Letter: Covid-19, and vitamin D
Abstract
LINKED CONTENT
This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15764.
EDITORS,
We read with interest the article by Tian Y et al reviewing the gastrointestinal aspects of the novel coronavirus disease (Covid-19).1 As digestive endoscopists, we have adopted personal protective equipment in the endoscopy setting. Moreover, considering the importance of viral persistence in stools, we agree with the incorporation of rectal swab testing before discharging patients for identification of potential Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) positivity.
Angiotensin converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 entry into intestinal and alveolar cells.2 Subsequent dysregulation of the renin-angiotensin system may lead to massive cytokine activation resulting in potentially fatal acute respiratory distress syndrome (ARDS). Covid-19 has a mortality rate that is currently higher in Northern latitudes, with Italy the highest (11.9%). Deaths and hospitalisations have to date occurred in 5.2% and 22% of patients in Northern latitudes, in 3.1% and 9.5% close to the Equator, in 0.7% and 8.7% in Southern latitudes, respectively (Table 1). Therefore, Covid-19 outbreaks and particularly mortality exhibit a decreasing North-South gradient.
Countries | Latitude degrees | Total cases (N) | Total deaths, N (%) | Deaths/1 Million population, N |
---|---|---|---|---|
Northern Hemisphere | ||||
Russia | 65 | 3548 | 30 (0.8) | 0.3 |
Iceland | 65 | 1220 | 2 (0.2) | 12 |
Norway | 64 | 4898 | 45 (0.9) | 13 |
Finland | 63 | 1518 | 17 (1.1) | 5 |
Canada | 61 | 9731 | 129 (1.3) | 7 |
Sweden | 59 | 4947 | 239 (4.8) | 40 |
Estonia | 59 | 858 | 11 (1.3) | 11 |
Denmark | 56 | 3355 | 104 (3.1) | 31 |
UK | 55 | 29 474 | 2352 (8.0) | 73 |
Lithuania | 55 | 649 | 8 (1.2) | 5 |
Belarus | 55 | 163 | 2 (1.2) | 0.8 |
Ireland | 53 | 3447 | 85 (2.5) | 32 |
Netherlands | 52 | 13 614 | 1173 (8.6) | 103 |
Poland | 52 | 2633 | 45 (1.7) | 2 |
Germany | 51 | 78 115 | 944 (1.2) | 19 |
Belgium | 50 | 15 348 | 1011 (6.6) | 125 |
Luxembourg | 50 | 2319 | 29 (1.2) | 58 |
Czechia | 50 | 3604 | 40 (1.1) | 6 |
Ukraine | 49 | 804 | 20 (2.5) | 0.8 |
UAE | 49 | 814 | 8 (1.0) | 1 |
Slovakia | 49 | 426 | 1 (0.2) | 0.2 |
Hungary | 47 | 585 | 21 (3.6) | 4 |
Switzerland | 47 | 18 117 | 505 (2.8) | 83 |
Austria | 47 | 10 877 | 158 (1.4) | 23 |
Moldova | 47 | 423 | 5 (1.2) | 4 |
Kazakhstan | 47 | 402 | 3 (0.7) | 0.3 |
France | 46 | 56 989 | 4032 (7.1) | 116 |
Romania | 46 | 2738 | 94 (3.4) | 8 |
Slovenia | 46 | 897 | 16 (1.8) | 13 |
Croatia | 45 | 963 | 6 (0.6) | 4 |
San Marino | 44 | 236 | 28 (11.9) | 943 |
Bosnia and Herzegovina | 44 | 512 | 15 (2.9) | 7 |
Serbia | 44 | 1060 | 28 (2.6) | 6 |
Montenegro | 43 | 140 | 2 (1.4) | 3 |
Italy | 42 | 110 574 | 13 155 (11.9) | 263 |
Andorra | 42 | 390 | 14 (3.6) | 233 |
Bulgaria | 42 | 449 | 10 (2.2) | 3 |
Albania | 41 | 277 | 16 (5.8) | 7 |
North Macedonia | 41 | 354 | 11 (3.1) | 9 |
Azerbaijan | 41 | 400 | 5 (1.2) | 0.7 |
Uzbekistan | 41 | 190 | 2 (1.0) | 0.006 |
Armenia | 41 | 663 | 4 (0.6) | 2 |
USA | 40 | 215 357 | 5113 (2.4) | 29 |
Portugal | 40 | 8251 | 187 (2.3) | 29 |
Spain | 39 | 110 238 | 10 003 (9.1) | 266 |
Greece | 39 | 1415 | 51 (3.6) | 7 |
Turkey | 39 | 15 679 | 277 (1.8) | 7 |
Japan | 36 | 2384 | 57 (2.4) | 0.6 |
S. Korea | 36 | 9976 | 169 (1.7) | 4 |
Diamond Princess | 36 | 712 | 11 (1.5) | n.a. |
China | 35 | 81 589 | 3318 (4.1) | 2 |
Cyprus | 35 | 320 | 9 (2.8) | 7 |
Lebanon | 34 | 494 | 16 (3.2) | 3 |
Tunisia | 34 | 423 | 12 (2.8) | 2 |
Afghanistan | 34 | 239 | 4 (1.7) | 0.2 |
Iraq | 33 | 728 | 52 (7.1) | 2 |
Iran | 33 | 50 468 | 3160 (6.2) | 43 |
Palestine | 32 | 155 | 1 (0.6) | 0.2 |
Morocco | 31 | 676 | 39 (5.8) | 2 |
Jordan | 31 | 278 | 5 (1.8) | 0.5 |
Israel | 31 | 6211 | 31 (0.5) | 6 |
Pakistan | 30 | 2291 | 31 (1.3) | 0.2 |
Algeria | 28 | 847 | 58 (6.8) | 3 |
Egypt | 26 | 779 | 52 (6.8) | 0.8 |
Saudi Arabia | 26 | 1720 | 16 (0.9) | 1.0 |
