Severe Coronavirus Disease 2019 Disease Research Articles

ACE2 protein expression in lung tissues of severe COVID-19 infection

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Can Peripheral Perfusion Index (PPI) Predict Disease Severity in COVID-19 Patients in the Emergency Department?

Abstract Background Coronavirus disease 2019 (COVID-19) causes significant mortality and morbidity in severe patients. Objective In this study, we aimed to examine the relationship between COVID-19 disease severity and peripheral perfusion index (PPI). Patients and Methods This prospective observational study included COVID-19 patients admitted to the tertiary hospital emergency department. Basal clinical and demographic data of the patients and PPI values at the time of admission were recorded. The patients were categorized to severe and nonsevere groups according to clinical severity. The relationship between COVID-19 severity and PPI was examined in comparison with the control group. Results A total of 324 patients who met the inclusion criteria were analyzed. COVID-19 (+) was detected in 180 of these patients. Ninety-two of the COVID-19 (+) patients were in the severe group, and 88 of them were in the non severe group. Note that 164 COVID-19 (–) patients were in the control group. PPI average was found to be 1.44 ± 1.12 in the severe group, and 3.69 ± 2.51 in the nonsevere group. PPI average was found to be significantly lower in the severe group than the nonsevere group (p< 0.01) As for the nonsevere group and control group, PPI averages were found to be 3.69 ± 2.51 and3.54 ± 2.32, respectively, and a significant difference was determined between the two groups (p< 0.05). PPI COVID-19 severity predicting activity was calculated as area under the curve: 0.833, sensitivity:70.4%, andspecificity:71%(p = 0.025) at 2.2 cutoff value. Conclusion The results of our study showed that PPI is an easy-to-apply and useful parameter in the emergency department in determining the severity of COVID-19 patients.

Hyponatremia in COVID-19 patients: Experience from Bangladesh.

BackgroundThe purpose of the study was to measure the prevalence of hyponatremia and its association with clinical and laboratory characteristics of hospitalized coronavirus disease 2019 (COVID‐19) patients at Dhaka Medical College and Hospital (DMCH).MethodsThis retrospective study was conducted in COVID‐19 dedicated wards at DMCH from June to August 2020. Demographic, clinical, and laboratory data were collected from patient treatment sheets. Two groups of COVID‐19 patients were retrospectively screened on the basis of plasma sodium level at admission: hyponatremic (sodium < 135 mM, n = 84) or normonatremic (sodium ≥ 135 mM, n = 48) patients. Severity was assessed using World Health Organization classification for COVID‐19 disease severity. To compare the two groups, Pearson's χ 2 (qualitative variables) and Student's T tests (quantitative variables) were applied. The link between patients' clinical data and outcomes was investigated using logistic regression model.ResultsA total of 132 patients were included in the study, with a mean age of 51.41 (±14.13) years. Hyponatremia was found in 84 patients (63.6%) and the remaining 48 patients (36.4%) had normal plasma Na+ values. Among them, 74 (56.06%) presented with severe disease and 53 (40.15%) with moderate disease. At presentation, patients with moderate COVID‐19 disease had 2.15 (1.04–4.5) times higher odds of suffering from hyponatremia. Besides, hyponatremia was independently associated with on admission SpO2 (p = 0.038), hemoglobin (p = 0.004), and C‐reactive protein (p = 0.001).ConclusionsThe authors suggest that patients' serum electrolytes be measured during initial hospital admission and then monitored throughout the hospital stay to predict the probability for referral for invasive ventilation and for better management.

