Results
The overall study population included 301 hospitalized patients (601 eyes). Of the 483 patients admitted to the COVID unit at the time of the study, 301 patients met the inclusion and exclusion criteria. A total of 41 patients were admitted to the intensive care unit, 135 patients were unable to adequately report previous eye events due to their clinical situation, cognitive impairment, or confusional state, and 6 patients did not give consent.
Of the 301 subjects included in the study, 180 patients (59.8%) were male and the median age was 72 years (IQ 59–82; 70 years in men and 75 years in women, P = 0.13). Overall, 35 patients (11.6%; 95% CI: 8.48–15.84) were diagnosed with acute conjunctivitis; of those, 10 (3.3%; 95% CI: 1.8–6.1) showed ocular manifestations on the day of the visit whereas 25 (8.3%; 95% CI: 5.6–12.1) reported having conjunctivitis in the previous days, seen by the primary care doctor. Upon ophthalmological examination of the 301 patients, other ocular disorders besides conjunctivitis were observed. Specifically, 3 patients presented subconjunctival hemorrhage, 4 patients had a moderate pterygion, and 2 patients had an hordeolum, which were managed with conservative treatment. In addition, a notification system was implemented for all healthcare personnel working at the COVID unit and evaluating the patients daily. Through this system, the on-call ophthalmologist was notified immediately with any new possible case of conjunctivitis until the date of discharge, which contacted the investigators.
Of the 35 cases that presented conjunctivitis, 13 cases suffered it before admission to the hospital, 12 cases in the time interval between admission and our evaluation, and 10 cases presented conjunctivitis at the time of evaluation. The main clinical characteristics found on the latter are shown in Table 1. None of the patients showed conjunctival petechiae, corneal infiltrates nor membranes or pseudomembranes.
Table 1 Clinical presentation of conjunctivitis
Overall (N = 35) Male (N = 21) Female (N = 14) P value
No. % 95% CI No. % 95% CI No. % 95% CI
Conjunctivitis Unilateral 19 54.2 37.1 70.5 10 47.7 26.7 69.3 9 64.2 35.7 85.3 0.49*
Bilateral 16 45.7 29.5 62.9 11 52.3 30.6 73.2 5 35.7 14.6 64.3
Conjunctival hyperemia Mild 28 80.0 62.6 90.5 17 80.9 57.1 93.1 11 78.5 48.1 93.5 0.99*
Moderate/severe 7 20.0 9.4 37.4 4 19.0 6.8 42.8 3 21.4 6.4 51.8
Mucopurulent discharge Mild 14 42.4 26.2 60.4 7 35.0 16.4 59.5 7 53.8 24.8 80.4 0.20*
Moderate 18 54.5 36.8 71.2 13 65.0 40.4 83.5 5 38.4 14.6 69.4
Severe 1 3.0 0.3 20.3 0 0.0 0.0 0.0 1 7.6 0.7 46.8
Tearing Yes 15 42.8 27.0 60.2 9 42.8 22.6 65.8 6 42.8 18.2 71.5 0.99*
No 20 57.1 39.7 72.9 12 57.1 34.1 77.3 8 57.1 28.4 81.7
Foreign body sensation Yes 12 34.2 20.0 52.0 8 38.1 19.0 61.6 4 28.5 9.6 60.1 0.72*
No 23 65.7 47.9 79.9 13 61.9 38.3 80.9 10 71.4 39.8 90.4
*Fisher’s exact test
The most common reported symptoms among all the 35 patients that presented conjunctivitis during the disease were mucopurulent discharge (100%; 42.8% mild, 51.4% moderate, 5.7% severe), tearing (62.8%), and foreign body sensation (57.1%). None of the patients of our study reported blurry vision associated.
The median time interval between the onset of COVID-19 symptoms and the appearance of conjunctivitis was 6 days (p25-p75: 2–13). There is no statistically significant difference in the time interval from the onset of COVID symptoms to the appearance of conjunctivitis between women and men (U Mann-Whitney; P = 0.56). According to the patient’s self-report, the median duration of ocular symptoms was 3 days (p25-p75: 1–3.5) with a minimum of 1 day and a maximum of 1 week.
Table 2 depicts the distribution of the covariates analyzed depending on the conjunctivitis status, the association between the presence of conjunctivitis, and clinical, laboratory, and radiological data.
