Estimated rates of progression to tuberculosis disease for persons infected with Mycobacterium tuberculosis in the United States.

BACKGROUND: In the United States, over 80% of tuberculosis (TB) disease cases are estimated to result from reactivation of latent TB infection (LTBI) acquired more than 2 years previously ("reactivation TB"). We estimated reactivation TB rates for the US population with LTBI, overall, by age, sex, race-ethnicity, and US-born status, and for selected comorbidities (diabetes, end-stage renal disease, and HIV). METHODS: We collated nationally representative data for 2011-2012. Reactivation TB incidence was based on TB cases reported to the National TB Surveillance System that were attributed to LTBI reactivation. Person-years at risk of reactivation TB were calculated using interferon-gamma release assay (IGRA) positivity from the National Health and Nutrition Examination Survey, published values for interferon-gamma release assay sensitivity and specificity, and population estimates from the American Community Survey. RESULTS: For persons aged ≥6 years with LTBI, the overall reactivation rate was estimated as 0.072 (95% uncertainty interval: 0.047, 0.12) per 100 person-years. Estimated reactivation rates declined with age. Compared to the overall population, estimated reactivation rates were higher for persons with diabetes (adjusted rate ratio [aRR] = 1.6 [1.5, 1.7]), end-stage renal disease (aRR = 9.8 [5.4, 19]), and HIV (aRR = 12 [10, 13]). CONCLUSIONS: In our study, individuals with LTBI faced small, non-negligible risks of reactivation TB. Risks were elevated for individuals with medical comorbidities that weaken immune function.

Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Systematic contact investigation: An essential infection prevention skill to prevent tuberculosis transmission in healthcare settings.

A systematic approach to contact investigations has long been a cornerstone of interrupting the transmission of tuberculosis in community settings. This paper describes the implementation of a systematic 10-step contact investigation within an acute care setting during a multistate outbreak of healthcare-associated tuberculosis. A systematic approach to contact investigations might have applicability to the prevention of other communicable infections within healthcare settings.

Outbreak of Multidrug-Resistant Tuberculosis - Kansas, 2021-2022.

An outbreak of multidrug-resistant (MDR) tuberculosis (TB) involved 13 persons in four households in a low-income, under-resourced urban Kansas community during November 2021-November 2022. A majority of the seven adults identified in the Kansas outbreak were born outside the United States in a country that had experienced an MDR TB outbreak with the same genotype during 2007-2009, whereas most of the six children in the Kansas outbreak were U.S.-born. Prompt identification, evaluation, and treatment of persons with MDR TB and their contacts is essential to limiting transmission.

Recommendations for Use of Video Directly Observed Therapy During Tuberculosis Treatment - United States, 2023.

U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently.

Transmission of Mycobacterium tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021-August 2022.

A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.

Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report.

BACKGROUND: Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in the USA linked to a bone graft product containing live cells derived from a single deceased donor. METHODS: In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis. FINDINGS: The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24-87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8-99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56-81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical. INTERPRETATION: Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered. FUNDING: None.

Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014-2018.

OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity.

Tuberculosis Among Native Hawaiian and Other Pacific Islander Persons: United States and U.S.-Affiliated Pacific Islands, 2010-2019.

Background: In recent years, tuberculosis (TB) incidence in the United States has declined overall but remained high among Native Hawaiian and Other Pacific Islander (NH/PI) persons. Few studies have examined the epidemiology of TB among NH/PI persons, particularly in the U.S.-Affiliated Pacific Islands (USAPI). We describe TB incidence and characteristics of NH/PI patients during 2010-2019. Methods: We used data from the National Tuberculosis Surveillance System to characterize TB cases reported among NH/PI persons born in the 50 U.S. states (defined to include District of Columbia) and the USAPI. We calculated annual TB incidence among NH/PI patients, stratified by place of birth (U.S. states or USAPI). Using Asian persons born outside the United States-persons historically grouped with NH/PI persons as one racial category-as the reference, we compared demographic, clinical, and socio-behavioral characteristics of NH/PI TB patients. Results: During 2010-2019, 4359 TB cases were reported among NH/PI patients born in the U.S. states (n=205) or the USAPI (n=4154). Median annual incidence per 100,000 persons was 6.5 cases (persons born in the U.S. states) and 150.7 cases (persons born in the USAPI). The proportion of TB patients aged <15 years was higher among NH/PI persons (U.S. states: 54%, USAPI: 24%) than among Asian persons born outside the United States (1%). Conclusions: TB incidence among NH/PI persons is high, particularly among persons born in the USAPI, emphasizing the need to enhance TB prevention strategies in these communities. Interventions should be tailored toward those who experience the highest risk, including NH/PI children and adolescents.

