Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: A sub-analysis of the STRONG-HF randomized clinical trial.

AIMS: STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC. METHODS AND RESULTS: Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73-1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32-0.82) than older patients (aHR 0.73, 95% CI 0.46-1.15, adjusted interaction p = 0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32-0.82) and older patients (aHR 0.63, 95% CI 0.32-1.02, adjusted interaction p = 0.56), with no treatment-by-age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean difference 5.51, 95% CI 3.20-7.82) than in older patients (1.77, 95% CI -0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients. CONCLUSION: High-intensity care after AHF was safe and resulted in a significant reduction of all-cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life.

Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.

BACKGROUND: In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity. METHODS: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). RESULTS: One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex. CONCLUSION: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered. TRIAL REGISTRATION: The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.

TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques.

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163+MRC1-, and TREM2+ populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection.

Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial.

BACKGROUND: The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19. METHODS: This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing. FINDINGS: Between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8-9]) than participants in the placebo group (11 days [10-11]; HR 1·30, 95% credible interval 0·92-1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial. INTERPRETATION: We found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive. FUNDING: Ridgeback Biotherapeutics, the UK National Institute for Health and Care Research, the Medical Research Council, and the Wellcome Trust.

Impact of the COVID-19 pandemic on prescription refills for immune-mediated inflammatory disorders: a time series analysis (January 2019 to January 2021) using the English Prescribing Dataset.

OBJECTIVE: To investigate monthly prescription refills for common immunosuppressive/immunomodulatory therapy (sulfasalazine, hydroxychloroquine, azathioprine, methotrexate, leflunomide) prescriptions in England during the complete first wave of the COVID-19 pandemic. Secondary analysis examined unit cost analysis and regional use. DESIGN AND SETTING: A national cohort of community-based, primary care patients who anonymously contribute data to the English Prescribing Dataset, dispensed in the community in England, were included. Descriptive statistics and interrupted time series analysis over 25 months (14 months before, 11 months after first lockdown) were evaluated (January 2019 to January 2021, with March 2020 as the cut-off point). OUTCOME MEASURES: Prescription reimbursement variance in period before the pandemic as compared with after the first lockdown. RESULTS: Fluctuation in monthly medicines use is noted in March 2020: a jump is observed for hydroxychloroquine (Mann-Whitney, SE 14.652, standardised test statistic 1.911, p value=0.059) over the study period. After the first lockdown, medicines use fluctuated, with wide confidence intervals. Unit-cost prices changed substantially: sulfasalazine 33% increase, hydroxychloroquine 98% increase, azathioprine 41% increase, methotrexate 41% increase, leflunomide 20% decrease. London showed the least quantity variance, suggesting more homogeneous prescribing and patient access compared with Midlands and East of England, suggesting that some patients may have received medication over/under requirement, representing potential resource misallocation and a proxy for adherence rates. Changepoint detection revealed four out of the five medicines' use patterns changed with a strong signal only for sulfasalazine in March/April 2020. CONCLUSIONS: Findings potentially present lower rates of adherence because of the pandemic, suggesting barriers to care access. Unit price increases are likely to have severe budget impacts in the UK and potentially globally. Timely prescription refills for patients taking immunosuppressive/immunomodulatory therapies are recommended. Healthcare professionals should identify patients on these medicines and assess their prescription-day coverage, with planned actions to flag and follow-up adherence concerns in patients.

Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial.

Molnupiravir is an antiviral, currently approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for treating at-risk COVID-19 patients, that induces lethal error catastrophe in SARS-CoV-2. How this drug-induced mechanism of action might impact the emergence of resistance mutations is unclear. To investigate this, we used samples from the AGILE Candidate Specific Trial (CST)-2 (clinical trial number NCT04746183). The primary outcomes of AGILE CST-2 were to measure the drug safety and antiviral efficacy of molnupiravir in humans (180 participants randomised 1:1 with placebo). Here, we describe the pre-specified exploratory virological endpoint of CST-2, which was to determine the possible genomic changes in SARS-CoV-2 induced by molnupiravir treatment. We use high-throughput amplicon sequencing and minor variant analysis to characterise viral genomics in each participant whose longitudinal samples (days 1, 3 and 5 post-randomisation) pass the viral genomic quality criteria (n = 59 for molnupiravir and n = 65 for placebo). Over the course of treatment, no specific mutations were associated with molnupiravir treatment. We find that molnupiravir significantly increased the transition:transversion mutation ratio in SARS-CoV-2, consistent with the model of lethal error catastrophe. This study highlights the utility of examining intra-host virus populations to strengthen the prediction, and surveillance, of potential treatment-emergent adaptations.

Epidemiological model based periodic intervention policies for COVID-19 mitigation in the United Kingdom.