Table 2 Clinical characteristics of patients with and without conjunctivitis
Measure All (n = 301) Conjunctivitis(n = 35, 11.6%) No conjunctivitis (n = 266, 88.4%) P value
Age, median (p25-p75) 72 (59–82) 75 (54–85) 71 (59–81) 0.38 **
Male, no. (%) 180 (59.8%) 21 (60%) 160 (60.1%) 0.98 *
Female, no. (%) 121 (40.2%) 14 (40%) 106 (39.8%) 0.98
Pneumonia, no. (%) 262 (87.0%) 29 (82.8%) 233 (87.5%) 0.42 ***
Bilateral pneumonia, no. (%) 218 (82.8%) 26 (89.6%) 192 (82.05%) 0.43 ***
Leucocytes, median (p25-p75) 7 (5–9.5) 7.7 (4.9–10.4) 7 (5–9.4) 0.56 **
Neutrophils, median (p25-p75) 5.7 (3.7–7.9) 6.4 (3.4–8.2) 3.7 (5.5–7.9) 0.55 **
Lymphocytes, median (p25-p75) 0.6 (0.4–1) 0.5 (0.3–0.9) 0.6 (0.4–1) 0.32 **
CRP, median (p25-p75) 7.22 (2.2–15.2) 6.75 (1.8–14.9) 7.25 (2.3–15.7) 0.68 **
Ferritin, median (p25-p75) 589.6 (287.3–1125.1) 548.3 (224.6–948.8) 591.8 (29.8–1150.8) 0.14 **
D-dimer, median (p25-p75) 1075 (606–2146) 1126 (577–2254) 1073.5 (622–2146) 0.89 **
Creatine, median (p25-p75) 0.81 (0.62–1.13) 0.88 (0.66–1.37) 0.805 (0.6–1.1) 0.29 **
LDH, median (p25-p75) 633 (482–8269 613 (463–886) 635.5 (482–825) 0.94 **
*Chi squared
**U Mann-Whitney
***Fisher’s exact test
LDH, lactate dehydrogenase; CRP, C-reactive protein
11.6% of the men and 10% of the women presented conjunctivitis. Twenty-one (60%) patients with conjunctivitis were male and 160 (60.1%) patients without conjunctivitis were male. The association between conjunctivitis and sex did not reach statistical signification (P = 0.98).
A total of 262 (87.0%) patients suffered from acute viral pneumonia, which was bilateral in 218 cases (82.8% of the pneumonias were bilateral). Twenty-seven (10.3%) patients with pneumonia and 6 (15.3%) patients without pneumonia presented conjunctivitis. Notwithstanding, Fisher’s exact test did not allow us to consider the association between pneumonia and conjunctivitis to be causal (P = 0.40). Likewise, the association between the laterality of the pneumonic process was not significantly associated with the presence of conjunctivitis (P = 0.18).
Table 3 illustrates the laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex.
Table 3 Laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex
Conjunctivitis No conjunctivitis
Male Female P Male Female P value
Variables p50 p25 p75 p50 p25 p75 p50 p25 p75 p50 p25 p75
Leucocytes 9 6.1 10.5 6 4 9 0.03* 7.1 5 9.45 6.6 4.9 9.1 0.58*
Neutrophils 7.4 5.2 9.1 4 3 8 0.04* 5.9 3.7 8 5.3 3.4 7.9 0.20*
Lymphocytes 0.5 0.3 0.8 1 0 1 0.68* 0.6 0.4 0.8 0.7 0.4 1.1 0.01*
PCR 9.64 2.32 14.9 4 2 12 0.34* 9.1 3.4 17.25 5.32 1.13 11.2 0.001*
Ferritin 654.2 313.9 1035.1 268 103 734 0.04* 859.6 389.5 1353.6 374.5 201.1 724.4 <0.001*
D-dimer 1700 618 4513 675 380 1127 0.01* 1088.5 663.5 2117.5 1008 512 2232 0.29*
Creatinine 1.07 0.82 2 1 1 1 0.03* 0.8 0.6 1.19 0.69 0.54 0.93 <0.001*
LDH 622 485 886 591 408 699 0.59* 635.5 491.5 794.5 640 466 871 0.62*
Variable No. (%) No. (%) No. (%) No. (%)
Pneumonia 17 (80.9%) 12 (85.7%) 0.99*** 138 (86.2%) 95 (89.6%) 0.41**
Pneumonia bilat 16 (94.1%) 10 (83.3%) 0.55*** 114 (82.0%) 78 (82.1%) 0.98**
Severity
Mild 1 (4.7%) 9 (64.2%) 0.001*** 68 (42.0%) 48 (45.2%) 0.17**
Moderate 12 (57.1%) 3 (21.4%) 53 (33.1%) 42 (39.6%)
Severe 8 (38.1%) 2 (14.2%) 39 (24.3%) 16 (15.1%)
*U Mann-Whitney
**Z-test
***Fisher’s exact test
Among the 301 patients, 41.8% were classified as mild, 36.5% cases classified as moderate, and 21.5% classified as severe disease. The biochemical profiles in men and women also showed differences between them. According to the chi-squared test, there is not a relationship between the COVID-19 severity score and the presence of conjunctivitis (P = 0.17). However, in the analysis of conjunctivitis patients by clinical severity, there were statistically significant differences by sex (Table 4). Conjunctivitis was more frequent in males with moderate clinical severity and in women classified as clinically mild.
Table 4 Differences in clinical severity by gender among all patients and those with conjunctivitis
All patients (N = 301)
Variable Male Female P value
Severity:
  1 69 (38.1%) 57 (47.5%) 0.06*
  2 65 (35.9%) 45 (37.5%)
  3 47 (25.9%) 18 (15%)
Conjunctivitis (N = 35)
Male Female P
Severity:
  1 1 (4.7%) 9 (64.2%) 0.001**
  2 12 (57.1%) 3 (21.4%)
  3 8 (38.1%) 2 (14.2%)
*Chi-squared test
**Fisher’s exact test