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VIEWPOINT
Year : 2020  |  Volume : 152  |  Issue : 1  |  Page : 6-8

Geographical & seasonal variation in COVID-19 related mortality


1 Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai 400 012, Maharashtra, India
2 Department of Epidemiology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai 400 012, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai 400 012, Maharashtra, India

Date of Submission18-May-2020
Date of Web Publication17-Sep-2020

Correspondence Address:
Rajendra A Badwe
Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmr.IJMR_2043_20

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How to cite this article:
Badwe RA, Dikshit R, Chaturvedi P, Gupta S. Geographical & seasonal variation in COVID-19 related mortality. Indian J Med Res 2020;152:6-8

How to cite this URL:
Badwe RA, Dikshit R, Chaturvedi P, Gupta S. Geographical & seasonal variation in COVID-19 related mortality. Indian J Med Res [serial online] 2020 [cited 2021 Apr 19];152:6-8. Available from: https://www.ijmr.org.in/text.asp?2020/152/1/6/291132

The difference in COVID-19 related mortality between India (5 per million population) and many developed countries such as Italy, France, United Kingdom and the United States (200-400 per million population) was striking[1],[2] [Figure 1]. While the number of cases is dependent on the number of tests performed and hence unreliable for comparison, the number of deaths can be more reliably compared between countries despite concerns about underreporting in some locations. In Mumbai, India, where the number of cases was highest in India and all deaths were documented, the COVID-19 mortality was 14 per million population[1],[2]. The all-cause mortality in Mumbai was reduced by 20 per cent in March 2020 compared with March 2019 and was also reduced compared with January and February 2020, indicating that the low COVID-19 related mortality was true[2],[3].
Figure 1: Time trends of COVID-19 deaths per million population in various locations. Source: Refs 1, 2.

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Studies from China[4], the Unites States[5] and Europe[6] indicate that venous thromboembolism (VTE) in major organ microcirculation is an important cause of poor gaseous exchange and death in COVID-19 patients, and D-dimer is an important predictor of mortality[7]. In the current context, we were reminded of the astute observation on venous thrombosis in the 17th edition of Bailey and Love's Short Practice of Surgery[8], “virtually unknown in Singapore and is believed to occur more frequently with the arrival of snow and ice”. This observation on the lower incidence of VTE in warmer climates is well supported by a meta-analysis[9] indicating greater predisposition to VTE in winter compared with summer and also in higher latitudes compared with closer to equator[10]. This seasonal and geographic variation in VTE could have the biological underpinning of variation in antiphospholipid antibodies (aPL), predisposing to VTE in colder climate[11]. In a randomized study from India evaluating peri-operative VTE prophylaxis, the incidence of VTE in the control arm was reported to be low[12]. The reduced predisposition to VTE in tropical countries is also seen in other contexts such as thrombotic complications of tamoxifen[13]. At our tertiary cancer centre at Mumbai, where annually about 20,000 women are on tamoxifen, the incidence of new VTE in such patients is <5 per annum (unpublished data). Identical observations have been reported from another cancer centre in India[14].

The aPLs have been found to be associated with COVID-19 related morbidity[15],[16]. These studies have reported the presence of anticardiolipin IgA, anti-β2-glycoprotein IgA and IgG and lupus anticoagulant associated with clinical thrombosis in some patients. These studies are not definitive because aPL can be present in other acute illnesses[17]. However, the association of thrombotic phenomenon with severe illness in COVID-19 combined with the presence of these antibodies in some of the patients point towards a pathogenetic association. The role of aPLs in inducing the macrophage activation syndrome-like state associated with possible immunothrombosis in the pulmonary vasculature in COVID-19 patients[18] remains to be elucidated. The geographic variation in COVID-19 mortality could be explained, at least in part, by the seasonal variation in aPL and the consequent propensity to VTE, further accentuated by COVID-19-induced increase in aPL. It may not be too optimistic to expect the seasonal variation in aPL and VTE to reduce mortality as we move closer to summer. Germline genetic associations of variation in aPL antibody prevalence in countries with low versus high COVID-19 population mortality could also be explored[19]. The striking geographic differences in mortality provide a unique opportunity for gaining insights into the pathophysiology of COVID-19 and possible solutions. It is likely that other differences such as those in age, comorbidity burden and other as yet unknown factors could account for the difference in population-level mortality between India and Western countries. Moreover, long-term data, when available, will allow more definitive conclusions about the final toll of this infection in various populations and account for possible differences in the stage of epidemic curve.

