Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses, shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort. Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics, 19 healthy controls), participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analyzed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high troughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis. Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile, however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed amongst immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. Conclusions: Antiviral cytokines responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not affected by TLR-induced immune responses.

Virus infections and T cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like β-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i) : drugs tend to bind to proteins and may even bind to immune receptors. In the absence of viral infections, this low affine binding may be insufficient to elicit T cell activation. During a viral infection immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T cell activation and symptoms. There is a situation, where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally acvitates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity with killing of herpes peptide-expressing cells and release of herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.

This article introduces current status of COVID-19 and its side-effects, and reviews emerging protective measures and strategies from lifestyle to traditional Chinese medicine (TCM) for fighting against the SARS-CoV-2 and its major variants (Delta and Omicron) as well as the global COVID-19 pandemic, which include “Carassius auratus lifestyle” for high effective isolation, social and high-tech related medical strategies, traditional Chinese herbs “Bark-Flower-Fruit-Grass-Leaf-Nucleolus-Root (BFFGLNR)”, as well the combination of Chinese and western medicine. As a choice, little is known whether Chinese acupuncture is an effective method for confirmed and suspected COVID-19 patients, which include imported and asymptomatic cases. Definitely, acupuncture is effective for the recovery of COVID-19 cases. However, its effects and related mechanisms need further animal experiments and clinical trials to confirm and disclose. In conclusion, these emerging protective measures and strategies for COVID-19 will help to effectively combat the SARS-CoV-2 and its variants during the pandemic and post-COVID-19 era.

Logical deductions from experimental data have been unable to explain the origin of the current monkeypox outbreaks in multiple countries. But upon illustrating the reality in which these outbreaks occur, it was found to be that in which different diseases of the same immunological nature, the nature that permits them to be rendered asymptomatic simultaneously without the elimination of their different causes, appear simultaneously when conditions that permitted immune mechanisms to bring about such protection disappear. An outbreak of such immunologically equivalent diseases therefore does not require the spread of those that are pathogens among the causes of such diseases to occur. And the manifestations of such diseases will become widespread in a population when factors that cause the disappearance of conditions that permitted them to be rendered asymptomatic by immune mechanisms become widespread in the population. If we will escape the threat that the catastrophically widespread appearance of manifestations such as Ebola and malignancies will pose to our species, our topmost research priority ought to be the immunological nature of the pathological effects of the pathogens that are linked with them.

Xenotransplantation with porcine organs has been recognized as a promising solution to alleviate the shortage of organs for human transplantation. Porcine endogenous retrovirus (PERV), whose proviral DNAs are buried in the genome of all pig breeds, is a main microbiological risk for xenotransplantation. Over the last decades, some advances on PERVs’ study have been achieved. Here we reviewed the current progress of PERVs including the classification, molecular structure, regulation , function in immune system and potential risk in xenotransplantation. We also discussed the problem of insufficient research on PERVs as well as the questions need to be answered in the future work.

This article introduces briefly current status of the Covid-19 pandemic and discusses “antidotes” of coronavirus (SARS-CoV-2 and its variants), that is, “ISISI” barriers from locals, nations or regions to the globe, namely, [Isolation with Masks, Unit protective clothing, Stay at “home”, and Travel restriction (MUST); Screening and testing; Individual immunity by healthy E(e)SEEDi lifestyle, bio-agents (chemical agents, convalescent plasma, neutralizing antibody, and Chinese medicine), and vaccination; Social and medical supports; International cooperation and information sharing]. Since there are several major coronavirus variants with more infectious, such as Delta and Omicron, many more cases with cardiac injury and cardiac arrest need better cardiovascular prevention and protection. With further understanding of the pathogenesis of Covid-19 and development of novel mRNA vaccines and discovery of new antiviral drugs, such as Molnupiravir and Paxlovid, people will do better in fighting against SARS-CoV-2 and its variants and cardiovascular protection in the pandemic and post-Covid-19 era.

The COVID-19 pandemic is still continuing. Current major variants of SARS-CoV-2 (Delta and Omicron) have lead to new uncertainties. Since the infection of SARS-CoV-2 and its major variants has been a high risk factor of cardiovascular health due to major adverse cardiovascular events (MACCE) and outcomes. Thus, the more coverage of vaccination, enough health workers, and related medical resources as well as the “ISISI” barriers from locals or regions to the globe play a critical role in combating COVID-19 and protection of human cardiovascular health.

