SARS-COV-2 INFECTION AND INVOLVEMENT OF PERIPHERAL NERVOUS SYSTEM: A CASE SERIES OF CARPAL TUNNEL SYNDROME AGGRAVATION OR NEW ONSET WITH COVID-19 DISEASE AND A REVIEW OF LITERATURE.

COVID-19 may be asymptomatic or have a typical presentation with fever, cough, anosmia, lymphocytopenia. In some cases, it occurs with a "chimeric" presentation, with more subtle and ambiguous symptoms which may be initially misdiagnosed and are referred to in long covid condition. A possible central and peripheral nervous system involvement has been recognized. We present our experience and review the literature about association between carpal tunnel syndrome (CTS) and hand's arthritis presenting a case series of patients who firmly state that their condition of CTS arised or got worse during a typical presentation of COVID-19. The outbreak of COVID-19 has resulted in significant global healthcare implications. While the respiratory manifestations of COVID-19 have been widely studied, there is emerging evidence suggesting potential associations between COVID-19 and various other health conditions. This review of the literature aims to investigate the potential relationship between COVID-19 and the development or exacerbation of CTS. By synthesizing the available literature on this topic, we aim to provide a comprehensive overview of the current knowledge and enhance our understanding of the potential implications of COVID-19 on CTS. Case series: In this article we report 13 cases of typical presentations of COVID-19 with fever, myalgia, and respiratory system involvement, with a simultaneous aggravation of the median nerve pre-existing neuralgia and some cases that developed a median nerve neuralgia during COVID-19, which came to the attention of the hand surgeon. Some cases had stable symptomatic CTS and were on waiting list for surgical carpal tunnel release, some cases were previously asymptomatic and developed a median nerve neuralgia during COVID-19. All patients referred to a rapid worsening of acral paraesthesia and neuralgic pain of the same quality of CTS and in the median nerve topography. Some patients developed typical COVID-19 symptoms and died; the others were surgically treated. CTS could be an atypical presentations of COVID-19 or a condition of long-covid disease and clinical and epidemiological significance needs to be fully studied. We presented cases of worsening of the median nerve neuralgia which presented among other symptoms of COVID infection. We conclude a causal relation may exist and needs to be further investigated.

Molecular events in chronic myeloid leukemia progression.

Chronic myelogenous leukemia presents two distinct clinical phases: the chronic phase is characterised by a marked expansion of the myeloid compartment which still retains a normal differentiative capacity, whereas a differentiation block is the clinical hallmark of the acute transformation. The molecular mechanism underlying the CML progression are still poorly understood. The occurrence of additional molecular lesions, involving the p53, the RAS and the p16 genes may complement and fulfil the BCR/ABL transforming potential, finally leading to an acute leukemic phenotype. However, several lines of evidence suggest that also quantitative changes of the BCR/ABL transcript amounts could explain the progression of the leukemic phenotype in the BCR/ABL-positive hematologic malignancies.

The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occuring in children with Down syndrome.

Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk of developing acute leukaemias, both of myeloid and lymphoid lineage. Although the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate genes include the ones on chromosome 21, and in particular AML1, the rearrangement of which in the t(8,21) is associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has been described by molecular analysis as the most recurrent genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to investigate whether the t(12;21) could give a molecular clue as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cases of ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1 rearrangement among the 11 cases tested. This data may be suggestive of alternative pathways involved in the pathogenesis of ALL in children with constitutional trisomy 21.

Molecular pathways in low grade B-cell lymphoma.

Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly heterogeneous group of lymphoproliferative disorders, including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid lymphoma (LPL), follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The molecular pathogenesis of low grade B-NHL is characterized by distinct genetic pathways which selectively associate with each clinicopathologic category. At diagnosis, B-CLL/SLL frequently display deletions of 13q14 and trisomy 12, whereas evolution to Richter's syndrome associates with disruption of p53. LPL carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of FL cases accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL are characterized by the frequent occurrence of trisomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutations in a fraction of cases. The identification of distinct genetic categories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL have proved to be a useful molecular marker for monitoring minimal residual disease.

Use of the Oximeter-539 WTW, equipped with a sensor Trioxmatic-300, for the functional analysis of dilute solutions of human Hb-A.

