Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses.

A subset of COVID-19 patients exhibit post-acute sequelae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median = 74 days) compared with 30 who had symptom resolution within 20 days. Individuals with prolonged symptom duration maintained antigen-specific T cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and circulating T follicular helper cell populations during late convalescence, while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 spike protein. Significant correlations between symptom duration and both SARS-CoV-2-specific T cells and antibodies were observed. Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups, suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2-specific immune responses are maintained in patients suffering from prolonged post-COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.

SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence.

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase in B lymphocytes. Our findings show increased frequencies of T cell activation markers (CD69, OX40, HLA-DR, and CD154) in hospitalized patients, with other T cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization followed by an increase in PD1 frequencies in nonhospitalized individuals. Interestingly, many of these changes were found to increase over time in nonhospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation after SARS-CoV-2 infection. Changes in T cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation after SARS-CoV-2 infection, highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

COVID-19 infection and thrombosis.

BACKGROUND: Recent reports on outbreak of SARS-CoV-2 coronavirus (COVID-19) have shown its association with abnormal blood clots. The viral infection initiates inflammatory responses leading to endothelial damage and coagulation cascade dysfnction. Spread of COVID-19 has been associated with disseminated intravascular coagulation (DIC) and subsequent coagulopathy. Initially coagulopathy in COVID-19 patients result in significant elevation of D-dimer, fibrin/fibrinogen degradation products (FDP), and abnormalities in coagulatory parameters, which resulting in formation of thrombus and eventually death. METHODOLOGY: Present report intends to summarize the information of the research reports available so far on the complications of formation of unusal blood clots (thrombosis) during COVID-19 infection and its therapeutic strategies. Extensive web search was done for various reports associating COVID-19 infection with increased coagulopathy and abnormal coagulatory parameters such as PT, PTT, and platelet counts; along with increased D-dimer and fibrinogen levels. RESULTS AND CONCLUSION: Findings of these research reports were summarized to recommend cautions for clinicians while treating COVID-19 patient. Screening of coagulatory parameters upon admission and during entire course of treatment is recommended, especially those who are at increased risk of thrombosis. Also, anticoagulant treatment can be used as thromboprophylaxis measure. Dose and duration of anticoagulation treatment requirement may vary and thus regular monitoring is needed.

SARS-CoV-2 infection: physiological and environmental gift factors at high altitude.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic. This viral disease primarily causes lung pneumonia and has a wide range of clinical manifestations. The severity of infection ranges from those who are asymptomatic or with mild symptoms which do not require hospital admission, to those who require ventilator support and eventually die, depending on immunity, age and other comorbidities existing with the patients. The present report is an attempt to study the effect of physiological and environmental factors existing at high altitudes (HA) with spread of SARS-CoV-2 infection. Analysis of existing data revealed that HA natives do possess certain physiological advantages such as (1) improved hypoxic ventilatory response, (2) higher concentration of oxygen carrying molecules, haemoglobin, (3) increased production of Vitamin D, due to intense solar radiation, (4) lower rates of comorbidities such as lung infections, obesity etc. and (5) most importantly reduced production of angiotensin converting enzyme 2, a carrier molecule for SARS-CoV-2 virus entry into the host cell; all of which can collectively account for improved tolerance to SARS-CoV-2 infection in HA natives. In addition, environmental factors at HA such as (6) dry and chilly winds, (7) low air density and (8) intense UV radiations may further inhibit viral growth and spread into the atmosphere. We thus conclude that, high altitude natives may posses physiological and environmental advantage over low landers in terms of reduced severity of SARS-CoV-2 infection and its limited spread. Graphic abstract: Gift factors associated with COVID-19 spread at high altitude.