. 2021 May 10;13(5):1589. doi: 10.3390/nu13051589

Table 1.

Studies assessing the micronutrient deficiency on outcomes.

Author, Year [Ref.]	Reported Study Design, Country of Study	Population Source: Period of Data Collection	Population Size (% Men); # Subjects with ≥1 Comorbidity	Mean Age in Years (SD)	Micronutrient in Question	Blood Sampling Timepoint	Micronutrient Categories, as Defined by Study: Cut-off for Each Category, as Defined by Study			Outcome Reported [I: Incidence of COVID-19 Episode; S, Severity of COVID-19 Episode]
Author, Year [Ref.]	Reported Study Design, Country of Study	Population Source: Period of Data Collection	Population Size (% Men); # Subjects with ≥1 Comorbidity	Mean Age in Years (SD)	Micronutrient in Question	Blood Sampling Timepoint	Quintile 1	Quintile 2	Quintile 3
Baktash, 2020 [20]	Prospective cohort; UK	Hospital: 1 Mar–30 Apr 2020	105 (54.3); 54	Cases (deficient): 79.46 (89.52) Cases (non-deficient): 81.16 (7.23) Controls: 83.44 (8.08)	Vitamin D	At admission	NA: measured as a continuous outcome			I: Incidence of COVID-19 episode
Bellmann-Weiler, 2020 [21]	Retrospective cohort; Austria	Hospital: 25 Feb–20 May 2020	259 (60.6);152	68 (53–80) *	Iron	At admission (Day 1 ± 1)	No Iron deficiency (ID)	Absolute ID: TSAT <20% + Serum ferritin <100 µg/L	Functional ID: TSAT <20% + Serum ferritin >100 µg/L	S: Death during hospitalisation from COVID-19 episode S: ICU admission due to COVID-19 episode
Carpagnano, 2020 [22]	Retrospective cohort; Italy	Hospital: 11 Mar–30 Apr 2020	42 (71.4); 36	≥30 ng/mL: 64 (18) 30 >Vitamin D ≥20 ng/mL: 64 (13) 20 > Vitamin D ≥10 ng/mL: 60 (6.9) <10 ng/mL: 74 (11)	Vitamin D	≤12 h following RICU admission	NR: ≥10 ng/mL	NR: <10 ng/mL	-	S: Death during hospitalisation from COVID-19 episode S: Hospitalisation duration due to COVID-19 episode S: ICU admission due to COVID-19 episode
D’Avolio, 2020 [23]	Retrospective cohort; Switzerland	Hospital: 1 Mar–14 Apr 2019, 1 Mar–14 Apr 2020	107 (54.2); NR	73 (63–81) *	Vitamin D	<7 weeks after PCR result, overall median days from result = 3.0 (IQR:0.0 to 7.0)	NA: measured as a continuous outcome			I: Incidence of COVID-19 episode
D’Avolio, 2020 [23]	Retrospective cohort; Switzerland	NR (controls): 1 March to 14 April 2019	1377 (45.3); NR	63 (46–76) *	Vitamin D		NA: measured as a continuous outcome			I: Incidence of COVID-19 episode
Dahan, 2020 [24]	Cross-sectional; Israel	Hospital: 21 Feb–30 Mar 2020	39 (59); 22	52.46 (2.76)	Iron (Serum ferritin)	On admission	NA: measured as a continuous outcome			S: Clinical severity of COVID-19 episode at admission (defined by Report of the WHO-China Joint Mission)
Hastie, 2020 [17]	Retrospective cohort; UK	Health registries: 5 Mar–25 Apr 2020	341,484 (NR); NR	37–73 (between 2006–2010) ^#	Vitamin D	Baseline measurement taken between 2006–2010	Sufficient: ≥50 nmol/L	Insufficient: <50 nmol/L	Deficient: <25 nmol/L	S: Death from COVID-19 episode S: Hospitalisation rate due to COVID-19 infection
Hastie, 2020 [17]	Retrospective cohort; UK	Health registries: 5 Mar–25 Apr 2020	341,484 (NR); NR	37–73 (between 2006–2010) ^#	Vitamin D	Baseline measurement taken between 2006–2010	NA: measured as a continuous outcome (per 10 nmol/L)
Im, 2020 [25]	Case-control; South Korea	Hospital: Feb–Jun 2020	Cases: 50 (42); NR Controls: 150 (sex-matched to cases); NR NR	Cases: 57.5 (34.5–68) Controls: NR. but age-matched to controls	Vitamin D3	≤7 days of admission (median number of days from admission = 2 days)	No deficiency	Deficiency: ≤20 ng/dL	Severe Deficiency: ≤10 ng/dL	I: Incidence of COVID-19 episode S: Progression to respiratory related complication due to COVID-19 episode (defined by pneumonia incidence, or requiring high-flow nasal cannula, mechanical ventilator, and extracorporeal membrane oxygenation or death).
