Four different endemic coronaviruses (eCoVs) are etiologic agents for the seasonal common cold, and these eCoVs share extensive sequence homology with human SARS coronavirus 2 (SARS-CoV-2). Here, we show that individuals with, as compared with those without, a recent documented infection with eCoV were tested at greater frequency for respiratory infections but had a similar rate of SARS-CoV-2 acquisition. Importantly, the patients with a previously detected eCoV had less-severe coronavirus disease 2019 (COVID-19) illness. Our observations suggest that preexisting immune responses against endemic human coronaviruses can mitigate disease manifestations from SARS-CoV-2 infection.

Almost 800 million people are chronically undernourished worldwide, 98% of them in low and middle-income countries where tuberculosis (TB) is endemic. In many TB-endemic countries, undernutrition is a driver of TB incidence and associated with a high population attributable fraction of TB and poor treatment outcomes. Data suggest that undernutrition impairs innate and adaptive immune responses needed to control Mycobacterium tuberculosis (Mtb) infection and may affect responses to live vaccines such as Bacillus Calmette-Guérin (BCG). Given its impact on TB, addressing undernutrition will be a vital component of the End-TB strategy. This narrative review describes the effect of undernutrition on the immune response, vaccine response, and TB incidence, severity, and treatment outcomes.

Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined. We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at 5 sites from 2015–2019. Using multivariable Poisson regression, we assessed associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after 2 months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion. Severe undernutrition (BMI <16 kg/m²) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR], 2.05; 95% confidence interval [CI], 1.42–2.91 and aIRR, 2.20; 95% CI, 1.16–3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR, 1.81; 95% CI, 1.27–2.61). Severe stunting (height-for-age z score <−3) was associated with unfavorable outcomes (aIRR, 1.52; 95% CI, 1.00–2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a 4- and 5-fold higher rate of death, respectively. Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need to address this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

Tuberculosis (TB) is a major cause of death worldwide, with 1.5 million deaths in 2020. While TB incidence and mortality had previously been on a downwards trend, in 2020, TB mortality actually rose for the first time in a decade, largely due to the COVID-19 pandemic. Undernutrition is the leading risk factor for TB, with a population attributable fraction (PAF) of 15%, compared to 7.6% for HIV. Individuals who are undernourished are more likely to develop active TB compared to those with a healthy bodyweight. They are also more likely to have greater severity of TB, and less likely to have successful TB treatment outcomes. The likelihood of TB mortality significantly increases as weight decreases. Nutritional interventions are likely to improve both nutritional status and TB treatment success, thereby decreasing TB mortality. However, many previous studies focusing on nutritional interventions have provided insufficient calories or been underpowered. Nutritional supplementation will be particularly important as factors such as the COVID-19 pandemic, climate change, and political conflict further threaten food security. The global TB elimination effort can no longer afford to ignore undernutrition.