key: cord-0725457-w6p9xq19 authors: Huang, Y. Hanna; Huang, Jong T. title: Use of chlorhexidine to eradicate oropharyngeal SARS‐CoV‐2 in COVID‐19 patients date: 2021-04-01 journal: J Med Virol DOI: 10.1002/jmv.26954 sha: 4c3a4576166f5e4c59f67383cbcb7fec2e1094f4 doc_id: 725457 cord_uid: w6p9xq19 As public distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is underway, prevention of coronavirus disease 2019 (COVID‐19) relies on minimizing spread. In this study, chlorhexidine gluconate was investigated as a topical antimicrobial agent against SARS‐CoV‐2. This was a randomized, prospective cohort study using chlorhexidine as an oral rinse and posterior oropharyngeal spray in hospitalized COVID‐19 patients. The primary outcome was presence or absence of laboratory‐confirmed SARS‐CoV‐2 in the oral and oropharyngeal cavities after 4 days of chlorhexidine use and standard of care (study group) or standard of care only (control group). SARS‐CoV‐2 was eliminated from the oropharynx in 62.1% of patients who used chlorhexidine as an oral rinse, versus 5.5% of the control group patients. Among patients who used a combination of oral rinse and oropharyngeal spray, 86.0% eliminated oropharyngeal SARS‐CoV‐2, versus 6.3% of control patients. Chlorhexidine is a simple and safe addition to current COVID‐19 prevention guidelines and may play a significant role in reducing disease spread. admitted to the COVID-19 wards at the above hospitals between May 20, 2020, and December 15, 2020 were identified for the study. All COVID-19 diagnoses were confirmed via detection of SARS-CoV-2 in nasopharyngeal swab specimens by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) by WestPac Labs with the use of the cobas 6800 SARS-CoV-2 test (Roche Molecular Systems). The study population included patients who were able to follow instructions to use chlorhexidine as an oral rinse. Patients with nasogastric or endotracheal tubes placed were excluded from the study. Patients who were symptomatic for over a week before admission were also excluded. From this population, patients were randomly assigned to the study and control groups. Both groups received the standard of care in their treatment plans. The study group was given chlorhexidine to use as an oropharyngeal rinse while the control group was not. For each administration of chlorhexidine, a unit dose cup containing 0.5 ounces (15 ml) of commercially available chlorhexidine gluconate (0.12%) was provided to each patient. Patients were then observed to self-administer the solution as a thorough oral rinse for 30 s twice a day. After 4 days, the oropharynx was swabbed and tested for the presence of SARS-CoV-2 by rRT-PCR. Since an oral rinse alone would not reach the posterior oropharynx effectively, a chlorhexidine spray was added to the oral rinse regimen in the second study group. After the patient used chlorhexidine as an oral rinse as stated above, a provider used a spray applicator to deliver three sprays (a total of approximately 1.5 ml) of the chlorhexidine solution to the posterior oropharynx. To open the posterior pharynx, the patient was instructed to vocalize "ah" for 5 s while the solution was sprayed. This process was performed twice a day for 4 days. After 4 days of chlorhexidine administration, the oropharynx was swabbed and tested for presence of SARS-CoV-2 by rRT-PCR. A paired t-test was used to compare findings, with a significance level of .05. Fourteen nurses and one physician in the hospitals where this study was conducted followed the above chlorhexidine oral rinse with oropharyngeal spray regimen twice a day in addition to social distancing, mask wearing, and hand washing to prevent contracting COVID-19. The healthcare workers were followed for the duration of the study, and adherence to the chlorhexidine regimen and COVID-19 status was self-reported. The rate of SARS-CoV-2 infection among this group was compared to the rate of infection among all healthcare workers in their respective hospitals. 684 patients with positive SARS-CoV-2 infection were identified ( Figure 1 ). The mean onset of symptoms was 5.6 days before admission (standard deviation, 2.3; range, 1-16). 390 patients were excluded for symptom onset of greater than 6 days before admission, placement of nasogastric or endotracheal tubes, or inability to follow instructions to use chlorhexidine. 58% of the study population was male, 42% was female, and the median age was 62 years (range, 23-89). 