					Vitamin B6			Deficiency: ≤5 µg/L	-	S: Progression to respiratory related complication due to COVID-19 episode (defined by pneumonia incidence, or requiring high-flow nasal cannula, mechanical ventilator, and extracorporeal membrane oxygenation or death).
					Vitamin B9			Deficiency: ≤4 µg/L	-
					Selenium			Deficiency: ≤95 µg/L	-
					≥1 deficiency			Any of the above	-
Jothimani, 2020 [26]	Prospective case-control; India	Hospital: 17 May–27 May 2020	Cases: 47 (61.5); NR Controls: 45 (67.7); 0	Cases: 34 (18–77) * Controls: 32 (18–60) *	Zinc ^a	6 h from admission	No deficiency	Deficiency: ≤80 µg/L	-	I: Incidence of COVID-19 episode S: Death during hospitalisation from COVID-19 episode S: Hospitalisation duration due to COVID-19 infection S: ICU admission due to COVID-19 episode S: Progression to respiratory related complication due to COVID-19 episode (defined by ARDS development)
Karahan, 2020 [27]	Retrospective cohort; Turkey	Hospital: 1 Apr–20 May 2020	149 (54.4); 85	63.5 (15.3)	Vitamin D3	NR	Normal: ≥ 30 ng/mL	Insufficiency: 21–29 ng/mL	Deficiency: ≤20 ng/mL	S: Death during hospitalisation from COVID-19 episode S: Clinical severity of COVID-19 episode (defined by Chinese Clinical Guideline)
Liu, 2020 [28]	Retrospective cohort; China	Hospital: 9 Feb–15 Feb 2020 (follow-up till 25 Feb 2020)	107 (49); 40	68 (61–76) *	Calcium (Serum Calcium)	≤24 h from admission	Normal: 2.15–2.5 mmol/L	Hypocalcemia: <2.15 mmol/L	-	S: Composite outcome for need for mechanical ventilation, ICU admission due to COVID-19 episode, or all-cause mortality during admission
Macaya, 2020 [29]	Retrospective cohort; Spain	Hospital: 5 Mar–31 Mar 2020	80 (43.8); 50	non-severe patients: 63 (50–72) * severe patients: 75 (66–84) *	Vitamin D3	At admission or ≤3 months before admission	No deficiency: ≥20 ng/mL	Deficiency: <20 ng/mL	-	S: Composite outcome for death, ICU admission or requiring high flow oxygen (greater than nasal cannula) due to COVID-19 episode
Maghbooli, 2020 [30]	Cross-sectional; Iran	Hospital: Till 1 May 2020 (start date unspecified)	235 (61.3); NR	58.72 (15.22)	Vitamin D3	At admission	No deficiency: ≥30 ng/mL	Deficiency/ Insufficiency: <30 ng/mL	-	S: Clinical severity of COVID-19 episode (defined by Chinese Clinical Guideline) S: Hospitalisation duration due to COVID-19 infection S: ICU admission due to COVID-19 episode S: Progression to respiratory related complication due to COVID-19 episode (defined by ARDS development)
Mardani, 2020 [31]	Cross-sectional; Iran	Medical Center: Mar 2020	123 (52.8); NR	42 (NR)	Vitamin D	At admission	NA: measured as a continuous outcome			I: Incidence of COVID-19 episode S: Death from COVID-19 Episode
Meltzer, 2020 [32]	Retrospective cohort; United States	Hospital: 3 Mar–10 Apr 2020	489 (25); 261	49.2 (18.4)	Vitamin D	Baseline measurement taken within 1 year to 14 days before patient’s COVID-19 test	No deficiency: ≥20 ng/mL OR ≥18 pg/mL	Deficiency: <20 ng/mL	-	I: Incidence of COVID-19 episode
Merzon, 2020 [33]	Retrospective cohort; Israel	Medical Center: 1 Feb–30 Apr 2020	7807 (41.4); 2136	COVID-19 positive: 35.58 (0.56) COVID-19 negative: 47.35 (0.24)	Vitamin D	NR	Sufficiency: ≥30 ng/mL	Insufficiency: 29–20 ng/mL	Deficiency: <20 ng/mL	I: Incidence of COVID-19 episode
