Link between fever, diarrhea, severe COVID-19, and persistent anti-SARS-CoV-2 antibodies

Authors: By Dr. Liji Thomas, MD Jan 7 2021

Ever since the coronavirus disease 2019 (COVID-19) pandemic began, there have been many attempts to understand the nature and duration of immunity against the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A new preprint research paper appearing on the medRxiv* server describes a link between the persistence of neutralizing antibodies against the virus, disease severity, and specific COVID-19 symptoms.

Permanent immunity is essential if the pandemic is to end. In the earlier SARS epidemic, antibodies were found to last for three or more years after infection in most patients. With the current virus, it may last for six or more months at least, as appears from some reports. Other researchers have concluded that immunity wanes rapidly over the same period, with some patients who were tested positive for antibodies becoming seronegative later on. This discrepancy may be traceable to variation in testing methods, sample sizes and testing time points, as well as disease severity.

Study details

The current study looked at a population of over a hundred convalescent COVID-19 patients, testing most of them for antibodies at five weeks and three months from symptom resolution.

The researchers used a multiplex assay that measured the Immunoglobulin G (IgG) levels against four SARS-CoV-2 antigens, one from SARS-CoV, and four from circulating seasonal coronaviruses. In addition, they carried out an inhibition assay against SARS-CoV-2 spike receptor-binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) binding and a neutralization assay against the virus. The antibody titers were then plotted against various clinical features and demographic factors.

Antibody titers higher in COVID-19 convalescents

The researchers found that severe disease is correlated with advanced age and the male sex. Patients with underlying vascular disease were more likely to be hospitalized with COVID-19, but those with asthma were relatively spared.

Convalescent COVID-19 patients had higher IgG levels against all four SARS-CoV-2 antigens, relative to controls, and in 98% of cases, at least one of the tests was likely to show higher binding compared to controls. IgGs targeting the viral spike and RBD were likely to be much more discriminatory between SARS-CoV-2 patients and controls. Interestingly, anti-SARS-CoV IgG, as well as anti-seasonal betacoronavirus antibodies, were likely to be higher in these patients.

Anti-spike and anti-nucleocapsid IgG levels, as well as neutralizing antibody titers, were higher in convalescent hospitalized COVID-19 patients than in convalescent non-hospitalized patients, and the titers were positively associated with disease severity.Antibodies against SARS-CoV-2 persist three months after COVID-19 symptom resolution. Sera from COVID-19 convalescent subjects (n=79) collected 5 weeks (w) and 3 months (m) after symptom resolution were subjected to multiplex assay to detect IgG that binds to SARS-CoV-2 S, NTD, RBD and N antigens (A), to RBD-ACE2 binding inhibition assay (B), and to SARS-CoV-2 neutralization assay (C). Dots, lines, and asterisks in red represent non-hospitalized (n=67) and in blue represent hospitalized (n=12) subjects with lines connecting the two time points for individual subjects (*p<0.05 and **p<0.01 by paired t test).Antibodies against SARS-CoV-2 persist three months after COVID-19 symptom resolution. Sera from COVID-19 convalescent subjects (n=79) collected 5 weeks (w) and 3 months (m) after symptom resolution were subjected to multiplex assay to detect IgG that binds to SARS-CoV-2 S, NTD, RBD and N antigens (A), to RBD-ACE2 binding inhibition assay (B), and to SARS-CoV-2 neutralization assay (C). Dots, lines, and asterisks in red represent non-hospitalized (n=67) and in blue represent hospitalized (n=12) subjects with lines connecting the two time points for individual subjects (*p<0.05 and **p<0.01 by paired t test).

Clinical correlates of higher antibody titer

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When antibody titers in non-hospitalized subjects were compared with clinical and demographic variables, they found that older males with a higher body mass index (BMI) and a Charlson Comorbidity Index score >2 were likely to have higher antibody titers. COVID-19 symptoms that correlated with higher antibody levels in these patients comprise fever, diarrhea, abdominal pain and loss of appetite. Chest tightening, headache and sore throat were associated with less severe symptoms.

The link between the specific symptoms listed above with higher antibody titers could indicate that they mark a robust systemic inflammatory response, which in turn is necessary for a strong antibody response. Diarrhea may mark severe disease, but it is strange that in this case, it was not more frequent in the hospitalized cohort. Alternatively, diarrhea may have strengthened the immune antibody response via the exposure of the virus to more immune cells via the damaged enteric mucosa. More study is required to clarify this finding.