294 patients were included in analysis, with 159 patients in the study group receiving chlorhexidine and 135 patients in the control group. All patients received the standard of care for COVID-19, which included remdesivir, anticoagulation, steroids, and oxygen therapy. There was no significant difference in response to treatment between the two groups. A total of 121 patients were included in the analysis of using chlorhexidine as an oral rinse in COVID-19 patients ( Table 1) A group of 15 healthcare workers (14 nurses and 1 physician) used chlorhexidine as an oral rinse and oropharyngeal spray twice a day as described above for the duration of the study. None were observed to develop SARS-CoV-2 infection during the course of this study. In contrast, the rate of COVID-19 among all healthcare workers in their respective hospitals during the same time period was near 50%. No adverse effects of using chlorhexidine as outlined were observed. Chlorhexidine is an antimicrobial agent that is commonly used in the preoperative preparation of skin to prevent postoperative infections, dental plaque prevention, and the prevention of ventilatorassociated pneumonia. [6] [7] [8] Due to its cationic nature, chlorhexidine has been shown to be effective in killing enveloped viruses. 9 As SARS-CoV-2 is an enveloped virus, chlorhexidine has been shown to be effective against SARS-CoV-2. 10 The data from this study show a significant elimination of SARS-CoV-2 with chlorhexidine application in the oral cavity and pharynx. In an effort to deliver chlorhexidine to the posterior oropharynx This process may be continued until the virus is naturally cleared from the body, which takes approximately 2-3 weeks. 11 For postexposure prophylaxis, the authors recommend the above chlorhexidine regimen for 2-4 days. The authors must emphasize that chlorhexidine cannot be used to treat COVID-19, and strongly caution against ingesting chlorhexidine in any attempt to eradicate the disease. This study has several limitations. First, the method of chlorhexidine application performed in this study does not reach the nasopharynx, which is a route of respiratory droplet transmission. 12 Chlorhexidine could theoretically be applied to the anterior nares, and further T A B L E 1 Detection of SARS-CoV-2 by rRT-PCR in the oropharynx of COVID-19 patients after a 4-day course of chlorhexidine oropharyngeal rinse Note: Patients in the study group used a chlorhexidine oral rinse and posterior oropharyngeal spray twice a day for 4 days. Patients in the control group received no chlorhexidine. Oropharyngeal specimens tested for presence of SARS-CoV-2 by rRT-PCR on the fourth day. P-value of chlorhexidine-treated versus control groups was <.01. study is needed to explore this topic. Second, the study was not blinded, which potentially led to biases in patient care and data reporting. Third, the study was conducted before the SARS-CoV-2 variants were identified in the United States. 13 Chlorhexidine should theoretically be effective against SARS-CoV-2 variants given its effect against enveloped viruses broadly, but variant strains were not investigated in this study. Chlorhexidine used as an oral rinse and posterior oropharyngeal spray is a simple and safe addition to the current COVID-19 prevention guidelines and may have significant effects on controlling the spread of the disease. When used with vaccination, proper social distancing, mask wearing, and hand washing, chlorhexidine may contribute to a more robust disease prevention regimen. Weekly Epidemiological Update -2 Viricidal treatments for prevention of coronavirus infection US Department of Health and Human Services, CDC Antiviral activity of reagents in mouth rinses against SARS-CoV-2 Lowering the transmission and spread of human coronavirus Strategies to prevent surgical site infections in acute care hospitals: 2014 update Chlorhexidine: is it still the gold standard? Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery Clinical significance of a high SARS-CoV-2 viral load in the saliva Viral dynamics in mild and severe cases of COVID-19 Coughs and sneezes: their role in transmission of respiratory viral infections, including SARS-CoV-2 First identified cases of SARS-CoV-2 variant B.1.1.7 in Minnesota Use of chlorhexidine to eradicate oropharyngeal SARS-CoV-2 in COVID-19 patients The authors declare that there are no conflict of interests. The data that support the findings of this study are available from the corresponding author on reasonable request. https://orcid.org/0000-0002-7949-5872