As the UK, together with numerous countries in the world, moves towards a new phase of the COVID-19 pandemic, there is a need to be able to predict trends in sufficient time to limit the pressure faced by the National Health Service (NHS) and maintain low hospitalisation levels. In this study, we explore the use of an epidemiological compartmental model to devise a periodic adaptive suppression/intervention policy to alleviate the pressure on the NHS. The proposed model facilitates the understanding of the progression of the specific stages of COVID-19 in communities in the UK including: the susceptible population, the infected population, the hospitalised population, the recovered population, the deceased population, and the vaccinated population. We identify the parameters of the model by relying on past data within the period from 1 October 2020 to 1 June 2021. We use the total number of hospitalised patients and the fraction of those infected who are being admitted to hospital to develop adaptive policies: these modulate the recommended level of social restriction measures and realisable vaccination target adjustments. The analysis over the period 1 October 2020 to 1 June 2021 demonstrates our periodic adaptive policies have the potential to reduce the hospitalisation by 58% on average per month. In a further prospective analysis over the period August 2021 to May 2022, we analyse several future scenarios, characterised by the relaxation of restrictions, the vaccination ineffectiveness and the gradual decay of the vaccination-induced immunity within the population. In addition, we simulate the surge of plausible variants characterised by an higher transmission rate. In such scenarios, we show that our periodic intervention is effective and able to maintain the hospitalisation rate to a manageable level.

Assessing the Association of Hispanic Ethnicity and Other Personal Characteristics with Pharmacy School Admissions.

Access to healthcare services for underrepresented minority populations can be improved by having a diverse profession that reflects the diversity of the patient population being served. The criteria used for pharmacy school admissions may inhibit or strengthen the opportunities that URM students have to be accepted into the University of Arizona R. Ken Coit College of Pharmacy (COP) program. It is currently unclear how personal characteristics are associated with pharmacy school admissions at the COP. This study evaluates whether Hispanic ethnicity was associated with pharmacy school admission status, and secondarily, determines other characteristics associated with admissions. This retrospective database study used admissions data from 2005 to 2018. Completed applications were included in the analysis. The outcome variable was admitted versus not admitted to the pharmacy program. A multivariable logistic regression model was used to identify variables associated with admission status using an a priori alpha level of 0.05. A total of 2096 applicants were included in the analysis (mean age 25.1 ± 5.2 years, 59.9% female, 13.0% Hispanic). Hispanic ethnicity was not associated with admission status. Characteristics significantly associated with admission to pharmacy school were age, gender, high school attended, previous application to the college, and Pharmacy College Admission Test (PCAT) biology and chemistry scores. Although bias was not seen in the admissions process, this study highlights the need for intervention to ensure future cohorts better reflect the diversity of the region.

Quality of critical care clinical practice guidelines involving pharmacotherapy recommendations.

PURPOSE: To assess the quality of critical care clinical practice guidelines (CPGs) involving pharmacotherapy recommendations. METHODS: A systematic electronic search was performed using PubMed, MEDLINE, and Embase for critical care CPGs published between 2012 and 2022 and involving pharmacotherapy recommendations. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument was employed to appraise CPG quality through independent assessment by 2 appraisers. RESULTS: Twenty-one CPGs were evaluated. The number of recommendations in each guideline ranged from 2 to 250, with a total of 1,604 recommendations. The number of strong (vs weak) recommendations in each guideline ranged from 0 to 31, with a total of 116 strong recommendations, or 7.23% of the total number of recommendations. There was at least 1 pharmacist author for 9 (43%) of the guidelines. The AGREE II domains for which mean quality scores of evaluated guidelines were highest were scope and purpose (0.88; 95% CI, 0.85-0.92), rigor of development (0.80; 95% CI, 0.77-0.83), clarity of presentation (0.84; 95% CI, 0.81-0.87), and editorial independence (0.86; 95% CI, 0.79-0.94), while those for which mean scores were lowest were stakeholder involvement (0.69; 95% CI, 0.63-0.75) and applicability (0.49; 95% CI, 0.43-0.55). Involvement of a pharmacist in CPG development was associated with significantly higher scoring for stakeholder involvement (P = 0.0356). CONCLUSION: Strong recommendations accounted for less than 10% of the recommendations in the evaluated CPGs. Moreover, there are concerns related to guideline applicability (ie, advice or tools for putting recommendations into practice) and stakeholder involvement (ie, inclusion of individuals from all relevant groups). It is important to involve pharmacists in CPGs with pharmacotherapy recommendations.

Follow Your Nose: A Key Clue to Understanding and Treating COVID-19.