In this study, a specific and simple method based on the dual priming oligonucleotide (DPO) system was developed to simultaneously detect transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine rotavirus A (PRV-A), porcine delta coronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), associated with the major enteric RNA viruses in pigs. The multiplex RT-PCR method based on the DPO system simplified the primer design and did not require optimization of the annealing temperature. Specificity analysis revealed that the method could specifically detect TGEV, PEDV, PRV-A, PDCoV, and SADS-CoV without any cross-amplification of other circulating swine viruses. The limit of detection of the method was as low as 103–104 copies/μL plasmid of each virus. The method also had good repeatability, and obvious results were seen in three repeat experiments with an interval of 45 days. This optimized multiplex RT-PCR method was used to evaluate 181 clinical swine samples that were collected from four provinces of China between September 2016 and August 2018. The results showed that the positive detection rates of PEDV, PDCoV, SADS-CoV, PRV-A, and TGEV were 30.94% (56/181), 17.67% (32/181), 11.6% (21/181), 9.39% (17/181), and 0.55% (1/181), respectively. Mixed infection of two or more viruses was also common. The DPO system-based multiplex RT-PCR could be a useful tool for detecting enteric virus infections. This method has the advantages of easy operation, low cost, high detection efficiency, and short running time for early diagnosis in clinical cases.

Japanese encephalitis (JE) is the major cause of viral encephalitis (VE) in most Asian-Pacific countries. In Vietnam, there is no nationwide surveillance system for JE due to lack of medical facilities and diagnoses. Culex tritaeniorhynchus, Culex Vishnui, and Culex quinquefasciatus have been identified as the major JE vectors in Vietnam. The main objective of this study was to forecast a risk map of Culex mosquitoes in Hanoi, which is one of the most densely populated cities in Vietnam. A total of 10,775 female adult Culex mosquitoes were collected from 513 trapping locations. We collected temperature and precipitation information during the study period and its preceding month. In addition, the other predictor variables (e.g., normalized difference vegetation index [NDVI], land use/land cover and human population density), were collected for our analysis. All the collected data was pre-processed with the same study extent and spatial resolution of 30 m. The final model selected for estimating the Culex mosquito abundance included centered rainfall, quadratic term rainfall, rice cover ratio, forest cover ratio, and human population density variables. The estimated spatial distribution of Culex mosquito abundance ranged from 0 to 200. Our model estimated that 87% of the Hanoi area had an abundance of mosquitoes from 0 to 50, whereas approximately 1.2% of the area showed more than 150 mosquitoes, which was mostly in the rural/peri-urban districts. Our findings may provide better insight into understanding the spatial distribution of Culex mosquitoes and its associated environmental risk factors. Such information can assist local clinicians and public health policymakers to identify the potential areas of risk for JE virus. Risk maps can be an efficient way of raising public awareness about the virus and further preventive measures need to be considered in order to prevent outbreaks and onwards transmission of the JE virus.

The ongoing COVID-19 pandemic has highlighted the central role of diagnostic tests in pandemic control. Although reverse transcriptase quantitative real-time PCR (RT-qPCR) is the gold standard for the diagnosis of COVID-19, several rapid antigen tests (RAT) have been commercialized as rapid point-of-care diagnostics. To the best of our knowledge, there are limited data on the effect of patient’s clinical and laboratory parameters on RAT performance and no studies exist that tested the importance of combining laboratory measurements in patient’s blood in enhancing the performance of RAT. Here we tried to fill these gaps by evaluating the diagnostic performance of the RAT “Standard ™ Q COVID-19 Ag” in participant’s subgroups studying the influence of viral load, sampling time-post symptoms, clinical and laboratory features on test performance. Eighty-three nasopharyngeal and oropharyngeal swabs were tested for sever acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) by both RT-qPCR and RAT. Diagnostic accuracy of the RAT was evaluated for participant’s subgroups that have various features. Support vector machine model was then used to investigate whether laboratory measurements in subject’s blood would enhance the predictive accuracy of this RAT. The sensitivity, specificity and accuracy of the RAT were 78.2, 64.2 and 75.9%, respectively. Samples with high viral load and those that were collected within one week post-symptom showed the highest sensitivity and accuracy. Measuring Laboratory indices did not enhance the predictive accuracy of this RAT. It is concluded that “Standard ™ Q COVID-19 Ag” should not be used alone for COVID-19 diagnosis due to its low diagnostic performance. This RAT is best used at early disease stage and in patients with high viral load.

