants respectively. After adjustment for covariates, the risk of the primary outcome (i.e., mortality) was significantly higher for those infected with the Delta variant compared to OBA2, (Odds ratio, OR = 2.07, 95% CI 1.04 – 4.10) and for the original Omicron strain (OR = 2.20, 95% CI 1.56 – 3.11).

In subgroup analysis, there were also higher risks of hospitalisation, intensive care admissions and the need for mechanical ventilation, for Delta and original Omicron infections compared to OBA2.

The authors concluded that after having accounted for a variety of confounding factors, it seemed that the Omicron BA.2 sub-variant was intrinsically less severe than other variants.

Citation
Strasser ZH et al. Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England JAMA Netw Open 2022

Adverse cardiovascular outcomes higher in patients hospitalised with COVID-19

4th November 2022

The risk of adverse cardiovascular outcomes is significantly higher in patients hospitalised with COVID-19 compared to uninfected controls

There is an elevated risk of several adverse cardiovascular outcomes among patients hospitalised with COVID-19 but the risk of both venous thromboembolism and death is still significant in non-hospitalised cases compared to a group of uninfected, matched controls. These were the key findings from a prospective analysis of participants in the UK Biobank by UK researchers.

Studies have suggested that infection with COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. Moreover, a retrospective study has revealed how cardiac arrhythmia is also a clinical sequelae following an acute infection with the virus. Nevertheless, whether these adverse cardiovascular events are restricted to patients with more severe disease, i.e., those who are hospitalised, or whether there is an increased risk among patients with less severe disease remains unclear. In the present study, UK researchers examined if exposure to COVID-19 was associated with incident cardiovascular disease and mortality. The used data from the UK Biobank and identified those infected with COVID-19, linking to Public Health England laboratory information to identify PCR test results. These individuals were then propensity matched to 2 control patients based on a number of factors including age, sex, body mass index, various co-morbidities (e.g., hypertension, diabetes), smoking status and ethnicity. The researchers considered several adverse cardiovascular outcomes including myocardial infarction (MI), venous thromboembolism (VTE), cardiovascular disease (CVD) mortality, stroke, heart failure, atrial fibrillation and pericarditis. In a further analysis, the team assessed if the risk of these adverse cardiovascular outcomes reduced over time.

Adverse cardiovascular outcomes and COVID-19

A total of 471,227 individuals with a median age of 69 years (44.7% male) were included in the analysis which included 17,871 COVID-19 patient cases. Individuals were followed-up for an average of 141 days. Among those with COVID-19, the majority (80%) were not hospitalised and in the hospitalised cohort (3567), 75.7% had primary diagnosis of COVID-19 whereas the remainder had COVID-19 recorded as a secondary diagnosis.

Among non-hospitalised COVID-19 patients (14,304), there was a more than two-fold higher risk of VTE compared to uninfected controls (Hazard ratio, HR = 2.74, 95% CI 1.38 – 5.45, p = 0.004). Additionally, there was a significantly increased risk of death (HR = 10.23, 95% 7.63 – 13.7, p < 0.0001). Interestingly, the risk of incident MI among the non-hospitalised COVID-19 group was significantly lower (HR = 0.19, 95% CI 0.06 – 0.65, p = 0.008).

In contrast to the non-hospitalised group, patients hospitalised with COVID-19 had significantly elevated risks of MI (HR = 9.9), heart failure (HR = 21.6), atrial fibrillation (HR = 14.9), VTE (HR = 27.6) and cardiovascular mortality (HR = 8.76). Furthermore, there were also increased adverse cardiovascular risks in patients for whom COVID-19 was the secondary diagnosis, e.g., MI (HR = 22.2), heart failure (HR = 13.1), atrial fibrillation (HR = 29.3) and cardiovascular mortality (HR = 14.6).

Next researchers examined the interaction with time and considered the risk of events 30 days before and after their acute infection. Although the risks for atrial fibrillation, VTE and heart failure were largely attenuated after 30 days, these risks still remained significant, e.g., for VTE (HR = 3.97) and heart failure (HR = 2.78).

The authors concluded that while infection with COVID-19 is associated with a higher risk of adverse cardiovascular outcomes, the risks are largely confined to hospitalised patients and highest within the first 30 days following infection.

Citation
Raisi-Estabragh Z et al. Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank Heart 2022

Limited recovery benefits from remdesivir following COVID-19

25th October 2022

Remdesivir recovery benefits one year after COVID-19 treatment are similar to standard care according to the findings of a follow-up study

Use of remdesivir for patients hospitalised with COVID-19 does not reduce the risk of continued symptoms after one year any more than standard care according to the findings of a study by Finnish researchers.

Though the majority of patients make a full recovery after infection with COVID-19, a proportion continue to experience what has been defined by the World Health Organisation (WHO) as post-COVID-19 condition. Throughout the pandemic it has become increasingly recognised that after an acute infection, patients continue to experience symptoms or develop new ones. While post-COVID-19 condition is the WHO preferred term, the persistence of symptoms has also been referred to as the short-term and long-term persistent post-acute sequelae of COVID-19 (PASC). Using this definition, a 2021 systematic review that included 57 studies with 250 351 survivors of COVID-19 found that more than half experienced PASC 6 months after recovery.

Treatment of COVID-19 with the anti-viral agent remdesivir in hospitalised patients is effective and reduces mortality for non-ventilated patients with COVID-19 requiring supplemental oxygen therapy. However, given that post-COVID-19 condition occurs in a number of patients, an equally important question is whether treatments such as remdesivir would reduce the risk of developing post-COVID-19 condition? One Italian observational study of 449 hospitalised patients found that use of remdesivir was independently associated with a reduced risk of what the authors referred to as ‘long-COVID syndrome‘. Nevertheless, no other studies have addressed this question and there remains a high level of uncertainty over whether vaccines or in fact, any treatments reduce the risk of post-COVID-19 condition.

In the present study, the Finnish researcher sought to try and answer this question for remdesivir in the SOLIDARITY trial, which was designed to examine the effects of remdesivir plus standard of care (SoC) compared to SoC alone, on post-COVID-19 condition, at one- and two-years post-discharge from hospital. The trial recruited adult patients with a PCR-confirmed diagnosis of COVID-19 and who received remdesivir 200 mg on the first day and then 100 mg daily until discharge or for a maximum of 10 days with SoC or SoC alone. In the follow-up, participants self-completed questionnaires to assess long-term recovery based on continued symptoms and quality-of-life measures.

Remdesivir recovery at 12 months

The SOLIDARITY trial recruited a total of 208 patients with a mean age of 58.3 years (64% male) were recruited and randomised to remdesivir (114) or standard care. After one year, data were available for 181 survivors although at this point in time, 4.4% of the remdesivir group and 5.3% in the standard of care group had died (relative risk, RR = 0.82, 95% CI 0.25 – 2.76).

Self-reported full or largely full, recovery occurred in 85% of those in the remdesivir arm and 86% in the standard of care group (RR = 0.94, 95% CI 0.47 – 1.90). In addition, a similar proportion (15.3% vs 14.5%) of participants reported that they were about halfway recovered to not recovered at all.

Moreover, exertional dyspnoea was experienced by a similar proportion in both groups (RR = 0.61, 95% CI 0.20 – 1.85) and there were similar scores between the two groups for all quality-of-life domain scores.

The authors concluded that there were no discernible effects of remdesivir on long-term recovery, quality of life or long-COVID-19 symptoms. However, they added that since the confidence intervals were wide this included evidence of substantial benefit and harm.

Citation
Nevalainen OPO et al. Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial Nat Commun 2022