							Normal: ≥30 ng/mL	Low: < 30 ng/mL	-	I: Incidence of COVID-19 episode
							NA: measured as a continuous outcome			I: Incidence of COVID-19 episode S: Hospitalisation rate due to COVID-19 episode
Moghaddam, 2020 [34]	Cross-sectional; Germany	Hospital: NR	33 (42.4); 22	77 (38–94) *	Selenium (Serum Selenium)	Throughout hospitalisation; mean (SD) samples drawn per patient = 5.03 (4.27)	Normal: 45.7–131.6 μg/L	Deficiency: <45.7 μg/L	-	S: Death during hospitalisation from COVID-19 episode
Moghaddam, 2020 [34]	Cross-sectional; Germany	Hospital: NR	33 (42.4); 22	77 (38–94) *	Selenium (Serum Selenium)		NA: measured as a continuous outcome			S: Death during hospitalisation from COVID-19 episode
Panagiotou, 2020 [35]	Cross-sectional; UK	Hospital: NR	134 (54.5); 114	severe: 61.1 (11.8) mild: 76.4 (14.9)	Vitamin D	NR	Normal: ≥50 nmol/L	Deficient: <50 nmol/L	-	S: Death during hospitalisation from COVID-19 episode S: Clinical severity of COVID-19 episode (defined by admission to intensive therapy unit)
Pizzini, 2020 [36]	Prospective cohort; Austria	Medical Center: From 29 Apr 2020 (end date unspecified)	109 (60); 88	58 (14)	Vitamin D	8 weeks after COVID-19 diagnosis	NA: measured as a continuous outcome			S: Clinical severity of COVID-19 episode (defined by study criteria requiring hospitalisation, respiratory support or intensive care treatment)
					Calcium (Total, ionised)		NA: measured as a continuous outcome
					Iron (Serum ferritin)		NA: measured as a continuous outcome
Radujkovic, 2020 [37]	Prospective cohort; Germany	Hospital: 18 Mar–18 Jun 2020	185 (51); 77	60 (49–70) *	Vitamin D	At admission and SARS-CoV-2 testing	No deficiency: ≥12 ng/mL	Deficiency: <12 ng/mL (<30 nM)	-	S: Death during hospitalisation from COVID-19 episode (all-cause mortality) S: Progression to respiratory-related complications (defined by requiring any form of oxygen therapy) S: Hospitalisation rate from COVID-19 episode S: Composite event of mechanical invasive ventilation and/or death from COVID-19 episode
							No insufficiency: ≥20 ng/mL	Insufficiency: <20 ng/mL	-	S: Death during hospitalisation from COVID-19 episode (all-cause mortality) S: Composite event of mechanical invasive ventilation and/or death from COVID-19 episode
							NA: measured as a continuous outcome			S: Hospitalisation rate from COVID-19 episode
Raisi-Estabragh, 2020 [38]	Prospective cohort; UK	Health registries: 16 Mar–18 May 2020	4510 (48.8); 2081	COVID-19 positive: 68.11 (9.23) COVID-19 negative: 68.91 (8.72)	Vitamin D	Baseline measurement taken between 2006–2010	NA: measured as a continuous outcome			I: Incidence of COVID-19 episode
Smith, 2020 [39]	Retrospective multi-centre cohort; United States	Hospital: 1 May–30 Mar 2020	86 (0); 86	68.5 (59–74.8)	Iron (Ferritin)	At admission	NA: measured as a continuous outcome			S: Clinical severity of COVID-19 episode (defined by study criteria of hospitalisation and/or ICU admission, requiring mechanical ventilation and/or death)
Sonnweber, 2020 [40]	Prospective multi-centre cohort; Austria	Hospital: NR	109 (60); 88	58 (14)	Iron (Ferritin)	60 days (SD ± 12) after the onset of first COVID-19 symptoms	NA: measured as a continuous outcome			S: Clinical severity of COVID-19 episode (defined by study criteria of ICU admission, requiring oxygen therapy or respiratory support)