Seneca Valley Virus (SVV) infection was recently spread the pig farm in the Canada, American and China, human, mice and housefly have been the host and reservoirs. Although such cross-species transmission events result in limited onward in the new cross-species transmission, sustained outbreak have posed a new mammalian host. Thus, to determine whether mink was one of a new mammalian host in our study with the molecular characteristics of isolated SVA genomes, challenge, pathological study, and immune respond. Here, our research was the first systemic analysis on a new isolation strain of SVV from pig, the new strain infected the mink in oral and intestine, which produced the pathological change in the intestine. And the SVV could stimulate the specific neutralizing antibody. This study highlights the importance of identifying SVV infection in the mink and host as a mutational pressure for the virus evolution that could threaten livestock, public health and economic growth.

West Nile Disease is a zoonotic vector-borne infection involving viral pathogens, human and animal hosts, vectors and habitats with a complex transmission cycle. Cooperation among different disciplines has been promoted by the Italian Public Health Authorities to introduce a robust surveillance system and an integrated West Nile Virus (WNV) Surveillance Plan has been in force in Italy since 2016, in order to establish a medical, veterinary and entomological network. This represents a unique model in Europe. This study aims to present this “One Health” approach applied following the first recorded autochthonous case of West Nile Neuroinvasive Disease (WNND) in Sicily (Southern Italy). Serological and molecular tests were conducted on the blood, liquor and urine of a 38-year-old man with encephalitis and meningitis: WNND was confirmed by serological analysis on liquor and serum. Consequently, a veterinary and entomological surveillance was started. Overall, 160 mosquito catches were collected from six different sampling sites and 2704 adult culicides were morphologically identified. Female mosquitoes were analyzed in pools for WNV RNA detection. Serological and molecular assays for WNV were carried out in 11 horses, 271 chickens and 2 dogs sampled in farms around the man’s residence. Collected mosquito species included Culex pipiens (93.6%), Aedes albopictus (5.25%), Culex hortensis (0.6%), Culiseta longiareolata (0.55%) and Anopheles maculipennis s.l. (0.04%). Mosquito pools were negative for WNV nucleic acid presence. Two dogs (100%) and two horses (18.2%) resulted positive for WNV-specific IgG antibodies. Since WNND epidemiology is influenced by several ecological factors and by the presence of several animal and vector species, the integrated surveillance system was crucial for understanding whether the virus had circulated/was circulating in the suburban, urban area and for preventing the spread of infection.

Letter to the editor

Avian leukosis virus subgroup J (ALV-J) is the most prevalent subgroup in chickens and exhibits increasing pathogenicity and stronger horizontal and vertical transmission ability in different kinds of chicken. Although vertical transmission of ALV-J from hens infected through artificial insemination with ALV-J infected semen was reported before by the detection of swabs and serum, there was no further research on the trasmission pattern of ALVs in the roosters. In the present study, the introduction of Hy-line brown roosters infected with ALV-J significantly increased the p27 positive rate of ALV in a indigenous flock detected by virus isolation. Sequence analysis and IFA showed that it is classified into ALV-J subgroup, locating in a new branch compared with the domestic and foreign referential sequences. Meanwhile, the gp85 gene of the ALV-J isolated in the hens and its albumens had a homology of 94.1-99.7% with that in the roosters, which means that the strain is quite likely transmitted to the hens and their offspring through insemination of the roosters. Moreover, Semens are directly detected by ELISA method is not completely accurate. There are four ALV-J infection status in plasma and semen of rooster (V+S+, V-S+, V+S-, V-S-), so the eradication of ALV in rooster requires simultaneous virus isolation of semen and plasma. Therefore, we speculate that the reason why there are still some sporadic findings of ALV-J in laying hens is probably due to the incomplete eradication process of roosters.

