Risk of COVID-19 infection among frontline healthcare workers during the COVID-19 pandemic

Table 1 Characteristics of the healthcare workers at baseline, n (%)

Characteristic	High-risk areas (n = 366)	Low-risk areas (n = 82)
Age, mean (SD) years	31.7 (8.3)	39.9 (10.4)
Gender, male sex	201 (54.9)	32 (39.1)
Comorbidities
Presence of at least one co-morbid illness	49 (13.4)	49 (13.4)
Diabetes mellitus	17 (4.6)	8 (9.7)
Hypertension	14 (3.8)	10 (12.2)
Obstructive airway disease	31 (8.5)	9 (10.9)
Duration of work in COVID-19 areas, mean (SD) months1	13 (4.6)	1.8 (1.2)
Vaccination details2
Vaccinated against (COVID-19)2	325 (88.8)	77 (93.9)
Received two doses	288 (78.7)	65 (79.3)
Received one dose	37 (10.1)	12 (14.6)
Unvaccinated	41 (11.2)	5 (6.1)
Type of vaccine
COVISHIELD™	306 (94.2)	69 (84.4)
COVAXIN™	18 (5.5)	8 (10.4)
Sputnik V	1 (0.3)	0 (0)

¹In the low-risk areas, healthcare workers were requested to work in coronavirus disease 2019 (COVID-19) wards during the peak of the 2^nd wave when the health system was overwhelmed with a large number of patients. However, there was a significant (P < 0.001) difference of 11.3 months between the two groups: 95%CI: 10.3-12.3 months.

²Vaccination for COVID-19 started in India for healthcare workers on January 16^th, 2021 (7 months after the study started), and the status is given as of August 31^st, 2021.

All values are expressed as numbers (n) and percentages unless specified otherwise. COVID-19: Coronavirus disease 2019.

Table 2 Clinical outcomes among healthcare workers who tested positive for coronavirus disease 2019 infection during the study period, n (%)

Parameter	COVID-19-positive in high-risk areas (n = 120)	COVID-19-positive in low-risk areas (n = 22)	P value
COVID-19 positivity rate	120/366 (32.8)	22/82 (26.8)	0.17
Treated as home isolation	67 (55.8)	10 (45.5)	0.51
Hospital admission	53 (44.2)	12 (54.5)	0.58
Admission duration, mean (SD), days	7.4 (3.6)	6.5 (4)	0.22
Oxygen requirement	1 (0.01)	0	Not applicable
Ventilation (invasive or non-invasive)	0	0	-
Mortality	0	0	-

All values are expressed as number (n) and percentage, the number of patients who were admitted is high since government directives mandated admission of even mildly symptomatic patients, particularly during the first wave of the pandemic in India. COVID-19: Coronavirus disease 2019.

Table 3 Cross-sectional data of clinical infection and seropositivity rates among healthcare workers at various study time periods

Time point	Clinical infection				Nucleocapsid (N) antibody				Spike (S) antibody
	Overall	HR	LR	P value	Overall	HR	LR	P value	Overall	HR	LR	P value
Baseline
T1 (n = 283) [HR (n = 204); LR (n = 79)]	0/283 (0)	0/204 (0)	0/79 (0)	-	3/283 (1.1)	3/204 (1.5)	0/79 (0)	-	0/283 (0)	0/204 (0)	0/79 (0)	-
First wave
T2 (n = 168) [HR (n = 121); LR (n = 47)]	5/168 (3.0)	3/121 (2.5)	2/47 (4.3)	0.56	30/168 (17.9)	21/121 (17.4)	9/47 (19.1)	0.82	13/168 (7.7)	10/121 (8.3)	3/47 (6.4)	0.70
T3 (n = 214) [HR (n = 146); LR (n = 68)]	38/214 (17.8)	32/146 (21.9)	6/68 (8.8)	0.046	73/214 (34.1)	54/146 (37)	19/68 (27.9)	0.36	59/214 (27.6)	46/146 (31.5)	13/68 (19.1)	0.15
Second wave
T4 (n = 156) [HR (n = 110); LR (n = 46)]	6/156 (3.9)	5/110 (4.5)	1/46 (2.2)	0.50	70/156 (44.9)	51/110 (46.4)	19/46 (41.3)	0.72	138/156 (88.5)	98/110 (89.1)	40/46 (86.9)	0.92
T5 (n = 175) [HR (n = 122); LR (n = 53)]	29/175 (16.6)	21/122 (17.2)	8/53 (15.1)	0.77	106/175 (60.1)	77/122 (63.1)	29/53 (54.7)	0.60	172/175 (98.3)	121/122 (99.1)	51/53 (96.2)	0.11
T51 (n = 166) [HR (n = 118); LR (n = 48)]	24/166 (14.5)	17/118 (14.4)	7/48 (14.6)	0.78	100/166 (60.2)	73/118 (61.9)	27/48 (56.3)	0.42	164/166 (98.8)	117/118 (99.2)	47/48 (97.9)	0.52

¹T5 excludes healthcare workers (HCWs) who were vaccinated with COVAXIN^®.

