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The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2., This work was primarily supported by a grant from the Health Department of the Government of Catalonia (DGRIS 1_5). This work was additionally supported in part by the Spanish Health Institute Carlos III (ISCIII, PI17/01470; PI19CIII/00004; PI21CIII/00025 and COV20-00679 (MPY 222-20)), the Spanish Secretariat of Science and Innovation and FEDER funds (grant RTI2018-101082-B-I00 [MINECO/FEDER]), the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007 and RD16CIII/0002/0001), the European Regional Development Fund (ERDF), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 201814- 10FMTV3), the Gilead fellowships GLD19/00084 and GLD18/00008 and the Becas Taller Argal 2020. M.J.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). N.M. is supported by a Ph.D. fellowship from the Vall d’Hebron Institut de Recerca (VHIR). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

The mechanistic pathways leading to immune dysregulation and complications driven by uncontrolled severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remain major challenges.1, 2 Hence, a detailed analysis of the proteome, metabolome and lipidome profile of coronavirus disease 2019 (COVID-19) patients showing different severity grades might shed light on the disease pathophysiology and unveil new predictive biomarkers to promptly ascertain patient's outcomes. Our COVID-19 study cohort included 273 SARS-CoV-2 infected individuals recruited during the first wave (March–April 2020) in three different hospitals and grouped by the disease severity following the medical inclusion criteria3 in mild, severe or critical (Figure 1A), from whom demographic, preexisting clinical conditions and COVID-19 treatments are summarized in Table S1. The greatest significant differences were observed between mild and critically ill patients. These findings indicated that older individuals with comorbidities such as hypertension, obesity, diabetes and cardiovascular disorders, mostly presenting dyspnea (Figure 1B), may be at higher risk of suffering from severe respiratory distress with subsequent oxygen and drug requirements and, eventually, died. Similarly, the serum biochemical composition analysis revealed a well-differentiated blood pattern previously defined for critically ill patients (Figure S1)., This work has been developed in the framework of the COVIDOMICS’ project supported by Direcció General de Recerca i Innovació en Salut (DGRIS), Departament de Salut, Generalitat de Catalunya (PoC-6-17 and PoC1-5). The research has also been funded by the Programa de Suport als Grups de Recerca AGAUR (2017SGR948), the SPANISH AIDS Research Network [RD16/0025/0006, RD16/0025/0007 and RD16/0025/0020]-ISCIII-FEDER (Spain), the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII [CB21/13/00020], Madrid, Spain and Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucía (research Project CV20-85418). Elena Yeregui was supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “FI20/00118″ through the programme “Contratos Predoctorales de Formación en Investigación en Salud”. Laia Revertéwas supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CD20/00105″ through the programme “Contratos Sara Borrell”. Francesc Vidal was supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by “Premi a la Trajectòria Investigadora dels Hospitals de l’ICS 2018″. Anna Rull was supported by a grant from IISPV through the project “2019/IISPV/05″ (Boosting Young Talent), by GeSIDA through the “III Premio para Jóvenes Investigadores 2019″ and by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CP19/00146″ through the Miguel Servet Program. Maria José Buzón was supported by the Miguel Servet Program (CP17/00179). Ezequiel Ruiz- Mateos was supported by the Spanish Research Council (CSIC). Alicia Gutiérrez-Valencia was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (grant CP19/00159). This project was also funded by a donation from the city Council of Perafort (to Teresa Auguet).

AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology, [EN] The continuous increase in our knowledge of HIV medicine and antiretroviral treatment has led us to draft specific consensus documents focused on topics other than antiretroviral therapy, such as treatment of opportunistic diseases, pre- and post-exposure prophylaxis, metabolic abnormalities, treatment of HBV or HCV coinfection, treatment of patients coinfected with tuberculosis, osteoporosis, kidney disorders, and cardiovascular risk. Accordingly, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology has promoted the drafting of this consensus document on the control and monitoring of adult patients infected with HIV. The document provides recommendations on the initial evaluation and subsequent monitoring of HIV-infected patients that will prove useful for all professionals involved in the management of this infection., [ES] La complejidad creciente de los conocimientos relativos a la infección por el VIH y al tratamiento antirretroviral (TAR) ha condicionado la elaboración de documentos de consenso específicos que abordan aspectos diferentes al TAR. Son ejemplos, la profilaxis y el tratamiento de las infecciones oportunistas, la profilaxis post y pre-exposición, las alteraciones metabólicas y el riesgo cardiovascular, la osteoporosis, los trastornos renales, la co-infección por el VHB y el VHC o el manejo de este en pacientes con tuberculosis, entre otros. En esta línea, la Junta Directiva de GeSIDA ha promovido la elaboración de un documento de consenso sobre el control y la monitorización de los adultos infectados por el VIH. El objetivo de este documento es proporcionar una serie de recomendaciones sobre la evaluación inicial y la posterior monitorización clínica de los pacientes infectados por el VIH, que pueda servir como referencia para todos los profesionales implicados en el cuidado de estos pacientes.