Since the beginning of the current coronavirus 2019 (COVID-19) outbreak, an intense number of studies have been done in an attempt to discover effective therapies, not only from the point of view of discovering new drugs, but also from its repurposing. Recent studies have proposed tranexamic acid (TXA), a hemostatic drug widely used in clinical practice, as a potential therapeutic option for COVID-19 as it reduces plasmin levels. Thus, this letter to the editor aims to provide a critical overview on the use of TXA in the treatment of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.

Persistent infection and tumourigenesis by papillomaviruses (PVs) require viral manipulation of various of cellular processes, including those involved in innate immune responses. Herein, we showed that bovine PV (BPV) E5 oncoprotein interacts with a tripartite motif-containing 25 (TRIM25) but not with Riplet in spontaneous BPV infection of urothelial cells of cattle. Statistically significant reduced protein levels of TRIM25, retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5) were detected by Western blot analysis. Real-time quantitative PCR revealed marked transcriptional downregulation of RIG-I and MDA5 in E5-expressing cells compared with healthy urothelial cells. Mitochondrial antiviral signalling (MAVS) protein expression did not vary significantly between diseased and healthy cells. Co-immunoprecipitation studies showed that MAVS interacted with a protein network composed of Sec13, which is a positive regulator of MAVS-mediated RLR antiviral signalling, phosphorylated TANK binding kinase 1 (TBK1), and phosphorylated interferon regulatory factor 3 (IRF3). Immunoblotting revealed significantly low expression levels of Sec13 in BPV-infected cells. Low levels of Sec13 resulted in a weaker host antiviral immune response, as it attenuates MAVS-mediated IRF3 activation. Furthermore, western blot analysis revealed significantly reduced expression levels of pTBK1, which plays an essential role in the activation and phosphorylation of IRF3, a prerequisite for the latter to enter the nucleus to activate type 1 IFN genes. Our results suggested that the innate immune signalling pathway mediated by RIG-I-like receptors (RLRs) was impaired in cells infected with BPVs. Therefore, an effective immune response is not elicited against these viruses, which facilitates persistent viral infection.

Porcine parvoviruses (PPVs) and porcine circoviruses (PCVs) infect pigs worldwide, with PPV1-7 and PCV2 infections common in pigs. Although PPV7 was only identified in 2016, co-infection of PPV7 and PCV2 is already common and PPV7 may stimulate PCV2 replication. PCV3, a novel type of circovirus, is prevalent worldwide and believed to cause reproductive disorders and dermatitis nephrotic syndrome. In recent studies, pigs were commonly infected with both PCV3 and PPV7. Our objective was to investigate co-infections between PPV7 and PCV3 in samples from swine on farms in Hunan, China, and assess potential impacts of PPV7 on PCV3 viremia. A total of 399 porcine serum samples, negative or positive for PCV3, were subjected to real-time PCR to detect PPV7; of these samples, 190 were from farms with long-standing histories of reproductive failure (RF) and were selected to determine whether PPV7 affected PCV3 viremia. Among 209 serum samples, 23% (48/209) were positive for PPV7 and the PPV7-positive rate was significantly higher in PCV3 positive serum (31.4%) than negative serum (14.4%). Among 190 serum samples, 45.1% (28/62) were positive for PPV7 and PCV3 and the PPV7-positive rate was significantly higher in PCV3 positive RF-serum (51.2%) than in non-PCV3 RF-serum (34.8%); furthermore, there was a higher PPV7 prevalence (55%) in PCV3-positive aborted fetus samples. In addition, the Ct value of PCV3 in PPV7 positive samples was significantly lower than that in PPV7 negative serum samples. Based on our findings, we concluded that PPV7 may stimulate PCV3 replication.

