Severe Cases Of Coronavirus Disease 2019 Research Articles

Safety and Efficacy of Interferon β-1b in the Treatment of Severe COVID-19 Patients: An Open-Label Randomized Controlled Trial

Background: About a year after the start of the coronavirus disease 2019 (COVID-19) pandemic, the results of the studies conducted to investigate the effectiveness of interferon (INF) compounds in this disease were contradictory. Objectives: This study was carried out to examine the safety and efficacy of a treatment protocol containing INF-β-1b, hydroxychloroquine, and Kaletra (lopinavir/ritonavir) in patients with severe COVID-19. Methods: In this open-label, randomized controlled trial, severe cases of COVID-19 were included. Patients were eligible if they had epidemiological and radiological evidence compatible with COVID-19 or a positive polymerase chain reaction result and their disease was severe. They were randomly allocated into a control group that received the standard regimen (hydroxychloroquine and Kaletra) and an intervention group that received INF-β-1b treatment and the standard treatment regimen. Then, the two groups were compared in terms of in-hospital mortality, intubation, length of hospital stay, oxygen saturation, and lactate dehydrogenase before and after the intervention. Results: A total of 91 cases of severe COVID-19 were enrolled for analysis [intervention (n = 47) and control (n = 44)]. The length of hospital stay in the intervention group was significantly longer than in the control group (13.21 ± 6.88 vs. 10.52 ± 5.77 days; P = 0.047). The mortality rate did not significantly differ between the intervention and control groups (19.15% and 13.64%, respectively; P = 0.509). The intubation rate did not significantly differ between the intervention and control groups (12.76% and 11.36%, respectively; P = 0.838). Conclusions: The use of INF-β-1b-containing treatment regimens does not reduce mortality and intubation rates among patients with severe COVID-19. Furthermore, it might even increase the severity of the disease and the length of hospital stay for some patients; therefore, it is not recommended to use INF-β-1b in severe cases of COVID-19.

LBODP001 Causal Associations Between Body Fat Accumulation and Covid-19 Severity: A Mendelian Randomization Study

Abstract Background Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Aims To elucidate the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity using Mendelian randomization (MR). Results We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 454,137 and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR)body fat mass = 1.61, 95% confidence interval [CI]: 1.28-2. 04, P = 5.51×10-5; ORbody fat-free mass = 1.31, 95% CI: 0.99-1.74, P = 5.77×10-2). Considering that body fat mass and fat-free mass were genetically correlated with each other (r = 0.64), we further evaluated the independent causal effects of body fat mass and fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (ORbody fat mass = 2.91, 95%CI: 1.71-4.96, P = 8.85×10-5 and ORbody fat-free mass = 1. 02, 95%CI: 0.61-1.67, P = 0.945). Conclusions This study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass. Presentation: No date and time listed

Clinical features of 19 children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 in Hangzhou, China

To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.

Real-world effectiveness of steroids in severe COVID-19: a retrospective cohort study

IntroductionRandomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19.MethodsClinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality.Results1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31–0.72)).ConclusionThe protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

Hemostatic system and COVID-19 crosstalk: A review of the available evidence.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.

Patients with severe coronavirus disease 2019 have high frequency of factor 5 Leiden and prothrombin gene mutations.

We investigated the frequency of factor 5 Leiden (FVL) and prothrombin gene (PTG) mutations in patients with severe coronavirus disease 2019 (COVID-19). Our primary aim is to reveal whether these mutations are associated with severity of disease and mortality. A total of 249 patients were included in this cross-sectional study. Severe COVID-19 cases (with oxygen saturation of less than 90 mmHg and who received ventilation support invasively or noninvasively) were included. FVL and PTG mutations were identified by real time- PCR technique. Frequency of mutations for FVL was 11.7%, whereas for PTG was 3.5%. The frequency of FVL and PTG's mutations in our patient group was found to be significantly higher than the normal population ( P < 0.0001, 0.004, respectively). There was no difference in the frequency of mutations of FVL and PTG between the patients ventilated - invasively and noninvasively. There was also no difference in D-dimer, ferritin, fibrinogen, ex status, and entubational status between the groups of FVL and PTG mutated and wild-type. To the best of our knowledge, it is the first time that we have examined the frequencies of FVL and PGM's mutations in severe COVID-19 disease on such a large scale. The frequencies of both mutations in severe COVID-19 patients were higher than in the healthy population. We believe that studies prospectively designed, including asymptomatic and mild COVID-19 patients, will provide more comprehensive information on the subject.