Dissociation curves for oxygen of dilute samples of human adult Hb-A were evaluated on this occasion, by using the Oximeter-539 WTW with its sensor, and a suitable spectrophotometer. At this purpose, Hb samples were desaturated in oxygen upon given experimental conditions, by bubbling pure nitrogen in them, and their re-oxigenation in air was followed, step by step, by multiple oximetries. In addition, all the spectrophotometric measurements of the saturation of Hb-O2%, corresponding to each individual oximetry, were carried out parallely but separately. Dilution of Hb-A was maintained at 0.1 mM in heme. The p50 at pH 7.3 was 4.435 +/- 0.299 Torr, with the n-value of 2.7 +/- 0.2; Bohr effect was -0.55 +/- 0.08, within a pH range between 6.8, 7.3 and 7.8, whereas chloride and DPG effects at pH 7.3 (the most useful value) were 0.42 +/- 0.44 and 0.453 +/- 0.0187 respectively. In conclusion, these results are similar to those obtained with automated procedures, upon comparable experimental conditions, but do not require expensive and sophisticated instruments. Such a technique could be very useful in the hemoglobinopathies, which are common in Italy, and it could be easily adapted to perform comparative studies on animal hemoglobins not far from human species.

A serologic survey of bovine rotavirus infection in Italy.

Serum neutralization tests conducted by microtiter procedure on 2970 serum samples from calves, heifers and adult cows from representative regions of Italy indicate that rotaviruses, and the infection which they cause, existed in Italy long before the virus was isolated. At the present time the infection is distributed fairly uniformly throughout the cattle population with both sexes and all age groups being equally susceptible.

Neonatal calf diarrhea induced by rotavirus.

This presentation summarizes the results of a comprehensive study on rotaviruses isolated in Italy from calves and rabbits affected by neonatal diarrhea. The results clearly indicated that rotavirus infection is widespread and supported the evidence for an etiologic role of these viruses in neonatal diarrhea. The evidence of differences in virulence among bovine rotaviruses appeared also to be confirmed. Conventionally reared calves were fully susceptible to the experimental infection induced by three rotaviruses originating from heterologous hosts, i.e. monkeys, pigs and rabbits, respectively. When rotavirus strains of bovine, simian, porcine and rabbit origin were compared by cross neutralization tests, it was found the simian and porcine strains were indistinguishable and both appeared to relate antigenically to the bovine strain. On the other hand, a reciprocal antigenic correlation was found between bovine and rabbit isolates. Finally, it was proven that feeding newborn calves with colostrum of their dams, previously vaccinated with an inactivated rotavirus vaccine, could prevent the neonatal diarrhea from occurring.

Experimental infection of calves with strains of Bovid herpesvirus-4.

Fourteen calves were inoculated intranasally (i.n.) with the viral isolates as follows: 5 with 85/BH 16TV, 1 with 85/BH 17TV, 1 with 85/BH 18TV, 2 with 85/BH 231TN and 5 with 85/BH 232TN. Strain 85/BH 16TV was the only one which caused overt respiratory-like disease in all inoculated calves. Onset of the disease was observed after 7-8 days of incubation and was characterized by fever, depression, nasal discharge and coughing. Virus was isolated from the nasal swabbings of calves obtained from post-infection day (PID) 2-10. The other viral strains did not cause any sign of disease although virus was isolated regularly from the nasal swabbings of the inoculated calves. Virus was recovered from central nervous system tissues of calves that were infected with 85/BH 16TV or 85/BH 232TN strains and were killed on PID 4 or 8. Virus was also isolated from other tissues, such as lymph node, nasal mucosa (PID 8), or lung (PID 4). It was speculated that the nervous system could be one of the target areas of the virus of the naturally occurring infection by BHV-4. This might indicate a possible role of the nervous system (site of latency?) in the pathogenesis of BHV-4 as is the case in certain herpesviral infections of man and the lower animals.

Experimental infection and cross protection tests in calves with cytopathic strains of bovine rotavirus.

Four cytopathic strains (81/32F, 81/36F, 81/40F, 82/80F) of bovine rotavirus were shown to be pathogenic for conventionally reared newborn calves. Calves were infected orally, using 3 calves for each isolate. All became febrile, were depressed and diarrhoeic. Two calves, one of which in the group of those infected with 81/36F isolate, and the other infected with strain 81/40F, were killed when moribund. A 3rd calf from the 81/36F infected group, died. At necropsy localized lesions of the small intestines, which are considered to be typical of rotavirus infection, were found. Virus was consistently isolated from the fecal samples of the inoculated calves up to 13 days post-inoculation. It was speculated that some differences existed in the virulence of the bovine rotaviruses tested. The cross protection tests revealed that 1 strain (81/36F) might be antigenically more complex than the others.