Tuberculosis Outbreaks in State Prisons, United States, 2011-2019.

Objectives. To understand the frequency, magnitude, geography, and characteristics of tuberculosis outbreaks in US state prisons. Methods. Using data from the National Tuberculosis Surveillance System, we identified all cases of tuberculosis during 2011 to 2019 that were reported as occurring among individuals incarcerated in a state prison at the time of diagnosis. We used whole-genome sequencing to define 3 or more cases within 2 single nucleotide polymorphisms within 3 years as clustered; we classified clusters with 6 or more cases during a 3-year period as tuberculosis outbreaks. Results. During 2011 to 2019, 566 tuberculosis cases occurred in 41 state prison systems (a median of 3 cases per state). A total of 19 tuberculosis genotype clusters comprising 134 cases were identified in 6 state prison systems; these clusters included a subset of 5 outbreaks in 2 states. Two Alabama outbreaks during 2011 to 2017 totaled 20 cases; 3 Texas outbreaks during 2014 to 2019 totaled 51 cases. Conclusions. Only Alabama and Texas reported outbreaks during the 9-year period; only Texas state prisons had ongoing transmission in 2019. Effective interventions are needed to stop tuberculosis outbreaks in Texas state prisons. (Am J Public Health. 2022;112(8):1170-1179. https://doi.org/10.2105/AJPH.2022.306864).

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Artifactual hypoglycemia in a patient with systemic sclerosis.

Artifactual hypoglycemia, defined as a discrepancy between different laboratory measurements and actual blood glucose levels, can occur due to clinical conditions affecting the capillary microcirculation leading to falsely low blood glucose assessment. Systemic sclerosis, hallmarked by auto-immunity, fibrosis of the skin and/or internal organs and small vessel vasculopathy, can interfere with capillary point-of-care (POC) glycemia measurements, leading to the misdiagnosis of hypoglycemia. We report an 87-year-old woman with recurrent, asymptomatic hypoglycemia of unknown cause. Clinical examination revealed multiple features of limited cutaneous systemic sclerosis causing microvascular damage leading to artifactual hypoglycemia. Artifactual hypoglycemia is rarely considered by physicians and knowledge of its causes is generally lacking. Early identification of causes of inaccurate glycemia assessment can prevent unnecessary investigations and treatment. In the future, continuous glucose monitoring (CGM) could become a reliable alternative for inpatient glucose monitoring.

Alleviating the burden of ion exchange brine in water treatment: From operational strategies to brine management.

Ion exchange (IX) using synthetic resins is a cost-efficient technology to cope with a wide range of contaminants in water treatment. However, implementing IX processes is constrained by the regeneration of IX resins that generates a highly concentrated brine (i.e., IX brine), the disposal of which is costly and detrimental to ecosystems. In an effort to make the application of IX resins more sustainable in water treatment, substantial research has been conducted on the optimization of IX resins operation and the management of IX brine. The present review critically evaluates the literature surrounding IX operational strategies and IX brine management which can be used to limit the negative impacts arising from IX brine. To this end, we first analyzed the physicochemical characteristics of brines from the regeneration of IX resins. Then, we critically evaluated IX operational strategies that facilitate brine management, including resin selection, contactor selection, operational modes, and regeneration strategies. Furthermore, we analyzed IX brine management strategies, including brine reuse and brine disposal (without or with treatment). Finally, a novel workflow for the IX water treatment plant design that integrates IX operational strategies and IX brine management is proposed, thereby highlighting the areas that make IX technology more sustainable for water treatment.