Risk-stratified management to remove low-risk penicillin allergy labels in the patients with COVID-19 in the intensive care unit

Through February 2022, more than 426 million cases of coronavirus disease 2019 (COVID-19) have been reported globally, resulting in more than 5.8 million deaths. Severe cases of COVID-19 may result in hypoxemic respiratory failure, acute respiratory distress syndrome, and septic shock.1

The patient-centered diabetes management during the COVID-19 pandemic.

Since December 2019, in the fight against the coronavirus disease 2019 (COVID-19) pandemic, we observed that glycemic control in people with diabetes is easily affected by lifestyle changes. To maintain a good health condition, a patient-centered approach with mental support and close monitoring is required. For these, telemedicine and online continuous glucose monitoring (CGM), are effective systems. Therefore, based on our experience during the two-year period, we reviewed the literature for appropriate actions required for the management of diabetes to prevent COVID-19 infection and avoid unfavorable outcomes in COVID-19 cases. Once infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a high risk of a poor prognosis in patients with diabetes. Glucocorticoid therapy in severe COVID-19 cases leads to further hyperglycemia. Since good glycemic control has been shown to improve outcomes, strict glycemic control using CGM is recommended. Using CGM data, insulin can be adequately titrated without causing hypoglycemia, and remote data monitoring can reduce the risk of infection for health care professionals, by reducing the frequency of patient contact. Among patients with COVID-19, some are found to have newly-diagnosed diabetes at admission. Those newly diagnosed patients present with a higher risk of poor prognosis compared to those with pre-existing diabetes. Therefore, glycemic status should be evaluated in all patients with COVID-19 admitted to hospitals.

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

Comparison of Immune Response and Immunobiology in COVID-19 (Coronavirus Disease 2019) Mild-Moderate Degree and Severe Degree

The difference in immunological profiles between mild-moderate and severe cases of COVID-19 can be seen in lower lymphocyte counts, leukocytes, and higher neutrophil-lymphocyte ratios. And lower percentages of monocytes, eosinophils, and basophils in severe COVID-19 cases. Proinflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as IL-8 and infection markers such as procalcitonin, ferritin, and C-reactive protein, were also found to be higher in severe clinical cases. T Helper, T suppressor, and T regulatory were found to be decreased in COVID-19 patients with lower numbers of T helper and T regulatory in severe cases.

Vitamin C Deficiency in Blood Samples of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is the most notable pandemic of the modern era. A relationship between ascorbate (vitamin C) and COVID-19 severity is well known, whereas the role of other vitamins is less understood. The present study compared the blood levels of four vitamins in a cohort of COVID-19 patients with different severities and uninfected individuals. Serum concentrations of ascorbate, calcidiol, retinol, and α-tocopherol were measured in a cohort of 74 COVID-19 patients and 8 uninfected volunteers. The blood levels were statistically compared and additional co-morbidity factors were considered. COVID-19 patients had significantly lower plasma ascorbate levels than the controls (p-value < 0.001), and further stratification revealed that the controls had higher levels than fatal, critical, and severe COVID-19 cases (p-values < 0.001). However, no such trend was observed for calcidiol, retinol, or α-tocopherol (p-value ≥ 0.093). Survival analysis showed that plasma ascorbate below 11.4 µM was associated with a lengthy hospitalization and a high risk of death. The results indicated that COVID-19 cases had depleted blood ascorbate associated with poor medical conditions, confirming the role of this vitamin in the outcome of COVID-19 infection.

A regression discontinuity analysis of the social distancing recommendations for older adults in Sweden during COVID-19.

BackgroundThis article investigates the impact of a non-mandatory and age-specific social distancing recommendation on isolation behaviours and disease outcomes in Sweden during the first wave of the coronavirus disease 2019 (COVID-19) pandemic (March to July 2020). The policy stated that people aged 70 years or older should avoid crowded places and contact with people outside the household.MethodsWe used a regression discontinuity design—in combination with self-reported isolation data from COVID Symptom Study Sweden (n = 96 053; age range: 39–79 years) and national register data (age range: 39–100+ years) on severe COVID-19 disease (hospitalization or death, n = 21 804) and confirmed cases (n = 48 984)—to estimate the effects of the policy.ResultsOur primary analyses showed a sharp drop in the weekly number of visits to crowded places (−13%) and severe COVID-19 cases (−16%) at the 70-year threshold. These results imply that the age-specific recommendations prevented approximately 1800–2700 severe COVID-19 cases, depending on model specification.ConclusionsIt seems that the non-mandatory, age-specific recommendations helped control COVID-19 disease during the first wave of the pandemic in Sweden, as opposed to not implementing a social distancing policy aimed at older adults. Our study provides empirical data on how populations may react to non-mandatory, age-specific social distancing policies in the face of a novel virus.

Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study.

Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity. We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 454,137 and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR)body fat mass = 1.61, 95% confidence interval [CI]: 1.28–2.04, P = 5.51 × 10-5; ORbody fat-free mass = 1.31, 95% CI: 0.99–1.74, P = 5.77 × 10-2). Considering that body fat mass and fat-free mass were genetically correlated with each other (r = 0.64), we further evaluated independent causal effects of body fat mass and fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (ORbody fat mass = 2.91, 95% CI: 1.71–4.96, P = 8.85 × 10-5 and ORbody fat-free mass = 1.02, 95%CI: 0.61–1.67, P = 0.945). In summary, this study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass.

Efficacy and safety of COVID-19 vaccination in patients with cirrhosis.

BACKGROUNDThe clinical efficacy and safety of vaccination against novel coronavirus disease 2019 (COVID-19) in patients with cirrhosis have not been evaluated yet. AIMTo evaluate the clinical efficacy and safety of vaccination against COVID-19 in patients with cirrhosis.METHODSThis was a retrospective cohort study of patients with cirrhosis. The first cohort included patients vaccinated with Gam-COVID-Vac (Sputnik V); the second one consisted of unvaccinated controls.RESULTSThe study included 89 vaccinated patients and 148 unvaccinated ones. There were 4 cases of COVID-19 in the vaccinated group and 24 cases in the unvaccinated group (P = 0.035). No severe cases of COVID-19 were revealed in the vaccinated group, while there were 12 ones in the unvaccinated group (P = 0.012) with 10 deaths detected (P = 0.012). The vaccine efficacy was 69.5% (95% confidence interval [CI]: 18.5%-94.4%) against symptomatic cases of COVID-19, 100% (95%CI: 25.1%-100.0%) against severe cases, and 100% (95%CI: 1.6%-100.0%) against death associated with COVID-19. The efficacy of full vaccination with revaccination against symptomatic cases of COVID-19 was 88.3% (95%CI: 48.0%-99.6%). The overall mortality rate was higher in the unvaccinated group than in the vaccinated group (17.1% vs 3.0%; P = 0.001). Higher Child-Turcotte-Pugh class cirrhosis (hazard ratio [HR] = 4.13, 95%CI: 1.82-9.35) and higher age (HR = 1.08, 95%CI: 1.04-1.15) were independent predictors of overall mortality, while vaccination had a protective effect (HR = 0.09, 95%CI: 0.01-0.76). There was no significant difference in liver-related mortality (P = 0.135) or the incidence of liver decompensation (P = 0.077), bleeding esophageal varices (P = 0.397), and vascular events (P = 0.651) between the two groups of patients. CONCLUSIONVaccination against COVID-19 in patients with cirrhosis is effective and safe.

Response to COVID-19 during the Tokyo Olympic Games: Did we properly assess the risk?

BackgroundThe number of coronavirus disease 2019 (COVID-19) cases was expected to increase during the Tokyo Olympic Games because of the increased physical contact within and between the domestic population and international participants of the Games. The rapid rise of the Delta variant (B.1.617) in Japan meant that hosting the Olympic Games without any restrictions was likely to lead to an increase in cases. We aimed to quantitatively assess possible COVID-19 response strategies for the Olympic Games, comparing the prevalence of severe cases and the cumulative number of COVID-19 deaths via scenario analysis. MethodsWe used a discrete-time deterministic compartmental model structured by age group. Parameters were calibrated using the age-stratified COVID-19 incidence data in Osaka. Numerical simulations incorporated the planned Olympics Games and nationwide COVID-19 vaccination into the proposed model, alongside various subjects and types of countermeasures. ResultsOur model-informed approach suggested that having spectators at the Tokyo Olympic Games could lead to a surge in both cases and hospitalization. Projections for the scenario that explicitly incorporated the spread of the Delta variant (i.e., time-dependent increase in the relative transmissibility) showed that imposing stringent social distancing measures (Rt=0.7) for more than 8 weeks from the end of the Olympic Games might be required to suppress the prevalence of severe cases of COVID-19 to avoid overwhelming the intensive care unit capacity in Tokyo. ConclusionsOur modeling analyses guided an optimal choice of COVID-19 response during and after the Tokyo Olympic Games, allowing the epidemic to be brought under control despite such a large mass gathering.

