Background and Objectives Although about 80% of coronavirus disease‐2019 (COVID‐19) cases are reported to be mild, the remaining 20% of cases often result in severe disease with the potential of crushing already overstrained health care services. There has been sustainable growth of COVID‐19 cases worldwide since mid‐May 2020. To keep tabs on community transmission of COVID‐19 infection screening of the samples from a large population is needed which includes asymptomatic/symptomatic individuals along with the migrant population. This requires extra resources, man power, and time for detection of severe acute respiratory syndrome coronavirus 2 by real‐time polymerase chain reaction (RT‐PCR). In the current scenario, the pooled sample testing strategy advocated by the Indian Council of Medical Research, New Delhi is a new approach that is very promising in resource‐limited settings. In this study, we have evaluated the pooled strategy in terms of accurate testing results, utilization of consumables, and identification of borderline positive cases. Materials and Methods Between April and June 2020, we performed COVID‐19 testing by RT‐PCR from areas with varying prevalence of population referred to COVID laboratory, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow. In the first step, the samples are collated into pools of 5 or 10. These pools are tested by RT‐PCR. Negative pools were reported as negative whereas positive pools of 5 and 10 are then deconvoluted and each sample is tested individually. Results In the present study, we tested 4620 samples in 462 pools of 10 and 14 940 samples in 2990 pools of 5. Among 10 samples pool, 61 (13%) pools flagged positive in the first step. In the second step, among 61 pools (610 samples) deconvoluted strategy was followed in which 72 individual samples came positive. The pooled‐sample testing strategy helps saves substantial resources and time during surge testing and enhanced pandemic surveillance. This approach requires around 76% to 93% fewer tests done in low to moderate prevalence settings and group sizes up to 5–10 in a population, compared to individual testing. Conclusions Pooled‐sample PCR analysis strategies can save substantial resources and time for COVID‐19 mass testing in comparison with individual testing without compromising the resulting outcome of the test. In particular, the pooled‐sample approach can facilitate mass screening in the early coming stages of COVID‐19 outbreaks, especially in low‐ and middle‐income settings, and control the spread by meticulous testing of all risk groups.
Cationic amino acid transporters (mCAT1 and mCAT2B) regulate the arginine availability in macrophages. How in the infected cell a pathogen can alter the arginine metabolism of the host remains to be understood. We reveal here a novel mechanism by which Salmonella exploit mCAT1 and mCAT2B to acquire host arginine towards its own intracellular growth within antigen presenting cells. We demonstrate that Salmonella infected bone marrow derived macrophages and dendritic cells show enhanced arginine uptake and increased expression of mCAT1 and mCAT2B. We show that the mCAT1 transporter is in close proximity to Salmonella containing vacuole (SCV) specifically by live intracellular Salmonella in order to access the macrophage cytosolic arginine pool. Further, Lysosome associated membrane protein 1, a marker of SCV, also was found to colocalize with mCAT1 in the Salmonella infected cell. The intra vacuolar Salmonella then acquire the host arginine via its own arginine transporter, ArgT for growth. The argT knockout strain was unable to acquire host arginine and was attenuated in growth in both macrophages and in mice model of infection. Together, these data reveal survival strategies by which virulent Salmonella adapt to the harsh conditions prevailing in the infected host cells.
Cognitive impairment has recently attracted researchers as one of the possible neuropsychiatric manifestations of COVID-19, although how the infection perpetuates impairment of cognitive functions is still obscure. We presented a 29-year-old male patient with COVID-19 who developed new-onset transient attention deficit and memory problems following a SARS-CoV-2 infection. Structural neuroimaging was normal. MR-spectroscopy (MRS) of the bilateral DLPFC revealed significant for decreased levels of N-acetylaspartate (NAA), glutamate, and glutamate/glutamine ratio. After a follow-up without any medical treatment but with suggestions of memory exercises for three months a control MRS screening of DLPFC showed improved levels of NAA, glutamate, and glutamate/glutamine ratio. This report may suggest that cognitive deficits in SARS-CoV-2 infection can result from glutamatergic dysfunction with decreased NAA and glutamate levels in bilateral DLPFC.
Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter-and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria. C urcumin, a pigment from turmeric, is known to have a vast array of therapeutic potential, ranging from anti-inflammatory to anticancer effects. It has also been shown to exhibit antimicrobial effects. However, its role as an antimicrobial agent remains controversial. Curcumin shows its antimicrobial effect against Helicobacter pylori (14,19), Bacillus subtilis (38), Plasmodium falciparum (11, 34), etc. On the other hand, the role of curcumin as a promicrobial has been demonstrated in Leishmania (1) and Salmonella spp. (30). Curcumin is known to suppress the type 1 immune response (1, 24), which is important for the clearance of intracellular pathogens. In the following study, we sought to assess the effect of curcumin on the virulence of a few medically important intracellular foodborne pathogens.The constant battle between the pathogen and host highlights the crux of host-pathogen interactions. The host has a repertoire of combative cells to keep the infection at bay (15,28,40). Similarly, pathogens employ different strategies to hijack the host immune system (15,28,40). Once the pathogen is sensed by the host immune system, it initiates an inflammatory response, recruiting different phagocytic cells to the site of infection. Macrophages, the key players in eliminating pathogens (32,46), phagocytose the bacteria and use various tools to clear pathogens (27,32,43). The foremost tool is lysosomal degradation of the invading pathogen. During the process of phagocytosis, the bacteria or any foreig...
Despite neuropsychiatric outcomes of SARS-CoV-2 infection are now under close scrutiny, psychoneuroimmunological characteristics of COVID-19 and precise pathophysiology of neuropsychiatric manifestations of the infection are still obscure. Moreover, there still exists a shortfall in demonstrating specific clinical manifestations of the brain involvement of the virus. Here, we presented a 33-year-old female patient with COVID-19, reporting acute-onset paranoid delusions symptoms, insomnia and irritability. Cranial MRI showed an hyperintense signal in the splenium of the corpus callosum with decreased apparent diffusion coefficient, which might possibly indicate the presence of cytotoxic edema related to the brain involvement of the infection. Following the completion of SARS-CoV-2 treatment, both cytotoxic edema and psychiatric symptoms resolved. In light of this report, we suggest that either heightened immune response and direct viral infection that SARS-CoV-2 may lead to such psychiatric manifestations and neuropsychiatric monitoring should be performed in patients with COVID-19. Prompt recognition of psychiatric consequences of COVID-19 may help clinicians provide guidance for differential diagnosis and manage them accordingly.
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