All values are expressed as numbers (n) and percentages and indicate the number of HCWs; the number of participants varies in the different time periods since not all HCWs provided samples for antibodies at all the time points. T1 to T5 indicates the time point at which seroprevalence was assessed and clinical data was collected. Only individuals who had given at least two antibody samples, including one between T1 to T3 and the second sample at T4 or T5 were included in this analysis. Data on clinical infection represents the number of HCWs who developed clinical infection during that period. COVID-19 antibody levels for Nucleocapsid (N) and Spike (S) proteins were measured using Elecsys^® anti-severe acute respiratory syndrome-coronavirus 2. The antibody levels were considered positive if either N or S antibody levels were above the cut-off index (COI) reference limits. The nucleocapsid antibody was considered positive if COI was ≥ 1.0 U/mL and the spike antibody was considered positive if COI was ≥ 0.8 U/mL. HR: High-risk; LR: Low-risk.

Table 4 Seropositivity among COVISHIELD™ vaccinated and unvaccinated healthcare workers at T4 or T5, n (%)

Antibody positive		High-risk areas (n = 143)	Low-risk areas (n = 59)	Inference1
Nucleocapsid +	Spike +	95 (66.4)	34 (57.6)	Infection with vaccination
Nucleocapsid -	Spike +	45 (31.5)	22 (37.3)	Vaccination
Nucleocapsid +	Spike -	0 (0)	1 (1.7)	Infection
Nucleocapsid -	Spike -	3 (2.1)	2 (3.4)	Not infected or vaccinated

¹The inference must be made cautiously since all infections and vaccinations do not necessarily produce an antibody response.

All values are expressed as number (n) of healthcare workers (HCWs) and percentage, (+) indicates positive for nucleocapsid or spike antibody while (-) indicates negative for nucleocapsid or spike antibody. Coronavirus disease 2019 (COVID-19) antibody levels for Nucleocapsid (N) and Spike (S) proteins were measured using Elecsys^® anti-severe acute respiratory syndrome-coronavirus 2. The antibody levels were considered positive if either N or S antibody levels were above the cut-off index (COI) reference limits. The nucleocapsid antibody was considered positive if COI was ≥ 1.0 U/mL and the spike antibody was considered positive if COI was ≥ 0.8 U/mL. Since COVAXIN^® can elicit nucleocapsid and spike antibodies and COVISHIELD™ elicits antibodies only to the spike protein, HCWs who were vaccinated with COVAXIN^® were excluded from this analysis to distinguish the antibody response between natural infection and vaccination. Only those who provided at least two samples for antibodies with the 2^nd sample given during the 2^nd wave of COVID-19 (T4 or T5) were included in this analysis. The 11/143 (7.7%) and 5/59 (8.5%) from high-risk (HR) and low-risk (LR) groups were unvaccinated. In the sero-study group, clinical infection occurred in 31.5% (45/143) and 23.7% (14/59) in the HR and LR groups respectively (P = 0.23) during the entire study period.

Table 5 Studies on seroprevalence among healthcare workers

Ref.	Country	Period	Sample size	Sero-prevalence
Current study	India	April 2020 (T1)	283	1.1%
		June 2020 to July 2020 (T2)	168	17.9%
		October 2020 (T3)	214	34.1%
		March 2021(T4)	156	44.9%
		June 2021(T5)	175	60.1%
Milazzo et al[19]	Italy	March 2020	697	0.5%
		May 2020		5.4%
Piccoli et al[22]	Switzerland	April 16th to April 30th 2020	4726	9.6%
Shields et al[25]	United Kingdom	April 2020	545	24.4%
Rudberg et al[24]	Sweden	April 2020 to May 2020	2149	19.1%
Self et al[21]	United States	April 2020 to June 2020	3248	6%
Airoldi et al[27]	Italy	May 2020 to June 2020	2252	17.1%
Oliveira et al[20]	Brazil	June 2020	1996	5.5%
Recanatini et al[23]	Netherlands	June 2020 to July 2020	2328	13.9%
Kataria et al[28]	United States	July 2020	1743	5.5%
Prakash et al[26]	India	August 2020	1710	23.65%
Sonmezer et al[30]	Turkey	October 2020	1974	19%
Halili et al[29]	Kosovo	October 2020 to December 2020	647	17.5%
Wiggen et al[31]	United States	November 2020 to February 2021 December 2020 to February 2021	459	9.47% 17.7%
Ige et al[32]	Nigeria	December 2020 to July 2021	413	30.9%
Kanamori et al[18]	Japan	2020	3788	0.3%
		2021		1.6%
		2022		17.7%
Taher et al[33]	Saudi Arabia	June 2022 to September 2022	404	94%

The presence of nucleocapsid (N) antibodies has been taken into account for the seroprevalence across the different time periods (T1 to T5).