SARS-CoV-2/COVID-19: a primer for cardiologists

In the late autumn of 2019, a new potentially lethal human coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The pandemic spread of this zoonotic virus has created a global health emergency and an unprecedented socioeconomic crisis. The severity of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV?2, is highly variable. Most patients (~85%) develop no or mild symptoms, while others become seriously ill, some succumbing to disease-related complications. In this review, the SARS-CoV?2 life cycle, its transmission and the clinical and immunological features of COVID-19 are described. In addition, an overview is presented of the virological assays for detecting ongoing SARS-CoV?2 infections and the serological tests for SARS-CoV-2-specific antibody detection. Also discussed are the different approaches to developing a COVID-19 vaccine and the perspectives of treating COVID-19 with antiviral drugs, immunomodulatory agents and anticoagulants/antithrombotics. Finally, the cardiovascular manifestations of COVID-19 are briefly touched upon. While there is still much to learn about SARS-CoV?2, the tremendous recent advances in biomedical technology and knowledge and the huge amount of research into COVID-19 raise the hope that a remedy for this disease will soon be found. COVID-19 will nonetheless have a lasting impact on human society.

     

Neuroinflammation and COVID-19

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.     

The seroprevalence of SARS-CoV-2 IgG antibodies among asymptomatic blood donors in Saudi Arabia

BackgroundIn late 2019, cases of severe pneumonia with unidentified etiology began to emerge in Wuhan, China, before progressively spreading first nationally and then globally.The current study sought to investigate the seroprevalence of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blood donors in Al-Madinah, Saudi Arabia. To our knowledge, this is the first study in Saudi Arabia to screen blood donors who were not known to be previously infected with SARS-CoV-2.MethodsThis study was a cross-sectional study to assess individuals who donated blood to the central blood bank in Al-Madinah between mid-May and mid-July 2020. An enzyme-linked immunosorbent assay (ELISA) was designed and established to detect antibodies directed against the SARS-CoV-2 spike protein in serum samples. A total of 1,212 healthy blood donors participated in this study. The donors were males and met the requirements for blood donation during the COVID-19 pandemic period in Saudi Arabia.ResultsThe SARS-CoV-2 seroprevalence among blood donors in Al-Madinah was 19.31% (n = 234/1212; 95% confidence interval: 17.12%–21.64%). No statistically significant difference was identified in seropositivity according to age. However, significant differences (p < 0.001) were identified according to ABO blood groups, with those with type A blood presenting the highest rate of seropositivity (29.18%) compared with the other blood groups (12.65% for type B, 16.36% for type AB, and 15.11% for type O).ConclusionA high prevalence of SARS-CoV-2 antibodies was detected among blood donors in Al-Madinah, which indicated a high level of exposure to the virus within the population. This further suggested that as high as one-fifth of the population may have acquired innate immunity against the virus.     

Shorter leukocyte telomere length is associated with severity of COVID-19 infection.

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.     

Colonoscopy screening and surveillance disparities during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has increased barriers to accessing preventive healthcare. This study identifies populations disproportionately underrepresented in screening and surveillance colonoscopies during the COVID-19 pandemic.MethodsIn this single-center cohort study, colonoscopy procedures were reviewed during 6-month intervals before the pandemic (July 1, 2019 - December 31, 2019) and during the pandemic (July 1, 2020 - December 31, 2020 and January 1, 2021 - June 30, 2021). 7095 patients were categorized based on procedure indication, demographics, Charlson Comorbidity Index and Social Vulnerability Index (SVI). Statistics performed using VassarStats.Results2387 (2019) colonoscopies pre-pandemic and 2585 (2020) and 2123 (2021) during the pandemic were identified. There was a decrease in colonoscopies performed during months when COVID-19 cases peaked. The total number of average CRC risk patients presenting for first colonoscopy declined during the pandemic: 232 (10 %) pre-pandemic to 190 (7 %) in 2020, 145 (7 %) in 2021 (p < 0.001). Fewer of these patients presented from highly vulnerable communities, SVI > 0.8, during the pandemic, 39 in 2019 vs 16 in 2020 and 22 in 2021. Of all screening and surveillance patients, fewer presented from communities with SVI > 0.8 during the pandemic, 106 in 2019 versus 67 in 2020 and 77 in 2021.ConclusionIt is important to address the decline in CRC preventive care during this pandemic among average CRC risk first-time screeners and vulnerable community patients. An emphasis on addressing social determinants of health and establishing patients in gastroenterology clinics is imperative to promote future health in these populations.     

Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing,China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).     

新型冠状病毒疫苗研究策略分析

新型冠状病毒(SARS-CoV-2)是一种可引起人新型冠状病毒肺炎(COVID-19)的新发呼吸道病原体,与重症急性呼吸道综合症冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)同属于β-冠状病毒,具有较高的传染性和一定的致死率。2019年12月在我国武汉被发现,随后蔓延到我国大部分省份,给我国人民健康和经济发展造成巨大损失。疫苗接种是预防和控制传染病的常规和有效手段,国内外多个机构已启动COVID-19疫苗研究工作。文中基于SARS和MERS疫苗研究的经验和教训,对COVID-19疫苗的研究策略和需要注意的关键问题进行了阐述,为相关研究人员提供参考。     

Durability of the humoral immune response in recovered COVID-19 patients

BackgroundThe immunological factors involved in protection against the disease caused by SARS-CoV-2 are insufficiently defined and understood. However, previous knowledge pertaining to the related SARS virus and other human coronaviruses may prove useful. Population-based serosurveys measuring anti-SARS-CoV-2 antibodies may provide a pattern for estimating infection degrees and observing the development of the epidemic. In this study, we aimed to investigate the persistence of antibody against the SARS-CoV-2 in recovered patients in Al Madinah region of Saudi Arabia.Materials and methodsA total of 150 recovered COVID-19 patients participated in this study. All the patients tested positive for the presence of SARS-CoV-2 RNA, using qualitative RT-PCR. An ELISA was used to measure anti-Spike (S) IgG antibodies in serum samples and screen for their persistence at various time points post-infection.ResultsThe patients were categorized as asymptomatic (27.3%), mild (28%) and moderate (44.7%) according to the disease severity. Amongst them, 35.3% were females (n = 53) and 64.7% were males (n = 97). Significant anti-S IgG antibody levels were observed among the different groups, with the patients in moderate group exhibiting the highest levels followed by the mild group; while the lowest levels were detected among the asymptomatic. There was a significant positive correlation between the patients’ age and anti-S IgG antibody concentrations (Pearson r = 0.45; p < 0.001).ConclusionOur findings provide a solid evidence to support the use of an anti-S IgG ELISA as a diagnostic tool to indicate SARS-CoV-2 infection. IgG seropositivity was sustained in recovered patients up to a hundred days' post-infection, the latest time point for antibody measurement in our study. Ours is the first report in Saudi Arabia to investigate the durability of humoral immune response in recovered COVID-19 patients.     

A mini-review on the effects of COVID-19 on younger individuals

Coronavirus disease 2019 (COVID-19) pandemic has uprooted our lives like never before since its onset in the late December 2019. The world has seen mounting infections and deaths over the past few months despite the unprecedented measures countries are implementing, such as lockdowns, social distancing, mask-wearing, and banning gatherings in large groups. Interestingly, young individuals seem less likely to be impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While the rate of transmission, symptom presentation, and fatality is lower in children than people from other age groups, they have been disproportionately affected by strict lockdown measures needed to curb viral spread. In this review, we describe the association between patient age and COVID-19, epidemiology of SARS-CoV-2 infection in children, psychological effects associated with lockdowns and school closures, and possible mechanisms underlying lower transmission rate of COVID-19 in children.     

An Impaired Inflammatory and Innate Immune Response in COVID-19

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.     

Capivasertib restricts SARS-CoV-2 cellular entry: a potential clinical application for COVID-19

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to more than 150 million infections and about 3.1 million deaths up to date. Currently, drugs screened are urgently aiming to block the infection of SARS-CoV-2. Here, we explored the interaction networks of kinase and COVID-19 crosstalk, and identified phosphoinositide 3-kinase (PI3K)/AKT pathway as the most important kinase signal pathway involving COVID-19. Further, we found a PI3K/AKT signal pathway inhibitor capivasertib restricted the entry of SARS-CoV-2 into cells under non-cytotoxic concentrations. Lastly, the signal axis PI3K/AKT/FYVE finger-containing phosphoinositide kinase (PIKfyve)/PtdIns(3,5)P2 was revealed to play a key role during the cellular entry of viruses including SARS-CoV-2, possibly providing potential antiviral targets. Altogether, our study suggests that the PI3K/AKT kinase inhibitor drugs may be a promising anti-SARS-CoV-2 strategy for clinical application, especially for managing cancer patients with COVID-19 in the pandemic era.     

Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.     

Prolonged humoral and cellular immunity in COVID-19-recovered patients

By the beginning of 2021, the battle against coronavirus disease 2019 (COVID-19) remains ongoing. Investigating the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, in patients who have recovered from this disease could contribute to our understanding of the natural host immune response. We enrolled 38 participants in this study. 7 healthy participants and 31 COVID-19 patients who had recovered from COVID-19 and categorized them into 3 groups according to their previous clinical presentations: 10 moderate, 9 mild, and 12 asymptomatic. Flow cytometry analysis of peripheral lymphocyte counts in recovered patients showed significantly increased levels of CD4⁺ T cells in patients with a history of mild and moderate COVID-19 symptoms compared with those healthy individuals (p < 0.05 and p < 0.0001 respectively). whereas no significant difference was observed in the CD8⁺ T cell percentage in COVID-19-recovered patients compared with healthy individuals. Our study demonstrated that antibodies against the SARS-CoV-2 spike protein (anti-S) IgG antibody production could be observed in all recovered COVID-19 patients, regardless of whether they were asymptomatic (p < 0.05)or presented with mild (p < 0.0001) or moderate symptoms (p < 0.01). Anti-S IgG antibodies could be detected in participants up to 90 days post-infection. In conclusion, the lymphocyte levels in recovered patients were associated with the clinical presentation of the disease, and further analysis is required to investigate relationships between different clinical presentations and lymphocyte activation and function.     

Incidence of gynaecological cancer during the COVID-19 pandemic: A population-based study in the Netherlands

ObjectiveTo study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.MethodsWe performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017–2021. Analyses were stratified for age, socioeconomical status (SES) and region.ResultsThe incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017–2019) and 68/100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID-19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20–34 %). Subsequently, large increases in number of diagnoses were visible (11–29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen.ConclusionIn the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands.     

Patterns of Gustatory Recovery in Patients Affected by the COVID-19 Outbreak

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From March 2020, several studies indicate that many subjects affected by mild-to-moderate COVID-19 presented olfactory/gustatory dysfunction (OD/GD) that appeared strongly correlated between them but not with the other symptoms suggestive of upper airway infectionIn order to evaluate patterns of gustatoy recovery, data from patients with confirmed COVID-19 were collected prospectively from 4 University Hospitals. At this relatively early point in the pandemic, the authors considered that subjective patterns of recovery of olfactory disfunction in COVID-19 patients are valuable for our patients, for hypothesis generation and treatment development.     

Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal

Background: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices. Aim: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45). Methods: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients. Results: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products. Conclusions: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic.     

Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.     

Impact of coronavirus disease 2019 on lung cancer patients: A meta-analysis

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the treatment of lung cancer patients.Materials and methodsThe PubMed, Embase, and Web of Science databases were searched for studies published before March 15, 2022, and Stata 14.0 software was used to perform a meta-analysis with a random-effects model. The odds ratio (OR) along with the corresponding 95% confidence interval (CI) was reported.ResultsOur meta-analysis included 80 articles with 318,352 patients involved. The proportion of lung cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 2.4% (95% CI: 0.02–0.03) prior to the Omicron variant outbreak. Among COVID-19 patients, those with lung cancer showed a higher mortality rate than those with other types of malignant solid tumors (OR = 1.82, 95% CI: 1.61–2.06) and non-cancer patients (OR = 4.67, 95% CI: 3.61–6.05); however, no significant difference was observed in the mortality rate between patients with lung cancer and those with hematologic malignancies (OR = 1.07, 95% CI: 0.85–1.33). SARS-CoV-2 infection significantly increased the mortality rate in lung cancer patients (OR = 8.94, 95% CI: 6.50–12.31). By contrast, the all-cause mortality rate in lung cancer patients (OR = 1.04, 95% CI: 0.69–1.57) and the proportion of patients diagnosed with advanced lung cancer (OR = 1.04, 95% CI: 0.85–1.27) did not significantly change before and after the pandemic.ConclusionsMore attention should be paid on improving the health of lung cancer patients during the COVID-19 pandemic.