key: cord-0735518-3m1iu9j2
authors: Singh, Awadhesh Kumar; Misra, Anoop
title: Impact of COVID-19 and comorbidities on health and economics: Focus on developing countries and India
date: 2020-08-27
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.08.032
sha: 2b517dcb38d1e7e36f6aec5a882c53489ccdd7b2
doc_id: 735518
cord_uid: 3m1iu9j2

BACKGROUND AND AIMS: Presence of comorbidities in patients with Coronavirus disease 2019 (COVID-19) have often been associated with increased in-hospital complications and mortality. Intriguingly, several developed countries with a higher quality of life have relatively higher mortality with COVID-19, compared to the middle- or low-income countries. Moreover, certain ethnic groups have shown a higher predilection to contract COVID-19, with heightened mortality. We sought to review the available literature with regards to impact of COVID-19 and comorbidities on the health and economics, especially in context to the developing countries including India. METHODS: A Boolean search was carried out in PubMed, MedRxiv and Google Scholar databases up till August 23, 2020 using the specific keywords to find the prevalence of comorbidities and its outcome in patients with COVID-19. RESULTS: All available evidence consistently suggests that presence of comorbidities is associated with a poor outcome in patients with COVID-19. Diabetes prevalence is highest in Indian COVID-19 patients compared to other countries. Majority of the patients with COVID-19 are asymptomatic ranging from 26 to 76%. CONCLUSIONS: Universal masking is the need of hour during unlock period. Low-income countries such as India, Brazil and Africa with less resources and an average socio-economic background, must adopt a strict policy for an affordable testing programs to trace, test, identify and home quarantine of asymptomatic cases. Despite the huge number of COVID-19 patients, India still has low volume research at the moment.

Since the Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan in December 2019, it has spread across every corner of the world including lowincome countries. Two low-income countries that bear the major brunt and tops the list along with USA with regards to the number of reported cases of COVID-19

include Brazil and India. Brazil has reported nearly 3.5 Million COVID-19 cases with more than 100 thousand deaths, while India has also crossed over 3.0 Million reported cases with more than 50 thousand deaths, as of August 23, 2020.

Although both Brazil and India are placed currently at second and third position respectively just after the USA with more than 6.0 Million reported cases, India is currently reporting highest number of new cases of COVID-19 day-wise, globally

[1]. Africa has crossed over 1.0 Million reported cases of COVID-19 with more than 27 thousand deaths, as of August 23, 2020 [2] . Emerging data clearly suggests, that associated comorbidities such as hypertension, diabetes, obesity, cardiovascular disease (CVD), cerebrovascular accident (CVA), chronic obstructive pulmonary disease (COPD), asthma, chronic kidney disease (CKD) and malignancy are often associated with increase in severity and or mortality in patients with COVID-19. We aimed to look at the impact of comorbidities in patients with COVID-19 across the world and present a descriptive analysis on health and economics with a special emphasis on low-income countries like India, Brazil and Africa.

A Boolean search was carried out to find the prevalence of comorbidities and its outcome in patients with COVID-19 in PubMed, MedRxiv and Google Scholar J o u r n a l P r e -p r o o f databases up till August 23, 2020 using the specific keywords that include "SARS-CoV2" OR "COVID-19", AND "risk", "severity", "mortality", "obesity", "diabetes", "hypertension", "cardiovascular disease", "chronic kidney disease", "cancer", "chronic pulmonary disease", "developing countries". Full text of all the related articles in English language with supplementary appendix were retrieved.

We selected the single largest data published from each country for the descriptive analysis that reported the prevalence and outcomes of comorbidities in patients with COVID-19. The descriptive analysis of overall result was also presented whenever meta-analysis included the pooled data of largest study representing each country that studied the prevalence of comorbidities and its outcome. We excluded smaller case series or retrospective cohort studies from the descriptive analysis whenever the largest data was available, in order to avoid overlapping. In addition, we excluded studies that did not report the prevalence of comorbidities and its outcome.

Several meta-analyses have reported the prevalence of comorbidities in patients with COVID-19 [3] [4] [5] [6] [7] [8] [9] . However, many of them have included studies only from China and notably, several Chinese studies included have apparently overlapped data that can limit any conclusions [10] . In this regard, our recent meta-analysis Table 1 summarizes the prevalence of comorbidities in patients with COVID-19 from the largest reported data from China, USA, UK, Italy, Mexico, Spain, Kuwait and India [13] [14] [15] [16] [17] [18] [19] . Unsurprisingly, diabetes prevalence is highest in Indian COVID-19 patients compared to other countries.

Interestingly, as many as 75.7% (95% CI, 73.0-80.2) patients in the study from India were asymptomatic and had no symptoms at the time of diagnosis [13] . A similar finding of disproportionately higher asymptomatic (46.3%) COVID-19 patients were also observed from Kuwait [19] . In contrast, studies from Taiwan study from Italy that analyzed and differentiated pre-symptomatic to asymptomatic cases reported a 42.5% (31.5-54.6) prevalence of asymptomatic cases [24] .