Clinical laboratory parameters and comorbidities associated with severity of coronavirus disease 2019 (COVID-19) in Kurdistan Region of Iraq

BackgroundThe pandemic coronavirus disease (COVID-19) dramatically spread worldwide. Considering several laboratory parameters and comorbidities may facilitate the assessment of disease severity. Early recognition of disease progression associated with severe cases of COVID-19 is essential for timely patient triaging. Our study investigated the characteristics and role of laboratory results and comorbidities in the progression and severity of COVID-19 cases. MethodsThe study was conducted from early-June to mid-August 2020. Blood samples and clinical data were taken from 322 patients diagnosed with COVID-19 at Qala Hospital, Kalar, Kurdistan Region of Iraq. Biological markers used in this study include complete blood count (CBC), D-dimer, erythrocyte sedimentation rate (ESR), serum ferritin, blood sugar, C-reactive protein (CRP) and SpO2. ResultsThe sample included 154 males (47.8%) and 168 females (52.2%). Most females were in the mild and moderate symptom groups, while males developed more severe symptoms. Regarding comorbidities, diabetes mellitus was considered the greatest risk factor for increasing the severity of COVID-19 symptoms. As for biological parameters, WBC, granulocytes, ESR, Ferritin, CRP and D-Dimer were elevated significantly corresponding to the severity of the disease, while lymphocytes and SpO2 showed the opposite pattern. Higher RBC was significantly associated with COVID-19 severity, especially in females. ConclusionGender, age and diabetes mellitus are important prognostic risk factors associated with severity and mortality of COVID-19. Relative to non-severe COVID-19, severe cases are characterized by an increase of most biological markers. These markers could be used to recognize severe cases and to monitor the clinical course of COVID-19.

Altered Hematological Profile

Background: Being a systemic infection, coronavirus disease 2019 (COVID-19) affects hematologic system, along with cardiovascular, pulmonary, gastrointestinal, and neurological systems, resulting in altered hematological parameters. These altered hematological findings are thought to have a role in early risk stratification and prognostication of COVID-19 patients. However, the data on hematological abnormalities associated with the disease among Eastern Indian COVID-19 patients, particularly the Bengalis, are limited. Aim: The aim is to study the association, if any, between various hematological parameters and disease severity of COVID-19. Materials and Methods: The study was a cross-sectional study involving 145 laboratory-confirmed cases of SARS-CoV-2 infection. Based on the disease severity, the patients were divided into three groups: mild, moderate, and severe. Various hematological parameters were analyzed. Results: Of the 145 patients, 82.8%, 9.6%, and 7.5% of the cases were in the mild, moderate, and severe groups, respectively. The mean age was 48 years. The result of our study showed that the age of the patients is directly proportional to the severity of the illness. About 62.1% of the patients were male, whereas the rest (37.9%) were female. Our study showed an independent association of Covid severity with male gender. Although mean total leukocyte count (TLC), absolute count of neutrophil, lymphocyte, eosinophil, neutrophil–lymphocyte ratio (NLR), neutrophil–monocyte ratio (NMR), lymphocyte–monocyte ratio, platelet–lymphocyte ratio, and systemic inflammatory index among mild, moderate, and severe COVID-19 cases were statistically significant (P &lt; 0.05), basophil, monocyte, and platelet count were statistically insignificant among the three groups. Nearly all of the hematological parameters could be used as potential diagnostic biomarkers for subsequent analysis because their area under the curve was higher than 0.50. Conclusion: Severity of COVID-19 is associated with older age, male sex, higher TLC, neutrophilia, lymphopenia, eosinopenia, high NLR, and high NMR. As complete blood count is an inexpensive routine blood investigation, it can be very useful in a resource-poor healthcare facility, which is unable to provide high-end investigations.

