Cytokine Profile in Different Post-Covid-19 Condition Phenotypes

Background: At least 10% of SARS-CoV-2 infected patients suffer from persistent symptoms for >12 weeks, known as post-COVID-19 condition (PCC) or Long Covid. Reported symptomatology is diverse with >200 physical and neurological debilitating symptoms. Here, we analyzed pro-inflammatory cytokine levels as a potential mechanism underlying persistent symptomatology. Method(s): Clinical data and samples used belong to the KING cohort extension, which includes clinically well characterized PCC (N=358, 59 persistent symptoms evaluated), COVID-19 recovered and uninfected subjects. We used Gower distances to calculate symptom's similarity between PCC and Ward's hierarchical clustering method to identify different symptom patterns among PCC patients. Cytokine levels of randomly selected PCC, recovered and uninfected subjects (N=193) were measured on plasma samples collected >6 months after acute infection using the 30-Plex Panel for Luminex. Mann- Whitney t-test was used to compare PCC vs recovered groups and Kruskal-Wallis t-test for >2 groups comparisons (PCC vs recovered vs Uninfected and within PCC clusters). FDR correction was applied for statistical significance (p-adj). Result(s): Hierarchical clustering identified 5 different PCC clusters according to their symptomatology, where PCC3 and PCC5 clusters showed higher prevalence of women ( >80%) and more persistent symptoms, while acute COVID-19 was mild in >80% of the patients. We selected 91 PCC (belonging to each cluster), 57 recovered and 45 uninfected subjects for cytokine profiling (Table 1). 13 soluble markers were significantly elevated (IL-1beta, Eotaxin, MIP-1beta, MCP-1, IL-15, IL-5, HGF, IFN-alpha, IL-1RA, IL-7, MIG, IL-4 and IL-8) in PCC and recovered groups compared to uninfected subjects (all p-adj< 0.04). In addition, PCC subjects tended towards higher levels of IL-1RA compared to recovered group (padj= 0.071). Within PCC clusters, FGF-basic and RANTES were elevated while IL-2 and MIG were decreased in PCC3 and PCC5 compared to the other PCC clusters (all p-adj< 0.04). TNF-alpha, IP-10, G-CSF and MIP-1alpha were decreased in PCC3 and PCC5 not reaching statistical significance (all p-adj=0.07). Conclusion(s): Some cytokines remained altered in all SARS-CoV-2 infected subjects independently of persistent symptoms after 6 months from acute infection. Differences between PCC and recovered individuals are limited after correction. Importantly, PCC cytokine profiles showed differences between clusters, which suggests different PCC subsyndromes with distinct etiology. Subjects Characteristics (Table Presented).

SARS-CoV-2 spike fails to induce inflammation in paediatric airway cells

Introduction/Aim: The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enables it to recognise and bind host receptors. These dynamics have been modelled in various cell types and immortalised lines, but rarely in primary airway epithelial cells (AEC), and especially not in children. Therefore, this study on AEC recapitulated earlier work testing the hypothesis that exposure to the spike protein would induce airway immune responses in airway cells of young children. Method(s): Primary AEC monolayer cultures from healthy children (n = 5, <10 years old, males = 5) were exposed to the spike protein S1 subunit (0.01, 1, and 10 mug/mL) over 48 h. Induced inflammatory cytokines, interleukin (IL) 6 and IL8, and viral-associated chemokines, CCL5 and CXCL10 were measured via ELISA. Basal receptor gene expression (ACE2 and TMPRSS2) was measured in monolayer (n = 5) and terminally differentiated (air-liquid interface [ALI];n = 5) cell models as well as in ex-vivo cells obtained directly from nasal brushings (n = 71). Generalised linear modelling, accounting for individual variability, identified any statistical difference (p < 0.05). Result(s): Exposure to the spike protein resulted in no increase in IL6 and IL8 production, however a significant (p < 0.05) decrease was observed at the highest dose tested (10 mug/mL). CXCL10 was only significantly induced at the highest dose (10 mug/mL) whereas CCL5 was not induced. When compared to ex-vivo samples, baseline expression of ACE2 and TMPRSS2 was significantly lower in monolayer cultures (~57- and ~4- fold respectively, p < 0.05), whereas ALI cultures had similar expression levels. Conclusion(s): The use of recombinant spike protein and monolayer cultures appears to not accurately model SARS-CoV-2 spike protein-host interactions. The lack of inflammatory responses may be attributed to the lower receptor gene expression in monolayer cultures. Future studies should utilise live virus and ALI cultures as a more biologically relevant model to study virus-host interactions.