Evaluation of the efficacy and safety of recombinant erythropoietin on the improvement of hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the effect of recombinant erythropoietin on hospitalised COVID-19 patients. TRIAL DESIGN: Concealed, randomized, single-blinded, phase 2 controlled clinical trial with two arm parallel-group design of 20 patients allocated with 1:1 ratio and using the placebo in the control group. PARTICIPANTS: This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas, Hormozgan in Iran. All positive (PCR confirmed) COVID-19 patients ≤65 years old who have Hb≤9 and at least one of the severe COVID-19 symptoms (tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 ≤93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50% of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100) and are willing to cooperate in this project will be included in the study. Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end-stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded. INTERVENTION AND COMPARATOR: Patients will receive the standard of care (SOC) based on the treatment protocols of the Iranian National Committee of COVID-19 and recombinant erythropoietin (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous (SQ) injection three times a day for 5 days and simultaneously Enoxaparin 1 mg/kg SQ daily is also taken to prevent thrombosis in the intervention group. Patients' blood pressure, along with other vital signs, are checked regularly and at regular intervals. In the control group, patients received SOC and the placebo (distilled water) is given as a subcutaneous injection three times a day for 5 days. We use sterile water for injection (EXIRpharmaceutical company) as the placebo. To the same appearance of the placebo and the recombinant erythropoietin, they are taken in a separate room in the same size syringes and cover with labels before injection. MAIN OUTCOMES: The main outcome for this study is a composite endpoint for Patient clinical symptoms (Respiratory rate, Oxygen saturation state and arterial oxygen partial pressure ratio, Lung infiltration status, blood pressure), Laboratory tests (LDH, CRP, Lymphocyte count, Endogenous erythropoietin, and Haemoglobin level). All of these will be assessed at the beginning of the study (before the intervention) and day 5 after the intervention. The study will also evaluate side effects and how to manage them. RANDOMISATION: Eligible participants (20) will be randomized in two arms in the ratio of 1: 1 (10 per arm) by permuted block randomization method using online web-based tools. BLINDING (MASKING): Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 patients will participate in this study, who are randomly allocated to the 2 arms with a 1:1 ratio; 10 patients in the intervention group will receive SOC and recombinant erythropoietin, and 10 patients in the control group will receive SOC and placebo. TRIAL STATUS: The protocol version is 3.0, approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on 6th June 2020, with the local grant number of 990108. The expected recruitment end date was on 21th December 2020 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 17th August 2020 and the updated expected recruitment end date is 1st August 2021. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: Evaluation of the effect of recombinant erythropoietin on the improvement of COVID-19 patients, IRCT20200509047364N1, at Iranian Registry of clinical trials ( https://en.irct.ir/trial/49282 ) on 2020/08/09. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Tuberculosis Genotype Clusters and Transmission in the U.S., 2009-2018.

INTRODUCTION: In the U.S., universal genotyping of culture-confirmed tuberculosis cases facilitates cluster detection. Early recognition of the small clusters more likely to become outbreaks can help prioritize public health resources for immediate interventions. METHODS: This study used national surveillance data reported during 2009-2018 to describe incident clusters (≥3 tuberculosis cases with matching genotypes not previously reported in the same county); data were analyzed during 2020. Cox proportional hazards regression models were used to examine the patient characteristics associated with clusters doubling in size to ≥6 cases. RESULTS: During 2009-2018, a total of 1,516 incident clusters (comprising 6,577 cases) occurred in 47 U.S. states; 231 clusters had ≥6 cases. Clusters of ≥6 cases disproportionately included patients who used substances, who had recently experienced homelessness, who were incarcerated, who were U.S. born, or who self-identified as being of American Indian or Alaska Native race or of Black race. A median of 54 months elapsed between the first and the third cases in clusters that remained at 3-5 cases compared with a median of 9.5 months in clusters that grew to ≥6 cases. The longer time between the first and third cases and the presence of ≥1 patient aged ≥65 years among the first 3 cases predicted a lower hazard for accumulating ≥6 cases. CONCLUSIONS: Clusters accumulating ≥3 cases within a year should be prioritized for intervention. Effective response strategies should include plans for targeted outreach to U.S.-born individuals, incarcerated people, those experiencing homelessness, people using substances, and individuals self-identifying as being of American Indian or Alaska Native race or of Black race.

Towards Water, Sodium Chloride and Natural Organic Matter Recovery from Ion Exchange Spent Brine.

