Direct Viral Damage Research Articles

NEUROLOGICAL COMPLICATIONS OF COVID-19: REVIEW OF LITERATURE AND OWN EXPERIENCE

According to the literature, the main neurological complications of COVID-19 are hyposmia, hypogeia, headache, dizziness, myalgia, and severe neurological syndromes like encephalopathy, stroke, and coma. The mechanisms of neurological complications of the acute period are direct viral damage, hypoxic damage, and immune damage due to the activation of inflammation, including autoantibodies. After the end of the acute phase of the disease, neurological complications in the form of asthenic syndrome, vascular syndrome, exacerbation of chronic diseases (deterioration of cognitive and communication functions in patients with autism, schizophrenia, exacerbation of autoimmune neurological diseases, aggravation of the condition of patients with tics, increased frequency of epileptic seizures in adults and children, resumption of epileptic seizures in patients who were previously in stable remission, the debut of epileptic seizures). These disorders are based on the following mechanisms: neuroinflammation, activation of pro-inflammatory cytokines (IL-1, -2, -6, -8, -10, -17, -18, CXCL10, CCL2), formation of autoantibodies, increased permeability of the blood-brain barrier, mitochondrial dysfunction, adrenal and thyroid dysfunction, venous dyscirculation. In the treatment of neurological complications after a COVID-19 infection, it is advisable to use anti-inflammatory therapy, mitochondrial therapy (including the technique of intermittent hypoxic-hyperoxic therapy), detoxication, correction of hormonal status (primarily the state of the adrenal glands and thyroid gland), vasoactive therapy, and symptomatic therapy.

Perioperative management of post-COVID-19 surgical patients: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

Perioperative management of post-COVID-19 surgical patients: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

A 22-year-old COVID-19 positive male with no prior medical history presented to the emergency department with pulmonary infarction

ABSTRACT Rapidly growing evidence has now shown a high incidence of venous thrombosis in patients with severe acute respiratory syndrome secondary to novel coronavirus 2, a disease now named COVID-19. Accumulating case reports and series have also shown a higher prevalence of arterial thrombosis in these patients as well. Although the pathophysiology remains unknown but likely multifactorial – including endotheliitis from direct viral damage and an underlying hyper-inflammatory state, arterial and venous thrombosis occurrence does not appear to be linked with underlying classic risk factors for venous thromboembolism and may present in healthy patients without significant comorbidities. We present a case of a 22-year-old healthy patient with COVID-19 who developed a pulmonary embolism with a pulmonary infarction, a complication that results from arterial and venous thrombosis of the pulmonary vascular supply resulting in tissue necrosis.

The case report of myocarditis caused by COVID-19

Introduction. Myocarditis is known to occur in 5–25 % of COVID-19 cases and is associated with increased mortality. According to studies, even a mild course of COVID-19 is associated with a high risk of cardiovascular disease. Possible mechanisms of myocarditis are a combination of direct viral damage to the myocardium and the human immune response to the affected myocardium. Along with acute manifestations, as fulminant myocarditis, COVID-19 may also be associated with an increased risk of long-term cardiovascular complications. Case report and discussion. The article presents a case of myocarditis that developed five weeks after active coronovirus infection in patient I., 47 years old, Ukraine, Kyiv. She described such symptoms as palpitations, shortness of breath, fever, general malaise. According to magnetic resonance imaging (MRI) of the heart: signs of focal myocarditis; according to laboratory tests, an increase in the level of acute phase indicators; according to Holter monitoring of the electrocardiogram (HM ECG) – AV blockade of the II degree (Mobitz II). The patient was prescribed : eplerinone, bisoprolol fumorate, rivaroxaban, trimetazidine. After four months of treatment, the condition of the patient gradually improved. Positive dynamics was revealed according to HM ECG and MRI of the heart. Thus, the patient was diagnosed with long-term consequences of coronavirus infection – focal myocarditis. Conclusions. Coronavirus infection causes myocardial damage with the development of myocarditis. Myocarditis can develop both in the acute period of the disease and in the long term. Scientists and physicians should pay attention to the possible consequences of COVID-19 from the first contact with the patient, and conduct long-term follow-up of patients in the long term.