Effect of SARS-CoV-2 Entry Factors on Myeloid Cancers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly pathogenic coronavirus that has spread rapidly worldwide and caused an international public health emergency. Patients with hematological cancers are regarded as a high-risk group for coronavirus disease 2019 (COVID-19). However, few reports have investigated factors that might account for the differential severity of COVID-19 disease in these patients. Gene expression of SARS-CoV-2 entry-promoting factors and entry-restricting factors and the associated effects on myeloid malignancies were evaluated. Gene expression levels of 11 SARS-CoV-2 entry-promoting factors and 4 SARS-CoV-2 entry-restricting factors were analyzed in patients with myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), and acute myeloid leukemia and its subtypes. Expression levels of promoting and restricting factors were most affected in MDS. Specifically, 4 of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (TMPRSS4, CD209, CLEC4G, and CTSB), and 2 of the 4 analyzed SARS-CoV-2 entry-restricting factors were significantly decreased (IFITM1 and IFITM2) in MDS. Patients with CML also exhibited a pattern of significant changes in SARS-CoV-2 entry-promoting and entry-restricting factors. Five of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (ACE2, TMPRSS2, TMPRSS4, ANPEP, CD209), and 1 of the 4 analyzed SARS-CoV-2 entry-restricting factors was significantly decreased (LY6E) in CML. The present and past results highlight the importance of investigating SARS-CoV-2 entry-promoting factors and entry-restricting factors, because of their crucial role in determining the differential severity of COVID-19 disease.

A correlation of disease severity and outcome with malnutrition status in adults with COVID-19

Background: Coronavirus disease 2019 (COVID-19) pathology increases catabolism and depletes the protein stores, causing malnutrition. However, nutrition assessment in COVID-19 is often overlooked in the current pandemic. The Controlling Nutritional Status (CONUT) score is a validated score to assess nutritional status in hospitalized patients. The objective of the study was to estimate malnutrition among hospitalized adult patients with COVID-19 using the - The Controlling Nutritional Status (CONUT) score and study its effect on the disease severity and outcomes.Methods: The study was a retrospective study on 146 patients with COVID-19. The history, demographic details were noted and the following parameters were noted at baseline and time of outcome- COVID-19 disease severity, radiological severity, CONUT score, inflammatory markers- serum LDH, CRP, Ferritin, D-Dimer. The outcome parameters- mortality, duration of hospital stay and severity of disease at outcome were measured.Results: Out of the 146 patients, 84 (57.53%) were male and 62 (42.47%) were female. 97.26% patients had malnutrition at baseline with 42 (28.77%) mild, 70 (47.95%) moderate and 30 (20.55%) severe malnutrition based on CONUT score. The CONUT scores were greater at outcome compared to baseline (p&lt;0.001). Higher grades of malnutrition were associated with greater baseline and outcome disease severity (p&lt;0.001), radiological severity (p&lt;0.001), higher levels of inflammatory markers (p&lt;0.001) and a higher mortality (p&lt;0.001). However, there was no significant difference in duration of hospital stay (p=0.67).Conclusions: Malnutrition results in worse outcomes and greater mortality in COVID-19. Individual tailored nutritional support in the hospitalized COVID-19 patients, can thus potentially improve outcomes.

Influence of Aerosol Delivered BCG Vaccination on Immunological and Disease Parameters Following SARS-CoV-2 Challenge in Rhesus Macaques.