Sun, 2020 [19]	Retrospective cohort; China	NR: NR	63 (58.7); 12	Median: 47 (Range: 3–85)	Iron (Serum Ferritin)	On admission	NA: measured as a continuous outcome			S: Clinical severity of COVID-19 episode (defined by New Coronavirus Pneumonia Prevention and Control Program, 7th edition)
Wu, 2020 [41]	Retrospective cohort; China	Hospital: 25 Dec 2019–26 Jan 2020 (follow-up till 13 Feb 2020)	201 (63.7); 39	51 (43–60) *	Iron (Serum Ferritin)	≤24 h from admission	NR: >300 ng/mL	NR: ≤300 ng/mL	-	S: Death from COVID-19 episode S: Progression to respiratory-related complication due to COVID-19 episode (defined by ARDS development)
Wu, 2020 [41]	Retrospective cohort; China		201 (63.7); 39	51 (43–60) *	Iron (Serum Ferritin)	≤24 h from admission	NA: measured as a continuous outcome
Yasui, 2020 [42]	Retrospective cohort; Japan	Health Center: 24 Mar–24 May 2020	62 (54.8);	NR, but 17 (27.4%) are aged ≥65 years	Iron (Ferritin)	Multiple timepoints: on first day of hospitalisation and 2–3 days later on an empty stomach in the early morning after hospitalisation	NR: ≥300 ng/mL (male), ≥200 ng/mL (female)	NR: <300 ng/mL (male), <200 ng/mL (female)	-	S: Clinical severity of COVID-19 episode (defined by study criteria of ICU admission, requiring oxygen therapy or respiratory support)
					Iron (Ferritin)		NA: measured as a continuous outcome
					Zinc		NR: ≥70 µg/dL	NR: <70 µg/dL	-
					Zinc		NA: measured as a continuous outcome
Ye, 2020 [43]	Case-control; China	Hospital: 16 Feb–16 Mar 2020	Cases: 62 (37); 16 Controls: 80 (42); 0	Cases: 43 (32–59) * Controls: 42 (31–52) *	Vitamin D	At admission	Sufficiency: ≥75 nmol/L	Insufficiency: 50 nmol/L ≤25(OH)D <75 nmol/L	Deficiency: <50 nmol/L	S: Clinical severity of COVID-19 episode (defined by Chinese National Health Commission Guidelines (6th edition))
							Non-deficiency: ≥50 nmol/L	Deficiency: <50 nmol/L	-	I: Incidence of COVID-19 episode S: Clinical severity of COVID-19 episode (defined by Chinese National Health Commission Guidelines (6th edition))
							NA: measured as a continuous outcome
Zhao, 2020 [44]	Retrospective cohort; China	Hospital: 1 Feb–29 Feb 2020	50 (60); 17	55 (44–66) *	Iron (Pre- and post-treatment serum iron)	NR	NA: measured as a continuous outcome			S: Death from COVID-19 episode S: Clinical severity of COVID-19 episode (defined by Chinese National Health Commission Guidelines (7th edition))
Zhou, 2020 [45]	Retrospective cohort; China	Hospital: 29 Dec 2019–31 Jan 2020	191 (62.3); 91	Survivor: 52 (45–58) * Non-survivor: 69 (63–76) *	Iron (Serum Ferritin)	NR: frequency of examinations determined by treating physician	NR: >300 ng/mL	NR: ≤300 ng/mL	-	S: Death from COVID-19 episode
Zhou, 2020 [45]	Retrospective cohort; China	Hospital: 29 Dec 2019–31 Jan 2020	191 (62.3); 91	Survivor: 52 (45–58) * Non-survivor: 69 (63–76) *	Iron (Serum Ferritin)		NA: measured as a continuous outcome			S: Death from COVID-19 episode

NA, Not Applicable; NR, Not Reported; UK, United Kingdom; CKD, chronic kidney disease; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome. * median (IQR); ^# range. ^a All patients received hydroxychloroquine, antibiotics, and multivitamins, including vitamin C 500 mg twice a day and zinc 150 mg once a day (after the test).