The lower population-level mortality from COVID-19 in India could form the basis of reducing the widespread anxiety related to this disease and for undertaking nuanced social-distancing measures and personal protective measures without enforcing strict lockdowns.

Conflicts of Interest: None.

 
   References Top

1.
The Github COVID-19 Repository. Available from: https://github.com/owid/covid-19-data/tree/master/public/data, accessed on May 2, 2020.  Back to cited text no. 1
    
2.
Brihanmumbai Municipal Corporation. Stop coronavirus in Mumbai. Available from: http://stopcoronavirus.mcgm.gov.in/about-coronavirus, accessed on April 11, 2020.  Back to cited text no. 2
    
3.
Iyer M, Mahamulkar S. BMC checking pneumonia, respiratory distress updates. The Times of India; March 22, 2020. Available from: https://timesofindia.indiatimes.com/city/mumbai/bmc-checking-pneumonia-respiratory-distressupdates/articleshow/74754556.cms, accessed on May 8, 2020.  Back to cited text no. 3
    
4.
Wang T, Chen R, Liu C, Liang W, Guan W, Tang R, et al. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol 2020; 7 : e362-3.   Back to cited text no. 4
    
5.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 2020; 383 : 120-8.  Back to cited text no. 5
    
6.
Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020; 18 : 1743-6.  Back to cited text no. 6
    
7.
Oudkerk M, Büller HR, Kuijpers D, Es N, Oudkerk SF, McLoud TC, et al. Diagnosis, prevention, and treatment of thromboembolic complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology 2020; 2016 : 29.  Back to cited text no. 7
    
8.
Bailey H, Love RJM. Veins. Bailey and Love's Short Practice of Surgery. 17th ed. London: H.K. Lewis & Co. Ltd.; 1977. p. 162-72.  Back to cited text no. 8
    
9.
Zhao H, Li Y, Wu M, Ren W, Ji C, Miao H, et al. Seasonal variation in the frequency of venous thromboembolism: An updated result of a meta-analysis and systemic review. Phlebology 2020; 35 : 480-94.  Back to cited text no. 9
    
10.
Damnjanović Z, Jovanović M, Stojanović M. Correlation between the climatic factors and the pathogenesis of deep vein thrombosis. Hippokratia 2013; 17 : 203-6.  Back to cited text no. 10
    
11.
Luong TH, Rand JH, Wu XX, Godbold JH, Gascon-Lema M, Tuhrim S. Seasonal distribution of antiphospholipid antibodies. Stroke 2001; 32 : 1707-11.  Back to cited text no. 11
    
12.
Shukla PJ, Siddachari R, Ahire S, Arya S, Ramani S, Barreto SG, et al. Postoperative deep vein thrombosis in patients with colorectal cancer. Indian J Gastroenterol 2008; 27 : 71-3.  Back to cited text no. 12
    
13.
Chen TW, Chen HM, Lin CH, Huang CS, Cheng AL, Lai MS, et al. No increased venous thromboembolism risk in Asian breast cancer patients receiving adjuvant tamoxifen. BreastCancer Res Treat 2014; 148 : 135-42.  Back to cited text no. 13
    
14.
Ashraf M, Biswas J, Majumdar S, Nayak S, Alam N, Mukherjee KK, et al. Tamoxifen use in Indian women-adverse effects revisited. Asian Pac J Cancer Prev 2009; 10 : 609-12.  Back to cited text no. 14
    
15.
Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, et al. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med 2020; 382 : e38.  Back to cited text no. 15
    
16.
Harzallah I, Debliquis A, Drenou B. Lupus anticoagulant is frequent in patients with COVID-19. J Thromb Haemost 2020; 10.1111/jth.14867.   Back to cited text no. 16
    
17.
Asherson RA, Cervera R. Antiphospholipid antibodies and infections. Ann Rheum Dis 2003; 62 : 388-93.  Back to cited text no. 17
    
18.
McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol 2020; 2 : e437-45.  Back to cited text no. 18
    
19.
Ochoa E, Iriondo M, Bielsa A, Ruiz-Irastorza G, Estonba A, Zubiaga AM. Thrombotic antiphospholipid syndrome shows strong haplotypic association with SH2B3-ATXN2 locus. PLoS One 2013; 8 : e67897.  Back to cited text no. 19
    


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