Caprine parainfluenza virus type 3 (CPIV3) was first identified in goats named JS2013 in China. In 2019, a sheep herd broke a disease with respiratory disease in Hebei province, China. In order to confirm the pathogen of the disease, the nasal swabs, stool swabs and blood samples were collected from the sheep. Virus isolation was performed on MDBK cells and identification was conducted by RT-PCR. The complete genome of the isolate was sequenced and phylogenetic analyzed. In order to evaluate the pathogenicity of the virus, five seronegative sheep were experimental infected with the virus suspension. The phylogenetic analyses based on the complete genome and the M gene indicated that the isolate strain was distinguished distinct from previously reported CPIV3 lineage of JS2013. The virus-inoculated sheep displayed the syndrome with depression, cough, and fever. Virus shedding were detected by RT-PCR from nasal swabs. All infected showed virus shedding during 2 - 21dpi and viremia could be detected in serum samples. Gross pathological assessment of sheep in infected group showed gross lesion in the lungs. Histopathological observation results indicated that lungs had mild to moderate interstitial pneumonia , with thickened alveolar walls, decreased alveolar space, and increased amounts of inflammatory cells infiltration. This is the first report of pathogenicity of the novel lineage of sheep-derived CPIV3. The results would be helpful for further studies on the prevention and control strategies for CPIV3 infections in goat and sheep.

Abstract – Highly pathogenic bovine Delta papillomaviruses (δPVs) were detected and quantified for the first time using digital droplet polymerase chain reaction (ddPCR) by liquid biopsy in 103 clinically healthy sheep. Overall, ddPCR detected bovine δPVs in 68 blood samples (66%). Bovine papillomavirus (BPV) infection by a single genotype was revealed in 59% of the blood samples, and BPV coinfection by double, triple or quadruple genotypes was observed in 41% of liquid biopsies. The BPV-2 genotype was most frequently seen in sheep, whereas BPV-1 was the least common. Furthermore, ddPCR was very useful for detection and quantification; the BPV-14 genotype was observed for the first time in ovine species, displaying the highest prevalence in some geographical areas (Apulia). In 42 of the positive samples (61.8%), a single BPV infection was observed, 26 of which were caused by BPV-2 (61.9%) and 7 by BPV-13 (16.7%). BPV-14 was responsible for 7 single infections (16.7%) and BPV-1 for 2 single infections (4.7%). Multiple BPV coinfections were observed in the remaining 26 positive samples (38.2%), with dual BPV-2/BPV-13 infection being the most prevalent (84.6%). BPV infection by triple and quadruple genotypes was also observed in 11.5% and 3.8% of cases, respectively. The present study showed that ddPCR, a biotechnological refinement of conventional PCR, is by far the most sensitive and accurate assay for BPV detection. Therefore, ddPCR displayed diagnostic and epidemiological value resulting in the identification of otherwise undetectable BPV genotypes as well as their geographical distributions and suggesting that animal husbandry practices contribute to cross-species transmission of BPVs.

Peste des petits ruminants (PPR) is an acute, highly contagious, world organization for animal health (OIE) notifiable and economically important transboundary viral disease of sheep and goats and caused by PPR virus (PPRV), which belongs to the genus Morbillivirus of the family Paramyxoviridae. The disease is endemic across Asia, the Middle East and African regions and is considered to be a major obstacle to the development of sustainable agriculture across the developing world due to huge burden for the economy and development of the affected countries and has recently been targeted by the OIE and the Food and Agriculture Organization (FAO) for eradication with the aim of global elimination of the disease by 2030. In this review, the regional epidemiology of PPR outbreaks and associated risk factors with special reference to the PPR-affected countries in South， Central and East Asia is comprehensively discussed.

Objective: This systematic review and meta-analysis was aimed to evaluate the therapeutic benefits and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19) and associated health complications. Methods: The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials (RCTs) and Google scholar databases to identify the randomized control trials. Mortality, incidences of ICU admission, need of mechanical ventilation (MV), length of stay in the hospital (LOS) and length of stay in the ICU (LOS-ICU) and the incidences of super-infection, bacteraemia, fugleman, pneumonia and pulmonary thrombosis were evaluated as the primary outcomes. The comparison will be between TCZ versus standard of care (SOC)/placebo. Results: Based on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (Mantel-Haenszel (M-H), random effects risk difference (RE-RD) of -0.11 (-0.18 to -0.04), at 95% CI, p = 0.001, I2 = 88%) and increased the incidences of super-infections (M-H, RE-Risk ratio (RR) of 1.49 (1.13 to 1.96) at 95% CI, p=0.004, I2 = 47%). However, there is no significant difference in ICU admissions rate, need of MV, LOS, LOS-ICU, and incidences of pulmonary thrombosis compared to SOC/control. Conclusion: Based on the outcomes of the meta-analysis we can conclude that administration of TCZ would reduce the risk of mortality, and however there is no much difference observed between the TCZ and SOC/control groups in other parameters.