This paper suggests that ATP release induced by the SARS-CoV-2 virus plays a key role in the genesis of the major symptoms and complications of COVID-19. Infection of specific cells which contain the Angiotensin-Converting Enzyme 2 (ACE2) receptor results in a loss of protection of the Mineralocorticoid Receptor (MR). Local activation by cortisol stimulates the release of ATP initially into the basolateral compartment and then by lysosomal exocytosis from the cell surface. This then acts on adjacent cells. In the nose ATP acts as a nociceptive stimulus which results in anosmia. It is suggested that a similar paracrine mechanism is responsible for the loss of taste. In the lung ATP release from type 2 alveolar cells produces the non-productive cough by acting on purinergic receptors on adjacent neuroepithelial cells and activating, via the vagus, the cough reflex. Infection of endothelial cells results in the exocytosis of WeibelPalade bodies. These contain the Von Willebrand Factor responsible for micro-clotting and angiopoietin-2 which increases vascular permeability and plays a key role in the Acute Respiratory Distress Syndrome. To test this hypothesis this paper reports proof of concept studies in which MR blockade using spironolactone and low dose dexamethasone (SpiDex) was given to PCR-confirmed COVID-19 patients. In 80 patients with moderate to severe respiratory failure 40 were given SpiDex and 40 conventional treatment with high dose dexamethasone (HiDex). There was 1 death in the HiDex group and none in the SpiDex. As judged by clinical, biochemical and radiological parameters there were clear statistically significant benefits of SpiDex in comparison to HiDex. A further 20 outpatients with COVID-19 were given SpiDex. There was no control group and the aim was to demonstrate safety. No adverse effects were noted and no patient became hyperkalaemic. 90% were asymptomatic at 10 days. The very positive results suggest that blockade of the MR can produce major benefit in COVID19 patients. Further larger controlled studies of inpatients and outpatients are required not only for SARS-CoV-2 infection per se but also to determine if this treatment affects the incidence of Long COVID.

Lupus, vaccinations and COVID-19: What we know now.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services, with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Patients with systemic lupus erythematosus (SLE) are at increased risk of viral infections, and recent data suggests they may be at an increased risk of poor outcomes with COVID-19. This may be particularly true for those on rituximab or high dose steroids. A huge international effort from the scientific community has so far resulted in the temporary authorisation of three vaccines which offer protection against SARS-CoV-2, with over 30 other vaccines being evaluated in ongoing trials. Although there has historically been concern that vaccines may trigger disease flares of SLE, there is little convincing evidence to show this. In general lupus patients appear to gain good protection from vaccination, although there may be reduced efficacy in those with high disease activity or those on immunosuppressive therapies, such as rituximab or high dose steroids. Recent concerns have been raised regarding rare clotting events with the AstraZeneca/Oxford vaccine and it is currently unknown whether this risk is higher for those patients with secondary antiphospholipid syndrome. With the possibility of annual COVID vaccination programmes in the future, prospective data collection and registries looking at the effect of vaccination on SLE disease control, the incidence of COVID-19 in SLE patients and severity of COVID-19 disease course would all be useful. As mass vaccination programmes begin to roll out across the world, we assess the evidence of the use of vaccines in SLE patients and in particular vaccines targeting SARS-CoV-2.

New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?

This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5'-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19-associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.

Clinical management of Lupus patients during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Historical evidence suggests that Lupus patients have a higher incidence of several viral infections. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities. In this context there has been concern that Lupus patients may be at a higher risk of developing COVID-19 and suffering a severe disease course. As a result, many Lupus patients have been advised to 'shield' by isolating from social contact in the hope that this will reduce the likelihood of infection. Early clinical data does not appear to show that the incidence of COVID-19 is higher in Lupus patients. Reassuringly, the clinical course of COVID-19 in Lupus does not generally seem to be more severe than in the general population. There has been huge interest in repurposing existing drugs as potential treatments, including several used to treat Lupus. Of these, corticosteroids and hydroxychloroquine are the most well researched so far. The current evidence suggests that the corticosteroid dexamethasone improves outcome for the sickest COVID-19 patients requiring respiratory support. Initial reports suggested that hydroxychloroquine could have a positive impact on the course of COVID-19, however larger prospective studies have not supported this. Janus kinase inhibitors, currently being investigated for efficacy in lupus, have been shown to have anti-viral effects in vitro and inhibiting the JAK-STAT pathway may dampen down the host hyper-inflammatory response. Several trials are ongoing to assess the outcome of the use of JAK inhibitors in COVID-19 positive patients. For most patients continuing with their existing therapies to prevent a lupus flare or adverse events associated with sudden corticosteroid withdrawal is important whilst an Individualised risk assessment remains vital.

Strategies to develop student support mechanisms in medical radiation sciences clinical education.

Clinical placement experience is an important component of medical radiation science (MRS) education, equipping students to safely transition into complex healthcare environments. This commentary draws on evidence from the literature that reports challenges allied health students face in clinical environments. As several factors are implicated that could result in a higher prevalence of psychological distress and mental ill-health in MRS students, there is a need to re-emphasize the importance of developing strategies to support students in clinical education. A key recommendation is to identify associated risk factors early as they can impact on the quality of education and in severe cases be detrimental to students' psychological well-being. This requires an understanding of the full extent and nature of the challenges through partnered approaches between professional organisations, clinical departments, academics and students. Developing evidence-based strategies for improving students' well-being in clinical environments is also essential.

The unleashing of the immune system in COVID-19 and sepsis: the calm before the storm?

The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19. In this article, we discuss fresh perspectives and insights into the potential role of immune dysregulation in COVID-19 as well as similarities with systemic inflammatory response in sepsis and the rationale for exploring novel treatment options affecting host immune response.