Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes

We reported recently that hypertension is a risk factor for severe cases of COVID-19, independent of age and other variables (Liu et al. 2020a). An important question is why patients with hypertension and diabetes yield poorer clinical outcomes than those without. Human pathogenic coronavirus SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for viral cell entry. Since the levels of ACE2 are substantially increased in patients with hypertension or diabetes, who are treated with ACE inhibitors (ACEIs) and angiotensin Ⅱ type-Ⅰ receptor blockers (ARBs) (Ferrario et al. 2005), Fang and colleagues hypothesized that ACE2-stimulating drugs could potentially increase the risk of developing severe COVID-19 (Fang et al. 2020). This was not supported by a recent study led by Dr. Reynolds (Reynolds et al. 2020), whose analysis showed no positive association for ACEIs or ARBs for either the risk of SARS-CoV-2 infection or severe illness (Reynolds et al. 2020). What else might explain the poorer clinical outcomes of COVID-19 patients with hypertension or diabetes?To explore this question, we re-analysed the same cohort of 99 COVID-19 patients discharged from the general wards of Renmin Hospital of Wuhan University between 5 February 2020 and 14 March 2020 (Ethics approval No: WDRY2020-K124) (Liu et al. 2020a, b).     

Epidemiological,Clinical and Serological Characteristics of Children with Coronavirus Disease 2019 in Wuhan: A Single-centered,Retrospective Study

In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future.     

SARS-CoV-2 Serological Survey of Cats in China before and after the Pandemic

The high percentage of seropositivity of cats in Wuhan, the epicentre of the SARS-CoV-2 epidemic, could be due to the large number of infected human cases (more than 14 folds than that in other cities) (Table 1) where cats may have been more frequently exposed to SARS-CoV-2 patients or contaminated environment. As yet, SARS-CoV-2 serological prevalence of cats in other Chinese cities remains unknown. Therefore, a serological survey including more cities with numbers of SARS-CoV-2 human cases in China will be valuable for elucidating the role of cats in transmission of the viruses and relieve public concerns. In this study, 630 cat serum samples collected before November 2019 and 423 cat serum samples collected during SARS-CoV-2 outbreak (from February 2020 to April 2020) in 20 cities in China for detecting the prevalence of SARS-CoV-2 specific antibodies.     

Fish ACE2 is not susceptible to SARS-CoV-2

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has reshaped our daily life and caused > 4 million deaths worldwide (https://covid19.who.int/). Although lockdown and vaccination have improved the situation in many countries, imported cases and sporadic outbreaks pose a constant stress to the prevention and control of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for COVID-19, has a positive-sense single-stranded RNA genome of 30 kb (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). We and other groups have demonstrated that the SARS-CoV-2 could use the angiotensin-converting enzyme 2 (ACE2) as cell receptor, including orthologs of a broad range of animal species such as human, bats, ferrets, pigs, cats, and dogs (Hoffmann et al., 2020; Zhou et al., 2020; Liu et al., 2021). Although the evolutionary origin of SARS-CoV-2 can be linked to the discoveries of diverse coronaviruses related to SARS-CoV-2 in wild animals such as bats (Zhou et al., 2020; Wacharapluesadee et al., 2021) and pangolins (Liu et al., 2019; Lam et al., 2020), the direct origin of SARS-CoV-2 in humans remains unknown. In China, several sporadic outbreaks of COVID-19 in 2020 were linked to food in cold chain sold at trade markets, including salmon meat (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) (Yang et al., 2020). The detection of SARS-CoV-2 RNA on the surface of frozen meat for as long as 20 days has also been reported (Feng et al., 2021). A concern regarding the potential role of fish in SARS-CoV-2 transmission has also been raised. Therefore, we investigated the susceptibility of fish ACE2 to SARS-CoV-2.     

An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.     

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

Background

Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.

Methods

To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.

Results

Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.

Conclusions

The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.     

Natural killer cell exhaustion in SARS-CoV-2 infection

At the end of 2019, an outbreak of a severe respiratory disease occurred in Wuhan China, and an increase in cases of unknown pneumonia was alerted. In January 2020, a new coronavirus named SARS-CoV-2 was identified as the cause. The virus spreads primarily through the respiratory tract, and lymphopenia and cytokine storms have been observed in severely ill patients. This suggests the existence of an immune dysregulation as an accompanying event during a serious illness caused by this virus. Natural killer (NK) cells are innate immune responders, critical for virus shedding and immunomodulation. Despite its importance in viral infections, the contribution of NK cells in the fight against SARS-CoV-2 has yet to be deciphered. Different studies in patients with COVID-19 suggest a significant reduction in the number and function of NK cells due to their exhaustion. In this review, we summarize the current understanding of how NK cells respond to SARS-CoV-2 infection.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases

正Emerging and re-emerging viral diseases are a public health concern for the whole world and pose a major threat to human health and life. In last decades, numerous major outbreaks of emerging and re-emerging viral diseases with gross public concern were recorded in different regions,including Ebola in western Africa, Zika in South America,     

Hepatitis B Virus Infection in HIV-Positive Individuals in the UK Collaborative HIV Cohort (UK CHIC) Study

Background

Hepatitis B virus (HBV) infection is an increasingly important cause of morbidity and mortality in HIV-infected adults. This study aimed to determine the prevalence and incidence of HBV in the UK CHIC Study, a multicentre observational cohort.

