Background Long-term effects of Coronavirus Disease of 2019 (COVID-19) and their sustainability are of the utmost relevance. We aimed to determine: 1) functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2) characteristics associated with cardiopulmonary exercise testing (CPET) performance; 3) safety and tolerability of CPET. Methods We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 discharged alive at Azienda Sanitaria Locale-3, Genoa. At 3-month from hospital discharge, complete clinical evaluation, trans-thoracic echocardiography, CPET, pulmonary function test, and dominant leg extension (DLE) maximal strength evaluation were performed. Results From 225 patients discharged from March to November 2020, we excluded 12 incomplete/missing cases, 13 unable to perform CPET leading to a final population of 200. Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3–103.1). Ninety-nine(49.5%) patients had %pVO2 below, whereas 101(50.5%) above the 85% predicted value (indicating normality). Of 61/99 patients with reduced %pVO2 but normal anaerobic threshold, 9(14.8%) had respiratory, 21(34.4%) cardiac, and 31(50.8%) non-cardiopulmonary limitation of exercise. One-hundred sixty(80.0%) patients complain at least one symptom, without relationship with pVO2. Multivariate linear regression analysis showed percent-predicted forced expiratory volume in one-second(β = 5.29, p = 0.023), percent-predicted diffusing capacity of lungs for carbon monoxide(β = 6.31, p = 0.001), and DLE maximal strength(β = 14.09, p = 0.008) independently associated with pVO2. None adverse event was reported during/after CPET neither the involved health professionals developed COVID-19. Conclusions CPET after COVID-19 is safe and about 1/3rd of COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.

Large differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS‐CoV‐2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS‐Cov‐2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT 1 R) axis associated with oxidative stress. This leads to insulin resistanceas well as lung and endothelial damage, two severe outcomes of COVID‐19. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT 1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are given: Kimchi in Korea, westernized foods and the slum paradox. It is proposed that fermented cabbage is a proof‐of‐concept of dietary manipulations that may enhance Nrf2‐associated antioxidant effects helpful in mitigating COVID‐19 severity.

IntroductionLong-term effects of Coronavirus Disease of 2019 (COVID-19) and their sustainability in a large number of patients are of the utmost relevance. We aimed to determine: 1)functional capacity of non-severe COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2)those characteristics associated with worse CPET performance.MethodsWe prospectively enrolled the first 150 consecutive subjects with laboratory-confirmed COVID-19 infection discharged alive from March to April 2020 at Azienda Sanitaria Locale (ASL)3, Genoa, Italy. At 3-month from hospital discharge, complete clinical evaluation, trans-thoracic echocardiography, cardiopulmonary exercise testing (CPET), pulmonary function test (PFT), and dominant leg extension (DLE) maximal strength evaluation were performed.ResultsExcluding severe and incomplete/missing cases, 110 patients were analyzed. Median percent predicted peak oxygen uptake (%pVO2) was 90.9(79.2-109.0)%. Thirty-eight(34.5%) patients had %pVO2 below, whereas 72(65.5%) above the 85% predicted value (indicating normality). Median PFT parameters were within normal limits.Eight(21.1%) patients had a mainly respiratory, 9(23.7%) a mainly cardiac, 3(7.9%) a mixed-cardiopulmonary, and 18(47.4%) a non-cardiopulmonary limitation of exercise. Eighty-one(73.6%) patients experimented at least one symptom, without relationship with %pVO2 (p>0.05).Multivariate linear regression analysis showed age (β=0.46, p=0.020), percent weight loss (β=-0.77, p=0.029), active smoke status (β=-7.07, p=0.019), length of hospital stay (β=-0.20, p=0.042), and DLE maximal strength (β=1.65, p=0.039) independently associated with %pVO2.ConclusionsHalf of non-severe COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, albeit cardiopulmonary causes are possible. These findings call for future research to identify patients at higher risk of long-term effects, that may benefit from careful surveillance and targeted rehabilitation.Take-home messagesat 3-month cardiopulmonary exercise testing 38/110(34.5%) non-severe COVID-19 survivors had percent predicted peak oxygen uptake (%pVO2) < 85% (indicating normality). Half of them had functional capacity limitation mainly explained by muscular impairment.