key: cord-1015446-vjg2auh7 authors: MacIntyre, C Raina; Chughtai, Abrar A; Seale, Holly; Dwyer, Dominic E; Quanyi, Wang title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS date: 2020-06-01 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.05.092 sha: a0cb2a92fd28eb89213d1e29ef0913a9f743c138 doc_id: 1015446 cord_uid: vjg2auh7 There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections. infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections. Keywords: coronavirus; masks; respirators; personal protective equipment; COVID-19 COVID-19 is caused by SARS-CoV-2, a beta-coronavirus which is genetically similar to SARS-CoV. Seasonal alpha-(NL63, 229E) and beta-(OC43, HKU1) coronaviruses cause common colds, croup and bronchiolitis. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. (1, 2) Currently, the WHO recommends surgical masks for healthcare workers (HCW) providing routine care to a COVID-19 patient, (3) whilst the US CDC (4) and ECDC (5) recommend respirators. There are several randomised controlled trials (RCT) of community mask use in well people (6) (7) (8) (9) (10) (11) (12) . Masks used in the community may provide some protection, especially if users are compliant, it is used early and it is combined with hand hygiene (6, 7, 10) . The use of masks as source control (i.e. preventing transmission by the symptomatic patient) is probably protective, (13, 14) but larger trials are needed. There are five HCW trials comparing masks and respirators, (15) (16) (17) (18) (19) with only two showing a difference in efficacy. (17, 18) Across all available trials, many tested only for influenza (7, 9) whilst others did not undertake laboratory testing at all, using clinical influenza-like illness as an outcome.(6, 15) Our trials tested for a range of viruses by multiplex PCR, including human coronaviruses. (10, 14, 18, 20) Only influenza and composite viral endpoints were presented in these trials. We reviewed the data on respiratory protection and human seasonal coronavirus infections from these four trials. In the community household trial in Australia, (10) we recruited children with influenza-like illness and studied the use of medical masks and P2 masks against control by well parents. Parents and children were tested by RT-PCR following collection of a nose and throat swab. One index child was positive for coronavirus OC43. One parent of this child, who was in the control (no mask) arm, developed infection with the same coronavirus. No parents in the medical mask or P2 mask arm developed coronavirus infection. In the two HCW trials in China (21), well HCWs wore a medical mask (n = 1064), a N95 respirator (n = 2046) or were controls (481) for four weeks while working in the hospital ward and were followed for symptom development. Symptomatic HCWs were tested by RT-PCR. There were eight coronavirus infections identified over a four-week period, one in the first trial and seven in the second trial. Across both trials, three cases (3/2043, 0.1%) were reported in the N95 respirator arm, 4/1060 (0.4%) in the medical mask arm and 1/480 (0.2%) in the control arm. CoV229E or NL63 was identified in six cases (three in the N95 respirator arm, two in the medical mask arm and one in the control arm), CoVOC43 or HKU1 was identified in one case (mask arm) and PIV1/229E/NL63 was also identified also in one case (mask arm). Although the rate of infection was lower in the N95 arm, the difference was not significant (Odds ratio 0.4, 95% confidence intervals 0.07-1.9). As most coronavirus cases (7/8) were reported in the second trial, we did a separate analysis of the second trial. There were 4/572 subjects (0.7%) in the medical mask arm and 3/1097 (0.3%) in the N95 respirator arms who developed coronavirus infection, with a risk ratio of 2.57 for medical masks (95% CI 0.5743, 11.39) but the difference was not significant (OR 0.39 (CI 0.08 to 1.75). In the source control trial, (14) 245 sick (index) patients recruited at a fever clinic in China wore a mask for one week while in the same room as their 597 household contacts. They ceased wearing the mask when symptoms ceased. There were 20 coronavirus NL63, C229E or OC43 infections in 19 index cases -11 NL63, seven C229E and one OC43/NL63 co-infection. There J o u r n a l P r e -p r o o f were 10 index cases positive for coronavirus in the mask group and 9 positive for coronavirus in the control group, including one person in the mask group who was co-infected with OC43 and NL63. No coronavirus cases were identified among the household contacts in either mask and control groups after seven days follow-up. There was some degree of mask use reported in the control group -5/9 infected index cases reported wearing a mask during the study period. In summary, despite small numbers of laboratory-confirmed coronavirus infections identified in our community, HCW and source control trials and lack of statistical significance, no coronavirus infections were transmitted in households to parents who wore P2 or surgical masks. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. A recent study from Hong Kong showed that seasonal coronaviruses can be exhaled in tidal breathing, and that this is blocked effectively by a mask. (23) For well health workers, we found there was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. A pre-publication report from China showed protection by N95 respirators for HCW treating COVID-19 patients. (22) It is important to gather more data on specific to coronaviruses, as the R0 of COVID-19 is estimated to be 2.3 compared to 1.28 for influenza, (24) so studies on influenza may not be generalizable. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections. Funding: There was no external funding involved in this research. What Do They Cause? Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA. 2020. 3. (WHO) WHO. Rational use of personal protective equipment for coronavirus disease 2019 (COVID-19). Interim guidance Interim Infection Prevention and Control Recommendations for Patients with Confirmed Coronavirus Disease 2019 (COVID-19) or Persons Under Investigation for COVID-19 in Healthcare Settings US Centers for Disease Control . 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