Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4⁺ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4⁺ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4⁺ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4⁺ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4⁺ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.     

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

Background and aimPathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache.MethodsThis cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied.ResultsThe mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels.ConclusionStronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.     

糖尿病对COVID-19患者疾病严重程度和死亡率影响的Meta分析

目的 糖尿病是一种慢性疾病,身体各个系统都有不同程度的损伤。大量研究指出糖尿病患者在新型冠状病毒肺炎(COVID-19)流行期间更加容易感染COVID-19并且更容易出现重症。本研究拟通过Meta分析来探明糖尿病与COVID-19严重程度和死亡率的关联性。方法 使用关键词(1)“COVID-19” OR “SARS-CoV-2” OR “Coronavirus” OR “novel coronavirus” AND “clinical characteristics” (2)“COVID-19” OR “SARS-CoV-2” AND “Diabetes” 检索PubMed, Embase和中国知网的数据,筛选截至2021年2月发表的英文和中文期刊论著,提取数据后使用RevMan 5.4进行Meta分析,并使用Stata 12.0评估发表偏倚。结果 共纳入82篇文献,合计35 715例患者。Meta分析结果显示,患糖尿病与COVID-19预后较差有关[OR 2.29 (2.14, 2.46), P<0.01; I²: 52%, P<0.01]。COVID-19患者中糖尿病患者相对非糖尿病患者发生重症[OR 2.40 (2.20, 2.62), P<0.01; I²: 49%, P<0.01]和死亡[OR 2.08 (1.70, 2.56 ), P<0.01; I²: 60%, P<0.01]的风险均升高。结论 糖尿病是影响COVID-19患者的重症率和死亡率升高的一个重要因素,而针对糖尿病如何影响COVID-19预后的确切作用机制亟需进一步研究阐明。     

Beta receptor blocker therapy for the elderly in the COVID-19 era

When the coronavirus disease 2019 (COVID-19) pandemic spread globally from the Hubei region of China in December 2019, the impact on elderly people was particularly unfavorable. The mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was highest in older individuals, in whom frailty and comorbidities increased susceptibility to severe forms of COVID-19. Unfortunately, in older patients, the course of COVID-19 was often characterized by significant cardiovascular complications, such as heart failure decompensation, arrhythmias, pericarditis, and myopericarditis. Ensuring that the elderly have adequate therapeutic coverage against known cardiovascular diseases and risk factors is particularly important in the COVID-19 era. Beta blockers are widely used for the treatment and prevention of cardiovascular disease. The clinical benefits of beta blockers have been confirmed in elderly patients, and in addition to their negative chronotropic effect, sympathetic inhibition and anti-inflammatory activity are theoretically of great benefit for the treatment of COVID-19 infection. Beta blockers have not been clearly shown to prevent SARS-CoV-2 infection, but there is evidence from published studies including elderly patients that beta blockers are associated with a more favorable clinical course of COVID-19 and reduced mortality. In this minireview, we summarize the most important evidence available in the literature on the usefulness of beta blocker therapy for older patients in the context of the COVID-19 pandemic.     

Nonalcoholic fatty liver disease and COVID-19: An epidemic that begets pandemic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, affecting all the individuals across the planet. COVID-19 has gained significant attention due to its high prevalence among individuals with diabetes, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome. NAFLD is the hepatic manifestation of metabolic syndrome and can be associated with a high risk of developing type 2 diabetes. The association of COVID-19 and NAFLD has also gained more attention because NAFLD is highly associated with the epidemic of obesity. NAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19, independent of metabolic syndrome. Importantly, it is not yet clear whether the epidemics of obesity and NAFLD have perpetuated the current pandemic of COVID-19. Further research is urgently needed to assess the following: (1) Whether NAFLD is a high risk factor for SARS-CoV-2 infection; (2) Whether NAFLD is associated with the severe form of COVID-19; and (3) Whether the presence of NAFLD can explain the racial variation in the morbidity and mortality associated with COVID-19. This review summarizes the interactions between COVID-19 and NAFLD, mechanism of liver injury by COVID-19, and effect of lockdown due to COVID- 19 on patients with NAFLD.     

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial

BackgroundThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.MethodIn this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.ResultsA total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.Conclusions and relevancerSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.

Key messages

• There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.
• In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

     

The effect of BMI on COVID-19 outcomes among older patients in South Korea: a nationwide retrospective cohort study*

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused deaths and shortages in medical resources worldwide, making the prediction of patient prognosis and the identification of risk factors very important. Increasing age is already known as one of the main risk factors for poor outcomes, but the effect of body mass index (BMI) on COVID-19 outcomes in older patients has not yet been investigated. Aim: We aimed to determine the effect of BMI on the severity and mortality of COVID-19 among older patients in South Korea. Methods: Data from 1272 COVID-19 patients (≥60 years old) were collected by the Korea Centers for Disease Control and Prevention. The odds ratios (ORs) of severe infection and death in the BMI groups were analyzed by logistic regression adjusted for covariates.Results: The underweight group (BMI<18.5 kg/m²) had a higher OR for death (adjusted OR = 2.23, 95% confidence interval [95% CI] = 1.06–4.52) than the normal weight group (BMI, 18.5–22.9 kg/m²). Overweight (BMI, 23.0–24.9 kg/m²) was associated with lower risks of both severe infection (adjusted OR = 0.55, 95% CI = 0.31–0.94) and death (adjusted OR = 0.50, 95% CI = 0.27–0.91). Conclusions: Underweight was associated with an increased risk of death, and overweight was related to lower risks of severe infection and death in older COVID-19 patients in Korea. However, this study was limited by the lack of availability of some information, including smoking status.