The tuberculosis vaccine, Bacille Calmette-Guerin (BCG), also affords protection against non-tuberculous diseases attributable to heterologous immune mechanisms such as trained innate immunity, activation of non-conventional T-cells, and cross-reactive adaptive immunity. Aerosol vaccine delivery can target immune responses toward the primary site of infection for a respiratory pathogen. Therefore, we hypothesised that aerosol delivery of BCG would enhance cross-protective action against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and be a deployable intervention against coronavirus disease 2019 (COVID-19). Immune parameters were monitored in vaccinated and unvaccinated rhesus macaques for 28 days following aerosol BCG vaccination. High-dose SARS-CoV-2 challenge was applied by intranasal and intrabronchial instillation and animals culled 6–8 days later for assessment of viral, disease, and immunological parameters. Mycobacteria-specific cell-mediated immune responses were detected following aerosol BCG vaccination, but SARS-CoV-2-specific cellular- and antibody-mediated immunity was only measured following challenge. Early secretion of cytokine and chemokine markers associated with the innate cellular and adaptive antiviral immune response was detected following SARS-CoV-2 challenge in vaccinated animals, at concentrations that exceeded titres measured in unvaccinated macaques. Classical CD14+ monocytes and Vδ2 γδ T-cells quantified by whole-blood immunophenotyping increased rapidly in vaccinated animals following SARS-CoV-2 challenge, indicating a priming of innate immune cells and non-conventional T-cell populations. However, viral RNA quantified in nasal and pharyngeal swabs, bronchoalveolar lavage (BAL), and tissue samples collected at necropsy was equivalent in vaccinated and unvaccinated animals, and in-life CT imaging and histopathology scoring applied to pulmonary tissue sections indicated that the disease induced by SARS-CoV-2 challenge was comparable between vaccinated and unvaccinated groups. Hence, aerosol BCG vaccination did not induce, or enhance the induction of, SARS-CoV-2 cross-reactive adaptive cellular or humoral immunity, although an influence of BCG vaccination on the subsequent immune response to SARS-CoV-2 challenge was apparent in immune signatures indicative of trained innate immune mechanisms and primed unconventional T-cell populations. Nevertheless, aerosol BCG vaccination did not enhance the initial clearance of virus, nor reduce the occurrence of early disease pathology after high dose SARS-CoV-2 challenge. However, the heterologous immune mechanisms primed by BCG vaccination could contribute to the moderation of COVID-19 disease severity in more susceptible species following natural infection.

Transcriptional landscape of circulating platelets from patients with COVID-19 reveals key subnetworks and regulators underlying SARS-CoV-2 infection: implications for immunothrombosis

BackgroundThrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID-19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Platelets are essential cells that regulate hemostasis, thrombus formation and inflammation; however, the mechanism underlying the interaction between platelets and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear.ResultsThe present study performed RNA sequencing on the RNA isolated from platelets obtained from 10 COVID-19 patients and eight healthy donors, and discovered that SARS-CoV-2 not only significantly altered the coding and non-coding transcriptional landscape, but also altered the function of the platelets, promoted thrombus formation and affected energy metabolism of platelets. Integrative network biology analysis identified four key subnetworks and 16 risk regulators underlying SARS-CoV-2 infection, involved in coronavirus disease-COVID-19, platelet activation and immune response pathways. Furthermore, four risk genes (upstream binding transcription factor, RNA polymerase II, I and III subunit L, Y-box binding protein 1 and yippee like 2) were found to be associated with COVID-19 severity. Finally, a significant alteration in the von Willebrand factor/glycoprotein Ib-IX-V axis was revealed to be strongly associated with platelet aggregation and immunothrombosis.ConclusionsThe transcriptional landscape and the identification of critical subnetworks and risk genes of platelets provided novel insights into the molecular mechanisms of immunothrombosis in COVID-19 progression, which may pave the way for the development of novel therapeutic strategies for preventing COVID-19-associated thrombosis and improving the clinical outcome of COVID-19 patients.

Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones

Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents.

Variation in COVID-19 Disease Severity and Clinical Outcomes Between Different ABO Blood Groups.

The primary objective of this study was to explore whether coronavirus disease 2019 (COVID-19) severity and outcomes varied between different ABO blood groups. This retrospective study included 363 COVID-19 confirmed patients who had their blood group recorded in the hospital medical records, from March to June 2020. Data representing demographics, clinical features, vital signs, laboratory findings, and COVID-19 outcomes were collected. Multivariate logistic regression was used for analysis and the results were adjusted for sociodemographic, clinical, and laboratory variables. The patients’ mean age was 50 ± 17.8 years. Of the 363 patients, 30% were blood group A, 22.3% were blood group B, 8.8% were blood group AB, and 38.8% were blood group O. Bivariate analysis showed that patients with blood group AB were more likely to be free of any medical disease (65.6%) compared to other blood groups (p = 0.007). Fever was the most common presenting complaint (66.7%), and it did not significantly vary with changes in ABO blood groups (p = 0.230). Regarding laboratory characteristics, only C-reactive protein (CRP) levels were significantly associated with the blood groups, with high levels seen in blood groups A, B, and O (p = 0.036). In multivariate analysis, variations in emergency department (ED) disposition, requirement of intensive care unit care, and requirement of mechanical ventilation were not statistically significant among the different ABO blood groups. Furthermore, no correlation was found between hospital death and the different ABO blood groups. In conclusion, COVID-19 is most prevalent among patients with blood group O and least prevalent among those with blood group AB. No particular blood group had worse COVID-19 disease severity and outcomes than other blood groups. Therefore, we believe that ABO blood grouping should not be used as a major assessment tool for COVID-19 disease severity and outcome, and other known risk factors should be investigated.