Methods and Findings

12 HIV treatment centres were included. Of 37,331 patients, 27,450 had at least one test (HBsAg, anti-HBs or anti-HBc) result post-1996 available. 16,043 were white, 8,130 black and 3,277 other ethnicity. Route of exposure was homosexual sex 15,223 males, heterosexual sex 3,258 males and 5,384 females, injecting drug use 862 and other 2,723. The main outcome measures used were the cumulative prevalence and the incidence of HBV coinfection. HBV susceptible patients were followed up until HBsAg and/or anti-HBc seroconversion incident infection, evidence of vaccination or last visit. Poisson regression was used to determine associated factors. 25,973 had at least one HBsAg test result. Participants with HBsAg results were typically MSM (57%) and white (59%) (similar to the cohort as a whole). The cumulative prevalence of detectable HBsAg was 6.9% (6.6 to 7.2%). Among the 3,379 initially HBV-susceptible patients, the incidence of HBV infection was 1.7 (1.5 to 1.9)/100 person-years. Factors associated with incident infection were older age and IDU. The main limitation of the study was that 30% of participants did not have any HBsAg results available. However baseline characteristics of those with results did not differ from those of the whole cohort. Efforts are on-going to improve data collection.

Conclusions

The prevalence of HBV in UK CHIC is in line with estimates from other studies and low by international standards. Incident infection continued to occur even after entry to the cohort, emphasising the need to ensure early vaccination.     

2型糖尿病患者乙型肝炎病毒感染率分析

目的：通过调查糖尿病患者乙型肝炎病毒（HBV）的携带率,阐明糖尿病发生是否与HBV感染有关,并观察糖尿病合并HBV感染时是否加重对肝功能的损害。方法：用ELISA方法检测533例2型糖糖尿病患者和1440例普通人群乙型肝炎表面抗原（HBsAg）以及HBV其他血清学标志,同时常规测定肝功能和血糖等。结果：2型糖尿病HBsAg阳性24例,阳性率4.50%,普通人群HBsAg阳性70例,阳性率4.86%,两组间阳性率差异无统计学意义（x2=0.110,P=0.740）。糖尿病患者感染HBV后的抗体应答与普通人群相似。糖尿病合并HBV感染者与无糖尿病HBV感染者的肝功能异常差异无统计学意义。糖尿病患者中83例（16.3%）谷氨酰转肽酶升高,在肝功能异常指标中最常见,这与HBV感染后丙氨酸转氨酶升高为主不同。结论：糖尿病发生与HBV感染无关,糖尿病合并HBV感染时不加重对肝脏的损害。     

Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020–2021

The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.     

SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.     

Prevalencia de infección por coronavirus SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en España

Background and goalsThe aim of the study is to know the prevalence of SARS-CoV-2 infection in patients and professional staff of a medium or long-stay hospital during the peak period of the pandemic in Spain, spring 2020.Material and methodsAt the end of February 2020, we developed at the hospital a strategy to diagnose the SARS-CoV-2 infection consisting of complementing the realization of PCR tests at real time with a quick technique of lateral flow immunochromatography to detect IgG and IgM antibodies against the virus. We also developed a protocol to realize those diagnostic tests and considered an infection (current or past) a positive result in any of the above tests.We included 524 participants in the study (230 patients and 294 hospital staff), and divided them into hospital patients and Hemodialysis outpatients. Furthermore, we divided the hospital staff into healthcare and non-healthcare staff. The documented period was from March, 20^th to April, 21^st, 2020.Results26 out of 230 patients tested positive in any of the diagnostic techniques (PCR, antibodies IgG, IgM) with a 11.30% prevalence. According to patients groups, we got a 14.38% prevalence in hospital patients vs. 5.95% in outpatients, with a significantly higher risk in admitted patients after adjustment for age and gender (OR=3,309, 95%CI: 1,154-9,495).24 out of 294 hospital staff tested positive in any of the diagnostic techniques, with a 8.16% prevalence. According to the groups, we got a 8.91% prevalence in healthcare staff vs. 4.26% in non-healthcare staff. Thus, we do not see any statistically significant differences between hospital staff and patients as far as prevalence is concerned (P=0,391), (OR=2,200, 95%CI: 0,500-9,689).ConclusionsThe result of the study was a quite low prevalence rate of SARS-CoV-2 infection, in both patients and hospital staff, being the hospital patients’ prevalence rate higher than the outpatients’, and the healthcare staff higher than the non-healthcare's. Combining PCR tests (gold standard) with antibodies tests proved useful as a diagnostic strategy.     

Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients

Background:

In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of viral replication by the immune system might be inactivated, and classical HBV infection in OBI patients may occur. Health care professionals should be aware of OBI in HIV patients. The routine test for HBV infection in Iran is the enzyme-linked immunosorbent assay for the HBV surface antigen (ELISA HBsAg); therefore, the aim of this study was to evaluate the prevalence of OBI in Iranian HIV patients.

Methods:

This cross-sectional study was conducted in 2012 on sera from all the known and accessible HIV patients in Jahrom and Fassa, two cities in southern Iran. All samples were tested for the HBsAg, HBV core antibody (HBcAb). All the results were analyzed using SPSS.

Results:

Of the 91 patients, seven (7.7%) were HBsAg-positive and forty-five (49.5%) were HBcAb-positive. In patients with negative HBsAg (84 patients), 39 (46.4%) were HBcAb positive and 53 (63%) were positive for HBV DNA.

Conclusion:

The prevalence of HBV infection is relatively high in HIV patients, and more accurate tests than those presently in use should be used for diagnosis.Key Words: Hepatitis B, HIV infection, Occult hepatitis     

Rare Detection of Occult Hepatitis B Virus Infection in Children of Mothers with Positive Hepatitis B Surface Antigen

The prevalence of occult Hepatitis B virus (HBV) infection in children was considerably varied from 0.1–64% in different reports. In this study we aimed to investigate the prevalence of occult HBV infection among the children born to mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China. Serum samples were collected from 210 children of 207 mothers with positive HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by nested PCR. Homology comparison of HBV sequences recovered from the child and mother was used to define the infection. Three children (1.43%) were positive for HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA positive by two nested PCR assays using primers derived from S and C genes. However, the sequence alignment showed that the sequences in each child were considerably different from those in his/her mother. Therefore, the sequences amplified from the children were very likely resultant from the cross-contaminations. Furthermore, the nine children with ‘positive HBV DNA’ were all negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti-HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV-infected mothers was found to have occult HBV infection. We conclude that the prevalence of occult HBV infection in vaccinated children born to HBsAg positive mothers should be extremely low. We recommend that homology comparison of sequences recovered from the child and mother be used to define the occult HBV infection in children born to HBV infected mothers.     

Prevalence of hepatitis-B surface antigen among blood donors and human immunodeficiency virus-infected patients in Jos, Nigeria

Information is very scarce on the prevalence of hepatitis-B virus (HBV) infection among blood donors and patients with human immunodeficiency virus (HIV) infection in Nigeria. Hepatitis-B surface antigen (HBsAg) ELISA was used to determined the prevalence of HBsAg among 175 blood donors (aged 20-40 years) and 490 HIV-infected patients (aged 17-60 years) in Jos, Nigeria. Twenty-five (14.3%) of the blood donors and 127 (25.9%) of the HIV-infected individuals were HBsAg seropositive, indicating a higher HBV infection among HIV-infected persons than among healthy blood donors. A slightly higher HBsAg seroprevalence was recorded in the males (14.6%) than females (12.9%) of the blood donors. Among the HIV-infected patients, the males had considerably higher HBsAg seroprevalence than the females (31.8 vs 22.1%) with the highest prevalence of HBsAg occurring in the 51-60 years age group (44%), followed by those of 31-40 years (28.2%). Results confirmed the high endemicity of HBV infection in Jos, Nigeria and the significantly greater prevalence of HBV infection among HIV-infected patients than among blood donors.     

乙型肝炎病毒感染血清流行病学规律的研究

1984～1987年,在湖南、河南、河北、黑龙江4个试点区,整群抽样采血10 484人,采血率达80％以上。HBsAg、抗-HBs和抗-HBc均用RIA法检测。结果4个点乙型肝炎病毒(HBV)标化感染率为58.2％。HBV感染率随年龄增长而升高,7岁时为51.6％,25岁时达63.7％,接近高峰值。HBsAg标化阳性率为10.1％。HBsAg阳性率显示两个高峰,一个在2～8岁时,即儿童峰。从零岁的3.8％至2周岁时的12.5％,已达高峰。湖南的儿童峰值较其它3个试点区高。故HBsAg阳性率南高北低的现象仍然存在(P<0.01)。另一个峰在20～45岁,即成人峰。 抗-HBs标化阳性率为32.2％。HBsAg:抗-HBs之比值,5岁以内为1:1,10岁以后上升为l:3.3～5.9。抗-HBc标化阳性率为45.5％。此结果表明,调查地区均为HBV高感染区,感染主要发生在儿童期。故新生儿是预防乙型肝炎的重点人群。