Potential substitute for neutralizing assay

The binding assay showed that the convalescent serum at five weeks inhibited RBD-ACE2 binding much more powerfully than control serum. Neutralizing activity was also higher in these sera, but in 15% of cases, convalescent patients showed comparable neutralizing antibody titers to those in control sera. On the whole, however, there was a positive association between neutralizing antibody titer, anti-SARS-CoV-2 IgG titers, and inhibition of ACE2 binding.

Persistent immunity at three months

This study also shows that SARS-CoV-2 antibodies persist in these patients at even three months after symptoms subside, with persistent IgG titers against the SARS-CoV-2 spike, RBD, nucleocapsid and N-terminal domain antigens. Binding and neutralization assays remained highly inhibitory throughout this period. The same was true of antibodies against the other coronaviruses tested as well, an effect that has been seen with other viruses and could be the result of cross-reactive anti-SARS-CoV-2 antibodies. Alternatively, it could be due to the activation of memory B cells formed in response to infection by the seasonal beta-coronaviruses.


IgG titers, particularly against S and RBD, and RBD-ACE2 binding inhibition better differentiate between COVID-19 convalescent and naive individuals than the neutralizing assay,” the researchers concluded.

These could be combined into a single diagnostic test, they suggest, with extreme sensitivity and specificity. The correlation with neutralizing antibody titers could indicate that the neutralizing assay, which is more expensive, sophisticated and expensive, as well as more dangerous for the investigators, could be replaced by the other antibody tests without loss of value.

In short, the study shows that specific antibodies persist for three months at least following recovery; antibody titers correlate with COVID-19-related fever, loss of appetite, abdominal pain and diarrhea; and are also higher in older males with more severe disease, a higher BMI and CCI above 2. Further research would help understand the lowest protective titer that prevents reinfection, and the duration of immunity.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.Journal reference:

The origin of SARS-CoV-2 furin cleavage site remains a mystery

Authors: By Dr. Liji Thomas, MD Feb 17 2021

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has largely defied attempts to contain its spread by non-pharmaceutical interventions (NPIs). With the massive loss of life and economic damage, the only way out, in the absence of specific antiviral therapeutics, has been the development of vaccines to achieve population immunity.

A new study on the Preprints server discusses the origin of the furin cleavage site on the SARS-CoV-2 spike protein, which is responsible for the virus’s relatively high infectivity compared to relatives in the betacoronavirus subgenus.

The furin cleavage site

The SARS-CoV-2 is a betacoronavirus, and is most closely related to the bat SARS-related coronavirus (SARSr-CoV) represented by the genome sequence RaTG13, which shares 96% identity with the former. This has made the bat virus the most probable precursor of the virus in current circulation.

The origin of this strain is linked to the emergence of the novel furin cleavage site in the viral spike glycoprotein. The furin is a serine protease widely expressed in human cells, that cleaves the SARS-CoV-2 spike at the interface of its two subunits. It is encoded by a gene on chromosome 15.

Furin acts on substrates with single or paired basic residues during the processing of proteins within cells. Such a polybasic furin cleavage site is found in various proteins from many viruses, including Betacoronavirus Embecoviruses, and the Merbecovirus. However, within the betacoronaviruses of the sarbecovirus lineage B, this type of site is unique to SARS-CoV-2.

The study used a bioinformatic approach using the genomic data available on the National Center for Biotechnological Information (NCBI) databases, to identify the origin of the furin cleavage site.

Same ancestor

They found three coronaviruses that were very similar to the SARS-CoV-2 at the genomic level. These are Pangolin-CoVs (2017, 2019), Bat-SARS-like (CoVZC45, CoVZXC21) and bat RatG13.

The three genomic fingerprints used to identify these matches include fingerprint 1, in the orf1a RNA polymerase gene, including the nsp2 and nsp3 genes; fingerprint 2, at the beginning of S gene, covering the part encoding the N-terminal domain and the receptor-binding domain (RBD) that mediates attachment to the host cell receptor, the angiotensin-converting enzyme 2 (ACE2).; and fingerprint 3, the orf8 gene.

These fingerprints are distinctive to the three closely related coronaviruses only at the RNA level, but the amino acid sequences in the translated proteins are similar to other sarbecoviruses.

The sharing of these genomic sequences indicates their common ancestry, supported by other short sequence features, with one deletion and three insertions. All three strains show the same deletion-insertion pattern at the same four different locations in the spike gene.

Spike gene recombination in a common ancestor

The analysis of the phylogeny of these three strains showed that the first to diverge was the pangolin coronavirus, with the RatG13 being the closest. However, when only the spike is analyzed, there is a high similarity between the pangolin CoV, RaTG13 and SARS-CoV-2.

