on the minimum infective dose of SARS-CoV-2 to identify what was the lowest range of SARS-CoV-2 dose that caused the COVID-19 in the related studies. Methods This review study was designed to encompass all the evidence related to the infective dose of COVID-19 that has been published by 25 July 2021. The authors aimed to investigate the minimum infective dose of novel coronavirus (SARS-CoV-2) and to ensure the reliability and validity of the results, the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist was applied ( Supplemental Material 1 ). Data sources The relevant literature was retrieved by a systematic search of the keywords on the online databases comprising PubMed, Web of Science, Scopus, and Cochrane, we extracted all pertinent records published from December 2019 to 25 July 2021. The search strategy contemplated numerous keyword combinations that were identified through the MeSH (medical subject headings) database or previous articles. All the search strategies were recorded in the Supplemental Material 2 , but the final search for PubMed is presented below in the query [C] (all the keywords were searched as title/abstract): A. “COVID-19” OR “SARS-CoV-2” OR “SARS-CoV2” OR “2019-nCoV” OR “Novel Coronavirus.” B. “Infective dose” OR “Infectious dose” OR “Minimum infective dose” OR “Minimum infectious dose” OR “Minimal infective dose” OR “minimum viral load” OR “minimum infectious viral load” OR “minimum infective level” OR “minimum infectious level” OR “Tissue culture infectious dose” OR “Plaque forming unit.” C. [A] AND [B]. Study selection Three independent researchers screened the retrieved studies and selected that serve the objectives of the present review by titles and abstracts. Later, the full texts of these articles were inspected carefully and based on the eligibility criteria, the most relevant studies were included in the qualitative synthesis. We included the original studies (including laboratory, animal, and The 3′ terminus of the genome encodes for structural and accessory proteins. 11 Dose means the number of particles to cause a detectable infection. For understanding viral pathogenicity, determining the number of particles that trigger infection is crucial. Low infectious doses mean that the organism is highly contagious from person to person through contact with infected surfaces. In a US study, isolation of SARS-CoV-2 from a sample of the oropharynx and nasopharynx, one patient and inoculation into Vero cells showed that SARS-CoV-2 proliferated rapidly, reaching 10 5 TCID 50 /mL within 24 h. 12 SARS-CoV-2 infection requires a minimal dose of infection because lower doses can be safe. The minimum infectious dose indicates how much virus has entered the body and caused the infection. To determine the pattern of transmission, we need the minimum infectious dose of the virus. Given the importance and necessity of the topic, we aimed to review the literature on the minimum infective dose of SARS-CoV-2 to identify what was the lowest range of SARS-CoV-2 dose that caused the COVID-19 in the related studies. Methods This review study was designed to encompass all the evidence related to the infective dose of COVID-19 that has been published by 25 July 2021. All the search strategies were recorded in the Supplemental Material 2 , but the final search for PubMed is presented below in the query [C] (all the keywords were searched as title/abstract): A. “COVID-19” OR “SARS-CoV-2” OR “SARS-CoV2” OR “2019-nCoV” OR “Novel Coronavirus.” B. “Infective dose” OR “Infectious dose” OR “Minimum infective dose” OR “Minimum infectious dose” OR “Minimal infective dose” OR “minimum viral load” OR “minimum infectious viral load” OR “minimum infective level” OR “minimum infectious level” OR “Tissue culture infectious dose” OR “Plaque forming unit.” C. [A] AND [B]. 32 Case series 2020 Japan SARS-CoV-2-positive samples N/A N/A N/A N/A SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; COVID-19: coronavirus disease 2019; qRT-PCR: quantitative real-time polymerase chain reaction; ALT: alanine aminotransferase; CRP: C-reactive protein; aPTT: activated partial thromboplastin time; CJ: conjunctivally; IT: intratracheally. The main methods for reporting the infective dose were through tissue culture infectious dose (TCID 50 ) and by counting plaque-forming units (PFU). 33 In TCID 50 , the viral dose in 5% of inoculated tissue culture made pathological changes or cell death. All the infected hamsters displayed severe systemic inflammatory responses TCID50: tissue culture infectious dose 50; PFU: plaque-forming unit; tgMice: transgenic mice; hACE2: human angiotensin converting enzyme 2; IN: intranasal; IG: intragastric; IO: intraocular; IT: intrathecal; IC: intracerebral; IP: intraperitoneal; CJ: conjunctivally; NR: not reported; DAA: Diasorin SARS-CoV-2 antigen detection assay; BAL: bronchoalveolar lavage. Human studies on infective dose of SARS-CoV-2 We found no experimental studies that assess the infective dose in human, so we included observational human studies. Also, in medium and high groups and one ferret of low group, viral RNA shedding in the upper respiratory tract was observed. At the end of study, all of the ferrets were alive. Mice A study on 23 15 showed that SARS-CoV-2 can be experimentally spread among hACE2 mice by close contact or through respiratory droplets, but it is hardly transmitted through aerosol inoculation. This could be justified by the amount of virus in the aerosol, which is less than droplets, in some cases is not even enough to cause infection; hence, a cut-off point for causing an infection known as minimum infective dose for the virus is a very useful indicator for virus infectivity in different exposure occasions. According to Basu, 16 based on a new computational strategy to quantify the infectious dose, it is estimated that the particles needed to infect humans is possibly in the order of hundreds.

Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as br