Bahrain | 26 | 635 | 4 (0.6) | 2 |
+/− 25 Degrees Latitude | ||||
Qatar | 25 | 835 | 2 (0.2) | 1 |
Taiwan | 24 | 339 | 5 (1.5) | 0.2 |
Cuba | 23 | 212 | 6 (2.8) | 0.7 |
India | 22 | 2032 | 58 (2.8) | 0.07 |
Mexico | 22 | 1378 | 37 (2.7) | 0.6 |
Hong Kong | 22 | 802 | 4 (0.5) | 0.5 |
Oman | 21 | 231 | 1 (0.4) | 0.4 |
Dominican Republic | 18 | 1284 | 57 (4.4) | 8 |
Guadeloupe | 16 | 125 | 6 (4.8) | 17 |
Honduras | 15 | 219 | 14 (6.4) | 2 |
Martinique | 15 | 135 | 3 (2.2) | 11 |
Thailand | 15 | 1875 | 15 (0.8) | 0.3 |
Senegal | 14 | 195 | 1 (0.5) | 0.1 |
Philippines | 13 | 2633 | 107 (4.1) | 1 |
Burkina Faso | 12 | 282 | 16 (5.7) | 0.8 |
Brazil | 10 | 6931 | 244 (3.5) | 2 |
Nigeria | 10 | 174 | 2 (1.1) | 0.02 |
Costa Rica | 10 | 375 | 2 (0.5) | 0.4 |
Ghana | 8 | 195 | 5 (2.6) | 0.2 |
Panama | 8 | 1317 | 32 (2.4) | 11 |
Venezuela | 8 | 144 | 3 (2.0) | 0.2 |
Ivory Coast | 8 | 190 | 1 (0.5) | 0.1 |
Sri Lanka | 7 | 148 | 3 (2.0) | 0.2 |
Cameroon | 5 | 255 | 6 (2.3) | 0.3 |
Malaysia | 5 | 3116 | 50 (1.6) | 2 |
Brunei | 4 | 133 | 1 (0.7) | 2 |
Colombia | 3 | 1065 | 17 (1.7) | 0.7 |
Singapore | 1 | 1000 | 4 (0.4) | 1 |
Ecuador | −1 | 2758 | 98 (3.5) | 10 |
Indonesia | −2 | 1790 | 170 (9.5) | 0.7 |
DRC | −4 | 123 | 11 (8.9) | 0.2 |
Peru | −7 | 1323 | 47 (3.6) | 3 |
Mayotte | −13 | 116 | 1 (0.9) | 7 |
Bolivia | −17 | 123 | 7 (5.7) | 0.9 |
Mauritius | −20 | 161 | 7 (4.3) | 6 |
Australia | −25 | 5137 | 25 (0.5) | 1 |
Southern Hemisphere | ||||
South Africa | −29 | 1380 | 5 (0.4) | 0.2 |
Chile | −31 | 3031 | 16 (0.5) | 2 |
Argentina | −34 | 1133 | 33 (2.9) | 1 |
Uruguay | −34 | 350 | 2 (0.6) | 1 |
New Zealand | −41 | 797 | 1 (0.1) | 0.1 |
Note
- Data extracted from https://www.worldometers.info/coronavirus/ (Accessed April 2, 2020).
One explanation of this North-South gradient might be the high prevalence of older people in Northern European populations, predisposing to a higher probability of cardio-pulmonary and metabolic co-morbidities. Another possibility might be vitamin D deficiency which may also contribute to airway/gastrointestinal infectious illnesses.3 Elderly Italians display a very high prevalence of hypovitaminosis D, especially during the winter.3
Vitamin D has immuno-modulatory properties, that include downregulation of pro-inflammatory cytokines,3-7 and has been shown to attenuate lipopolysaccharide-induced acute lung injury in mice by blocking effects on the angiopoietin (Ang)-2-Tie-2 signalling pathway and on the renin-angiotensin pathway.8 Tsujino I et al have recently shown, both in a mouse model of bleomycin-induced interstitial pneumonia and in human cell lines, that vitamin D3 is locally activated in lung tissue and has a preventive effect on experimental interstitial pneumonitis.9 Although it is more likely that any protective effect of vitamin D against Covid19 is related to suppression of cytokine response and reduced severity/risk for ARDS, there is also evidence from a meta-analysis that regular oral vitamin D2/D3 intake (in doses up to 2000 IU/d without additional bolus), is safe and protective against acute respiratory tract infection, especially in subjects with vitamin D deficiency.10
It therefore seems plausible that Vitamin D prophylaxis (without over-dosing) may contribute to reducing the severity of illness caused by SARS-CoV-2, particularly in settings where hypovitaminosis D is frequent. This will include people currently living in Northern countries and those with underlying gastroenterological conditions where vitamin D deficiency is more prevalent. This may become even more important with absence of sunlight exposure as a consequence of “shut-down” measures to control the spread of Covid19. For this to be effectively implemented will require worldwide government guidelines, and further studies looking at possible impacts of vitamin D deficiency on Covid-19 outcomes are urgently needed.
ACKNOWLEDGEMENT
Declaration of personal interests: We thank everyone who is working to resolve the SARS-CoV-2 pandemic.