Colchicine Against SARS-CoV-2 Infection: What is the Evidence?

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of concern worldwide and a huge challenge for rheumatologists. Indeed, several antirheumatic drugs are currently used at different stages of COVID-19, such as several cytokine inhibitors and colchicine. Colchicine is one of the oldest medicines with potent anti-inflammatory properties. In rheumatic diseases it is widely used for the treatment of gout, calcium pyrophosphate deposition disease, and familial Mediterranean fever. It is also used off-label in cardiology to treat atrial fibrillation, pericarditis, and myocardial infarction. Over the last few years, advances in the understanding of colchicine’s mechanism of action and its pharmacology and safety have made colchicine a promising candidate agent for the fight against COVID-19. In this review, we discuss COVID-19 pathophysiology highlighting colchicine’s mode of action, its pleiotropic effects on neutrophils, inflammasome inhibition, and its viral activity. Finally, we discuss the main clinical studies dealing with the use of colchicine in COVID-19. Given the large body of evidence that demonstrates its effectiveness, safety, and its simple way of administration, colchicine seems to be a promising drug to reduce the risk of severe COVID-19 disease.

PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A single-stranded RNA virus from a β-Coronaviridae family causes acute clinical manifestations. Its high death rate and severe clinical symptoms have turned it into the most significant challenge worldwide. Up until now, several effective COVID-19 vaccines have been designed and marketed, but our data on specialized therapeutic drugs for the treatment of COVID-19 is still limited. In order to synthesis virus particles, SARS-CoV-2 uses host metabolic pathways such as phosphoinositide3-kinase (PI3K)/protein kinase B (PKB, also known as AKT)/mammalian target of rapamycin (mTOR). mTOR is involved in multiple biological processes. Over-activation of the mTOR pathway improves viral replication, which makes it a possible target in COVID-19 therapy. Clinical data shows the hyperactivation of the mTOR pathway in lung tissues during respiratory viral infections. However, the exact impact of mTOR pathway inhibitors on the COVID-19 severity and death rate is yet to be thoroughly investigated. There are several mTOR pathway inhibitors. Rapamycin is the most famous inhibitor of mTORC1 among all. Studies on other respiratory viruses suggest that the therapeutic inhibitors of the mTOR pathway, especially rapamycin, can be a potential approach to anti-SARS-CoV-2 therapy. Using therapeutic methods that inhibit harmful immune responses can open a new chapter in treating severe COVID-19 disease. We highlighted the potential contribution of PI3K/Akt/mTOR inhibitors in the treatment of COVID-19.

Abstract TMP18: Global Estimates Of Frequency And Outcomes Of Coronavirus Disease 2019 Associated Stroke And Myocardial Infarction