Clinical observation of Xuanfei Baidu Decoction in treatment of severe coronavirus disease 2019 (COVID-19)

The present study evaluated the effectiveness and safety of Xuanfei Baidu Decoction(XFBD) for severe cases with coronavirus disease 2019(COVID-19).Forty-one patients(diagnosed as severe or critical type) admitted to Hubei Provincial Hospital of Integrated Chinese and Western Medicine and Wuhan Hospital of Traditional Chinese Medicine from February 1 to March 1, 2020, were included.All patients were treated with XFBD based on conventional therapies.Clinical outcomes, length of hospital stay, and lung CT images of patients were observed.Laboratory indicators were compared between admission and the 14 th day of treatment.Traditional Chinese medicine(TCM) symptoms and signs on the 7 th and 14 th days of treatment were also compared with baseline.The differences in clinical characteristics and clinical outcomes between XFBD and western medicine or conventional therapies were analyzed with the published trials on severe COVID-19 cases during the same period as external controls.According to the results, among the 41 cases, 40 were cured and discharged, and 1 died; the median length of hospital stay was 22 days, and the improvement rate of lung CT was 87.2%(34/39).Compared with the conditions on admission, the levels of white blood cells(WBC), C-reactive protein(CRP), fibrinogen(FIB), and lactate dehydrogenase(LDH) were reduced(P&lt;0.05, P&lt;0.01), and levels of procalcitonin(PCT), prothrombin time(PT), creatine kinase(CK), alanine aminotransferase(AST), total bilirubin(TBiL), and other indicators showed a downward trend.Moreover, symptoms like fever, cough, chest tightness/shortness of breath, dyspnea, head and body pain, anorexia, and greasy tongue coating were significantly improved on the 7 th and 14 th days of treatment(P&lt;0.05, P&lt;0.01), and fatigue was improved on the 14 th day of treatment(P&lt;0.01).The mortality, adverse reactions, and major events of the XFBD group were significantly lower than those of the western medicine and conventional treatment groups in the same period, and the usage of antibiotics, hormones, vasopressin, and invasive mechanical ventilation during treatment were generally less than other groups.In conclusion, XFBD has good efficacy and safety in the treatment of severe COVID-19 cases by improving inflammation and clinical symptoms, promoting the absorption of lung inflammation, and reducing mortality.

In Vitro Exposure of Primary Human T Cells and Monocytes to Polyclonal Stimuli Reveals a Basal Susceptibility to Display an Impaired Cellular Immune Response and Develop Severe COVID-19.

The contribution of the cellular immune response to the severity of coronavirus disease 2019 (COVID-19) is still uncertain because most evidence comes from patients receiving multiple drugs able to change immune function. Herein, we conducted a prospective cohort study and obtained blood samples from 128 unvaccinated healthy volunteers to examine the in vitro response pattern of CD4+ and CD8+ T cells and monocyte subsets to polyclonal stimuli, including anti-CD3, anti-CD28, poly I:C, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) recombinant spike S1 protein, and lipopolysaccharide. Then, we started a six-month follow-up and registered 12 participants who got SARS-CoV-2 infection, from whom we retrospectively analyzed the basal immune response pattern of T cells and monocytes. Of the 12 participants infected, six participants developed mild COVID-19 with self-limiting symptoms such as fever, headache, and anosmia. Conversely, six other participants developed severe COVID-19 with pneumonia, respiratory distress, and hypoxia. Two severe COVID-19 cases required invasive mechanical ventilation. There were no differences between mild and severe cases for demographic, clinical, and biochemical baseline characteristics. In response to polyclonal stimuli, basal production of interleukin-2 (IL-2) and interferon (IFN-) gamma significantly decreased, and the programmed cell death protein 1 (PD-1) increased in CD4+ and CD8+ T cells from participants who posteriorly developed severe COVID-19 compared to mild cases. Likewise, CD14++CD16- classical and CD14+CD16+ non-classical monocytes lost their ability to produce IFN-alpha in response to polyclonal stimuli in participants who developed severe COVID-19 compared to mild cases. Of note, neither the total immunoglobulin G serum titers against the virus nor their neutralizing ability differed between mild and severe cases after a month of clinical recovery. In conclusion, using in vitro polyclonal stimuli, we found a basal immune response pattern associated with a predisposition to developing severe COVID-19, where high PD-1 expression and low IL-2 and IFN-gamma production in CD4+ and CD8+ T cells, and poor IFN-alpha expression in classical and non-classical monocytes are linked to disease worsening. Since antibody titers did not differ between mild and severe cases, these findings suggest cellular immunity may play a more crucial role than humoral immunity in preventing COVID-19 progression.

IgG N-glycome changes during the course of severe COVID-19: An observational study

SummaryBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation.MethodsUsing ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78).FindingsMultiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19.InterpretationThe IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19.FundingThis work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.