The emergence of novel coronavirus infectious disease-2019 (COVID-19) in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has traumatized the whole world with the ongoing devastating pandemic. After droplet mediated transmission of infectious virus particle, and subsequent tissue tropism through the upper and lower respiratory tract, the acute clinical disease is manifested by severe respiratory illness accompanied by shortness of breath, progressive pneumonia, multi-organ dysfunction and ultimate death in SARS-CoV-2 infected patients. The involvement of other microbial co-infections leading to extortionate ailment in critically ill patients has not been significantly reviewed along with conclusive reporting on underlying molecular mechanisms in COVID-19 patients. Although the incidence of co-infections could be up to 94.2% in laboratory-confirmed COVID-19 cases, the fate of co-infections among SARS-CoV-2 infected hosts often depends on the balance between the host’s protective immunity and immunopathology. The cross-talk between co-pathogens (especially lung microbiomes), SARS-CoV-2 and host is an important factor that ultimately increases the difficulty of diagnosis, treatment, and prognosis of COVID-19, and even increase the symptoms and mortality of the disease. Simultaneously, co-infecting microorganisms may use new strategies to escape host defense mechanisms (by altering both innate and adaptive immune responses) to further aggravate SARS-CoV-2 pathogenesis. This review of literature suggests that clinicians should rule out SARS-CoV-2 infection by ruling in other respiratory co-pathogens, and must have a high index of suspicion for co-infection among COVID-19 patients. Thus, after recognizing the possible pathogens causing co-infection among COVID-19 patients, and the underlying molecular mechanisms of co-infections appropriate curative and preventive interventions can be recommended.

An experimental compound (CNS004), reported to have various biological activities including antiviral, antimalarial, antiprotozoal and immunomodulatory effects, has been identified to potentiate NMDA subtype of glutamate receptors that are expressed in human lungs and central nervous system. We hypothesize that potentiating NMDA receptors will increase calcium ion influx and promote downstream signaling mechanisms associated with cellular contractions which is disrupted in severe acute respiratory syndrome. Pharmacological effects generated by triggering central nervous system glutamate receptor function, coupled with concurrent stimulation of the respiratory tract, may produce a synergetic effect in improving the airway smooth muscle function. Further, an antiviral activity combined with immunomodulatory effect of this experimental compound may improve the symptoms of viral diseases. This novel multipronged intervention to simultaneously inhibit viral proteins and promote host cell functions would be helpful to develop clinically useful compounds for the treatment of emerging viral diseases that deteriorate peripheral and central nervous system function before causing death in human beings.

The global distribution of canine parvovirus (CPV-2), derived from a closely related carnivore parvovirus, has caused a considerable threat to the dog population. The virus continuously underwent genetic evolution, giving rise to several variants. To investigate the prevalence of Chinese CPV-2 strains in recent years, a total of 25 CPV-2 strains were isolated from 33 canine samples collected from 2018 to 2020, and then sequenced and analyzed. Two variants, New CPV-2a and CPV-2c were identified. Contrary to previous reports, the CPV-2c variant has gained an epidemiological advantage over the New CPV-2a variant in China. To make up for the relatively limited sample, 683 Chinese CPV-2 records identified between 2014 to 2019 were retrieved from Genbank and associated publications, whose result further supported our finding. That should be caught concern since the CPV-2c variant has been frequently related to vaccine failure in adult dogs. VP2 protein sequences analysis revealed several amino acid substitutions, including Ala5Gly, Pro13Ser, Phe267Tyr, Tyr324Ile, Gln370Arg, Thr440Ala, and Lys570Arg. Phylogenetic analysis indicated a close relationship between Chinese strains with Asian strains, suggesting the mutual transmission between Asian countries. Furthermore, the intercontinental transmission should be a cause for concern. Surprisingly, two feline panleukopenia (FPLV) strains with Ile101Thr mutation in VP2 protein were also successfully isolated from canine fecal samples, which was considered incapable of infecting dogs. This study clarified the epidemic characteristics of Chinese CPV-2 strains between 2014 and 2019, offering a reference for epidemic control. Besides, the detection of FPLV in canine samples may provide information for future studies on the evolution of carnivore parvovirus.