Collectively, these findings suggest a large proportion of patients with COVID-19 could be asymptomatic and therefore a due care is urgently required to recognize these cases though trace, test and treat (quarantine) approach [25] . Study has clearly shown that universal use of mask effectively reduces the chance of contracting COVID-19 amongst the health workers [26] .

The largest Chinese data found significantly increased case-fatality rate (CFR) in presence of any comorbidity. Although overall CFR was 2.3% for overall population (N=44,672), the presence of comorbidities such as CVD, diabetes, COPD, hypertension and cancer increases the CFR to 10.5%, 7.3%, 6.3%, 6.0%, . UK data also found chronic cardiac disease, COPD, CKD, obesity and liver disease to be associated with significant increase in mortality, apart from male sex and increasing age [12] . Several meta-analyses have shown a significant increase in severity and mortality in individuals with comorbidities with COVID-19, apart from increasing age [3, 4, 6, 8, 9] . Our metaanalysis that pooled the studies from China, USA and Italy found a significant 1.5 to 3-fold increase in severe COVID-19 associated with either hypertension or diabetes or CVD or COPD or CKD and or cancer. Similarly, patients with COVID-19 with CVD or hypertension or diabetes had a significantly 2-fold increase in mortality [11] . In addition, other studies from USA and UK have also found obesity to be associated with a significant increase in mortality [12, 29] .

No large published data is currently available from the developing countries with regard to the association of comorbidities to mortality. Detailed available data of 176 deceased from a total 206 reported cases of deaths as of April 10, 2020 from India found 50.5% of the deceased had one of these preexisting comorbidities, of which diabetes was present in 27.8% (49/176), hypertension in 22.1% (39/176), respiratory disease (COPD and asthma) in 13.6% (24/176) and CVD in 6.2%.

Notably, while 13% of the deceased had both diabetes and hypertension, 2.8% had all the three comorbidities (diabetes, hypertension and CVD). Thus, diabetes was the leading comorbidity present in deceased COVID-19 individuals from India [30] . A latest report of July 2, 2020 by the Integrated Disease Surveillance [36, 37] . Notwithstanding, the consistent association between BCG vaccination and reduced severity of COVID-19 observed in epidemiological explorations, there is still insufficient evidence to establish causality between BCG vaccination and protection from severe COVID-19. To this end, two randomized placebo-controlled clinical trials are currently ongoing with BCG vaccine in health workers in Holland and Australia that will determine to what extent BCG vaccination in adults can confer protection from the COVID-19 [38, 39] . Meanwhile, it appears that the "Trained immunity" gained over the years, defined as an enhancement of innate immune response due to repeated exposure to the subsequent repeated infection (viral, malarial, bacterial infections in developing countries) which is achieved through a metabolic programming of J o u r n a l P r e -p r o o f immune cells as well as epigenetic factors, along with the universal BCG vaccination that has provided cellular immunity, both combined together, might be offering some role in having less severe COVID-19, as well as lesser mortality in developing countries including India [36, 40] .

The national surveillance agencies of two countries USA (Centers for Disease Control and Prevention) and UK (Public Health England) have assessed the outcomes of COVID-19 based on ethnicity. While a systematic review from initial pre-print studies from both USA and UK found that the risk of infection, hospitalization, severe COVID-19 were higher in Blacks and Minority Ethnic (BAME) groups, the risk of mortality was also higher in BAME population in UK and in particular in Blacks in USA [41] . In addition, several recent cross-sectional, prospective-observational and retrospective studies from UK have also consistently found a significant greater mortality in BAME groups including the South Asians (Bangladeshi > Pakistani > Indians) [42] [43] [44] [45] [46] [47] . It should be recalled that migrant South Asians have been found to have a several fold increase in obesity, diabetes, heightened cardiovascular risk, associated complications and mortality from noncommunicable diseases. Moreover, the latest Morbidity and Mortality Weekly Report (MMWR) from CDC (July 17, 2020) also found that non-white and black populations are more affected with COVID-19, especially in <65 years of age [28] .

While several hypothetical reasons for the heightened rate of infection and mortality with COVID-19 in the BAME group has been hypothesized by the researchers [48, 49] , one potential contributing factor that could be the most likely explanation seems to be a higher percentage of BAME population engaged in certain occupations such as service industry or essential activities or paramedical J o u r n a l P r e -p r o o f or frontline staffs that may preclude physical distancing. Future research is further required for understanding the mechanism and further steps are needed to prevent devastating outcomes in the minor ethnic community.

The latest estimates of International diabetes federation (IDF), Diabetes Atlas 9 th edition, 2019, suggests that worldwide nearly 463 million adults in the age of 20-79 year have diabetes, of which nearly 80% of them live in low-or middle-income countries and nearly 60% of them are Asians. The estimates also found, 1 in 11 adults have diabetes and 1 in 5 of the people with diabetes in the world come from South-East Asia, and 1 in 6 adults with diabetes in the world come from India [50].

These large numbers pose a major challenge in managing diabetes during the COVID-19 pandemic. Expectedly, a large chunk of patients with diabetes have increased snacking/carbohydrate intake and decreased physical activity during the lockdown period that have resulted in weight gain and de-stabilize the glucose control which might results in a likely increase in diabetes-related complications [51] . Moreover, as per one estimate, weight gain during lockdown may increase

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