This may indicate the occurrence of recombination events between the Pangolin-CoV (2017) and RatG13 ancestors. This was followed by the shift of the pangolin CoV to pangolin hosts.Phylogenetic tree of the closely related SARS-CoV-2 coronaviruses based on complete genomesPhylogenetic tree of the closely related SARS-CoV-2 coronaviruses based on complete genomes.

Unique codons encoding arginines in the furin cleavage site

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The furin cleavage site consists of four amino acids PRRA, which are encoded by 12 inserted nucleotides in the S gene. A characteristic feature of this site is an arginine doublet.

This insertion could have occurred by random insertion mutation, recombination or by laboratory insertion. The researchers say the possibility of random insertion is too low to explain the origin of this motif.

Surprisingly, the CGGCGG codons encoding the two arginines of the doublet in SARS-CoV-2 are not found in any of the furin sites in other viral proteins expressed by a wide range of viruses.

Even within the SARS-CoV-2, where arginine is encoded by six codons, only a minority of arginine residues are encoded by the CGG codon. Again, only two of the 42 arginines in the SARS-CoV-2 spike are encoded by this codon – and these are in the PRRA motif.

For recombination to occur, there must be a donor, from another furin site and probably from another virus. In the absence of a known virus containing this arginine doublet encoded by the CGGCGG codons, the researchers discount the recombination theory as the mechanism underlying the emergence of PRRA in SARS-CoV-2.

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The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT



The characteristics and evolution of pulmonary fibrosis in patients with coronavirus disease 2019 (COVID-19) have not been adequately studied. AI-assisted chest high-resolution computed tomography (HRCT) was used to investigate the proportion of COVID-19 patients with pulmonary fibrosis, the relationship between the degree of fibrosis and the clinical classification of COVID-19, the characteristics of and risk factors for pulmonary fibrosis, and the evolution of pulmonary fibrosis after discharge. The incidence of pulmonary fibrosis in patients with severe or critical COVID-19 was significantly higher than that in patients with moderate COVID-19. There were significant differences in the degree of pulmonary inflammation and the extent of the affected area among patients with mild, moderate and severe pulmonary fibrosis. The IL-6 level in the acute stage and albumin level were independent risk factors for pulmonary fibrosis. Ground-glass opacities, linear opacities, interlobular septal thickening, reticulation, honeycombing, bronchiectasis and the extent of the affected area were significantly improved 30, 60 and 90 days after discharge compared with at discharge. The more severe the clinical classification of COVID-19, the more severe the residual pulmonary fibrosis was; however, in most patients, pulmonary fibrosis was improved or even resolved within 90 days after discharge.


Pulmonary fibrosis can occur as a serious complication of viral pneumonia, which often leads to dyspnea and impaired lung function. It significantly affects quality of life and is associated with increased mortality in severe cases [12]. Patients with confirmed severe acute respiratory syndrome coronavirus (SARS‐CoV) or Middle East respiratory syndrome coronavirus (MERS‐CoV) infections were found to have different degrees of pulmonary fibrosis after hospital discharge, and some still had residual pulmonary fibrosis and impaired lung function two years later. In addition, wheezing and dyspnea have also been reported in critically ill patients [35].

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel Betacoronavirus that is responsible for an outbreak of acute respiratory illness known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 shares 85% of its genome with the bat coronavirus bat-SL-CoVZC45 [6]. However, there are still some considerable differences between SARS-CoV-2 and SARS‐CoV or MERS‐CoV. Whether COVID-19 can trigger irreversible pulmonary fibrosis deserves more investigation. George reported that COVID-19 was associated with extensive respiratory deterioration, especially acute respiratory distress syndrome (ARDS), which suggested that there could be substantial fibrotic consequences of infection with SARS-CoV-2 [7]. Moreover, it has also been shown that the pathological manifestations of COVID-19 strongly resemble those of SARS and MERS [8], with pulmonary carnification and pulmonary fibrosis in the late stages.

Chest X-rays and high-resolution computed tomography (HRCT) of the chest play important auxiliary roles in the diagnosis and management of patients with suspected cases of COVID-19 [910]. The newly applied artificial intelligence (AI)-assisted pneumonia diagnosis system has been described as an objective tool that can be used to qualitatively and quantitatively assess the progression of pulmonary inflammation [11]. At present, although COVID-19 has been classified as a global epidemic for months, the risk factors for and severity and evolution of pulmonary fibrosis have not yet been reported. In this study, this new technology was applied to investigate the pulmonary imaging characteristics and related risk factors in COVID-19 patients at the time of hospital discharge, as well as the evolution of pulmonary fibrosis 30, 60 and 90 days after discharge, with the aim of providing an important basis for the clinical diagnosis, treatment and prognostic prediction of COVID-19-related pulmonary fibrosis.

