Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

Abstract

S ince 2002, three novel coronaviruses have emerged into human populations, causing severe respiratory disease: severe acute respiratory syndrome coronavirus (SARS-CoV) during 2002-2004; Middle East respiratory syndrome coronavirus (MERS-CoV), starting in 2012; and most recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), starting in 2019 (1,2). All 3 of these highly pathogenic coronaviruses can cause lethal respiratory disease characterized by acute atypical pneumonia. Subclinical or asymptomatic infection has been reported for both MERS-CoV and SARS-CoV-2, but the actual number of asymptomatic infections and the pathogenesis of mild cases are not well understood (3,4). Onset of clinical disease from highly pathogenic coronaviruses typically follows an incubation period of 2-14 days, beginning as mild and nonspecific influenza-like illness including fever, fatigue, rhinorrhea, or dry cough. Many patients progress to symptoms of dyspnea and atypical pneumonia, often requiring hospitalization or supportive medical intervention, including ventilation. Coronaviridae is a family of positive-sense, singlestranded RNA genome enveloped viruses that includes the genera alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus. Highly pathogenic coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 (all betacoronaviruses), likely emerged from bats, which are a diverse reservoir of alphacoronaviruses and betacoronaviruses (5-8). Cross-species transmission of MERS-CoV or similar zoonotic precursor viruses from bats to camels established an intermediate reservoir of MERS-CoV in dromedary camels (9). MERS-CoV replicates in the upper respiratory tract of camels, but camels demonstrate only mild disease signs, and a high percentage of camels are seropositive for MERS-CoV antibodies (10,11). The MERS-CoV enzootic cycle within dromedary camels likely facilitates continued emergence in humans, where animal workers and healthcare workers are at risk for occupational exposure to MERS-CoV transmission (12,13). Sporadic MERS cases on the Arabian Peninsula continue to seed outbreaks primarily in Saudi Arabia with the potential for exported MERS cases by travelers to other regions. A major outbreak of MERS occurred in 2015 in South Korea, where a single case in a traveler returning from Saudi Arabia resulted in 186 cases and an additional ≈16,000 contacts were traced to prevent viral spread (13). Outbreaks of MERS since 2012 have resulted in a total of >2,500 cases of MERS, whereas 8,096 cases were

Airborne transmission of respiratory viruses

“…Many viruses have been isolated from breath and indoor air samples, including adenovirus ( 29 , 99 ), coxsackievirus ( 100 ), influenza viruses ( 22 , 23 , 98 , 101 ), rhinovirus ( 9 , 26 – 28 ), measles virus ( 16 , 17 ), RSV ( 25 , 102 ), SARS-CoV ( 31 ), MERS-CoV ( 32 , 103 ), and SARS-CoV-2 ( 34 , 35 , 40 – 44 ) ( Table 1 ). The concentration of SARS-CoV-2 in the air of a hospital room with two COVID-19 patients was between 6 and 74 TCID 50 per liter (median tissue culture infectious dose per liter) ( 35 ).…”

What were the historical reasons for the resistance to recognizing airborne transmission during theCOVID‐19 pandemic?

“…There is also evidence for airborne transmission of rhinovirus, 141 , 142 , 143 , 144 , 145 adenovirus, 146 SARS‐CoV‐1, 110 , 147 MERS‐CoV, 148 , 149 and RSV. 150 , 151 Limited data suggest a role of airborne transmission for enteroviruses, 152 , 153 filovirus, 154 and other pathogens.…”

“…This is supported by recovery of infectious MERS‐CoV in air samples from patient wards 148 and successful experimental infection of rhesus macaques and African green monkeys using aerosol inocula. 149 …”

“…137,138 However, likely due to the same kinds of resistance as described above for other diseases, airborne transmission of influenza virus has not been widely accepted, and it is still described by WHO and CDC on their websites as a droplet/fomite disease, with no mention of airborne transmission. 139,140 There is also evidence for airborne transmission of rhinovirus, [141][142][143][144][145] adenovirus, 146 SARS-CoV-1, 110,147 MERS-CoV, 148,149 and RSV. 150,151 Limited data suggest a role of airborne transmission for enteroviruses, 152,153 filovirus, 154 and other pathogens.…”

Review of selected animal models for respiratory coronavirus infection and its application in drug research

“…The pathological changes were multifocal interstitial pneumonia, and the virus can be detected in the nose swab serum. 18 Importantly, African green monkeys also support the replication of SARS‐CoV‐2 in vivo and exhibit severe respiratory disease. African green monkeys infected with SARS‐COV‐2 showed decreased appetite, increased body temperature, and higher partial pressure of oxygen dioxide.…”