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      Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle

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          Abstract

          Purpose

          Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone ( T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19).

          Methods

          Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO 2)/fraction of inspired oxygen (FiO 2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality.

          Results

          Subjects low T values (< 8 nmol/L; 176 cases) were significantly older ( P = 0.001) and had higher serum interleukin-6 ( P = 0.001), C-reactive protein ( P < 0.001), lactate dehydrogenase ( P < 0.001), ferritin ( P = 0.012), lower P/F ratio ( P = 0.001), increased prevalence of low T3 syndrome ( P = 0.041), acute respiratory insufficiency ( P < 0.001), more frequently need of ventilation ( P < 0.001) and higher mortality rate ( P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79–0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69–0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation.

          Conclusion

          Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40618-021-01700-7.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Post-acute COVID-19 syndrome

              Ani Nalbandian, Kartik Sehgal, Aakriti Gupta … (2021)
              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
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                Author and article information

                Contributors
                A. G. Lania:
                ORCID: http://orcid.org/0000-0001-5458-701X
                andrea.lania@hunimed.eu
                Journal
                Journal ID (nlm-ta): J Endocrinol Invest
                Journal ID (iso-abbrev): J Endocrinol Invest
                Title: Journal of Endocrinological Investigation
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 0391-4097
                ISSN (Electronic): 1720-8386
                Publication date (Electronic): 18 November 2021
                Pages: 1-10
                Affiliations
                [1 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Endocrinology, Diabetology and Medical Andrology Unit, , IRCCS Humanitas Research Hospital, ; via Manzoni 56, Rozzano, 20089 Milan, Italy
                [2 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Emergency Unit, , IRCCS Humanitas Research Hospital, ; via Manzoni 56, Rozzano, 20089 Milan, Italy
                [3 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Pneumology Unit, , IRCCS Humanitas Research Hospital, ; via Manzoni 56, Rozzano, 20089 Milan, Italy
                [4 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Nephrology Unit, , IRCCS Humanitas Research Hospital, ; via Manzoni 56, Rozzano, 20089 Milan, Italy
                [5 ]GRID grid.7548.e, ISNI 0000000121697570, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, , University of Modena and Reggio Emilia, ; Modena, Italy
                [6 ]GRID grid.452490.e, Department of Biomedical Sciences, , Humanitas University, ; via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
                Author information
                http://orcid.org/0000-0001-5458-701X
                Article
                Publisher ID: 1700
                DOI: 10.1007/s40618-021-01700-7
                PMC ID: 8600346
                PubMed ID: 34792796
                SO-VID: 8b12a73b-1e44-4939-b9d2-dc8fdf87349f
                Copyright © © Italian Society of Endocrinology (SIE) 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 9 August 2021
                Date accepted : 1 November 2021
                Categories
                Subject: Original Article

                Keywords: testosterone,sars-cov-2 infection,hypogonadism,covid-19,pneumonia,mortality
                Data availability:
                Keywords: testosterone, sars-cov-2 infection, hypogonadism, covid-19, pneumonia, mortality

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