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Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)—A Systemic Review and Comparison of Clinical Presentation and Symptomatology

Authors: Timothy L. Wong* and Danielle J. Weitzer


Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness—myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.

1. Introduction

Coronavirus disease 2019 (COVID-19), a highly contagious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was declared a pandemic by the World Health Organization in March 2020 [1]. As of 7 March 2021, there are over 100 million cumulative cases, with over 2.5 million deaths worldwide [2]. Within the United States alone, there have been almost 30 million cumulative cases, with over half a million deaths as of mid-March [3].

In terms of clinical profile and disease symptomatology, individuals afflicted with COVID-19 vary greatly in terms of clinical presentation [4,5]. While some individuals remain asymptomatic, others experience symptoms generally associated with other viral respiratory diseases, such as fever, cough, dyspnea, headache, and sore throat [6,7,8]. During the acute phase of COVID-19, various other systemic impacts including gastrointestinal, renal, hepatological, rheumatological, and neurological symptoms and complications have been reported [9,10]. While there continues to be significant public concern and research centered around the acute course and presentation of COVID-19, there is increasing public and academic interest in the chronic sequelae of the disease [11,12,13].

There is currently no uniform terminology for this so-called long COVID [14], or, as it has also been termed, long-haul COVID-19 [15,16], post-COVID syndrome [17], chronic COVID syndrome [18], and more recently, post-acute sequelae of SARS-COV-2 infection (PASC) [19]. There is no established case definition or diagnostic criteria, but some have suggested long COVID as being defined by persistent signs and symptoms more than four weeks after initial infection with SARS-COV-2 [20,21]. Research into the prevalence of long COVID is ongoing, but one study has estimated that over 87% of COVID patients continue to experience at least one symptom, two months after COVID symptom onset [22]. The risk for developing long COVID does not appear to be correlated with the severity of acute illness [23]. The etiologies of long COVID are uncertain, with some linking it to autoimmune condition or hyperinflammatory states after resolution of acute COVID [24,25,26].

The characteristics and mysterious nature of long COVID led some to suggest a connection to a debilitating but lesser-known chronic medical condition: myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [27,28,29]. ME/CFS is a long-term complicated illness characterized by at least six months of fatigue and exhaustion. This illness is estimated to account for USD 18–51 billion dollars in economic costs. In total, 2.5 million Americans suffer from chronic fatigue syndrome, with one quarter of those diagnosed being house or bed bound [30]. Within the general population, the prevalence of chronic fatigue ranges between ten and forty percent. Despite this, due to a lack in diagnostic testing without consistent and established treatments, there has been disputes regarding the actual existence of chronic fatigue syndrome. As the diagnosis is mostly based upon patient’s subjective feedback, this has sparked stigma that has led to dismissive behaviors in the medical community. The misconception regarding chronic fatigue syndrome may have been started because of how it was initially characterized. For example, early reports of chronic fatigue were described as a derogatory term known as the Yuppie Flu, which initially characterized the illness among young workers, with the implication of individuals trying to get out of their job responsibilities. However, since this time, the illness has come to be understood to rather affect a broader array of populations, but with a predominance of women being more affected than men [31]. To better understand this illness, improved knowledge of the research and definitions surrounding the illness is needed.

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Long covid—mechanisms, risk factors, and management

Authors: Harry Crook, research assistant1,  Sanara Raza, research assistant1,  Joseph Nowell, research assistant1,  Megan Young, clinical research officer1,  Paul Edison, clinical senior lecturer, honorary professor12


Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.


Coronavirus disease 2019 (covid-19) has spread across the world. As of 4 July 2021, more than 183 million confirmed cases of covid-19 have been recorded worldwide, and more than 3.97 million deaths have been reported by the World Health Organization .1 The clinical spectrum of covid-19 ranges from asymptomatic infection to fatal disease.23 The virus responsible for causing covid-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters cells via the angiotensin-converting enzyme 2 (ACE2) receptor.4 Once internalized, the virus undergoes replication and maturation, provoking an inflammatory response that involves the activation and infiltration of immune cells by various cytokines in some patients.5 The ACE2 receptor is present in numerous cell types throughout the human body, including in the oral and nasal mucosa, lungs, heart, gastrointestinal tract, liver, kidneys, spleen, brain, and arterial and venous endothelial cells, highlighting how SARS-CoV-2 can cause damage to multiple organs.67

