Runx3 drives a CD8+ T cell tissue residency program that is absent in CD4+ T cells.

Tissue-resident memory T cells (TRM cells) provide rapid and superior control of localized infections. While the transcription factor Runx3 is a critical regulator of CD8+ T cell tissue residency, its expression is repressed in CD4+ T cells. Here, we show that, as a direct consequence of this Runx3-deficiency, CD4+ TRM cells lacked the transforming growth factor (TGF)-ß-responsive transcriptional network that underpins the tissue residency of epithelial CD8+ TRM cells. While CD4+ TRM cell formation required Runx1, this, along with the modest expression of Runx3 in CD4+ TRM cells, was insufficient to engage the TGF-ß-driven residency program. Ectopic expression of Runx3 in CD4+ T cells incited this TGF-ß-transcriptional network to promote prolonged survival, decreased tissue egress, a microanatomical redistribution towards epithelial layers and enhanced effector functionality. Thus, our results reveal distinct programming of tissue residency in CD8+ and CD4+ TRM cell subsets that is attributable to divergent Runx3 activity.

Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses.

The sympathetic nervous system (SNS) controls various physiological functions via the neurotransmitter noradrenaline. Activation of the SNS in response to psychological or physical stress is frequently associated with weakened immunity. Here, we investigated how adrenoceptor signaling influences leukocyte behavior. Intravital two-photon imaging after injection of noradrenaline revealed transient inhibition of CD8+ and CD4+ T cell locomotion in tissues. Expression of ß-adrenergic receptor in hematopoietic cells was not required for NA-mediated inhibition of motility. Rather, chemogenetic activation of the SNS or treatment with adrenergic receptor agonists induced vasoconstriction and decreased local blood flow, resulting in abrupt hypoxia that triggered rapid calcium signaling in leukocytes and halted cell motility. Oxygen supplementation reversed these effects. Treatment with adrenergic receptor agonists impaired T cell responses induced in response to viral and parasitic infections, as well as anti-tumor responses. Thus, stimulation of the SNS impairs leukocyte mobility, providing a mechanistic understanding of the link between adrenergic receptors and compromised immunity.

Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions.

Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBPε transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses.

Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8+ T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity.

Probiotic potential of Streptomyces levis strain HFM-2 isolated from human gut and its antibiofilm properties against pathogenic bacteria.

BACKGROUND: Antimicrobial resistance (AMR) is a serious worldwide public health concern that needs immediate action. Probiotics could be a promising alternative for fighting antibiotic resistance, displaying beneficial effects to the host by combating diseases, improving growth, and stimulating the host immune responses against infection. This study was conducted to evaluate the probiotic, antibacterial, and antibiofilm potential of Streptomyces levis strain HFM-2 isolated from the healthy human gut. RESULTS: In vitro antibacterial activity in the cell-free supernatant of S. levis strain HFM-2 was evaluated against different pathogens viz. K. pneumoniae sub sp. pneumoniae, S. aureus, B. subtilis, VRE, S. typhi, S. epidermidis, MRSA, V. cholerae, M. smegmatis, E. coli, P. aeruginosa and E. aerogenes. Further, the ethyl acetate extract from S. levis strain HFM-2 showed strong biofilm inhibition against S. typhi, K. pneumoniae sub sp. pneumoniae, P. aeruginosa and E. coli. Fluorescence microscopy was used to detect biofilm inhibition properties. MIC and MBC values of EtOAc extract were determined at 500 and 1000 µg/mL, respectively. Further, strain HFM-2 showed high tolerance in gastric juice, pancreatin, bile, and at low pH. It exhibited efficient adhesion properties, displaying auto-aggregation (97.0%), hydrophobicity (95.71%, 88.96%, and 81.15% for ethyl acetate, chloroform and xylene, respectively), and showed 89.75%, 86.53%, 83.06% and 76.13% co-aggregation with S. typhi, MRSA, S. pyogenes and E. coli, respectively after 60 min of incubation. The S. levis strain HFM-2 was susceptible to different antibiotics such as tetracycline, streptomycin, kanamycin, ciprofloxacin, erythromycin, linezolid, meropenem, amikacin, gentamycin, clindamycin, moxifloxacin and vancomycin, but resistant to ampicillin and penicillin G. CONCLUSION: The study shows that S. levis strain HFM-2 has significant probiotic properties such as good viability in bile, gastric juice, pancreatin environment, and at low pH; proficient adhesion properties, and antibiotic susceptibility. Further, the EtOAc extract of Streptomyces levis strain HFM-2 has a potent antibiofilm and antibacterial activity against antibacterial-resistant clinical pathogens.

Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration.

Leukocyte homing driven by the chemokine CCL21 is pivotal for adaptive immunity because it controls dendritic cell (DC) and T cell migration through CCR7. ACKR4 scavenges CCL21 and has been shown to play an essential role in DC trafficking at the steady state and during immune responses to tumors and cutaneous inflammation. However, the mechanism by which ACKR4 regulates peripheral DC migration is unknown, and the extent to which it regulates CCL21 in steady-state skin and lymph nodes (LNs) is contested. Specifically, our previous findings that CCL21 levels are increased in LNs of ACKR4-deficient mice [I. Comerford et al., Blood 116, 4130-4140 (2010)] were refuted [M. H. Ulvmar et al., Nat. Immunol. 15, 623-630 (2014)], and no differences in CCL21 levels in steady-state skin of ACKR4-deficient mice were reported despite compromised CCR7-dependent DC egress in these animals [S. A. Bryce et al., J. Immunol. 196, 3341-3353 (2016)]. Here, we resolve these issues and reveal that two forms of CCL21, full-length immobilized and cleaved soluble CCL21, exist in steady-state barrier tissues, and both are regulated by ACKR4. Without ACKR4, extracellular CCL21 gradients in barrier sites are saturated and nonfunctional, DCs cannot home directly to lymphatic vessels, and excess soluble CCL21 from peripheral tissues pollutes downstream LNs. The results identify the mechanism by which ACKR4 controls DC migration in barrier tissues and reveal a complex mode of CCL21 regulation in vivo, which enhances understanding of functional chemokine gradient formation.

CD8+ and CD4+ T Cells Infiltrate into the Brain during Plasmodium berghei ANKA Infection and Form Long-Term Resident Memory.

In the Plasmodium berghei ANKA mouse model of malaria, accumulation of CD8+ T cells and infected RBCs in the brain promotes the development of experimental cerebral malaria (ECM). In this study, we used malaria-specific transgenic CD4+ and CD8+ T cells to track evolution of T cell immunity during the acute and memory phases of P. berghei ANKA infection. Using a combination of techniques, including intravital multiphoton and confocal microscopy and flow cytometric analysis, we showed that, shortly before onset of ECM, both CD4+ and CD8+ T cell populations exit the spleen and begin infiltrating the brain blood vessels. Although dominated by CD8+ T cells, a proportion of both T cell subsets enter the brain parenchyma, where they are largely associated with blood vessels. Intravital imaging shows these cells moving freely within the brain parenchyma. Near the onset of ECM, leakage of RBCs into areas of the brain can be seen, implicating severe damage. If mice are cured before ECM onset, brain infiltration by T cells still occurs, but ECM is prevented, allowing development of long-term resident memory T cell populations within the brain. This study shows that infiltration of malaria-specific T cells into the brain parenchyma is associated with cerebral immunopathology and the formation of brain-resident memory T cells. The consequences of these resident memory populations is unclear but raises concerns about pathology upon secondary infection.

Investigating the plant growth promoting and biocontrol potentiality of endophytic Streptomyces SP. SP5 against early blight in Solanum lycopersicum seedlings.

