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“About 14% of patients who recovered from the novel coronavirus and were discharged from hospitals in southern China’s Guangdong province were tested positive again in later check-ups”
“All 4 patients were exposed to the novel 2019 coronavirus through work as medical professionals. Two were male and the age range was 30 to 36 years. Among 3 of the patients, fever, cough, or both occurred at onset. One patient was initially asymptomatic and underwent thin-section CT due to exposure to infected patients.
All 4 patients had 2 consecutive negative RT-PCR test results. The time from symptom onset to recovery ranged from 12 to 32 days.
After hospital discharge or discontinuation of quarantine, the patients were asked to continue the quarantine protocol at home for 5 days. The RT-PCR tests were repeated 5 to 13 days later and all were positive. All patients had 3 repeat RT-PCR tests performed over the next 4 to 5 days and all were positive. An additional RT-PCR test was performed using a kit from a different manufacturer and the results were also positive for all patients. The patients continued to be asymptomatic by clinician examination and chest CT findings showed no change from previous images. They did not report contact with any person with respiratory symptoms. No family member was infected.”
“SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury.
Most of the infected cells were T cells. Some B cells and NK cells also were infected by the virus.
Spleen and Lymph nodes
In situ hybridization identified the SARS viral sequence in the enlarged macrophages and in the isolated and sometimes clustered T lymphocytes, which were distributed mostly at the periphery of the germinal centers of the splenic white pulp, lymph nodes, and peripheral blood
The lymphoid component of the intestine showed widespread degenerative changes. The lymphoid follicles (Peyer's patches) showed markedly decreased lymphocytes (Fig. 3 A), and in severe cases only the depleted stromal framework of the structure remained.
In addition, the epithelial cells of mucosa of the small and large intestines were found to be infected by the virus by in situ hybridization and EM
The kidneys were focally hemorrhagic.
SARS genome sequences were detected in the brain of all SARS autopsies with LM, EM, and with real-time RT-PCR. The signals were confined to the cytoplasm of numerous neurons in the hypothalamus and cortex (Fig. 3 O). Edema and scattered red degeneration of the neurons were present in the brains of six of the eight confirmed cases of SARS.
The testes of the seven male patients displayed focal atrophy.
It is evident that infection by the SARS virus is not confined to the lungs, but also involves other parts of the respiratory tract and other organ systems, most importantly immune cells, particularly the T lymphocytes, monocytes, and macrophages. The finding of early and consistent decreases of T lymphocytes in 65 patients who had SARS, but not in the 35 misdiagnosed patients, further suggests that lymphocyte damage is the hallmark of SARS. Administration of glucocorticoids contributed to a decrease in lymphocyte counts in both groups of patients; however, the difference in counts between the two groups persisted after glucocorticoid therapy. It was reported that lymphopenia is one of the earliest changes, and is a reliable prognostic predictor in SARS (13–18). An extensive literature search has not revealed a report of any other type of pneumonitis producing such severe lymphopenia. As the only logical explanation for the early and consistent lymphopenia that is demonstrated in patients who have SARS, we suggest that lymphocytes—particularly T lymphocytes—are infected and destroyed by the virus or by other immune cells.
The observation of virus in neurons may provide an explanation for the higher than usual incidence of neuronal and psychologic abnormalities that are seen in patients who have late-stage SARS
The damage to the immune system, more than damage to the lungs, determines whether a patient recovers or dies from the infection. In a way, the name “sudden acute respiratory syndrome” is inappropriate because it diverts attention from the primary pathologic changes that result from SARS virus infection. It must be emphasized that immune damage most likely is the primary determinant of clinical outcome.”
“While MHV proteins are generally restricted to the cytoplasm, the nucleocapisd proteins of coronaviruses representing groups I, II, and III were shown to localize to the nucleolus as well as to the cytoplasm (343). This report suggests that N protein induces a cell cycle delay or arrest, most likely in the G2/M phase, possibly by inhibition of cytokines.
the E protein of SARS-CoV has been shown to induce apoptosis when expressed in Jurkat T cells, and this activity is inhibited by expression of the antiapoptotic protein Bcl-xL (348). Those authors suggest that T-cell apoptosis may contribute to the SARS-CoV-induced lymphopenia that is observed in most SARS patients.
Like other RNA viruses, all coronaviruses encode, in addition to structural proteins and replicase proteins, small nonessential proteins of unknown function. There are many examples of such proteins, encoded by RNA viruses, which interact with and compromise the alpha/beta interferon response
Analysis of gene expression of PBMCs of SARS patients by using a microarray platform that includes more than 8,000 gene sequences suggests that the response of SARS patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection. Those authors did not find significant upregulation of major histocompatibility complex class I genes or major cytokines, including IFNs (IFN-α, IFN-β, and IFN-γ), or genes involved in complement-mediated cytolysis. They concluded that the immune response against the SARS-CoV may be different from that in other viral infections or that the virus may be using an unusual strategy to evade the host immune system and cause the pathogenesis and mortality.