Chapter 9: Immunology of TBEV-Infection

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although viral infection is known to trigger inflammatory processes contributing to tissue injury and organ failure, it is unclear whether direct viral damage is needed to sustain cellular injury. An understanding of pathogenic mechanisms has been handicapped by the absence of optimized methods to visualize the presence and distribution of SARS-CoV-2 in damaged tissues. We first developed a positive control cell line (Vero E6) to validate SARS-CoV-2 detection assays. We then evaluated multiple organs (lungs, kidneys, heart, liver, brain, intestines, lymph nodes, and spleen) from fourteen COVID-19 autopsy cases using immunohistochemistry (IHC) for the spike and the nucleoprotein proteins, and RNA in situ hybridization (RNA ISH) for the spike protein mRNA. Tissue detection assays were compared with quantitative polymerase chain reaction (qPCR)-based detection. SARS-CoV-2 was histologically detected in the Vero E6 positive cell line control, 1 of 14 (7%) lungs, and none (0%) of the other 59 organs. There was perfect concordance between the IHC and RNA ISH results. qPCR confirmed high viral load in the SARS-CoV-2 ISH-positive lung tissue, and absent or low viral load in all ISH-negative tissues. In patients who die of COVID-19-related organ failure, SARS-CoV-2 is largely not detectable using tissue-based assays. Even in lungs showing widespread injury, SARS-CoV-2 viral RNA or proteins were detected in only a small minority of cases. This observation supports the concept that viral infection is primarily a trigger for multiple-organ pathogenic proinflammatory responses. Direct viral tissue damage is a transient phenomenon that is generally not sustained throughout disease progression.

Extrapulmonary manifestations of COVID-19 patient presenting with abdominal pain and skin lesions as primary symptoms

COVID-19 is basically a respiratory disease and pulmonary manifestations constitute main presentations of the disease however in some patients SARS-CoV-2 infection is not limited to the respiratory system and other organs can also be affected and may be the primary manifestations of the disease.Renal dysfunction, gastrointestinal complications, liver dysfunction, cardiac manifestations, neurological abnormalities, haematological and thrombotic manifestations are among the reported extrapulmonary features. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thrombo-inflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to evaluate patients presenting with abdominal symptoms and skin lesions even without respiratory complaints to increase the diagnostic accuracy to detect COVID-19 and its complications in early stage. Our case report documents a patient who presented with abdominal symptoms and skin lesions whose RT-PCR was positive for COVID-19. It remains to be seen whether these patients will eventually develop respiratory symptoms. Further studies are needed to elaborate and confirm the causative relationship between SARS-CoV-2 and the reported extrapulmonary manifestations of COVID-19.

Viral Respiratory Pathogens and Lung Injury.

Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.

SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids.

In this Review, we briefly describe the basic virology and pathogenesis of SARS-CoV-2, highlighting how stem cell technology and organoids can contribute to the understanding of SARS-CoV-2 cell tropisms and the mechanism of disease in the human host, supporting and clarifying findings from clinical studies in infected individuals. We summarize here the results of studies, which used these technologies to investigate SARS-CoV-2 pathogenesis in different organs. Studies with in vitro models of lung epithelia showed that alveolar epithelial type II cells, but not differentiated lung alveolar epithelial type I cells, are key targets of SARS-CoV-2, which triggers cell apoptosis and inflammation, while impairing surfactant production. Experiments with human small intestinal organoids and colonic organoids showed that the gastrointestinal tract is another relevant target for SARS-CoV-2. The virus can infect and replicate in enterocytes and cholangiocytes, inducing cell damage and inflammation. Direct viral damage was also demonstrated in in vitro models of human cardiomyocytes and choroid plexus epithelial cells. At variance, endothelial cells and neurons are poorly susceptible to viral infection, thus supporting the hypothesis that neurological symptoms and vascular damage result from the indirect effects of systemic inflammatory and immunological hyper-responses to SARS-CoV-2 infection.

SARS-CoV-2 and neurological disorders: the revelance of biomarkers?

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.

