As of May 12, 2020, the SARS-CoV-2 pandemic has resulted in more than 3.5 million confirmed cases and 250,000 deaths (1) . In the US alone, there are more than 1.3 million confirmed cases, with an overall cumulative hospitalization rate of 50.3 per 100,000 (2) . In the US, the highest rates of hospitalization is in people 65 years and older (162.2 per 100,000), who contribute 80% of the 78,000 deaths (3) .
In the ongoing battle against SARS-CoV-2, much effort has focused on screening and testing effective anti-viral drugs and developing vaccines. In contrast, co-infection is largely understudied. This is problematic, as co-infection has proven to be critical in the severity of other respiratory diseases and significantly impacts patient clinical management, infection control, and antimicrobial stewardship programs.
Secondary bacterial pneumonia, a common form of co-infection, was a predominant cause of death in the 1918-1919 and the 1957-1958 influenza pandemics (4). Bacterial co-infection also was reported in approximately 20% of the 2009 H1N1 influenza patients, and was associated with poor outcome (5,6). Thus, it is reasonable to suspect significant levels of co-infection in the current pandemic. The level of co-infection is particularly important as it is reported that broadspectrum empirical antibiotics are frequently prescribed (72%) in SARS-CoV-2 patients despite a paucity of evidence of bacterial co-infection (7). A better understanding of co-infection levels in patients with SARS-CoV-2 will facilitate better evaluation of patient prognosis and allow development of more effective clinical management plans (8).
Co-infection with coronavirus, especially with its three most prominent members, SARS-CoV-1, MERS and SARS-CoV-2, has been reported only infrequently, due in part to the novel nature of this viral group (7). For SARS-CoV-2, co-infection with bacteria, other respiratory viruses, and/or fungi has been described, with a mean co-infection rate of approximately 8% across all studies (7). For example, Zhou et al. reported 15% secondary lung infection that existed in 50% of all fatal cases (9). Chen et al. reported 4% co-infection of bacteria and fungi with SARS-CoV-2 (10).
However, most studies were case reports or based on scattered available clinical information, and not designed to systematically evaluate the prevalence or the characteristics of co-infections. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Patient and facility characteristics were described by frequency and percentages. SARS-CoV-2 detection rate among the full sample, and the co-occurrence of respiratory bacteria and other respiratory viruses among SARS-CoV-2-positive patients were calculated and compared by patient characteristics using chi-square test, separately.
The overall associations between SARS-CoV-2 with respiratory bacteria and other respiratory viruses were reported by crosstab and chi-square test. The three-way detection rate of SARS-CoV-2, respiratory bacteria, and other respiratory viruses were depicted in a bar chart. The infection rate of each individual respiratory bacterium and other respiratory virus was calculated overall and compared by SARS-CoV-2-positive/negative status. Multivariate logistic regression model with robust variance at facility level to account for clustering of patients within the same facility was used to assess whether SARS-CoV-2 was independently associated with the co-All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted June 25, 2020. . https://doi.org/10.1101/2020.06.24.20138941 doi: medRxiv preprint occurrence of respiratory bacteria. Lastly, sensitivity analyses were run by excluding the patients with multiple tests to assess the robustness of the study findings. The analyses were performed using SAS version 9.4 and StataSE 16.
Patient characteristics. Capstone Healthcare tested a total of 3,586 nasopharyngeal and oropharyngeal specimens from 3,348 adult patients; 3,115 had one test, 228 had 2 tests, and 5 had Table 1 provides detailed characteristics of the study subjects. All patients were from either nursing homes (55.8%) or assisted living facilities (44.2%). The mean age was 76.9 years old, with 78.6% subjects being 65 years or older. There were 2,367 (70.7%) females and 981 (29.3%) males. Patients were mainly from three states, FL (22.5%), GA (25.1%), and NJ (24.0%).
Of the 3,348 patients, 1,413 (42.2%) tested positive for SARS-CoV-2, with no significant difference between males and females (p=0.54) ( Table 1 ). In contrast, older patients (≥ 65) tested positive more frequently than younger ones (p<0.0001). Test results also differed by facility type with more positive results from nursing homes than from assisted living facilities (<0.0001). They also differed by location (state) of the facility (<0.0001). Table 2 lists the co-occurrence of respiratory bacteria and other respiratory viruses with SARS-CoV-2, stratified by gender, age, facility type and facility location (by state). In total, of the 1,413 SARS-CoV-2-positive patients, 1,082 (76.6%) and 734 (52.2%) were detected with at least one respiratory bacterium or other respiratory virus, respectively. Patient age (p=0.005) and facility type (<0.0001) were associated with co-occurrence of SARS-CoV-2 with respiratory bacteria, but not with other respiratory viruses. Facility location was more strongly associated with respiratory bacteria (p<0.0001) than other respiratory viruses (p=0.019). (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted June 25, 2020. . https://doi.org/10.1101/2020.06.24.20138941 doi: medRxiv preprint Table 1 . Patient characteristics and SARS-CoV-2 positive rates Patient gender, age, facility type and location by state, and SARS-CoV-2 positivity status are summarized in table 1. * Indicates the states with less than 10 patients enrolled in the study.
Co-occurrences of SARS-CoV-2 with other respiratory viruses and bacteria stratified with patient gender, age, facility type and location by state are summarized in table 2. * Indicates states with less than 10 patients enrolled in the study. Table 4 . The detection rates of individual other organisms, overall and by SARS-CoV-2 status SARS-CoV-2 and a total of 32 other respiratory viruses and bacteria were tested in the study. The 32 organisms include 24 other respiratory viruses and 8 respiratory bacteria. Table 4 only lists the 8 organisms (4 other respiratory viruses and 4 respiratory bacteria) with prevalence of 1% or above. Detection and co-occurrence information for the organisms with less than 1% prevalence are listed in Supplementary Table 1 .
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted June 25, 2020. . https://doi.org/10.1101/2020.06.24.20138941 doi: medRxiv preprint Figure 1 . Frequencies of co-occurrence of SARS-CoV-2, other respiratory viruses, and respiratory bacteria All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted June 25, 2020. . https://doi.org/10.1101/2020.06.24.20138941 doi: medRxiv preprint