Lymphopenia and increasing viral load in the first 10 days of SARS suggest immune evasion by SARS-CoV. The lack of an IFN-β response in SARS-CoV-infected cells has been reported in vitro, using human primary myeloid-derived dendritic cells (176) and the epithelial 293 cell line (291). Law et al. (176) proposed a mechanism of immune evasion by SARS-CoV in DCs, based on their findings of low expression of antiviral cytokines (IFN-α, IFN-β, IFN-γ, and IL-12p40), moderate upregulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and IL-6), and significant upregulation of proinflammatory cytokines (MIP-1α, RANTES, IP-10, and MCP-1). Spiegel et al. (291) demonstrated that SARS-CoV escapes interferon-mediated growth inhibition by preventing the induction of IFN-β through interfering with the activation of IFN regulatory factor 3. The mechanism of lymphopenia remains unclear. The rapid decrease in both CD4 and CD8 T cells may be associated with an adverse outcome (185, 338). Due to the absence of ACE2 expression in T- and B-cell lymphocytes (126), it seems unlikely that SARS-CoV-induced lymphopenia may be caused by direct viral infection. Rather it has been suggested that apoptosis of uninfected lymphocytes may lead to the acute lymphopenia observed in SARS patients. In this sense, various SARS-CoV proteins have been suggested to induce apoptosis in vitro. These include ORF 7a (305), ORF 3a (177), and ORF 3b (366), in addition to E protein (see above) and N protein”
“We previously reported that a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers triggered infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents
SARS-CoV-induced pathology is not confined to the respiratory tract but also involves other tissues and organs, most importantly cells of the gastrointestinal tract and the immune system
The outcome of infection with SARS-CoVpp in the presence of anti-Spike immune-serum depended on the target cell type. Although heat-inactivated serum inhibited SARS-CoVpp entry into the permissive VeroE6 cell line in a dose-dependent fashion, as demonstrated by a dramatic drop in the intensity of luminescence (Fig. 1A and B, hatched bars), it facilitated infection of the human monocytic cell line THP-1 and of the B cell lines Daudi and Raji. In contrast, no infection of these cell lines was noticed when SARS-CoVpp were preincubated with control serum
Taken together, these experiments indicate that anti-Spike serum can trigger infection of immune cells by live SARS-CoV, similarly to that observed with the pseudotyped viral particles.
Altogether, these results indicate that despite the ability of SARS-CoV to exploit antiviral antibodies to invade Raji B cells, only abortive replication occurs upon infection, and no infectious virus is released from the ADE-infected Raji cells.
We demonstrate here that anti-Spike antibody potentiates infection of immune cells by SARS Spike-pseudotyped lentiviral particles and replication-competent SARS-coronavirus.
Our experiments conclusively demonstrate with several lines of evidence that both SARS-CoVpp and replication-competent SARS-coronavirus infect certain immune cells only in the presence of anti-Spike immune serum and not in its absence.
The observation of a change of tropism of SARS-CoV in the presence of antiviral immune serum distinguishes the ADE of SARS-CoV infection from many other examples of antibody-mediated viral infection
Altogether, our results report a novel mechanism by which SARS-CoV can enter into target cells that do not express the conventional virus receptor and are otherwise refractory to the virus. This may have implications for understanding the tropism and pathogenesis of the virus and highlight potential pitfalls associated with immunization against this coronavirus. These findings should prompt further investigations for a better understanding of the molecular and cellular mechanisms underlying ADE of SARS-CoV infection. The consequences of this alternative infection pathway on the functionality and/or homeostasis of the target cells also need to be resolved.”
“Mice depleted of both CD4+ and CD8+ T cells, which therefore lacked both T-cell and Ab responses to the virus, were able to control SARS-CoV replication in the lungs by day 12 p.i., suggesting an immune mechanism independent of Abs and T cells.
The activation of the innate defense system at the early phase of infection appears to play an important role in the control of SARS-CoV replication. A second wave of inflammatory mediators noted on day 7 p.i. involved an increase of the cytokines TNF-α and IL-6 and chemokines CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL9/MIG, and CXCL10/IP-10 and an increase of T-cell-mediated inflammatory cytokines IFN-γ, IL-2, and IL-5.”
“While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae
No evidence of inflammation was detected in the brains of any infected K18-hACE2 mice even when infection was widespread
GFAP expression by astrocytes was detected in limited areas in SARS-CoV-infected animals with a distribution and intensity of staining similar to that observed in naïve animals (Fig. 6A). In contrast, JHMV-infected brains displayed upregulation of GFAP, and the GFAP-positive cells were found throughout the brain. These findings suggest that astrocytes in SARS-CoV-infected mice were not activated, despite extensive neuronal infection.
In all studies that examined brain sections from Human SARS patients, virus was detected almost exclusively in neurons.
Our results suggest that SARS-CoV primarily entered the brain via the olfactory nerve. However, the rate at which SARS-CoV spread within the brain was striking. Viral antigen was not detected until 60 to 66 h p.i. and, by this time, was already present in the olfactory bulb and several brain regions connected to this structure. Furthermore, 6 to 12 h later, viral antigen was detected throughout the brain and had spread to first- and second-order structures connected with the olfactory bulb as well as structures only remotely connected with the olfactory system.
SARS-CoV infects dendritic cells… may be one mechanism that would result in a diminished inflammatory response. It is also striking that we detected no evidence of apoptosis (Fig. 5B). Cells that die by necrosis would be expected to induce an immune response, but this was not detected in the SARS-CoV-infected CNS”
originally posted by: scraedtosleep
a reply to: SoulReaper
I honestly think we should stop worrying about the virus and focus on the power the government has granted itself.
That power move is much scarier than any virus imo.