Sedating Mechanically Ventilated COVID-19 Patients with Volatile Anesthetics: Insights on the Last-Minute Potential Weapons

Coronavirus Disease 2019 (COVID-19) has spread globally with the number of cases exceeding seventy million. Although trials on potential treatments of COVID-19 Acute Respiratory Distress Syndrome (ARDS) are promising, the introduction of an effective therapeutic intervention seems elusive. In this review, we explored the potential therapeutic role of volatile anesthetics during mechanical ventilation in the late stages of the disease. COVID-19 is thought to hit the human body via five major mechanisms: direct viral damage, immune overactivation, capillary thrombosis, loss of alveolar capillary membrane integrity, and decreased tissue oxygenation. The overproduction of pro-inflammatory cytokines will eventually lead to the accumulation of inflammatory cells in the lungs, which will lead to ARDS requiring mechanical ventilation. Respiratory failure resulting from ARDS is thought to be the most common cause of death in COVID-19. The literature suggests that these effects could be directly countered by using volatile anesthetics for sedation. These agents possess multiple properties that affect viral replication, immunity, and coagulation. They also have proven benefits at the molecular, cellular, and tissue levels. Based on the comprehensive understanding of the literature, short-term sedation with volatile anesthetics may be beneficial in severe stages of COVID-19 ARDS and trials to study their effects should be encouraged.

Hypercoagulability in COVID-19: A review of the potential mechanisms underlying clotting disorders.

Severe acute respiratory syndrome coronavirus-2 has emerged as a new viral pandemic, causing Coronavirus disease 2019 (COVID-19) leading to a wide array of symptoms ranging from asymptomatic to severe respiratory failure. However, coagulation disorders have been found in some patients infected with SARS-CoV-2, leading to either a clotting disorder or hemorrhage. Several mechanisms attempt to explain the mechanism behind the pro-coagulant state seen with COVID-19 patients, including different receptor binding, cytokine storm, and direct viral endothelial damage. SARS-CoV-2 has also been recently found to bind to CLEC4M receptor, a receptor that participates in the clearance of von Willebrand Factor and Factor VIII. The competitive binding of SARS-CoV-2 to CLEC4M could lead to decreased clearance, and therefore a promotion of a pro-coagulative state; however, an experimental study needs to be done to prove such an association.

COVID-19 and Acute Coronary Syndromes: From Pathophysiology to Clinical Perspectives.

Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.

Liver injury in Northern American patients with COVID-19

Presenter: Aleksandr Kalabin MD ;Columbia University at Harlem Hospital Background: Direct viral damage of organs/systems with subsequent inflammatory cascade is considered to be a major contributor to the pathogenesis of SARS-CoV-2 infection. Although lung is contemplated to be the primary organ targeted by the virus, recent reports predominantly from China and Europe provided evidence of affinity of COVID-19 to Angiotensin-converting enzyme 2(ACE 2) receptors expressed on gastrointestinal tract and liver parenchymal cells. The goal of our study was to investigate if SARS-CoV-2 virus affects liver function of Northern American population and if liver injury correlates with the disease severity in COVID-19 patients. Methods: Retrospective analysis of patients admitted with SARS-CoV-2 infection between March – April 2020 and liver function tests done within first 24h of admission. The primary outcome of interest was to determine if liver function is affected by COVOD-19 and assess the correlation with the disease severity. Patients were grouped into Non-intubated(NI-T) vs Intubated(I-T) patients and Survived(S) vs Deceased(D). Patients defined as survived were alive at the time of data accrual. Unpaired Student’s t-test was used for continues variables, Pearson Chi-square(χ2) test for categorical. P value < 0.05 was considered to represent statistically significant difference. Results: 183 patients were included, 73 Females(39.89%) and 110 males(60.11%). 114(62.30%) patients were African-Americans, 58(31.69%) Hispanics and 11 Asians(6.01%). Mean age was 64.77(SD 14.09), mean BMI 29.03(SD 7.36), mean body temperature 100.89(SD 1.68). 93 patients(50.82%) had GI complaints on presentation: most common symptoms were anorexia(54 patients, 29.51%), diarrhea(more than 3 loose stools per day, 41 patients, 22.40%), nausea/vomiting(33 patients, 18.03%) and abdominal pain(18 patients, 9.84%). Evaluation of LFTs on admission revealed mean aspartate aminotransferase(AST) of 63.83(SD 115.87), mean alanine transaminase(ALT) – 47.08(SD 85.64). Total bilirubin for the cohort was 0.64(SD 0.51), mean albumin 3.60(SD 0.52), mean Prothrombin time(PT) 14.38(SD 3.46), mean platelet count 220.94(83.59). Intubated patients tended to have significantly higher levels of AST(109.17 vs 53.97, P = 0.018), ALT(79.53 vs 40.03, P = 0.02) and total bilirubin(0.82 vs 0.60, P = 0.03) compared to non-intubated patents. This correlated with body temperature that was higher(101.38) for Intubated vs Non-intubated patients(100.70) (p = 0.0006), and acute phase reactants CRP(24.06 v 15.96, P = 0.019) and lactate(3.28 vs 2.13, P = 0.009). No difference between groups was observed for PT, platelets and albumin. Mean AST for Survived patients was 66.40 vs 50.41 for Deceased group(P = 0.51), mean ALT 48.89 vs 37.63(P = 0.53) and mean bilirubin 0.65 vs 0.60(P = 0.65) respectively. No difference between groups was observed for PT, platelets and albumin. CRP and lactate were higher in Deceased group compared to the Survived group:(27.09 vs 16.39, P = 0.008) and (3.33 vs 2.10 P = 0.005) respectively. Conclusion: Our study suggests direct viral injury to the liver parenchymal and biliary cells in Northern American patients with COVID-19 infection. Moreover, patients with elevated liver enzymes tended to have severe disease course, but no correlation with mortality was observed. Interestingly enough liver synthetic function of patients with SARS-CoV-2 infection was not significantly affected. While exact mechanisms of direct damage to the liver currently remain unclear and other explanations of elevated liver enzymes have been offered, more studies are needed to prove unambiguous interrelation between liver dysfunction and SARS-CoV-2 virus. [Formula presented]

