Conjunctival Swabs Reveal Higher Detection Rate Compared to Schirmer Strips for SARS-CoV-2 RNA Detection in Tears of Hospitalized COVID-19 Patients

Abstract

Purpose: To determine the prevalence of SARS-CoV-2 in tear samples and to investigate whether it correlates with ocular findings and patients’ prognosis in Brazil. Methods: Tears were collected using Schirmer strips (SS) and conjunctival swabs (CS) from patients hospitalized with laboratory-confirmed SARS-CoV-2 infection. Samples were analyzed using qRT-PCR. Demographic and clinical data, ocular symptoms, and Schirmer tests (ST) were collected from patients. Charlson Comorbidity Index (CCI) was used to rate comorbidities, and patients were monitored until hospital discharge or death. Results: There were 61 hospitalized patients, 33 of which were diagnosed with COVID-19. Within the confirmed COVID-19 patients, SARS-CoV-2 was detected in 18.2% (n = 6) of CS and 12.1% (n = 4) of SS samples. Subjective and objective parameters for dry eye syndrome (e.g., ST COVID-19: 8.3 ± 6.4mm, non-COVID-19: 8.9 ± 6.6mm, p > 0.05) were comparable between COVID-19 (n = 33) and non-COVID-19 patients (n = 28). Among the 16 COVID-19 patients exhibiting ocular symptoms, only tearing was reported significantly more frequently when tear samples were positive for SARS-CoV-2 (p < 0.05). Strikingly, patients whose tears tested positive for SARS-CoV-2 had significantly inferior CCI (pos.: 34.0 ± 31.8%, neg.: 67.6 ± 36.4%, p < 0.05) and higher mortality rates (pos.: 50.0%, neg.: 7.4%, p < 0.01). Conclusions: SARS-CoV-2 was detected with a prevalence of 18.2% on the ocular surface. Decreased CCI and increased mortality rate in the positive tear group suggests that viral detection may relate to prognosis and highlight the need of personal protective measures for healthcare professionals. Most of the patients, regardless of COVID-19 diagnosis, had low tear production and eye discomfort, possibly pointing to the need for artificial tear use during hospitalization.

Keywords: Brazil; COVID-19; SARS-CoV-2; comorbidity; dry eyes; prognosis; tears.

Figure 1

Samples were collected using Schirmer strips and conjunctival swab after hospitalization, and patients were followed until discharge or death. (A) Collection of Schirmer strips. (B) Collection of conjunctival swab. (C) Overview of timepoints of sample collection. Numbers indicate mean days and standard deviation between the indicated event and tear sample collection.

Figure 2

Nasopharyngeal swabs had lower cycle threshold values than tear samples. (A) Internal control. (B) Nucleocapsid. (C) Envelope. (D) RNA-Dependent RNA Polymerase. Colored and grey lines represent, respectively, patients with a positive and negative detection of SARS-CoV-2 in tear samples, each different colored line represent the same patient. Black line shows the cut off value for test positivity. Each dot corresponds to one patient. CS: conjunctival swab; E: envelope; IC: internal control; N: nucleocapsid; Na: nasopharynges; RdRp: RNA-dependent RNA polymerase; SS: Schirmer strip.

Figure 3

SARS-CoV-2 detection in tear samples is associated with mortality rate, Charlson Comorbidity Index, and sample collection timing. (A) Patients who had viral particles detected in tear samples had a higher mortality rate. (B) Boxplot comparing CCI and SARS-CoV-2 detection in tear samples. (C) Boxplot comparing critical periods of sample collection. Timing represents the number of days between tear collection and the events on the X-axis. *: p < 0.05. Ho.: hospitalization; Neg.: negative SARS-CoV-2 in tear samples; NS: nasopharyngeal swab; Pos.: positive SARS-CoV-2 in tear samples; SSO: systemic symptoms onset.