The impact of covid-19 thus far has been unparalleled, and long term symptoms could have a further devastating effect.8 Recent evidence shows that a range of symptoms can remain after the clearance of the acute infection in many people who have had covid-19, and this condition is known as long covid. The National Institute for Health and Care Excellence (NICE) defines long covid as the symptoms that continue or develop after acute covid-19 infection and which cannot be explained by an alternative diagnosis. This term includes ongoing symptomatic covid-19, from four to 12 weeks post-infection, and post-covid-19 syndrome, beyond 12 weeks post-infection.9 Conversely, The National Institutes of Health (NIH) uses the US Centers for Disease Control and Prevention (CDC) definition of long covid, which describes the condition as sequelae that extend beyond four weeks after initial infection.10 People with long covid exhibit involvement and impairment in the structure and function of multiple organs.11121314 Numerous symptoms of long covid have been reported and attributed to various organs, an overview of which can be seen in fig 1. Long term symptoms following covid-19 have been observed across the spectrum of disease severity. This review examines the long term impact of symptoms reported following covid-19 infection and discusses the current epidemiological understanding of long covid, the risk factors that may predispose a person to develop the condition, and the treatment and management guidelines aimed at treating it.

Multi-organ complications of covid-19 and long covid. The SARS-CoV-2 virus gains entry into the cells of multiple organs via the ACE2 receptor. Once these cells have been invaded, the virus can cause a multitude of damage ultimately leading to numerous persistent symptoms, some of which are outlined here.

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COVID-19 – A vascular disease

Authors: Hasan K. Siddiqi,a,bPeter Libby,a,⁎ and Paul M Ridkera,b


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to multi-system dysfunction with emerging evidence suggesting that SARS-CoV-2-mediated endothelial injury is an important effector of the virus. Potential therapies that address vascular system dysfunction and its sequelae may have an important role in treating SARS-CoV-2 infection and its long-lasting effects.

SARS-CoV-2 infection and vascular dysfunction

In health, the vascular endothelium maintains homeostasis through regulation of immune competence, inflammatory equilibrium, tight junctional barriers, hemodynamic stability as well as optimally balanced thrombotic and fibrinolytic pathways. In the novel coronavirus disease of 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dysregulation of many of these pathways has emerged as a mediator of severe disease. The constellation of clinical and biomarker derangements seen in COVID-19 can be classified into disruption of the immune, renin-angiotensin-aldosterone (RAA), and thrombotic balance, all of which converge on the vascular endothelium as a common pathway. Accumulating evidence from basic science, imaging and clinical observations, has clarified the picture of COVID-19 as a vascular disease. Understanding the disease in this context may provide novel avenues of understanding COVID-19 and lead to critically needed improvements in therapeutic strategies.

SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) to facilitate entry into target cells and initiate infection. This viral entry into the cell is further mediated by transmembrane serine protease 2 (TMPRSS2) and cathepsin L which cleave the S protein on the viral particle to permit engagement with ACE2 [1]. Endothelial cells (ECs) in general and cardiac pericytes in particular express abundant ACE2, making them a direct target of SARS-CoV-2 infection (Fig. 1 ) [2]. Examination of the pulmonary vascular bed shows severe derangements in COVID-19, compared to control and influenza patients, particularly with widespread thrombosis and microangiopathy, endothelial activation and extensive angiogenesis [3]. These studies and pervasive findings establish the role of viral injury to the vascular system with resulting vascular dysfunction in COVID-19 patients [4].

Fig. 1

Open in a separate windowFig. 1

SARS-CoV-2 Induced Endothelial Injury

Legend: A schematic of SARS-CoV-2 infection and proposed resulting endothelial injury, involving immune activation, pro-thrombotic milieu, and RAAS dysregulation. These insults interact with each other to cause end-organ dysfunction that is manifest in many COVID-19 patients.

TMPRSS2 = Transmembrane protease serine 2; ADAM17 = A disintegrin and metalloproteinase 17; TNF = Tumor necrosis factor; TNFr = Tumor necrosis factor receptor; TLR = toll-like receptor; DAMPs = Damage-associated molecular patterns; PAMPs = Pathogen-associated molecular patterns; PAI-1 = plasminogen activator inhibitor-1; vWF = von Willebrand factor; eNOS = endothelial nitric oxide; tPA = tissue plasminogen activator; AT1R = angiotensin 1 receptor; ARDS = acute respiratory distress syndrome.

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