Reactivation of Bovid herpesvirus 1 and 2 and parainfluenza-3 virus in calves latently infected.

Two experiments were carried out to determine whether Bovid herpesvirus (BHV) 2 is able to induce a recurrent infection in experimentally infected calves. In the first experiment the stress induced by dexamethasone (DMS) treatment failed to reactivate the clinical condition or to induce shedding of BHV2. However, treatment with DMS reactivated a latent BHV1 infection in all calves previously inoculated with BHV2 and also in two noninoculated controls. Probably, because of the interference by BHV1 the study failed to resolve the question as to whether BHV2 could induce a recurrent infection. Consequently, a second experiment was performed using calves devoid of antibody to BHV1 and, therefore, probably, free of virus. By this study it was demonstrated that BHV2 can remain as a latent infection in cattle, which, when immunosuppressed as with DMS, can be reactivated. A finding of considerable interest in this experiment was that in 1 calf a concurrent piroplasma infection was also, unexpectedly, discovered. Recrudescence of latent BHV1 infection was induced by DMS treatment of calves possessing antibody to the virus. The infection once reactivated, was readily transmitted by contact to three other calves devoid of antibody to BHV1. In the same experiment Parainfluenza-3 (PI-3) virus was unexpectedly isolated from all calves. It was speculated that all calves were latently infected with PI-3 virus with concurrent infection by HBV1 acting as a stress inducing PI-3 reactivation. These studies seem to indicate that mixed infections could have an important role in the mechanism involved in the establishment of latent infections and viral reactivation.

A study of cytopathic rotavirus strains isolated from calves with acute enteritis.

Nine cytopathic bovine rotavirus strains were isolated in MA-104 cell cultures from fecal specimens of dairy calves suffering from diarrhea. Isolation of the virus was accomplished from three outbreaks which occurred on dairy farms located in Central and Southern Italy. Fecal suspensions were treated with a high concentration (1000 micrograms/ml) of trypsin, and inoculated into MA-104 cell cultures grown out in Eagle's minimum essential medium (MEM) containing 5 micrograms/ml of the enzyme. Cytopathic effects (CPE), characterized by intracytoplasmic inclusion bodies of different sizes and shapes, were observed on the 1st passage with five of the strains and on the 2nd (2 strains) or the 3rd (2 strains) passage for the others. The presence of trypsin and the use of MA-104 cells appeared to be essential for the occurrence of CPE, inasmuch as no CPE was detected when trypsin was omitted in the MA-104 cell system. Replication failed to occur when primary bovine embryo kidney cell cultures with or without trypsin were used. Electron microscopy revealed the presence of particles with a typical rotavirus morphology. In MA-104 cells, the titre of virus reached its maximum 48 hr after inoculation. Small, clear-cut plaques were produced by the isolates in MA-104 cells under the overlay of MEM containing carboxymethyl cellulose, trypsin and DEAE-dextran. The nine rotavirus strains were antigenically related, whereas the relationship to either the Nebraska or the Compton rotaviruses was quite weak.

The efficacy of colostrum from cows vaccinated with rotavirus in protecting calves to experimentally induced rotavirus infection.

Calves which were continuously fed colostrum from vaccinated cows for the first ten days of life, were fully refractory to experimental infection with strain 81/36 F of bovine rotavirus. By contrast, the response to virus exposure of calves which were treated with normal colostrum was identical to that of the control calves, in that they underwent severe diarrhea and a significant slowing of the growth rate. The antibody titer in the milk of vaccinated cows tends to decline rapidly so that it no longer provides any protective effect. Two alternatives were considered feasible in improving prophylaxis for rotavirus infections: (a) the continuous feeding of calves with 1st day colostrum as part of the ration throughout the period of greatest risk (first week of life), or (b) enhancing the efficacy of the vaccine in pregnant cows to the point where antibody concentration in the milk would remain at a protective level.

Comparative study of rotavirus strains of bovine and rabbit origin.