BACKGROUND: Early blight (EB), caused by Alternaria solani, is one of the alarming diseases that restrict tomato production globally. Existing cultural practices and fungicide applications are not enough to control early blight diseases. Therefore, the study aimed to isolate, identify, and characterize an endophytic Streptomyces exhibiting the potential to control early blight in tomato and also promote plant growth. RESULTS: From a Citrus jambhiri leaf, an endophytic Streptomyces sp. with antagonistic activity against Alternaria solani, Colletotrichum acutatum, Cladosporium herbarum, Alternaria brassicicola, Alternaria sp., Fusarium oxysporum and Fusarium sp. was isolated. It was identified as a Streptomyces sp. through 16S ribosomal DNA sequence analysis and designated as SP5. It also produced indole acetic acid which was confirmed by Salkowski reagent assay, TLC and HPLC analysis. Treatment of pathogen infected plants with Streptomyces sp. SP5 antagonists (culture cells/culture supernatant/solvent extract/ acetone precipitates) decreased the early blight disease incidence and significantly increased the various agronomic traits. CONCLUSION: The present study concluded that Streptomyces sp. SP5 possessed antifungal activity against different fungal phytopathogens and had significant potential to control early blight disease and promote plant growth.

Display of Native Antigen on cDC1 That Have Spatial Access to Both T and B Cells Underlies Efficient Humoral Vaccination.

Follicular dendritic cells and macrophages have been strongly implicated in presentation of native Ag to B cells. This property has also occasionally been attributed to conventional dendritic cells (cDC) but is generally masked by their essential role in T cell priming. cDC can be divided into two main subsets, cDC1 and cDC2, with recent evidence suggesting that cDC2 are primarily responsible for initiating B cell and T follicular helper responses. This conclusion is, however, at odds with evidence that targeting Ag to Clec9A (DNGR1), expressed by cDC1, induces strong humoral responses. In this study, we reveal that murine cDC1 interact extensively with B cells at the border of B cell follicles and, when Ag is targeted to Clec9A, can display native Ag for B cell activation. This leads to efficient induction of humoral immunity. Our findings indicate that surface display of native Ag on cDC with access to both T and B cells is key to efficient humoral vaccination.

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus.

Nonclassical monocytes undergo intravascular patrolling in blood vessels, positioning them ideally to coordinate responses to inflammatory stimuli. Under some circumstances, the actions of monocytes have been shown to involve promotion of neutrophil recruitment. However, the mechanisms whereby patrolling monocytes control the actions of neutrophils in the circulation are unclear. Here, we examined the contributions of monocytes to antibody- and neutrophil-dependent inflammation in a model of in situ immune complex-mediated glomerulonephritis. Multiphoton and spinning disk confocal intravital microscopy revealed that monocytes patrol both uninflamed and inflamed glomeruli using ß2 and α4 integrins and CX3CR1. Monocyte depletion reduced glomerular injury, demonstrating that these cells promote inappropriate inflammation in this setting. Monocyte depletion also resulted in reductions in neutrophil recruitment and dwell time in glomerular capillaries and in reactive oxygen species (ROS) generation by neutrophils, suggesting a role for cross-talk between monocytes and neutrophils in induction of glomerulonephritis. Consistent with this hypothesis, patrolling monocytes and neutrophils underwent prolonged interactions in glomerular capillaries, with the duration of these interactions increasing during inflammation. Moreover, neutrophils that interacted with monocytes showed increased retention and a greater propensity for ROS generation in the glomerulus. Also, renal patrolling monocytes, but not neutrophils, produced TNF during inflammation, and TNF inhibition reduced neutrophil dwell time and ROS production, as well as renal injury. These findings show that monocytes and neutrophils undergo interactions within the glomerular microvasculature. Moreover, evidence indicates that, in response to an inflammatory stimulus, these interactions allow monocytes to promote neutrophil recruitment and activation within the glomerular microvasculature, leading to neutrophil-dependent tissue injury.

Microarray analysis of gene expression patterns in the leaf during potato tuberization in the potato somatic hybrid Solanum tuberosum and Solanum etuberosum.

Genes involved in photoassimilate partitioning and changes in hormonal balance are important for potato tuberization. In the present study, we investigated gene expression patterns in the tuber-bearing potato somatic hybrid (E1-3) and control non-tuberous wild species Solanum etuberosum (Etb) by microarray. Plants were grown under controlled conditions and leaves were collected at eight tuber developmental stages for microarray analysis. A t-test analysis identified a total of 468 genes (94 up-regulated and 374 down-regulated) that were statistically significant (p ≤ 0.05) and differentially expressed in E1-3 and Etb. Gene Ontology (GO) characterization of the 468 genes revealed that 145 were annotated and 323 were of unknown function. Further, these 145 genes were grouped based on GO biological processes followed by molecular function and (or) PGSC description into 15 gene sets, namely (1) transport, (2) metabolic process, (3) biological process, (4) photosynthesis, (5) oxidation-reduction, (6) transcription, (7) translation, (8) binding, (9) protein phosphorylation, (10) protein folding, (11) ubiquitin-dependent protein catabolic process, (12) RNA processing, (13) negative regulation of protein, (14) methylation, and (15) mitosis. RT-PCR analysis of 10 selected highly significant genes (p ≤ 0.01) confirmed the microarray results. Overall, we show that candidate genes induced in leaves of E1-3 were implicated in tuberization processes such as transport, carbohydrate metabolism, phytohormones, and transcription/translation/binding functions. Hence, our results provide an insight into the candidate genes induced in leaf tissues during tuberization in E1-3.

Impacts of lockdown on the dynamics of forestry biomass, wildlife species and control of atmospheric pollution.

In this paper, we have formulated and analysed a mathematical model to investigate the impacts of lockdown on the dynamics of forestry biomass, wildlife species and pollution. For this purpose, we have considered a nonlinear system of four ordinary differential equations representing rates of change of the density of forestry biomass, the density of wildlife species, the concentration of pollutants and lockdown. Conditions for the existence, uniqueness and local stability of all equilibria along with the global stability of the interior equilibrium point are derived. Furthermore, conditions that influence the persistence of the system are obtained. By formulating an optimal control problem, the optimal strategies for minimizing the cost of implementation of lockdown as well as the concentration of pollutants are also studied. Numerical simulations are carried out to verify and validate our analytical findings. By this study, we have observed that implementation of lockdown for a sufficient period of time minimizes excessive harvesting of both forestry biomass and wildlife species and the concentration of pollutants in the environment. It is also found that lockdown policy is effective in the optimal control of atmospheric pollution. Therefore, lockdown plays a significant role in the dynamics of forestry biomass, wildlife species and control of pollution in the environment.

Induction of systemic resistance in Solanum lycopersicum and Capsicum annum seedlings against Fusarium wilt by Streptomyces bioformulations.

Plant diseases induced by various phytopathogens pose a significant threat to contemporary agricultural systems around the world. In modern agriculture, the use of pesticides is still a valuable and effective method to control plant diseases. However, agrochemicals are becoming less popular because of the accretion of toxic compounds perilous and potentially hazardous to humans and the environment. Taking into consideration these aspects, the present study was conducted to explore the biocontrol potential of an endophytic Streptomyces sp. SP5 bioformulations against Fusarium wilt. Three bioformulations were prepared using cell biomass and different carriers, i.e., B1 (talc-kaolin), B2 (MgSO4/glycerol/Na-alginate/talc/Ca-lignosulfonate), and B3 (calcium carbonate/CMC/talc). Apart from antagonistic action against Fusarium wilt, the influence of bioformulations on plant growth and systemic resistance was investigated by analyzing morphological parameters (root length, shoot length, root weight, shoot weight), biochemical parameters (photosynthetic pigments, non-enzymatic antioxidants), and induction of antioxidative enzymes, e.g., catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and superoxide dismutase (SOD), in S. lycopersicum and C. annum seedlings. The results revealed that Streptomyces bioformulations effectively controlled Fusarium wilt in S. lycopersicum and C. annum (82.6-83.4% and 81.8-100%, respectively). Besides reducing disease prevalence, bioformulations significantly increased all the morphological parameters and increased the activity of antioxidative enzymes, i.e., CAT, APX, GPX, and SOD, in plants. The current findings display that bioformulations can be utilized as environment-friendly biocontrol agents against Fusarium wilt and also as plant growth promoters.

Purification and biological analysis of antimicrobial compound produced by an endophytic Streptomyces sp.

Fungal phytopathogens and drug-resistant bacteria are two significant challenges in agriculture and public health, respectively. As a result, new sources of antimicrobial compounds are urgently needed. Taking into consideration these aspects, the present study was carried out to explore the antimicrobial activity of Streptomyces sp. SP5 against drug-resistant bacteria, especially methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus  and fungal phytopathogens. MRSA and VRE are both types of antibiotic-resistant bacteria that pose significant challenges to public health. In vitro analysis of the metabolites of Streptomyces sp. SP5 exhibited broad-spectrum antimicrobial activity against drug-resistant bacteria and phytopathogenic fungi. Further chemical investigation of the diethyl ether extract led to the isolation and purification of an antimicrobial compound. The structure of the purified compound was elucidated by performing detailed spectroscopic analysis including MS, IR, and NMR. The compound was identified as plicacetin. Plicacetin is a nucleoside antibiotic that has been reported for antibacterial activity against Gram-positive bacterium Mycobacterium tuberculosis. According to our knowledge, the present study is the first to demonstrate the antimicrobial properties of plicacetin against Fusarium oxysporum, Alternaria brassicicola, Fusarium solani, VRE and Bacillus subtilis. The outcome of the current study endorses that compound produced by Streptomyces sp. SP5 can be used as an antimicrobial agent against fungal phytopathogens and drug-resistant bacteria.

Insecticidal potential of endophytic Streptomyces sp. against Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) and biosafety evaluation.

Fruit flies of Tephritidae family pose a serious threat to cultivation of fruits and vegetables across the world. Among them, melon fruit fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) is a devastating pest of plants from Cucurbitaceae family. In a rising concern about the harmful effects associated with the use of chemical insecticides and development of resistance in pest insects, safer pest management strategies such as, use of biopesticides of microbial origin are being contemplated. Therefore, the present study aimed to evaluate the insecticidal potential of Streptomyces sp. SP5 protein extract against Z. cucurbitae. MTT assay, Ames mutagenicity, DNA nicking, and comet assay were conducted to determine the biosafety of protein extract. Second instar larvae of Z. cucurbitae were treated with various concentrations (1, 100, 200, 300, 400, and 500 µg/ml) of Streptomyces sp. SP5 protein extract. The protein extract showed significant larvicidal effects with LC50 value of 308.92 µg/ml. The percentage of adults emerged declined with increase in concentration. There was significant prolongation in developmental durations of the larvae. Various morphological aberrations in the form of deformed adults and pupae and decline in pupal weight were also observed. The nutritional physiology of the treated larvae was also adversely affected. The results from biosafety evaluation revealed antimutagenic and non-toxic nature of Streptomyces sp. proteins. This study indicates that Streptomyces sp. SP5 has the potential to be used as an ecologically safe biocontrol agent against Z. cucurbitae.

Eosinophilic Enteritis Flare-Up Mimicking Acute Gastroenteritis: A Rare Case.

Eosinophilic enteritis is a rare subset of eosinophilic gastrointestinal disorders. It typically presents with chronic symptoms of abdominal pain, nausea, vomiting, diarrhea, and ascites. However, the clinical presentation can vary due to acute flare-ups. Here, we present a case of eosinophilic enteritis in a young female patient with intractable vomiting and diarrhea, mimicking acute gastroenteritis in the absence of other gastrointestinal symptoms. This case illustrates the challenge of diagnosing acute and diverse presentations of eosinophilic enteritis. It also highlights the importance of promptly treating and confirming the diagnosis through urgent tissue histopathology in adolescents with unexplained vomiting and diarrhea.

Association of Deja vu With Cardiovascular Diseases.

Recent studies have suggested a link between déjà vu and cardiovascular diseases (CVDs). While the mechanism for this association is not fully understood, 1 theory suggests that déjà vu may be a result of a disruption in the temporal lobe, which is also responsible for regulating blood pressure and heart rate. Another theory suggests that there may be a shared genetic factor between the 2 conditions, with certain individuals being predisposed to experiencing both. The Apolipoprotein E (APOE) gene, in particular, has been associated with memory processing, Alzheimer's disease, and an increased risk of CVD. The protein encoded by this gene is involved in the metabolism of lipoproteins, including cholesterol and triglycerides, and is also involved in the development of atherosclerosis, which is a key risk factor for CVD. Several hypotheses have been proposed to explain how the APOE4 isoform contributes to CVD, including impairing the clearance of lipoproteins, promoting inflammation, and causing endothelial dysfunction. Psychological factors such as stress may also contribute to the development of CVD, and déjà vu may be associated with emotional arousal and stress. Further research is needed to fully understand the link between déjà vu and CVDs and to explore potential treatment options for individuals who experience both conditions.

Delayed Ventricular Septal Rupture Repair After Myocardial Infarction: An Updated Review.

Ventricular septal rupture (VSR) is a rare but serious complication that can occur after myocardial infarction (MI) and is associated with significant morbidity and mortality. The optimal management approach for VSR remains a topic of debate, with considerations including early versus delayed surgery, risk stratification, pharmacological interventions, minimally invasive techniques, and tissue engineering. The pathophysiology of VSR involves myocardial necrosis, inflammatory response, and enzymatic degradation of the extracellular matrix (ECM), particularly mediated by matrix metalloproteinases (MMPs). These processes lead to structural weakening and subsequent rupture of the ventricular septum. Hemodynamically, VSR results in left-to-right shunting, increased pulmonary blood flow, and potentially hemodynamic instability. The early surgical repair offers the advantages of immediate closure of the defect, prevention of complications, and potentially improved outcomes. However, it is associated with higher surgical risk and limited myocardial recovery potential during the waiting period. In contrast, delayed surgery allows for a period of myocardial recovery, risk stratification, and optimization of surgical outcomes. However, it carries the risk of ongoing complications and progression of ventricular remodeling. Risk stratification plays a crucial role in determining the optimal timing for surgery and tailoring treatment plans. Various clinical factors, imaging assessments, scoring systems, biomarkers, and hemodynamic parameters aid in risk assessment and guide decision-making. Pharmacological interventions, including vasopressors, diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, antiplatelet agents, and antiarrhythmic drugs, are employed to stabilize hemodynamics, prevent complications, promote myocardial healing, and improve outcomes in VSR patients. Advancements in minimally invasive techniques, such as percutaneous device closure, and tissue engineering hold promise for less invasive interventions and better outcomes. These approaches aim to minimize surgical morbidity, optimize healing, and enhance patient recovery. In conclusion, the management of VSR after MI requires a multidimensional approach that considers various aspects, including risk stratification, surgical timing, pharmacological interventions, minimally invasive techniques, and tissue engineering.

Efficacy of Molnupiravir for the Treatment of Mild or Moderate COVID-19 in Adults: A Meta-Analysis.

The aim of this meta-analysis is to evaluate the efficacy of molnupiravir among mild or moderate COVID-19 patients. This meta-analysis was reported according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Two authors independently performed a comprehensive search for relevant studies in PubMed, Cochrane Library, and Web of Science. The keywords used to search for relevant records were "Molnupiravir," "COVID-19," and "efficacy." This meta-analysis included studies that compared the effectiveness of molnupiravir with a placebo for COVID-19 treatment. The primary outcome assessed in this meta-analysis was the composite of hospitalization and all-cause mortality (30 days). In addition, we assessed all-cause mortality and hospitalization separately and the number of patients who tested negative for viral RNA on day five. A total of 10 studies were included in the meta-analysis. Among the 10 studies, five were randomized controlled trials and five were observational studies. Based on the results presented in the meta-analysis, it can be concluded that molnupiravir has a significant impact on reducing all-cause mortality and improving the proportion of patients who test negative for viral RNA on day five. The risk of hospitalization and composite outcome was also lower in molnupiravir-treated patients, although the difference was statistically insignificant. The subgroup analysis showed consistent results across all subgroups, indicating that the effect of molnupiravir is consistent regardless of patient characteristics.