Characterization of Mesenchymal Cell from BAL of post COVID-19 patient whit fibrosis

Increasing number of severe COVID 19 patients develop pulmonary Fibrosis, but the management of this complication is still unclear due to a lack of clinical trials. Aim of this study was to characterize mesenchymal cells (MC) isolated from 10 broncho-alveolar lavage (BAL, at 2 months after discharge) from patients with COVID19 fibrosis (COVID19-f) and to compare them with those isolated from 8 patients with collagen tissue diseaseassociated interstitial fibrosis(CTD-ILD). BAL fluid (BALf) levels of TGFbeta, VEGF, TIMP2, RANTES, IL6, IL8, and PAI1 were assessed by ELISA. Primary MC foci were cultured and expanded in D-MEM +10% FBS, characterized by flow cytometry and osteogenic and adipogenic differentiation. Collagen 1 production (+/-TGF-beta) was tested by WB and mRNA expression. BALf cytokine and GF levels were comparable in the two groups. Efficiency of MC isolation from BAL was 100% in COVID-f compared to 65% in CTD-ILD. MC antigen surface expression of CD105, CD73, CD90 (>90%, respectively), CD45, CD34, CD19 and HLA-DR (<5%, respectively) was comparable. None of MC samples differentiated in adipocytes, while COVID19-f were positive for calcium deposition. COVID19-f MC showed at WB, higher Collagen 1 production with respect to CTD-ILD with TGF-beta stimulation. Our preliminary data suggest MC from COVID19-f share several features with CTD-ILD but might have a higher response to fibrogenic and differentiation signals.

Delayed immunological reaction of Human Microvascular Lung Endothelium in response to Human Coronavirus 229E infection

Introduction: In the natural conditions first and major target for respiratory viruses (RVs) are epithelial cells. Nonetheless, recently we have demonstrated that RVs are able to infect not only epithelium, but also Human Microvascular Lung Endothelial Cells (HMVEC-L) which increased network is observed during severe asthma due to increased angiogenesis. Furthermore, on the surface of HMVEC-L we observed intense expression of aminopeptidase N (AP-N)- an entry receptor for Human Coronavirus 229E (HCoV-229E). Due to the facts, that possibility of being infected by HCoV-229E should be considered and there is no research based on this model the aim of this study was to assess the vulnerability of HMVEC-L to HCoV-229E infection. Method(s): HMVEC-L was incubated with HCoV-229E (MOI 0,1;1,0;3,0) for 3 hours, 3x PBS washed and cultured for 120 hours. In relevant time points (5;24;48;72;96 and 120h) viral copy number and mRNA expression of inflammatory, anti-viral and receptor factors were evaluated in Real-Time PCR. Confocal microscopy (CM) and flow cytometry (FACS) were used to measure AP-N surface expression. Result(s): FACS and CM confirmed intense surface expression of AP-N on HMVEC-L. HCoV-229E efficiently infected HMVEC-L (604 945,5 +/-194 930,2 viral copies/mul) in 48h cultures (MOI 0,1) and induced relatively late (between 72- 96h) mRNA expression of RANTES (1181,12);IL-6 (89,6);IFN-beta (53,7);OAS-1 (64,3);PKR (11,4) and TLR-3 (42,4). Increased mRNA expression was also accompanied by protein release to the supernatants. Conclusion(s): HCoV-229E may efficiently infect HMVEC-L and induce delayed inflammatory and anti-viral response.