KEY MESSAGES

• Underweight is an independent risk factor of death in older COVID-19 patients.
• Overweight patients have a lower risk of death and severe infection than normal-weight patients.

     

The effectiveness of high-dose intravenous vitamin C for patients with coronavirus disease 2019: A systematic review and meta-analysis

ObjectivesVitamin C has anti-inflammatory effects. This review aimed to investigate the therapeutic effect of high-dose intravenous vitamin C (HDIVC) in patients with coronavirus disease 2019 (COVID-19).MethodsThe following key phrases were searched for article inclusion: “Vitamin C OR ascorbic acid” AND “COVID-19 OR coronavirus disease 2019 OR severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2″. Articles that utilized HDIVC for the management of patients with COVID-19 were included, whereas review articles and case reports were excluded from this review. Moreover, we performed a meta-analysis to evaluate whether HDIVC can reduce the length of hospital stay and in-hospital mortality rate of patients with severe COVID-19.ResultsIn total, eight articles were included in this review, and five studies were included in the meta-analysis. The length of hospital stay was not significantly different between the HDIVC and control groups. Also, although our meta-analysis showed a tendency for HDIVC to reduce the in-hospital mortality rate in patients with severe COVID-19, the in-hospital mortality rate was not significantly different between patients treated with HDIVC and those who did not receive HDIVC.ConclusionsEvidence supporting the therapeutic use of HDICV in COVID-19 patients is lacking. Further studies are required for drawing a clear conclusion on this topic.     

The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis

BackgroundStatins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use.Materials and methodsA systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables.ResultsA total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55–0.92, I²=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69–0.95, I²=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55–1.51, I²=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death.ConclusionsThe use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.

Key messages

• Participants in five types of studies were shown to have even lower odds of death when taking statins.
• The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.
• The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.

     

Transmission of SARS-CoV-2 during air travel: a descriptive and modelling study

ObjectivesTo explore the potential of SARS-CoV-2 spread during air travel and the risk of in-flight transmission.MethodsWe enrolled all passengers and crew suspected of being infected with SARS-CoV-2, who bounded for Beijing on international flights. We specified the characteristics of all confirmed cases of COVID-19 infection and utilised Wells-Riley equation to estimate the infectivity of COVID-19 during air travel.ResultsWe screened 4492 passengers and crew with suspected COVID-19 infection, verified 161 confirmed cases (mean age 28.6 years), and traced two confirmed cases who may have been infected in the aircraft. The estimated infectivity was 375 quanta/h (range 274–476), while the effective infectivity was only 4 quanta/h (range 2–5). The risk of per-person infection during a 13 h air travel in economy class was 0.56‰ (95% CI 0.41‰–0.72‰).ConclusionWe found that the universal use of face masks on the flight, together with the plane''s ventilation system, significantly decreased the infectivity of COVID-19.

KEY MESSAGES

• The COVID-19 pandemic is changing the lifestyle in the world, especially air travel which has the potential to spread SARS-CoV-2.
• The universal use of face masks on the flight, together with the plane''s ventilation system, significantly decreased the infectivity of COVID-19 on an aircraft.
• Our findings suggest that the risk of infection in aircraft was negligible.

     

Characterisation of clinical,laboratory and imaging factors related to mild vs. severe covid-19 infection: a systematic review and meta-analysis

Abstract

Background

Early detection of disease progression associated with severe COVID-19, and access to proper medical care lowers fatality rates of severe cases. Currently, no studies had systematically examined the variables in detecting severe COVID-19.     

Comparison of 2 fully automated tests detecting antibodies against nucleocapsid N and spike S1/S2 proteins in COVID-19

Automated assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in coronavirus disease 2019 (COVID-19) diagnostics have recently come available. We compared the performance of the Elecsys® Anti–SARS-CoV-2 and LIAISON® SARS-CoV-2 S1/S2 IgG tests. The seroconversion panel comprised of 120 samples from 13 hospitalized COVID-19 patients. For the sensitivity and specificity testing, samples from COVID-19 outpatients >15 days after positive nucleic acid amplification test (NAAT) result (n = 35) and serum control samples collected before the COVID-19 era (n = 161) were included in the material. Samples for the detection of possible cross-reactions were also tested. Based on our results, the SARS-CoV-2 antibodies can be quite reliably detected 2 weeks after NAAT positivity and 3 weeks after the symptom onset with both tests. However, since some COVID-19 patients were positive only with Elecsys®, the antibodies should be screened against N-antigen (Elecsys®) and reactive samples confirmed with S antigen (LIAISON®), but both results should be reported. In some COVID-19 patients, the serology can remain negative.