Background: We evaluated the frequency and outcomes of Coronavirus Disease 2019 (COVID-19) associated stroke (ischemic and hemorrhagic) and myocardial infarction (MI) in a global research network. Methods: All adult (≥ 18 years) patients with ICD-10 diagnoses of COVID-19 were included and those with a stroke (ischemic stroke, intracerebral hemorrhage [ICH], transient ischemic attach [TIA] or subarachnoid hemorrhage [SAH]) or myocardial infarction (MI) ± 28 days from COVID-19 diagnosis were flagged. Individuals with a prior history of stroke / MI were excluded. COVID-19 associated stroke (CAS) and MI (CAM) frequencies were compared to prior AHA-reported population-based incidences. Severe COVID-19 disease (use of ventilator, intubation, or life support) and 90-day mortality were evaluated among no-stroke/MI and stroke/MI subgroups utilizing general linear models adjusted for age, sex, race/ethnicity, and Charlson Comorbidity Index scores. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. Results: Between Jan 2020 and Jul 2021, we identified 637,820 COVID-19 patients of whom 4,559 (0.71%) had a CAS and 6,972 (1.09%) had a CAM. COVID-19 was associated with significantly higher stroke/MI rates compared to population based reported incidence (ORs, CI for CAS 1.99, 1.93 - 2.05 and CAM 3.09, 3.01 - 3.16). Severe COVID disease was observed among 1.07% of COVID-19 only patients, 11.25% of CAS patients (aOR, CI: 4.82, 4.35 - 5.34), and 14.81% of CAM patients (aOR, CI: 5.77, 5.34 - 5.22). 90-Day mortality was 1.92% for COVID-19 only patients, 14.35% for CAS patients (aOR, CI: 3.16, 2.87 - 3.46), and 20.52% for CAM patients (aOR, CI: 4.12, 3.85 - 4.41). Group specific demographic and outcome proportions are reported (Figure). Conclusion: The COVID-19 pandemic has tremendously exacerbated the burden of cerebrovascular and cardiovascular disease globally. Continued work is needed to understand drivers of poor outcomes among COVID-19 patients.

POS-935 OUTCOME OF COVID-19 IN DIALYSIS PATIENTS IN KELANTAN

Coronavirus disease 2019 (COVID-19)outbreak had occurred since December 2019 and rapidly spread worldwide including Malaysia. Chronic kidney disease and kidney failure are substantial comorbidities that are associated with untoward outcomes in patients with COVID-19. Kidney failure is an independent risk factor for severe COVID-19 disease presentation and mortality after accounting coexisting comorbidities. Therefore, the purpose of this cross sectional analysis is to study outcome of COVID-19 patients on dialysis in Kelantan that will give additional sight for healthcare providers in managing COVID-19.

IgG Against Human Betacoronavirus Spike Proteins Correlates With SARS-CoV-2 Anti-Spike IgG Responses and COVID-19 Disease Severity.

BackgroundA protective antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to decrease morbidity and mortality from severe coronavirus disease 2019 (COVID-19) disease. The effects of preexisting anti-human coronavirus (HCoV) antibodies on the SARS-CoV-2–specific immunoglobulin G (IgG) responses and severity of disease are currently unclear.MethodsWe profiled anti-spike (S), S1, S2, and receptor-binding domain IgG antibodies against SARS-CoV-2 and 6 HCoVs using a multiplex assay (mPLEX-CoV) with serum samples from SARS-CoV-2 infected (n = 155) and pre–COVID-19 (n = 188) cohorts.ResultsCOVID-19 subjects showed significantly increased anti-S SARS-CoV-2 IgG levels that were highly correlated with IgG antibodies against OC43 and HKU1 S proteins. However, OC43 and HKU1 anti-S antibodies in pre–COVID-19 era sera did not cross-react with SARS-CoV-2. Unidirectional cross-reactive antibodies elicited by SARS-CoV-2 infection were distinct from the bidirectional cross-reactive antibodies recognizing homologous strains RaTG13 and SARS-CoV-1. High anti-OC43 and anti-S2 antibody levels were associated with both a rapid anti–SARS-CoV-2 antibody response and increased disease severity. Subjects with increased sequential organ failure assessment (SOFA) scores developed a higher ratio of S2- to S1-reactive antibodies.ConclusionsEarly and rapid emergence of OC43 S- and S2-reactive IgG after SARS-CoV-2 infection correlates with COVID-19 disease severity.

Chest radiological finding of COVID-19 in patients with and without diabetes mellitus: Differences in imaging finding.