Adenosine A2A Receptor (A2AR) Agonist Apadenoson Promotes Survival in K28-hACE2 Mice and Syrian Hamsters Infected with Sars-CoV-2

Purpose: To determine if Apadenoson or Regadenoson has a therapeutic effect in attenuating hyper-inflammation and improving survival rate in K18-hACE2mice or Syrian hamsters infected with SARS-CoV-2. Method(s): 6-8 weeks old male K18-hACE2mice were divided into Control group that received vehicle;Test group 1 that received the drug (Apadenoson or Regadenoson) 24hrs prior to challenge with SARS-CoV-2;and Test Group 2 (Drug-delay), that received the drug with a 5 hr delay post-viral infection (n=6/grp). Viral dose was 1250 PfuHong Kong/VM20001061/2020 delivered via intranasal route. Drug was delivered subcutaneously using 1007D ALZET pumps. 6 weeks old Syrian hamsters were divided into Control group that received Vehicle and Virus (n=4) and 2 test groups (n=5/group) that received Apadenoson+Virus and Regadenoson+Virus. Drugs were delivered by 2ML2 ALZET pumps (4ug/kg/hr). Hamsters were inoculated intratracheally with 750PFU SARS-CoV-2 WA1 strain prior to treatment. Mice were weighed and clinical scores recorded daily. Bronchoalveolar lavage fluid (BALF) and serum were collected along with lungs. Plethysmography was done on days 0, 2, 4 and 7. Result(s): Apadenoson administered post-infection was efficacious in decreasing weight loss, improving clinical score, and increasing the survival rate in K18-hACE2 mice, i.e. 50% survival was observed at Day 5 and at Day 7 post-infection for drug given before or after infection respectively. Apadenoson given post-infection improved the histopathology that was observed in the vehicle control group, decreased pro-inflammatory IL-6, IFN-gamma, MCCP-1, MIP-1beta, IP-10, and Rantes in serum, increased anti-inflammatory Ang1-7 levels, and decreased monocytes in BALF. 42% of mice that received Regadenoson pre-challenge survived infection compared to 6.25% in the vehicle or Drug delay (drug given post-infection) groups. Viral titers in the lungs of Regadenoson-treated mice were found decreased. Treatment also significantly decreased CD4+, CD8+T cells, eosinophils, and neutrophils in BALF. Plethysmography, in hamsters, showed significant improvement of pulmonary function parameters, Rpef and PenH, following treatment with Apadenoson given post-infection. Apadenoson cleared the virus from BALF and maintained Ang1-7 levels. Both drugs decreased plasma IFN-gamma levels. Conclusion(s): Treatment with Apadenoson attenuated inflammation, improved pulmonary function, decreased weight loss, and enhanced survival rate following infection with SARS-CoV-2 virus. The results demonstrate the translational significance of Apadenoson in the treatment of COVID-19.

Impact of Influenza Virus and E-cigarette Vaping Pre-Exposures on Outcomes of SARS-CoV-2 Infection in Hamster

Rationale. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the third leading cause of death in the United States. While many risk factors for severe COVID-19 are emerging, the effects by which other inhalational exposures affect susceptibility are not well defined. Patients with COVID-19 demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV). When infected with IAV, human small airway epithelial cells (SAEC) exhibit increased abundance of angiotensin-converting enzyme 2 (ACE2), the primary receptor for SARS-CoV-2. However, it remains unknown if this effect increases the risk for COVID-19. Similarly, there are conflicting reports of the effect of e-cigarette (E-cig) vaping on COVID-19 manifestations. We hypothesized that exposures to IAV or E-cig increase the severity of SARS-CoV-2 infection. Methods. Golden Syrian hamsters (male and female) were exposed to E-cig vapor via nebulization for 5d. IAV was administered intranasally once on day 6 (A/California/07/2009 H1N1, 106 PFU/hamster). On day 3 post-IAV infection, SARSCoV- 2 was administered intranasally (WA01;104 PFU/hamster). On day 7 post-SARS-CoV-2 infection animals were sacrificed, bronchoalveolar lavage fluid (BALF) cell differentials were obtained, and inflated lung sections were stained and scored for immunohistology. Lung RNA was quantified for ACE2, TMPRSS2, STAT1, CXCL10, IFN-gamma, gene expression using RT-qPCR. Results: SARS-CoV-2 infection caused progressive weight loss that was less pronounced in animals pre-infected with IAV. SARS-CoV-2 titers from nasal swabs peaked at day 2 in both groups. IAV pre-infection reduced PMN and eosinophils in the BALF, and the overall inflammatory cell infiltration in the lung parenchyma of SARS-CoV-2-infected animals. IAV pre-infection reduced lung levels of STAT1, CXCL10 (2.5-fold;p<0.01), CCL5, and IFN-gamma in SARS-CoV-2-infected animals compared to animals that were only infected with SARS-CoV-2. Pre-exposure to E-cig worsened the SARS-CoV-2-induced weight loss in female animals only. E-cig pre-exposure increased lymphocytes and decreased PMN and eosinophils in the BALF compared to animals that were only infected with SARS-CoV-2. E-cig pre-exposure increased lung levels of STAT1, CXCL10 (2.5-fold;p<0.05), CCL5, and IFN-gamma in SARS-CoV-2-infected animals compared to animals that were only infected with SARS-CoV-2. Conclusion: Pre-infection with IAV resulted in decreased inflammatory response to SARS-CoV-2 infection. In contrast, pre-exposure to E-cig vaping increased the severity of the inflammatory response to SARS-CoV-2 with notable differences between sexes. Whereas anti-viral priming effects of prior viral infection are well described, the mechanisms that explain the worsening effects of E-cig on SARS-CoV-2 outcomes remain unknown.