Despite the tremendous success of the application of anion exchange resins (IX) in natural organic matter (NOM) removal over conventional removal methods, the considerable amount of brine spent during its regeneration cycle makes its sustainability questionable. This polluting saline stream can be challenging to manage and costly to discharge. Alternatively, and with the recent shift in perception of resource recovery, the produced spent brine can no longer be seen as a polluting waste but as an unconventional source of water, minerals and nutrients. In this research, for the first time, we evaluated the effectiveness of an integrated monovalent selective electrodialysis (MSED) and direct contact membrane distillation (DCMD) system in IX spent brine desalination and resource recovery. Of particular interest were the effects of operating time on the characteristics of the monovalent permselective ion exchange membranes, the impact of the DCMD stack configuration on minimizing heat loss to the ambient environment and the efficacy of the recovered NaCl in the regenerating cycle of the exhausted IXs. Our findings demonstrated that although the recovered NaCl from the stand-alone MSED can restore nearly 60% ion exchange capacity of the exhausted IXs, coupling MSED with DCMD led to minimizing the consumption of fresh NaCl (in the IX regeneration cycle) significantly, the potential application of NOM in agriculture and diminishing the risk of the IX spent brine disposal. In addition, the initial characteristics of the ion permselective membranes were maintained after 24 h of MSED and the transmembrane flux was increased when the feed/hot compartment (in the DCMD stack) was encapsulated on two outer ends with coolant/permeate compartments as a result of less heat loss to the ambient environment.

State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity.

INTRODUCTION: Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. METHODS: We created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. RESULTS: We estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). CONCLUSIONS: Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.

The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to investigate the effect of Famotidine on the recovery process of COVID-19 patients. TRIAL DESIGN: This phase III randomized clinical trial was designed with two parallel arms, placebo-controlled, single-blind, and concealed allocation. PARTICIPANTS: All COVID-19 patients admitted to Shahid Mohammadi Hospital in Bandar Abbas whose PCR test results are positive for SARS-Cov-2 and sign the written consent of the study are included in the study and immunocompromised patients, end-stage renal disease, moderate renal failure (clearance Creatinine 30 to 50 ml/min) or stage 4 severe chronic kidney disease or need for dialysis (creatinine clearance lesser than 30 ml/min), history of liver disease, hepatitis C infection or alcoholism, Glucose 6 phosphate dehydrogenase deficiency(G6PD), the ratio of Alanine transaminase to Aspartate transaminase 5 times above the normal limit, history or evidence of long QT segment on Electrocardiogram, psoriasis or porphyria, pregnancy, use of oral contraceptives, Dasatinib, Neratinib, Ozanimod, Pazopanib, Rilpivirine, Siponimod and/or Tizanidine and allergies to any study drug are excluded. INTERVENTION AND COMPARATOR: Intervention group receives standard pharmacotherapy according to the treatment protocols of the National Committee of COVID-19 and oral famotidine 160 mg (Manufactured by Chemidarou Pharmaceutical Company) four times a day until the day of discharge, for a maximum of fourteen days. Comparator group receives standard drug therapy according to the treatment protocols of the National Committee of COVID-19 and placebo in the same dosage. MAIN OUTCOMES: Patients' temperature, respiration rate, oxygen saturation, lung infiltration, lactate dehydrogenase and complete blood count were measured at the baseline (before the intervention) and on day 14 after the intervention or on the discharge day. RANDOMISATION: The person who has no role in admitting patients and assigning patients to random codes preparing random sequences using online tools and by permuted block randomization method. Eligibility criteria are monitored by the person responsible for admitting patients. Codes in a random sequence are assigned to patients by the treatment team without knowing that each code is in the intervention or comparator group. Patient codes are then matched to randomly generated sequence information for interventions. BLINDING (MASKING): All participants are unaware of which group of this study they are in and after grouping patients in the groups, Patients receive Famotidine in the treatment group and receive a placebo in the control group. The lead researcher, care givers, data collectors, and outcome assessors are aware of the grouping of patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. A total of 20 patients participate in this study, which are randomly divided into two groups of 10 as intervention or control groups. TRIAL STATUS: Version 3 of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on August 2, 2020, with the local code 990245, and the recruitment started on August 17, 2020. recruitment ended on August 31, 2020. Since the recruitment ended earlier than expected (the expected recruitment end date was 21/12/2020), we submitted post recruitment but prior to publication of the results. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: The effect of Famotidine on the improvement of patients with COVID-19, IRCT20200509047364N2, at Iranian Registry of clinical trials ( https://www.irct.ir/trial/49657 ) on 17 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).