Целесообразность комплексного подхода к лечению заболеваний печени у различных пациентов при реабилитации после COVID-19

COVID-19 pandemic has made the problem of its complex pharmacotherapy urgent, taking into account the common presence of symptoms from the digestive system in the clinical picture. The gastrointestinal tract (GIT) is actively involved in the pathogenesis of COVID-19 both in the period of prodromal events and the acute disease phase, with the preservation of several complaints and during the post-COVID-19 syndrome. The liver is one of the main organs that is commonly affected by COVID-19 after the respiratory system. The polyetiological nature of liver lesions in COVID-19 includes the following: direct viral damage to hepatocytes and cholangiocytes, systemic inflammatory response and cytokine aggression, reactive hepatitis, drug toxicity, hypoxia associated with acute respiratory distress syndrome, as well as sepsis and multiple organ dysfunction in terminal patients. Special attention should be paid to the liver condition in COVID-19 in comorbid patients with metabolic syndrome and non-alcoholic fatty liver disease, as well as chronic liver diseases with a history of viral and autoimmune genesis. Rehabilitation issues concerning patients after COVID-19 are currently under active development. At the same time, the experience of clinical cases leaves no doubt that it is necessary to take into account the hepatobiliary system condition and the presence of comorbidity when implementing rehabilitation programs. Methods customization to the issues of early recovery of post-COVID-19 patients implies knowledge of the differentiated use of hepatotropic drugs based on Russian and foreign clinical recommendations. KEYWORDS: liver diseases, COVID-19, rehabilitation, essential phospholipids, milk thistle extract, non-alcoholic fatty liver disease, cytokine damage, angiotensin converting enzyme, liver transaminases, drug-induced liver injuries. FOR CITATION: Selivanova G.B., Poteshkina N.G. Feasibility of an integrated approach to the treatment of liver diseases in various patients during post-COVID-19 rehabilitation. Russian Medical Inquiry. 2021;5(6):413–420 (in Russ.). DOI: 10.32364/2587-6821-2021- 5-6-413-420.

Review of COVID-19 and male genital tract.

COVID‐19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi‐organ injuries have been reported by describing potential SARS‐CoV‐2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors’ expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS‐CoV‐2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS‐CoV‐2 infection. Presence of SARS‐CoV‐2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.

Virus-Negative Myopericarditis in Human Coronavirus Infection: Report From an Autopsy Series.

Virus-Negative Myopericarditis in Human Coronavirus Infection: Report From an Autopsy Series.