The pandemic of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diabetes mellitus is a risk factor for developing severe illness and a leading cause of death in patients with COVID-19. Diabetes can precipitate hyperglycaemic emergencies and cause prolonged hospital admissions. Insulin resistance is thought to cause endothelial dysfunction, alveolar capillary micro-angiopathy and interstitial lung fibrosis through pro-inflammatory pathways. Autopsy studies have also demonstrated the presence of microvascular thrombi in affected sections of lung, which may be associated with diabetes. Chest imaging using x-ray (CXR) and computed tomography (CT) of chest is used to diagnose, assess disease progression and severity in COVID-19. This article reviews current literature regarding chest imaging findings in patients with diabetes affected by COVID-19. A literature search was performed on PubMed. Patients with diabetes infected with SARS-CoV-2 are likely to have more severe infective changes on CXR and CT chest imaging. Severity of airspace consolidation on CXR is associated with higher mortality, particularly in the presence of co-morbidities such as ischaemic heart disease. Poorly controlled diabetes is associated with more severe acute lung injury on CT. However, no association has been identified between poorly-controlled diabetes and the incidence of pulmonary thromboembolism in patients with COVID-19.

Interleukin-1 Inhibitors and Vaccination Including COVID-19 in Inflammatory Rheumatic Diseases: A Nonsystematic Review.

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.

Impact of cytokine storm on severity of COVID-19 disease in a private hospital in West Jakarta prior to vaccination.

Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms. This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled. The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days. Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.

Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy.

To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

Does COVID-19 cause pre-eclampsia?

Does COVID-19 cause pre-eclampsia?

Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study.

Background:The coronavirus disease 2019 (COVID-19) is a highly infectious respiratory disease. There is no recommended antiviral treatment approved for COVID-19 in Sierra Leone, and supportive care and protection of vital organ function are performed for the patients. This study summarized the clinical characteristics, drug treatments, and risk factors for the severity and prognosis of COVID-19 in Sierra Leone to provide evidence for the treatment of COVID-19.Methods:Data of 180 adult COVID-19 patients from the 34th Military Hospital in Freetown Sierra Leone between March 31, 2020 and August 11, 2020 were retrospectively collected. Patients with severe and critically ill are classified in the severe group, while patients that presented asymptomatic, mild, and moderate disease were grouped in the non-severe group. The clinical and laboratory information was retrospectively collected to assess the risk factors and treatment strategies for severe COVID-19. Demographic information, travel history, clinical symptoms and signs, laboratory detection results, chest examination findings, therapeutics, and clinical outcomes were collected from each case file. Multivariate logistic analysis was adopted to identify the risk factors for deaths. Additionally, the clinical efficacy of dexamethasone treatment was investigated.Results:Seventy-six (42.22%) cases were confirmed with severe COVID-19, while 104 patients (57.78%) were divided into the non-severe group. Fever (56.67%, 102/180) and cough (50.00%, 90/180) were the common symptoms of COVID-19. The death rate was 18.89% (34/180), and severe pneumonia (44.12%, 15/34) and septic shock (23.53%, 8/34) represented the leading reasons for deaths. The older age population, a combination of hypertension and diabetes, the presence of pneumonia, and high levels of inflammatory markers were significantly associated with severity of COVID-19 development (P < 0.05 for all). Altered level of consciousness [odds ratio (OR) = 56.574, 95% confidence interval (CI) 5.645–566.940, P = 0.001], high levels of neutrophils (OR = 1.341, 95%CI 1.109–1.621, P = 0.002) and C-reactive protein (CRP) (OR = 1.014, 95%CI 1.003–1.025, P = 0.016) might be indicators for COVID-19 deaths. Dexamethasone treatment could reduce mortality [30.36% (17/56) vs. 50.00% (10/20)] among severe COVID-19 cases, but the results were not statistically significant (P > 0.05).Conclusions:The development and prognosis of COVID-19 may be significantly correlated with consciousness status, and the levels of neutrophils and CRP.