Newborn calves were susceptible to infection with a rotavirus strain isolated from rabbits and, conversely, rabbits 4-5 weeks of age became ill and some died when inoculated with the rotavirus strain of bovine origin. However, the latter isolate appeared to be more virulent than the rabbit isolate in either calves or rabbits. Moreover, in reciprocal cross protection tests, carried out in calves and in rabbits, the rabbit rotavirus antiserum afforded only weak protection to challenge infection with either the homologous or the heterologous virus. By contrast, the protective level of the bovine rotavirus antiserum was relatively high.

A study of bovid herpesvirus 2 infection in calves inoculated intradermally or intranasally.

Bovid herpesvirus 2 infection was studied in calves exposed to the virus by intradermal inoculation of the skin of the left cheek or by nasal spray. In either case a localised infection developed and virus replication was shown to occur mostly in the tissues of its primary localisation, i.e. the skin of the left cheek or the nasal mucosa. There were neither secondary lesions, except at the site of virus injection, nor any serious systemic involvement on the part of the animals. The virus was also recovered from some areas of the skin (right cheek, perineum and scrotum) that were free of macroscopic lesions; moreover, intranuclear inclusions were found in several tissues of the nervous system (brain, superior cervical, stellate and Gasserian ganglia) which did not show any signs of inflammatory or degenerative changes. These findings suggest that the skin and the nervous system play an important role in the naturally-occurring disease since they could be the sites where the virus is maintained latently in the host.

A study of a herpesvirus isolated from dairy cattle with a history of reproductive disorders.

Three strains of herpesvirus were recovered from cows with vulvovaginitis. The three isolates (85/BH 16TV, 85/BH 17TV, 85/BH 18TV), when compared by cross serum neutralization (SN) tests, were found to be antigenically identical. They were serologically distinct from infectious bovine rhinotracheitis (IBR) virus and Bovid herpesvirus 2 (BHV2), while they cross reacted with bovine herpesvirus DN-599. Besides the serologic aspects, the three isolates appeared to share common biological, physical and morphological properties with the newly recognized bovine herpesviruses, of which DN-599 is a representative strain.

Comparative studies of strains of infectious bovine rhinotracheitis virus isolated from latently infected calves.

Three strains (479 C, 778 TL, 982 LE) of infectious bovine rhinotracheitis (IBR) virus isolated from latently infected calves were compared with the prototype strain of IBR virus (LA strain) in studies which included restriction endonuclease analysis, experimental infection, and reciprocal cross protection tests in cattle. From the restriction endonuclease analysis it appeared that the 3 "latent" viruses were derived from the same isolate, and that it differed slightly from the LA strain. However, latency does not seem to have affected the pathogenicity or the immunogenicity of the virus. This is demonstrated by the identical clinical and virologic response of calves subjected to experimental infection with the various strains under study, and by the finding that when the LA strain and a "latent" strain (982 LE) were tested in cross protection tests in cattle, they proved to be mutually protective.

Distribution of Bovid herpesvirus 2 in calves inoculated intravenously.

The behavior of Bovid herpesvirus 2 in the skin, lymph nodes, and nervous system of calves injected intravenously with the virus was studied. After a latent phase that lasted up to 40 hours after inoculation, the virus produced a systemic infection which was characterized by primary localization of virus in the skin, lymph nodes, and nervous system. Between postinoculation days 7 and 12, the infection tended to persist in the skin only. The finding of intranuclear inclusions in the pyramidal cells of the cerebral cortex and in the neurons of the superior cervical and stellate ganglia supports the hypothesis that the virus might utilize the structures of the nervous system for its replicative cycle in the calf.

Attempts to reactivate bovid herpesvirus-2 in experimentally infected calves.

A study was carried out to determine whether bovid herpesvirus-2 (BHV-2) is able to induce a recurrent infection in experimentally infected calves. Twelve calves infected with the virus were treated with dexamethasone (DMS) beginning 69 days after the infection, ie, several weeks after the animals had recovered from the disease and were negative for BHV-2. The stress induced by DMS treatment failed to reactivate the clinical condition or to induce shedding of BHV-2. However, treatment with DMS reactivated a latent infectious bovine rhinotracheitis (IBR) virus infection in all calves previously inoculated with BHV-2, and also in 2 noninoculated controls. The reactivation of IBR virus occurred without any clinical evidence of the disease, but the virus was isolated from nasal and pharyngeal swabbings and from the organs. A proliferative ganglionitis of the trigeminal ganglion was also observed. Because of the interference by IBR virus, this study did not resolve the question as to whether BHV-2 can induce a recurrent infection.