ANOSMIA NO COVID-19

Resumo&#x0D; O Brasil teve o primeiro caso registrado de Coronavirus Disease 2019 (COVID-19) no dia 26 de fevereiro de 2020. Desde o início da pandemia houve muito desconhecimento da doença e suas sequelas. Atualmente sabe se que o coronavírus pode causar a sintomatologia de um resfriado comum incluindo febre, tosse, dor de garganta, congestão nasal, mal estar geral, fadiga, cefaleia, mialgia e anosmia. Este estudo tem como objetivo destacar o aumento da preocupação entre os médicos, devido ao crescente número de casos relatados de anosmia em pacientes com COVID-19, pois sugere dano viral direto aos receptores olfatórios e degeneração neuronal retrógrada das vias de condução centrais. Nesse contexto, para avaliação de um paciente com perda olfativa é necessário ter uma anamnese em que conste o tempo de perda, fatores concomitantes como a Síndrome Respiratória Aguda Grave do Coronavírus 2 (SARS-CoV-2), se há ausência completa ou parcial (que caracteriza uma hiposmia) e outros sintomas nasais associados. Além disso, como método diagnóstico é fundamental a avaliação do olfato a partir da apresentação de substâncias odoríferas ao paciente e pedir para nomeá-las. A queixa de diminuição ou perda total do olfato durante o cenário pandêmico atual evidencia um sintoma de alerta que necessita de investigação médica para confirmar a suspeita de infecção pelo SARS-CoV-2 com diagnóstico precoce e controle de disseminação da doença.&#x0D;

A "Window of Therapeutic Opportunity" for Anti-Cytokine Therapy in Patients With Coronavirus Disease 2019.

The effects of cytokine inhibition in the different phases of the severe coronavirus disease 2019 (COVID-19) are currently at the center of intense debate, and preliminary results from observational studies and case reports offer conflicting results thus far. The identification of the correct timing of administration of anti-cytokine therapies and other immunosuppressants in COVID-19 should take into account the intricate relationship between the viral burden, the hyperactivation of the innate immune system and the adaptive immune dysfunction. The main challenge for effective administration of anti-cytokine therapy in COVID-19 will be therefore to better define a precise “window of therapeutic opportunity.” Only considering a more specific set of criteria able to integrate information on direct viral damage, the cytokine burden, and the patient’s immune vulnerability, it will be possible to decide, carefully balancing both benefits and risks, the appropriateness of using immunosuppressive drugs even in patients affected primarily by an infectious disease.

Human Lungs Show&amp;nbsp;Limited Permissiveness for SARS-CoV-2 Due to Scarce ACE2 Levels But Strong Virus-Induced Immune Activation in Alveolar Macrophages

SARS-CoV-2 utilizes the ACE2 transmembrane peptidase as essential cellular entry receptor. Several studies have suggested abundant ACE2 expression in the human lung, inferring strong permissiveness to SARS-CoV-2 infection with resultant alveolar damage and lung injury. Against this expectation, we provide evidence that ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation in the human alveolus. Instead, spectral imaging of ex vivo infected human lungs and COVID-19 autopsy samples depicted that alveolar macrophages were frequently positive for SARS-CoV-2, indicating viral phagocytosis. Single-cell transcriptomics of SARS-CoV-2 infected human lung tissue further revealed strong inflammatory and anti-viral activation responses in macrophages and monocytes, comparable to those induced by MERS-CoV, but with virus-specific gene expression profiles. Collectively, our findings indicate that severe lung injury in COVID-19 likely results from an overwhelming immune activation rather than direct viral damage of the alveolar compartment.Funding: ACH, LES, SH were supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre-Exploration Project). ACH, SH, TW and CD were supported by BMBF (RAPID) and ACH, SH by BMBF (alvBarriereCOVID-19). KH, LB, SL, SH, CD, TW, ACH were funded by BMBF (NFN-COVID 19, Organo-Strat). KH, NS, LES, MW, SH, ADG, CD, TW and ACH were supported by DFG (SFB-TR 84). ACH was supported by BIH, Charite 3R, and Charité-Zeiss MultiDim. KH was supported by BMBF (Camo-COVID-19). MW, NS and SH was supported by BMBF (PROVID). MW and NS was supported by BIH and BMBF (SYMPATH, CAPSyS, NAPKON). BO and DB were funded through the BIH Clinical Single Cell Bioinformatics Pipeline. LB was supported by the BMBF (CoIMMUNE), the DFG (KFO 342) and the IZKF of the Medical Faculty of the WWU. Conflict of Interest: The authors declare no competing interests.Ethical Approval: The study was approved by the ethics committee at the Charité clinic (projects EA2/079/13) and Ärztekammer Westfalen-Lippe and of the Westfälischen Wilhelms-Universität (AZ: 2016-265-f-S). Written informed consent was obtained from all patients.