Discovery of a Novel Coronavirus in Swedish Bank Voles (Myodes glareolus).

The unprecedented pandemic COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with bats as original reservoirs, has once again highlighted the importance of exploring the interface of wildlife diseases and human health. In this study, we identified a novel Betacoronavirus from bank voles (Myodes glareolus) in Grimsö, Sweden, and this virus is designated as Grimso virus. Repeated detection over three years and an overall prevalence of 3.4% suggest that the virus commonly occurs in bank voles. Furthermore, phylogenetic analyses indicate that the Grimso virus belongs to a highly divergent Embecovirus lineage predominantly associated with bank voles. Given that bank voles are one of the most common rodent species in Sweden and Europe, our findings indicate that Grimso virus might be circulating widely in bank voles and further point out the importance of sentinel surveillance of coronaviruses in wild small mammalian animals, especially in wild rodents.

Corrigendum to "Presymptomatic viral shedding and infective ability of SARS-CoV-2; a case report" [Heliyon 7, (2), (February 2021), Article e06328].

[This corrects the article DOI: 10.1016/j.heliyon.2021.e06328.].

Is heparan sulfate a target for inhibition of RNA virus infection?

Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.

SARS-CoV-2 in hospital indoor environments is predominantly non-infectious.

BACKGROUND: The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of infection remain the most important existing tools to prevent further spread. METHODS: Here we investigated the presence of the SARS-CoV-2 virus in the hospital environment at the Uppsala University Hospital Infectious Disease ward by RT-qPCR and determined the infectivity of the detected virus in vitro on Vero E6 cells. RESULTS: SARS-CoV-2 RNA was detected in several areas, although attempts to infect Vero E6 cells with positive samples were unsuccessful. However, RNase A treatment of positive samples prior to RNA extraction did not degrade viral RNA, indicating the presence of SARS-CoV-2 nucleocapsids or complete virus particles protecting the RNA as opposed to free viral RNA. CONCLUSION: Our results show that even in places where a moderate concentration (Ct values between 30 and 38) of SARS-CoV-2 RNA was found; no infectious virus could be detected. This suggests that the SARS-CoV-2 virus in the hospital environment subsides in two states; as infectious and as non-infectious. Future work should investigate the reasons for the non-infectivity of SARS-CoV-2 virions.

Risk factors for the delayed viral clearance in COVID-19 patients.

Comorbidities are important for the disease outcome of COVID-19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID-19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID-19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan-Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS-CoV-2 virus clearance, however, the use of Angiotensin-Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients' virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID-19 patients.

Live and Wet Markets: Food Access versus the Risk of Disease Emergence.

Emerging zoonotic diseases exert a significant burden on human health and have considerable socioeconomic impact worldwide. In Asia, live animals as well as animal products are commonly sold in informal markets. The interaction of humans, live domestic animals for sale, food products, and wild and scavenging animals, creates a risk for emerging infectious diseases. Such markets have been in the spotlight as sources of zoonotic viruses, for example, avian influenza viruses and coronaviruses, Here, we bring data together on the global impact of live and wet markets on the emergence of zoonotic diseases. We discuss how benefits can be maximized and risks minimized and conclude that current regulations should be implemented or revised, to mitigate the risk of new diseases emerging in the future.

Presymptomatic viral shedding and infective ability of SARS-CoV-2; a case report.

Possible pre- or asymptomatic transmission has been reported, both from SARS-CoV and from MERS-CoV outbreaks, although this appears to be uncommon. In contrast, during the COVID-19 pandemic, an increasing number of studies and case reports indicate that pre- or asymptomatic transmission of SARS-CoV-2 is not only possible but also occurs frequently. We report repeated rRT-PCR detection of SARS-CoV-2 in a health care worker and demonstrate infective ability up to three days prior to mild COVID-19 symptoms. rRT-PCR indicated high viral levels approximately three days after exposure. Viral samples collected one and three days prior to symptoms exhibited infectivity on Vero E6 cells, confirmed by detection of double-stranded RNA by immunofluorescence, assessment of cytopathic effect (CPE) and rRT-PCR. SARS-CoV-2 specific IgM and IgG antibodies were detected by day 9 and 15, respectively, after symptom onset. We propose that this provides evidence for potential early presymptomatic transmission of SARS-CoV-2 and that infectivity may be manifest shortly after exposure.

Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards.

Evidence suggests that SARS-CoV-2, as well as other coronaviruses, can be dispersed and potentially transmitted by aerosols directly or via ventilation systems. We therefore investigated ventilation openings in one COVID-19 ward and central ducts that expel indoor air from three COVID-19 wards at Uppsala University Hospital, Sweden, during April and May 2020. Swab samples were taken from individual ceiling ventilation openings and surfaces in central ducts. Samples were subsequently subjected to rRT-PCR targeting the N and E genes of SARS-CoV-2. Central ventilation HEPA filters, located several stories above the wards, were removed and portions analyzed in the same manner. In two subsequent samplings, SARS-CoV-2 N and E genes were detected in seven and four out of 19 room vents, respectively. Central ventilation HEPA exhaust filters from the ward were found positive for both genes in three samples. Corresponding filters from two other, adjacent COVID-19 wards were also found positive. Infective ability of the samples was assessed by inoculation of susceptible cell cultures but could not be determined in these experiments. Detection of SARS-CoV-2 in central ventilation systems, distant from patient areas, indicate that virus can be transported long distances and that droplet transmission alone cannot reasonably explain this, especially considering the relatively low air change rates in these wards. Airborne transmission of SARS-CoV-2 must be taken into consideration for preventive measures.

Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro.

The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 µM and 400 µM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.

Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic

Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites ≥5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 ×10−3 substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches.