Genomic epidemiology of SARS-CoV-2 in Sudan: A retrospective analysis 2020-2022 (preprint)

SARS-CoV-2 was first detected in Sudan on 13th March 2020. Here, we describe the genomic epidemiology of SARS-CoV-2 in Sudan between May 2020 and April 2022 to understand the introduction and transmission of SARS-CoV-2 variants in the country. A total of 667 SARS-CoV-2 positive samples were successfully sequenced using the nCoV-19 Artic protocol on the Oxford Nanopore Technology ([≥]70% genome completeness). The genomes were compared with a select contemporaneous global dataset to determine genetic relatedness and estimate import/export events. The genomes were classified into 37 Pango lineages within the ancestral strain (107 isolates across 13 Pango lineages), Eta variant of interest (VOI) (78 isolates in 1 lineage), Alpha variant of concern (VOC) (10 isolates in 2 lineages), Beta VOC (26 isolates in 1 lineage), Delta VOC (171 isolates across 8 lineages) and Omicron VOC (242 isolates across 12 lineages). We estimated a total of 144 introductions of the observed variants from different countries across the globe. Multiple introductions of the Eta VOI, Beta VOC and Omicron VOC were observed in Sudan mainly from Europe and Africa. These findings suggest a need for continuous genomic surveillance of SARS-CoV-2 to monitor their introduction and spread consequently inform public health measures to combat SARS-CoV-2 transmission.

Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases. (preprint)

Background: COVID-19 disease is characterized by a spectrum of disease phases (mild, moderate, and severe). Each disease phase is marked by changes in omics profiles with corresponding changes in the expression of features (biosignatures). However, integrative analysis of multiple omics data from different experiments across studies to investigate biosignatures at various disease phases is limited. Exploring an integrative multi-omics profile analysis through a network approach could be used to determine biosignatures associated with specific disease phases and enable the examination of the relationships between the biosignatures. Aim: To identify and characterize biosignatures underlying various COVID-19 disease phases in an integrative multi-omics data analysis. Method: We leveraged the correlation network approach to integrate transcriptomics, metabolomics, proteomics, and lipidomics data. The World Health Organization (WHO) Ordinal Scale (WOS) was used as a disease severity reference to harmonize COVID-19 patient metadata across two studies with independent data. A unified COVID-19 knowledge graph was constructed by assembling a disease-specific interactome from the literature and databases. Disease-state omics-specific graphs were constructed by integrating multi-omics data with the unified COVID-19 knowledge graph. We expanded on the network layers of multiXrank, a random walk with restart on multilayer network algorithm, to explore disease state omics-specific graphs and perform enrichment analysis. Results: Network analysis revealed the biosignatures involved in inducing chemokines and inflammatory responses as hubs in the severe and moderate disease phases. We observed more shared biosignatures between severe and moderate disease phases as compared to mild-moderate and mild-severe disease phases. We further identified both biosignatures that discriminate between the disease states and interactions between biosignatures that are either common between or associated with COVID-19 disease phases. Interestingly, cross-layer interactions between different omics profiles increased with disease severity. Conclusion: This study identified both biosignatures of different omics types enriched in disease-related pathways and their associated interactions that are either common between or unique to mild, moderate, and severe COVID-19. These biosignatures include molecular features that underlie the observed clinical heterogeneity of COVID-19 and emphasize the need for disease-phase-specific treatment strategies. In addition, the approach implemented here can be used for other diseases.

Role of NOX4 in Modulating Alveolar Type II (AT2) Epithelial Cell Phenotype and Mitochondrial Dynamics in Hyperoxic Acute Lung Injury

Introduction: Management of acute respiratory distress including COVID-19 pneumonia involves O2 supplementation, which is lifesaving, but causes severe hyperoxic acute lung injury (HALI). AT2 cells are the most affected cell type in hyperoxia (HO). NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) in HO. NOX4, the only functionally active NOX present in mitochondria, and primarily produces H2O2 as well as mtROS has been shown to be involved in several human pathologies. Not much is known about NOX4-induced mitochondrial injury in HALI. The current study aims to determine the role of AT2 epithelial cell NOX4 in HALI and the impact of HO on the modulation of mtROS and mitochondrial dynamics in HALI. Methods: Nox4-/-Spc-Cre animals were generated using tamoxifen induction and the knockdown was validated. The Nox4- /-Spc-Cre knockout (KO) and wild type (WT) mice were exposed to room air (NO) or 95% O2 (HO) for 66h to study the structural and functional changes in the lung. Transmission Electron Microscopy (TEM) was used to study the HO-induced changes in mitochondria. Isolated primary AT2 and/ mouse lung epithelial (MLE) cell line was investigated for mtROS, mt dynamics and apoptosis. Mitochondrial injury was assessed in Nox4 WT and Nox4 silenced cells. Results: C57BL/6J WT animals subjected to HO for 66h showed increased expression of NOX4, determining the role of NOX4 in HALI. The H&E staining demonstrated significant HALI in Nox4 WT animals exposed to HO compared to Nox4 KO as determined by increased infiltration of neutrophils, alveolar wall thickening and presence of proteinaceous debris in the alveolar space. Further, increased BAL cell count and protein levels, increased AT2 cell death and elevation of the proinflammatory cytokine IL- 6 and the chemokine KC was seen in WT animals compared to Nox4 KO. Analysis of lung tissues by TEM showed mitochondrial swelling, cristae damage and mitophagy in AT2 cells due to HO. Changes in mt injury markers were also observed. HO-induced NOX4 increase in primary AT2/ MLE-12 cells resulted in increased mtROS production and apoptosis, which was reduced with Nox4 siRNA silencing. Conclusion: This study suggests that the HO induced NOX4 expression in mouse lung, and deletion of Nox4 gene in AT2 cells reduced mtROS production and apoptosis and protected the lungs from severe hyperoxic lung injury. These results suggest NOX4 as a potential target for the treatment of HALI.

Soluble signal inhibitory receptor on leukocytes-1 is released from activated neutrophils by proteinase 3 cleavage (preprint)

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human granulocytes and monocytes which dampens antimicrobial functions. We previously showed that sputum neutrophils from infants with severe respiratory syncytial virus (RSV) bronchiolitis have decreased SIRL-1 surface expression compared to blood neutrophils, and that SIRL-1 surface expression is rapidly lost from in vitro activated neutrophils. This led us to hypothesize that activated neutrophils lose SIRL-1 by ectodomain shedding. Here, we developed an ELISA and measured the concentration of soluble SIRL-1 (sSIRL-1) in RSV bronchiolitis and hospitalized COVID-19 patients, which are both characterized by neutrophilic inflammation. In line with our hypothesis, sSIRL-1 concentration was increased in sputum compared to plasma of RSV bronchiolitis patients, and in serum of hospitalized COVID-19 patients compared to control serum. In addition, we show that in vitro activated neutrophils release sSIRL-1 by proteolytic cleavage, which can be prevented by proteinase 3 inhibition. Finally, we found that SIRL-1 shedding is prevented by extracellular adherence protein (Eap) from S. aureus. Notably, we recently showed that SIRL-1 is activated by PSM3 from S. aureus, suggesting that S. aureus may counteract SIRL-1 shedding to benefit from preserved inhibitory function of SIRL-1. In conclusion, we are the first to report that SIRL-1 is released from activated neutrophils by proteinase 3 cleavage and that endogenous sSIRL-1 protein is present in vivo.

Evolution of Clinical Phenotypes of COVID-19 Patients During Intensive Care Treatment: An Unsupervised Machine Learning Analysis (preprint)

Background: Identification of distinct clinical phenotypes in critically ill COVID-19 patients could improve understanding of the disease heterogeneity and enable prognostic and predictive enrichment facilitating more personalized treatment. However, previous attempts did not take into account temporal dynamics of the disease. By including the dimension of time, we aim to gain further insights into the heterogeneity of COVID-19.Methods: We used highly granular data from 3202 adult critically ill COVID patients in the multicenter Dutch Data Warehouse that were admitted to one of 25 Dutch ICUs between February 2020 and March 2021. Parameters including demographics, clinical observations, medications, laboratory values, vital signs, and data from life support devices were selected based on relevance and availability. Twenty-one consecutive datasets were created that each covered 24 hours of ICU data for each day of ICU treatment up until day 21. After aggregation and multiple imputation of the temporal data, clinical phenotypes in each dataset were identified by performing multiple cluster analyses. Clinical phenotypes were identified by aggregating values from all patients per cluster. Both evolution of the clinical phenotypes over time and patient allocation to these clusters over time were tracked.Results: The final patient cohort consisted of 2438 critically ill COVID-19 patients with a registered ICU mortality outcome. Forty-one parameters were chosen for the cluster analysis. On admission, both a mild and a more severe clinical phenotype were found. After day 4, the severe phenotype split into an intermediate and a severe phenotype for 11 consecutive days. Heterogeneity between phenotypes appears to be strongly driven by inflammation and dead space ventilation. During the 21-day period only 8.2% and 4.6% of patients in the initial mild and severe clusters remained assigned to the same phenotype respectively. The clinical phenotype half-life was between 5 and 6 days for the mild and severe phenotypes, and about 3 days for the medium severe phenotype.Conclusions: Patients typically do not remain in the same cluster throughout intensive care treatment. This may have important implications for prognostic or predictive enrichment. Prominent dissimilarities between clinical phenotypes are predominantly driven by inflammation and dead space ventilation.

Exploring the association of androgen modulation therapy among men hospitalized with covid19: A retrospective observational study

INTRODUCTION AND OBJECTIVE: While primarily associated with prostate cancer pathogenesis, TMPRSS2 has recently been identified as a co-receptor for ACE2, the target protein used by SARSCoV2 for viral entry. This protein is primarily regulated by the androgen receptor, and this mechanism may partly explain the disproportionate burden of disease among males. We hypothesized that the use of androgen modulation therapies (AMT) such as 5-a-reductase inhibitors (5-ARI) and androgen deprivation therapy (ADT) may affect inpatient outcomes among hospitalized men with COVID-19. METHODS: In a single-center retrospective analysis in a large urban hospital system, hospitalized males with laboratory-confirmed diagnosis of COVID-19 and a history of benign prostatic hyperplasia (BPH) and/or prostate cancer was identified from February to June 2020. Men were then stratified by use of specific AMT (ADT or 5- ARI). Baseline patient and hospital characteristics were analyzed using descriptive statistics, and multivariable regression models were used to explore the association of AMT with inpatient mortality, length of hospital stay (LOS), and other ICU outcomes (ICU admission, ICU Length of Stay, Non-Invasive Mechanical Ventilation, Intubation, and ARDS). RESULTS: A total of 396 inpatients were identified, with 130 (32.8%) having prior use of AMT. Of these, a large majority used 5-ARI (n=122, 93.8%). Mean (SD) age of patients was higher for those using AMT (76.5 (10.7) vs. 71.1 (11.8) years;p<0.001). No significant differences were identified in AMT use by race, body mass index, smoking status, or Charlson Comorbidity Index. Despite adjustment for these factors, AMT use was not associated with ICU admission, ventilation status, length of ICU stay, or length of hospital stay. However, a non-significant trend of decreased mortality was identified with the use of AMT (adjusted OR: 0.56;95% CI: 0.29e1.02;p=0.06) (Table 1). CONCLUSIONS: Preliminary analysis suggests that AMT does not appear to improve inpatient outcomes among hospitalized males with COVID-19. The non-significant trend of decreased inpatient mortality, however, may be attributed to insufficient power. Future research with large sample sizes may uncover potential benefits of androgen modulation on COVID19 pathogenesis and outcomes.

Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants (preprint)

BackgroundEmerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. MethodsIn a prospective cohort of 165 SARS-CoV-2 naive health care workers, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. FindingsFour weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of BNT162b2 and mRNA-1273 (geometric mean titers (GMT) of 197 [95% CI 149-260] and 313 [95% CI 218-448], respectively), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 26 [95% CI 18-37] and 14 [95% CI 8-25] IU/ml, respectively). These findings were robust for adjustment to age and sex. VOCs neutralization was reduced in all vaccine groups, with the largest (9- to 80-fold) reduction in neutralization observed against the Omicron variant. The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. Study limitations include the lack of cellular immunity data. ConclusionsOverall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination.

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination (preprint)

Emerging SARS-CoV-2 variants pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three variants of concern (B.1.1.7, B.1.351 and P.1) in cohorts of COVID-19 patients ranging in disease severity (n = 69) and recipients of the Pfizer/BioNTech vaccine (n = 50). Spike binding and neutralization against all three VOC was substantially reduced in the majority of samples, with the largest 4-7-fold reduction in neutralization being observed against B.1.351. While hospitalized COVID-19 patients and vaccinees maintained sufficient neutralizing titers against all three VOC, 39% of non-hospitalized patients did not neutralize B.1.351. Moreover, monoclonal neutralizing antibodies (NAbs) show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1, but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOC and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOC.

Is the heparin-induced thrombocytopenia-like syndrome associated with ChAdOx vaccine related to the vaccine itself or to an autoimmune reaction to severe acute respiratory syndrome 2 coronavirus: insights and implications from previous reports in infected cases?

Prothrombotic states, similar to heparin-induced thrombocytopenia (HIT) in recipients of the ChAdOx vaccine, sounded alarm bells internationally. Equivalent episodes of HIT were detailed in several case reports of coronavirus disease 2019. This suggests a common pathogenesis and warrants a shift in the management of implicated cases.

Single-dose SARS-CoV-2 vaccine in a prospective cohort of COVID-19 patients (preprint)

Background The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection. Methods We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients. Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses. Results Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: -0.16 to -0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response. Conclusion A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

Outcome Disparities Among Men and Women With COVID-19: An Analysis of the New York City Population Cohort

BACKGROUND: Growing evidence suggests a possible sex disparity in COVID-19 disease related outcomes. OBJECTIVE: To explore the sex disparity in COVID-19 cases and outcomes using New York City (NYC) population level data. SETTING: NYC surveillance data from February 29 to June 12, 2020. PARTICIPANTS: Individuals tested for COVID-19 in metropolitan NYC.Outcome Measurements and Statistical Analysis: Outcomes of interest included rates of COVID-19 case positivity, hospitalization and death. Relative risks and case fatality rates were computed for all outcomes based on sex and were stratified by age groups. RESULTS AND LIMITATIONS: 911,310 individuals were included, of whom 434,273 (47.65%) were male and 477,037 (52.35%) were female. Men represented the majority of positive cases (n=106,275, 51.36%), a majority of hospitalizations (n=29,847, 56.44%), and a majority of deaths (n=13,054, 59.23%). Following population level adjustments for age and sex, testing rates of men and women were equivalent. The majority of positive cases and hospitalizations occurred in men for all age groups except age >75 years, and death was more likely in men of all age groups. Men were at a statistically significant greater relative risk of case positivity, hospitalization, and death across all age groups except those <18 years of age. The most significant difference for case positivity was observed in the 65–74 age group (RR 1.22, 95%CI 1.19–1.24), for hospitalization in the 45–65 age group (RR 1.85, 95% 1.80–1.90), and for death in the 18–44 age group (RR 3.30, 95% CI 2.82–3.87). Case fatality rates were greater for men in all age-matched comparisons to women. Limitations include the use of an evolving surveillance data set and absence of further demographic characteristics such as ethnographic data. CONCLUSION: Men have higher rates of COVID-19 positivity, hospitalization, and death despite greater testing of women;this trend remains after stratification by age. J Drugs Dermatol. 2020;19(10):960-967. doi:10.36849/JDD.2020.5590.

EUAdb: a resource for COVID-19 test development (preprint)

Due to the sheer number of COVID-19 (coronavirus disease 2019) cases, the prevalence of asymptomatic cases and the fact that undocumented cases appear to be significant for transmission of the causal virus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), there is an urgent need for increased SARS-CoV-2 testing capability that is both efficient and effective1. In response to the growing threat of the COVID-19 pandemic in February, 2020, the FDA (US Food and Drug Administration) began issuing Emergency Use Authorizations (EUAs) to laboratories and commercial manufacturers for the development and implementation of diagnostic tests1. So far, the gold standard assay for SARS-CoV-2 detection is the RT-qPCR (real-time quantitative polymerase chain reaction) test2. However, the authorized RT-qPCR test protocols vary widely, not only in the reagents, controls, and instruments they use, but also in the SARS-CoV-2 genes they target, what results constitute a positive SARS-CoV-2 infection, and their limit of detection (LoD). The FDA has provided a web site that lists most of the tests that have been issued EUAs, along with links to the authorization letters and summary documents describing these tests1. However, it is very challenging to use this site to compare or replicate these tests for a variety of reasons. First, at least 12 of 18 tests that were issued EUAs prior to March 31, 2020, are not listed there. Second, the data are not standardized and are only provided as longhand prose in the summary documents. Third, some details (e.g. primer sequences) are absent from several of the test descriptions. Fourth, for tests provided by commercial manufacturers, summary documents are completely missing. To address at least the first three issues, we have developed a database, EUAdb (EUAdb.org), that holds standardized information about EUA-issued tests and is focused on RT-qPCR diagnostic tests, or "high complexity molecular-based laboratory developed tests"1. By providing a standardized ontology and curated data in a relational architecture, we seek to facilitate comparability and reproducibility, with the ultimate goal of consistent, universal and high-quality testing nationwide. Here, we document the basics of the EUAdb data architecture and simple data queries. The source files can be provided to anyone who wants to modify the database for his/her own research purposes. We ask that the original source of the files be made clear and that the database not be used in its original or modified forms for commercial purposes.

Insights into the dynamics of SARS-CoV-2 pandemicvia Shannon-Fisher causality plane (preprint)

This paper performs a systematic investigation into the temporal evolution of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) pandemic considering 15 diverse countries. Based on the foundations of Information Theory, we apply the Shannon-Fisher causality plane (SFCP), to map the dynamics behavior inherent to SARS-CoV-2 and their respective locations along the (SFCP). Our results show that this dynamics varies widely along the SFCP from the lower-right region, characterized by high entropy and low degree of reliability in relation to the information extracted from the analyzed data set to the top-right region, characterized by the less entropic and high degree of reliability in relation to the information extracted from the analyzed data set. It reveals that we have three different groups of countries in controlling the SARS-CoV-2 pandemic. A country that was proactive in implementing measures such as social distancing, quarantine, orders to stay at home, testing symptomatic and asymptomatic loads and hygienic measures to limit the impacts of SARS-Cov-2 (China) and that today is clearly in    the decay phase with the number of cases tending to zero and is no longer in a pandemic situation (efficient). Moderately proactive countries, ie, implemented measures only when the spread of SARS-Cov-2 was already reaching the country (France, Germany, United Kingdom, Spain, Sweden, Italy, Ireland, USA, Austria, and Canada) (moderately efficient) and the reactive countries, which took a long time to implement the measures and/or the infection came later and as a result are not managing to reduce the number of daily cases of SARS-CoV-2 (Russia, Iran, Brazil, and India) (inefficient) and are the new epicenters of the SARS-COV-2 pandemic. Besides, we applied the Bandt Pompe permutation entropy (H) and the Fisher Information (F) to obtain the rank of the most efficient countries to the fight against the SARS-CoV-2. To the best of our knowledge, no researches have been ranking the most proactive countries in the fight against the SARS-CoV-2 dissemination.  We truly believe that the empirical results showed in this research draws new perspectives that can collaborate in the formulation of more efficient healthy public policies to combat SARS-CoV-2 spread.

A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains (preprint)

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans via the dromedary camel reservoir and can transmit between humans, most commonly via nosocomial transmission. Currently, no licensed vaccine is available. Previously we showed that vaccination of transgenic mice with ChAdOx1 MERS, encoding the MERS S protein, prevented disease upon lethal challenge. In the current study we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. Upon MERS-CoV challenge vaccinated animals were protected against respiratory injury and pneumonia and had a reduction in viral load in lung tissue of several logs. Furthermore, we did not detect MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS vaccinated animals. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Finally, we investigated the ability of ChAdOx1 MERS to protect against six different MERS-CoV strains, isolated between 2012 to 2018, from dromedary camels and humans in the Middle East and Africa. Antibodies elicited by ChAdOx1 MERS in rhesus macaques were able to neutralize all MERS-CoV strains. Vaccination of transgenic hDPP4 mice with ChAdOx1 MERS completely protected the animals against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS supported by CEPI. One Sentence Summary Prime-only vaccination with ChAdOx1 MERS provides protective immunity against HCoV-EMC/2012 replication in rhesus macaques, and a wide variety of MERS-CoV strains in mice.

Forecasting of COVID-19 Confirmed Cases in Different Countries with ARIMA Models (preprint)

The epidemic of a novel coronavirus illness (COVID-19) becomes as a global threat. The aim of this study is first to find the best prediction models for daily confirmed cases in countries with high number of confirmed cases in the world and second to predict confirmed cases with these models in order to have more readiness in healthcare systems. This study was conducted based on daily confirmed cases of COVID-19 that were collected from the official website of Johns Hopkins University from January 22th, 2020 to March 1th, 2020. Auto Regressive Integrated Moving Average (ARIMA) model was used to predict the trend of confirmed cases. Stata version 12 was used. Mainland China and Thailand had almost a stable trend. The trend of South Korea was decreasing and will become stable in near future. Iran and Italy had unstable trends. Mainland China and Thailand were successful in haltering COVID-19 epidemic. Investigating their protocol in this control like quarantine should be in the first line of other countries program