PERFIL IMUNOLÓGICO DE DOADORES DE SANGUE COM E SEM INFECÇÃO PRÉVIA POR SARS-COV-2

Objetivo: Comparar o perfil imunológico de indivíduos positivos e negativos para IgG anti-SARS-CoV-2. Métodos: Amostras de soro (n = 7.837) de doadores de sangue da Fundação Hemominas, coletadas no período de março a dezembro de 2020, foram testadas por quimioluminescência para IgG anti-SARS-CoV-2. As amostras positivas foram separadas em quatro grupos considerando-se os intervalos interquartis do index de anticorpos detectados no teste sorológico. Amostras positivas e negativas foram utilizadas na dosagem de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gama e IL-17A) e quimiocinas (CXCL8, CCL5, CXCL9, CCL2 e CXCL10). Resultados: Dos doadores testados, 441 (5,6%) foram positivos para IgG anti-SARS-CoV-2 com mediana de index de 3,65 (IQR 2,43-5,40). As concentrações séricas (ng/mL) de IL-10 (mediana, 0,51;IQR, 0,18-0,86;p < 0,0001), TNF (mediana, 0,65;IQR, 0,00-0,77;p = 0,0279) e IFN-gama (mediana, 0,36;IQR, 0,00-0,88;p < 0,0001) foram significativamente maiores em doadores de sangue positivos para IgG anti-SARS-CoV-2. As concentrações séricas (ng/mL) de CXCL8 (mediana, 13,60;IQR, 5,98-28,04;p = 0,0013), CCL5 (mediana, 4.017,00;IQR, 2.674,00-4.736,00;p < 0,0001), CXCL9 (mediana, 33,08;IQR, 17,88-54,14;p < 0,0001), CCL2 (mediana, 40,39;IQR, 23,38-61,52;p = 0,0068) e CXCL10 (mediana, 111,70;IQR, 56,98-178,00;p < 0,0001) foram significativamente maiores em doadores de sangue positivos para IgG anti-SARS-CoV-2. Análises de correlação revelaram que todas as citocinas (exceto IL-4, IL-6 e IL-17A) têm correlação negativa significativa com o index de IgG anti-SARS-CoV-2, mas com coeficiente de Spearman (r) menores que 0,5. Todas as quimiocinas testadas tiveram correlação negativa significativa, com destaque para CCL5 (r = -0,79), CXCL9 (r = -0,57) e CXCL10 (r = -0,51). Discussão: A análise do perfil imunológico de indivíduos positivos e negativos evidenciou que a produção de IgG anti-SARS-CoV-2 depende de uma resposta imune inata caracterizada pela alta concentração sérica de quimiocinas e de uma resposta pró-inflamatória potencializada por TNF e IFN-gama e regulada por IL-10. Os resultados evidenciam ainda que a produção de mais anticorpos contra o vírus depende de uma síntese controlada de citocinas e quimiocinas, indicando que menores níveis destes biomarcadores estão relacionados à maior produção de IgG anti-SARS-CoV-2. Conclusão: Os resultados deste estudo evidenciaram que um perfil imune pró-inflamatório associado a biomarcadores de resposta imune inata é importante para o desenvolvimento de anticorpos IgG anti-SARS-CoV-2. Suporte financeiro: Fundação HEMOMINAS, CNPq.

ANÁLISE DE CITOCINAS E QUIMIOCINAS NO PLASMA DE PACIENTES COM COVID-19 E DOADORES DE SANGUE ASSINTOMÁTICOS INFECTADOS COM SARS-COV-2

Objetivos: Comparar níveis de citocinas e quimiocinas entre indivíduos infectados com SARS-CoV-2 com COVID-19 grave ou com a forma assintomática da infecção, a fim de avaliar quais destes marcadores biológicos de resposta inflamatória são indicadores de gravidade da infecção viral. Métodos: Foram analisados dados clínicos de 48 pacientes com COVID-19 hospitalizados no Hospital Eduardo de Menezes (FHEMIG, MG) no período de 07 de julho a 21 de novembro de 2020, que necessitaram ou não de assistência em terapia intensiva (grupos UTI e sem UTI, respectivamente). Foi feita a quantificação dos níveis de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-, IL-17A) e quimiocinas (CCL2, CCL5, CXCL8, CXCL9 e CXCL10) do plasma de 14 pacientes UTI e 17 pacientes sem UTI que tinham COVID-19 grave no momento da coleta da amostra, além de 24 doadores de sangue da Fundação Hemominas com infecção ativa pelo SARS-CoV-2 (RT-PCR positiva) que eram assintomáticos no momento da coleta da amostra. Resultados: A análise clínica dos pacientes UTI (n = 19) em comparação àqueles que não usaram UTI (n = 29) não mostrou diferença estatística quanto à frequência de comorbidades e de sinais e sintomas para COVID-19 na admissão hospitalar. A comorbidade mais comum foi hipertensão (62,5%), seguida por diabetes (37,5%) e obesidade (22,9%). Tosse, dispneia, febre, fatiga e mialgia foram os sinais e sintomas mais prevalentes de COVID-19 em ambos os grupos. Entretanto, os pacientes UTI desenvolveram doença grave ou crítica que requereu um período de hospitalização em média duas vezes mais longo que o grupo sem UTI (p < 0,001). O conjunto dos pacientes com COVID-19 mostrou níveis significativamente mais altos de IL6, IL10 e CCL5 que os doadores assintomáticos. Na comparação dos grupos dos pacientes houve diferença significativa apenas para IFN, com níveis mais elevados nos pacientes UTI. Discussão: Apesar do grupo de pacientes UTI apresentarem quadro de COVID-19 mais grave que os pacientes sem UTI, a frequência de sinais e sintomas da doença e de comorbidades não foi significativamente diferente entre os grupos. A evolução da COVID-19 de assintomática para grave e crítica tem sido associada com intensa resposta inflamatória, o que está de acordo com maiores níveis de IL6, IL10 e CCL5 observados nos pacientes em comparação aos doadores assintomáticos. Nível de IFN pode ser especial indicador de gravidade da doença. Conclusão: Marcadores biológicos, como citocinas e quimiocinas, podem ser melhores preditores de evolução da COVID-19 que sinais clínicos e sintomas. Suporte financeiro: Fundação Hemominas e SES/MG.

Insights into forsythia honeysuckle (Lianhuaqingwen) capsules: A Chinese herbal medicine repurposed for COVID-19 pandemic.

Background: In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished. Purpose: LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism. Methods: Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck. Results: This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6. Conclusion: This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified.

Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab.

Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.

Interferon gamma, TGF-ß1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients.

Upper respiratory tract is the primary site of SARS-CoV-2 replication. Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-ß1 and RANTES at mRNA level. Forty five SARS-CoV-2 infected patients were enrolled, whose were divided in two groups: asymptomatic and symptomatic. Twenty healthy persons, SARS-CoV-2 negative were included as controls. Higher IFN-γ expression was detected in SARS-CoV-2 infected patients in comparison with controls (p = 0.0393). IFN-γ expression was increased in symptomatic patients (p = 0.0405). TGF-ß1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p < 0.0001; p = 0.0011, respectively). A significant correlation between IFN-γ and TGF-ß1 was observed in SARS-CoV-2 asymptomatic patients (r = +0.61, p = 0.0014). The findings suggest that imbalance between IFN-γ and TGF-ß1 expression could be an impact in clinical expression of SARS-CoV-2 infection.

Immune response in children with COVID-19 is characterized by lower levels of T-cell activation than infected adults.

Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1ß in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children.